curcumin and piperine

Metabolic syndrome is characterized by multiple metabolic disorders. Several studies indicated that curcumin plus piperine could affect lipids profiles in various diseases. The present meta-analysis aims to assess the effect of curcumin plus piperine on lipid profiles in patients with MetS and associated disorders using a systematic review and meta-analysis of randomized controlled trials. Trials were searched by several electronic databases up to May 2022. The Comprehensive Meta-Analysis (CMA) version3 software carried out this systematic review and meta-analysis. Random-effects model and the inverse variance method were used to conduct the meta-analysis. We evaluated the publication bias and heterogeneity of all eligible studies. In addition, subgroup analyses and sensitivity assessments were performed to assess potential sources of heterogeneity. The combined results by the random-effects model demonstrated that curcumin plus piperine significantly decreased total cholesterol and LDL-C in patients suffering from metabolic syndrome. In comparison, the results of the overall effect size did not show any significant change in triglyceride concentrations. Our results were robust in sensitivity analysis and were not dependent on the dose of curcumin, the dose of piperine, and the duration of treatment. Our results showed that co-administration of piperine and curcumin supplementation improves the lipid profile in metabolic syndrome. However, further long-term RCTs are required to ascertain their clinical benefit.

Topics: Curcumin; Dietary Supplements; Humans; Metabolic Syndrome; Randomized Controlled Trials as Topic; Triglycerides

Curcumin is extracted from the rhizomes Curcuma longa L. It is known for its anti-inflammatory and anti-oxidant activities. Despite its safety and potential for use against various diseases, curcumin's utility is restricted due to its low oral bioavailability. Co-administration of curcumin along with piperine could potentially improve the bioavailability of curcumin. The present review aimed to provide an overview of the efficacy and safety of curcumin-piperine co-supplementation in human health. The findings of this comprehensive review show the beneficial effects of curcumin-piperine in improving glycemic indices, lipid profile and antioxidant status in diabetes, improving the inflammatory status caused by obesity and metabolic syndrome, reducing oxidative stress and depression in chronic stress and neurological disorders, also improving chronic respiratory diseases, asthma and COVID-19. Further high-quality clinical trial studies are needed to firmly establish the clinical efficacy of the curcumin-piperine supplement.

Topics: Alkaloids; Antioxidants; COVID-19; Curcumin; Dietary Supplements; Humans

Natural plant phytochemicals are effective against different types of diseases, including cancer. Curcumin, a powerful herbal polyphenol, exerts inhibitory effects on cancer cell proliferation, angiogenesis, invasion, and metastasis through interaction with different molecular targets. However, the clinical use of curcumin is limited due to poor solubility in water and metabolism in the liver and intestine. The synergistic effects of curcumin with some phytochemicals such as resveratrol, quercetin, epigallocatechin-3-gallate, and piperine can improve its clinical efficacy in cancer treatment. The present review specifically focuses on anticancer mechanisms related to the co-administration of curcumin with other phytochemicals, including resveratrol, quercetin, epigallocatechin-3-gallate, and piperine. According to the molecular evidence, the phytochemical combinations exert synergistic effects on suppressing cell proliferation, reducing cellular invasion, and inducing apoptosis and cell cycle arrest. This review also emphasizes the significance of the co-delivery vehicles-based nanoparticles of such bioactive phytochemicals that could improve their bioavailability and reduce their systemic dose. Further high-quality studies are needed to firmly establish the clinical efficacy of the phytochemical combinations.

Topics: Curcumin; Humans; Neoplasms; Phytochemicals; Quercetin; Resveratrol

The hypoglycemic properties of curcumin supplements in therapeutic doses are well-known and may represent a useful tool for the treatment of chronic diseases such as metabolic syndrome, insulin resistance and type 2 diabetes. The poor bioavailability of curcumin can be improved with the concomitant administration of piperine, with no severe adverse effects on glycemia reported so far in the literature. In this article, we further discuss a previously reported case of a helicopter pilot, affected by grade I obesity who, under curcumin and piperine treatment, experienced a transient loss of consciousness (TLOC), during a low-altitude flight. This episode led to a diagnosis of insulinoma, previously asymptomatic. We hypothesized that the combined effects of curcumin and piperine might have caused a severe hypoglycemic episode and subsequent TLOC. Therefore, further studies should be conducted to evaluate the safety of curcumin and piperine supplementation in subjects with impaired glucose metabolism and insulin secretion.

Topics: Curcumin; Diabetes Mellitus, Type 2; Glucose; Humans; Hypoglycemic Agents; Insulinoma; Pancreatic Neoplasms; Polyunsaturated Alkamides; Unconsciousness

Curcumin is a polyphenolic compound derived from rhizomes of Curcuma longa, the golden spice. Curcumin has drawn much attention in recent years of biomedical research owing to its wide variety of biologic and pharmacologic actions. It exerts antiproliferative, antifibrogenic, anti-inflammatory, and antioxidative effects, among various imperative pharmacologic actions. In spite of its well-documented efficacies against numerous disease conditions, the limited systemic bioavailability of curcumin is a continuing concern. Perhaps, the poor bioavailability of curcumin may have curtailed its significant development from kitchen to clinic as a potential therapeutic agent. Subsequently, there have been a considerable number of studies over decades researching the scientific basis of curcumin's reduced bioavailability and eventually improvement of its bioavailability employing a variety of therapeutic approaches, for instance, in combination with piperine, the bio-active constituent of black pepper. Piperine has remarkable potential to modulate the functional activity of metabolic enzymes and drug transporters, and thus there has been a great interest in the therapeutic application of this widely used spice as alternative medicine and bioavailability enhancer. Growing body of evidence supports the synergistic potential of curcumin against numerous pathologic conditions when administered with piperine.. In light of current challenges, the major concern pertaining to poor systemic bioavailability of curcumin, its improvement, especially in combination with piperine, and the necessity of additional research in this setting are together described in this review. Besides, the recent advances in the potential therapeutic rationale and efficacy of curcumin-piperine combination, a promising duo, against various pathologic conditions are delineated.

Topics: Alkaloids; Biological Availability; Curcumin; Humans; Polyunsaturated Alkamides

The continued spread of 2019-nCoV has prompted widespread concern around the world. WHO formally named COVID-19 and International Committee on Taxonomy called it Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Due to this viral attack, the whole world is in lockdown. Presently, there is no effective way to control it, except social distancing and hygienic activity. World class scientists and researchers are trying to make vaccine and discover the medicine against the control and cure to this deadly viral disease. Our aim to presenting this article is kick-off deadly viral disease i.e COVID-19 by an easy way with minimum intervention and effort. Different ayurvedic therapeutic agents (Curcuma Longa L, Green tea and Piper nigrum) inhabit entry of virus in host cell, transmission of pathogen and improve the immunity. Curcumin and piperine (1-piperoylpiperidine) interact to each other and form a π-π intermolecular complex which enhance the bioavailability of curcumin by inhibition of glucuronidation of curcumin in liver. Both the molecules curcumin and catechin get bound directly to receptors binding domain of S-protein and ACE-2 receptors of host cell, due to which these molecules inhibit the entry of virus in host cell i. e. animal survives from being infected.

Topics: Alkaloids; Angiotensin-Converting Enzyme 2; Animals; Antiviral Agents; Benzodioxoles; COVID-19; COVID-19 Drug Treatment; Curcumin; Humans; Piperidines; Polyunsaturated Alkamides; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Virus Internalization

Spices have been widely used as food flavorings and folk medicines for thousands of years. Numerous studies have documented the antioxidant, anti-inflammatory and immunomodulatory effects of spices, which might be related to prevention and treatment of several cancers, including lung, liver, breast, stomach, colorectum, cervix, and prostate cancers. Several spices are potential sources for prevention and treatment of cancers, such as Curcuma longa (tumeric), Nigella sativa (black cumin), Zingiber officinale (ginger), Allium sativum (garlic), Crocus sativus (saffron), Piper nigrum (black pepper) and Capsicum annum (chili pepper), which contained several important bioactive compounds, such as curcumin, thymoquinone, piperine and capsaicin. The main mechanisms of action include inducing apoptosis, inhibiting proliferation, migration and invasion of tumors, and sensitizing tumors to radiotherapy and chemotherapy. This review summarized recent studies on some spices for prevention and treatment of cancers, and special attention was paid to bioactive components and mechanisms of action.

Topics: Alkaloids; Antineoplastic Agents, Phytogenic; Apoptosis; Benzodioxoles; Benzoquinones; Capsaicin; Capsicum; Cell Proliferation; Crocus; Curcuma; Curcumin; Garlic; Humans; Neoplasms; Nigella sativa; Phytotherapy; Piper nigrum; Piperidines; Polyunsaturated Alkamides; Spices; Zingiber officinale

Multidrug resistance is a principal mechanism by which tumors become resistant to structurally and functionally unrelated anticancer drugs. Resistance to chemotherapy has been correlated with overexpression of p-glycoprotein (p-gp), a member of the ATP-binding cassette (ABC) superfamily of membrane transporters. P-gp mediates resistance to a broad-spectrum of anticancer drugs including doxorubicin, taxol, and vinca alkaloids by actively expelling the drugs from cells. Use of specific inhibitors/blocker of p-gp in combination with clinically important anticancer drugs has emerged as a new paradigm for overcoming multidrug resistance. The aim of this paper is to review p-gp regulation by dietary nutraceuticals and to correlate this dietary nutraceutical induced-modulation of p-gp with activity of anticancer drugs.

Topics: Abietanes; Alkaloids; Allyl Compounds; Animals; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B; Benzodioxoles; beta Carotene; Biflavonoids; Capsaicin; Catechin; Catechols; Curcumin; Dietary Supplements; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Synergism; Fatty Alcohols; Furocoumarins; Humans; Indoles; Limonins; Neoplasms; Phytotherapy; Piperidines; Polyunsaturated Alkamides; Proanthocyanidins; Quercetin; Resveratrol; Stilbenes; Sulfides; Tea; Triterpenes; Xanthophylls

Excessive free radical generation overbalancing the rate of their removal leads to oxidative stress. Oxidative stress has been implicated in the etiology of cardiovascular disease, inflammatory diseases, cancer, and other chronic diseases. Antioxidants are compounds that hinder the oxidative processes and thereby delay or suppress oxidative stress. There is a growing interest in natural antioxidants found in plants. Herbs and spices are most important targets to search for natural antioxidants from the point of view of safety. A wide variety of phenolic compounds present in spices that are extensively used as food adjuncts possess potent antioxidant, anti-inflammatory, antimutagenic, and cancer preventive activities. This paper reviews a host of spice compounds as exogenous antioxidants that are experimentally evidenced to control cellular oxidative stress, both in vitro and in vivo, and their beneficial role in preventing or ameliorating oxidative-stress-mediated diseases, from atherosclerosis to diabetes to cataract to cancer. The antioxidative effects of turmeric/curcumin, clove/eugenol, red pepper/capsaicin, black pepper/piperine, ginger/gingerol, garlic, onion, and fenugreek, which have been extensively studied and evidenced as potential antioxidants, are specifically reviewed in this treatise.

Topics: Alkaloids; Anti-Inflammatory Agents; Antimutagenic Agents; Antioxidants; Benzodioxoles; Capsaicin; Cardiotonic Agents; Catechols; Curcumin; Eugenol; Fatty Alcohols; Garlic; Humans; Neoplasms; Onions; Oxidative Stress; Phenols; Piperidines; Polyunsaturated Alkamides; Spices; Trigonella

The current review emphasizes on the herbal bioenhancers which themselves do not possess inherent pharmacological activity of their own but when co-administered with Active Pharmaceutical Ingredients (API), enhances their bioavailability and efficacy. Herbal bioenhancers play a crucial role in enhancing the bioavailability and bioefficacy of different classes of drugs, such as antihypertensives, anticancer, antiviral, antitubercular and antifungal drugs at low doses. This paper highlights various natural compounds that can be utilized as an efficient bioenhancer. Several herbal compounds including piperine, quercetin, genistein, naringin, sinomenine, curcumin, and glycyrrhizin have demonstrated capability to improve the pharmacokinetic parameters of several potent API. This article also focuses on various United States patents on herbal bioenhancers, which has proved to be beneficial in improving oral absorption of nutraceuticals like vitamins, minerals, amino acids and certain herbal compounds. The present paper also describes proposed mechanism of action, which mainly includes absorption process, drug metabolism, and action on drug target. The herbal bioenhancers are easily available, safe, free from side effects, minimizes drug toxicity, shortens the duration of treatment, lowers the drug resistance problems and minimizes the cost of treatment. Inspite of the fact that herbal bioenhancers provide an innovative concept for enhancing the bioavailability of several potent drugs, there are numerous bioenhancers of herbal origin that are yet to be explored in several vital areas. These bioenhancers must also be implied to enhance the bioavailability and bioefficacy through routes other than the oral route of drug delivery. There is a vast array of unexploited plants which can be investigated for their drug bioenhancing potency. The toxicity profiles of these herbal bioenhancers must not be overlooked. Researches must be carried out to solve these issues and to deliver a safe and effective dose of drugs to attain desired pharmacological response.

Topics: Adjuvants, Pharmaceutic; Alkaloids; Benzodioxoles; Biological Availability; Carum; Cuminum; Curcumin; Ergolines; Flavanones; Genistein; Glycyrrhizic Acid; Humans; Morphinans; Piperidines; Plant Extracts; Polyunsaturated Alkamides; Quercetin; Zingiber officinale

Cancer stem cells often have phenotypic and functional characteristics similar to normal stem cells including the properties of self-renewal and differentiation. Recent findings suggest that uncontrolled self-renewal may explain cancer relapses and may represent a critical target for cancer prevention. It is conceivable that the loss of regulatory molecules resulting from inappropriate consumption of specific foods and their constituents may foster the aberrant self-renewal of cancer stem cells. In fact, increasing evidence points to the network delivering signals for self-renewal from extracellular compartments to the nucleus including changes in stem cell environments, inducible expression of microRNAs, hyperplastic nuclear chromatin structures, and the on/off of differentiation process as possible sites of action for bioactive food components. Diverse dietary constituents such as vitamins A and D, genistein, (-)-epigallocatechin-3-gallate (EGCG), sulforaphane, curcumin, piperine, theanine and choline have been shown to modify self-renewal properties of cancer stem cells. The ability of these bioactive food components to influence the balance between proliferative and quiescent cells by regulating critical feedback molecules in the network including dickkopf 1 (DKK-1), secreted frizzled-related protein 2 (sFRP2), B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) and cyclin-dependent kinase 6 (CDK6) may account for their biological response. Overall, the response to food components does not appear to be tissue or organ specific, suggesting there may be common cellular mechanisms. Unquestionably, additional studies are needed to clarify the physiological role of these dietary components in preventing the resistance of tumor cells to traditional drugs and cancer recurrence.

Topics: Alkaloids; Benzodioxoles; Catechin; Cell Differentiation; Cell Proliferation; Choline; Curcumin; Cyclin-Dependent Kinase 6; Diet; Epigenesis, Genetic; Gene Expression Regulation; Genistein; Glutamates; Humans; Intercellular Signaling Peptides and Proteins; Isothiocyanates; Membrane Proteins; Mesenchymal Stem Cells; Neoplastic Stem Cells; Nuclear Proteins; Piperidines; Plant Extracts; Polycomb Repressive Complex 1; Polyunsaturated Alkamides; Proto-Oncogene Proteins; Repressor Proteins; STAT1 Transcription Factor; Sulfoxides; Thiocyanates; Vitamin A; Vitamin D; Wnt Proteins

In India, Ayurveda has made a major contribution to the drug discovery process with new means of identifying active compounds. Recent advancement in bioavailability enhancement of drugs by compounds of herbal origin has produced a revolutionary shift in the way of therapeutics. Thus, bibliographic investigation was carried out by analyzing classical text books and peer-reviewed papers, consulting worldwide-accepted scientific databases from last 30 years. Herbal bioenhancers have been shown to enhance bioavailability and bioefficacy of different classes of drugs, such as antibiotics, antituberculosis, antiviral, antifungal, and anticancerous drugs at low doses. They have also improved oral absorption of nutraceuticals like vitamins, minerals, amino acids, and certain herbal compounds. Their mechanism of action is mainly through absorption process, drug metabolism, and action on drug target. This paper clearly indicates that scientific researchers and pharmaceutical industries have to give emphasis on experimental studies to find out novel active principles from such a vast array of unexploited plants having a role as a bioavailability and bioefficacy enhancer. Also, the mechanisms of action by which bioenhancer compounds exert bioenhancing effects remain to be explored.

Topics: Alkaloids; Animals; Antineoplastic Agents, Phytogenic; Benzodioxoles; Biological Availability; Curcumin; Databases, Factual; Dietary Supplements; Drug Compounding; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Herb-Drug Interactions; Humans; Phenytoin; Piperidines; Plant Preparations; Plants, Medicinal; Polyunsaturated Alkamides

The emergence of cancer stem cell theory has profound implications for cancer chemoprevention and therapy. Cancer stem cells give rise to the tumor bulk through continuous self-renewal and differentiation. Understanding the mechanisms that regulate self-renewal is of greatest importance for discovery of anticancer drugs targeting cancer stem cells. Naturally occurring dietary compounds have received increasing attention in cancer chemoprevention. The anticancer effects of many dietary components have been reported for both in vitro and in vivo studies. Recently, a number of studies have found that several dietary compounds can directly or indirectly affect cancer stem cell self-renewal pathways. Herein we review the current knowledge of most common natural dietary compounds for their impact on self-renewal pathways and potential effect against cancer stem cells. Three pathways (Wnt/β-catenin, Hedgehog and Notch) are summarized for their functions in self-renewal of cancer stem cells. The dietary compounds, including curcumin, sulforaphane, soy isoflavone, epigallocatechin-3-gallate, resveratrol, lycopene, piperine and vitamin D(3), are discussed for their direct or indirect effect on these self-renewal pathways. Curcumin and piperine have been demonstrated to target breast cancer stem cells. Sulforaphane has been reported to inhibit pancreatic tumor-initiating cells and breast cancer stem cells. These studies provide a basis for preclinical and clinical evaluation of dietary compounds for chemoprevention of cancer stem cells. This may enable us to discover more preventive strategies for cancer management by reducing cancer resistance and recurrence and improving patient survival.

Topics: Alkaloids; Animals; Anticarcinogenic Agents; Benzodioxoles; beta Catenin; Carotenoids; Catechin; Cell Differentiation; Cell Proliferation; Cholecalciferol; Curcumin; Diet; Humans; Isoflavones; Isothiocyanates; Lycopene; Neoplasms; Neoplastic Stem Cells; Piperidines; Polyunsaturated Alkamides; Resveratrol; Signal Transduction; Stilbenes; Sulfoxides; Thiocyanates; Wnt Proteins

Non-alcoholic Fatty Liver Disease (NAFLD) is a global health problem that can progress to steatohepatitis and cirrhosis. The aim of this study was to determine the effect of curcumin + piperine on cardiometabolic risk factors, as well as hepatic steatosis and fibrosis in NAFLD patients with moderate-to-high hepatic steatosis. Patients diagnosed with moderate-to-high NAFLD by liver sonography were randomized to either curcumin + piperine (500 mg/day curcumin plus 5 mg/day piperine) for 12 weeks (n = 30) or placebo groups (n = 30). Liver fibroscan, anthropometric measurements, dietary intake, physical activity, blood pressure, lipid profile, high-sensitivity C-reactive protein, fasting blood glucose (FBG), and liver enzymes were assessed at baseline and after 12 weeks of follow-up. Intention-to-treat analysis was undertaken. Curcumin + piperine decreased waist circumference (p = 0.026), systolic blood pressure (p = 0.001), total cholesterol (p = 0.004), low-density lipoprotein-cholesterol (p = 0.006), FBG (p = 0.002), alanine transaminase (p = 0.007) and aspartate transaminase (p = 0.012) compared with placebo. However, fibroscan measurement did not differ between curcumin + piperine and placebo groups (p > 0.05). Fibroscan measurement as a marker of NAFLD improvement did not differ after 12 weeks of curcumin + piperine; however, curcumin + piperine may be considered as an adjunct therapy to improve anthropometric measures, blood pressure, lipid profile, blood glucose, and liver function in NAFLD patients.

Topics: Blood Glucose; Cholesterol; Curcumin; Dietary Supplements; Double-Blind Method; Humans; Lipids; Non-alcoholic Fatty Liver Disease

Curcumin is a traditional remedy for diseases associated with hyper-inflammatory responses and immune system impairment. Piperine, a bioactive compound in black pepper, has the potential to enhance curcumin bioavailability. 0This study aims to examine the effect of the curcumin-piperine co-supplementation in patients infected with SARS-CoV-2 and admitted to the intensive care unit (ICU).. In this parallel randomized, double-blind, placebo-controlled trial, 40 patients with COVID-19 admitted to ICU were randomized to receive three capsules of curcumin (500 mg)-piperine (5 mg) or placebo for 7 days.. After 1 week of the intervention, serum aspartate aminotransferase (AST) (p = 0.02) and C-reactive protein (CRP) (p = 0.03) were significantly decreased, and hemoglobin was increased (p = 0.03) in the curcumin-piperine compared to the placebo group. However, compared with the placebo, curcumin-piperine had no significant effects on the other biochemical, hematological, and arterial blood gas and 28-day mortality rate was three patients in each group (p = 0.99).. The study results showed that short-term curcumin-piperine supplementation significantly decreased CRP, AST, and increased hemoglobin in COVID-19 patients admitted to the ICU. Based on these promising findings, curcumin appears to be a complementary treatment option for COVID-19 patients, although some parameters were not affected by the intervention.

Topics: COVID-19; Critical Care; Curcumin; Dietary Supplements; Double-Blind Method; Humans; SARS-CoV-2

Alopecia areata is a common non-scarring alopecia, mainly manifested as sudden localized patchy alopecia. It is currently believed to be related to autoimmune, genetic, emotional stress, and endocrine factors.. The aim of this study was to evaluate the efficacy and safety of the mixed preparation of piperine, capsaicin, and curcumin on alopecia areata treatment.. Sixty patients were enrolled in this study and divided into 2 groups randomly: topical treated with the mixed preparation (case) twice daily and 5%minoxidil (control) once daily for 3 months. The degree of hair loss was assessed by SALT and dermoscopy.. On the completion of the study, compared with baseline, statistically significant regrowth occurred in both groups (p < 0.05). The mean SALT scores and hair follicle status under trichoscopy at baseline and at the end of 12 weeks in the mixed preparation group and in the minoxidil group were comparable, respectively. The effective rate of mixed preparation group was 63.33% and minoxidil group was 70%. Adverse symptoms were temporary and no serious adverse event occurred.. Based on our findings, the mixed preparation of piperine, capsaicin, and curcumin is effective in treating alopecia areata, but it has not been shown to be superior to minoxidil in short-term therapy.

Topics: Administration, Topical; Alopecia; Alopecia Areata; Capsaicin; Curcumin; Humans; Minoxidil

COVID-19 pandemic has made the disease a major global problem by creating a significant burden on health, economic, and social status. To date, there are no effective and approved medications for this disease. Curcumin as an anti-inflammatory agent can have a positive effect on the control of COVID-19 complications. This study aimed to assess the efficacy of curcumin-piperine supplementation on clinical symptoms, duration, severity, and inflammatory factors in patients with COVID-19.. Forty-six outpatients with COVID-19 disease were randomly allocated to receive two capsules of curcumin-piperine; each capsule contained 500 mg curcumin plus 5 mg piperine or placebo for 14 days.. Mean changes in complete blood count, liver enzymes, blood glucose levels, lipid parameters, kidney function, and c-reactive protein (CRP) were not significantly different between the two groups. There was a significant improvement in health status, including dry cough, sputum cough, ague, sore throat, weakness, muscular pain, headache, and dyspnea at week 2 in both curcumin-piperine and placebo groups (P value < 0.05); however, the improvement in weakness was more in the curcumin-piperine group than with placebo group (P value 025).. The present study results showed that curcumin-piperine co-supplementation in outpatients with COVID-19 could significantly reduce weakness. However, in this study, curcumin-piperine co-supplementation could not significantly affect the other indices, including biochemical and clinical indices.. Iranian Registry of Clinical Trials IRCT20121216011763N46 . 2020-10-31.

Topics: Alkaloids; Benzodioxoles; Cough; COVID-19 Drug Treatment; Curcumin; Dietary Supplements; Double-Blind Method; Humans; Iran; Outpatients; Pandemics; Piperidines; Polyunsaturated Alkamides

Premenstrual syndrome (PMS) and primary dysmenorrhea (PD) are common gynecological complications and there is evidence that inflammation may be an important factor in their etiology. There is a relationship between PMS and PD with susceptibility to allergic disorders. We aimed to assess the effect of curcumin co-administered with piperine on serum IL-10, IL-12 and IgE levels in patients with PD and PMS.. A sample of 80 patients were recruited to this triple-blind, placebo-controlled clinical trial. Participants were randomly allocated to curcumin (n = 40) and control groups (n = 40). Each participant received one capsule (500 mg of curcuminoid plus piperine, or placebo) daily, from 7 days before until 3 days after menstruation for three consecutive menstrual cycles.. Serum IgE, IL-10 and IL-12 levels were quantified by using an ELISA kit. No significant differences were found between the two groups at baseline, including: age, BMI, and dietary intakes (P > 0.05). Curcumin + piperine treatment was associated with a significant reduction in the mean serum levels of IgE [from 223.6 ± 258.7 IU/mL to 161.3 ± 240.7; P = 0.001]; but there were no significant changes in the placebo group (P = 0.12). Serum concentrations of IL-10 and IL-12 before and after the trial period did not differ significantly between the two groups (P > 0.05).. Curcumin plus piperine might be have positive effect on serum IgE levels with no significant changes on serum IL-10 and IL-12 in healthy young women with PMS and PD. Studies with higher doses and longer durations of treatment with curcumin are required to confirm these findings.

Topics: Curcumin; Dietary Supplements; Double-Blind Method; Dysmenorrhea; Female; Humans; Immunoglobulin E; Interleukin-10; Interleukin-12; Premenstrual Syndrome

Turmeric has renop rotective effects that can act to reduce oxidative stress and inflammation in hemodialysis (HD) patients. Piperine has been indicated as a bioavailability enhancer of turmeric and consequently of its biological effects. However, data on the efficacy of the turmeric/piperine combination in HD patients are limited. We aimed to verify whether turmeric supplementation in combination with piperine has a superior effect to turmeric alone in increasing antioxidant capacity and reducing oxidative stress and inflammation in HD patients.. This randomized, double-blind clinical trial was conducted in HD patients (age 20-75 years). Patients were supplemented with turmeric (3 g/day) or turmeric/piperine (3 g turmeric + 2 mg piperine/day) for 12 weeks. Malondialdehyde (MDA), antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), high-sensitivity C-reactive protein (hs-CRP), and ferritin were evaluated at baseline and the end of the study.. There was a reduction in the MDA and ferritin levels in the turmeric/piperine group and in the comparison between groups at the end of the study [MDA: -0.08(-0.14/0.01) nmol/mL versus -0.003(-0.10/0.26) nmol/mL, p = 0.003; ferritin: -193.80 ± 157.29 mg/mL versus 51.99 ± 293.25 mg/mL, p = 0.018]. In addition, GPx activity reduced in the turmeric group (p = 0.029). No changes were observed for CAT, GR, and hs-CRP.. Turmeric plus piperine was superior to turmeric alone in decreasing MDA and ferritin levels. The use of a combination of turmeric and piperine as a dietary intervention may be beneficial for modulating the status oxidative and inflammation in HD patients.. RBR-2t5zpd; Registration Date: May 2, 2018.

Topics: Antioxidants; C-Reactive Protein; Curcuma; Dietary Supplements; Double-Blind Method; Ferritins; Inflammation; Oxidative Stress; Renal Dialysis

Experimental and clinical studies have revealed that curcumin may be an effective therapy for non-alcoholic fatty liver disease (NAFLD). Hence, the aim of this study was to assess the effect of curcumin plus piperine administration on NAFLD.. Adults 18-65 years-old diagnosed with NAFLD by liver sonography were randomly allocated to curcumin (500 mg/day) or placebo groups for 2 months. All participants received both dietary and exercise advice. Anthropometric and biochemical measurements as well as hepatic ultrasound were performed at baseline and final conditions.. Seventy-nine participants were recruited and randomly allocated into the curcumin (n = 39) or placebo (n = 40) groups. There were no significant differences between placebo and curcumin groups for demographic and clinical characteristics and NAFLD grade at baseline. After the treatment period, the curcumin group exhibited lower alkaline phosphatase (-16.2 ± 22.8 versus -6.0 ± 22.5 mg/dL, p = 0.04) concentrations and severity of NAFLD compared with the placebo group (p = 0.04).. Results of this clinical trial suggest that short-term treatment with curcumin plus piperine administration improves NAFLD severity.

Topics: Adolescent; Adult; Aged; Alkaloids; Benzodioxoles; Curcumin; Dietary Supplements; Double-Blind Method; Humans; Liver; Middle Aged; Non-alcoholic Fatty Liver Disease; Piperidines; Polyunsaturated Alkamides; Young Adult

Acute myocardial infarction (AMI) is a leading cause of death and disability worldwide. Previous investigations have demonstrated that curcumin has a cardioprotective effect and may improve myocardial injury. So this study was performed to assess whether supplementation with curcumin could diminish myocardial injury following AMI.. To conduct this randomized, double-blinded, and placebo-controlled clinical trial, seventy-two patients with acute myocardial infarction, aged 18-75 years, were enrolled and randomly divided into the active intervention and control groups. The active intervention group (n = 38) received curcumin capsules with piperine supplement (500 mg/day, 95% curcuminoids) for 8 weeks, whereas the control group (n = 34) received a placebo capsule. At the baseline and end of the study, ejection fraction was assessed, and blood samples were taken from all patients to measure the levels of cardiac troponin I(cTnI), lipid profile, FBG, HbA1C, liver enzymes, renal function parameters, and electrolytes.. In this trial, curcumin supplementation significantly reduced the levels of HbA1C (-0.3 ± 2.2 vs. +1.1 ± 1.3, P = 0.002), LDL (-10.3 ± 20.7 vs. +0.2 ± 22.5, P = 0.039), ALT (-10.2 ± 28.5 vs. +7.3 ± 39.2, P = 0.029), and ALP (+6.4 ± 39.5 vs. +38.0 ± 69.0, P = 0.018) compared to the placebo group. Moreover, the serum concentration of HDL significantly improved in comparison with the placebo group (+4.5 ± 8.9 vs. -1.6 ± 7.7, P = 0.002). However, no substantial difference was perceived between the groups regarding the ejection fraction and serum levels of cTnI, FBG, renal function parameters, and electrolytes.. Our results indicated that daily intake of 500 mg of curcumin capsules with piperine supplement for 8 weeks modified lipid profile, liver enzymes, and glycemic status, but did not have any effect on ejection fraction and serum concentration of cardiac troponin I, renal function parameters, and electrolytes in acute myocardial infarction patients.

Topics: Alkaloids; Benzodioxoles; Curcumin; Dietary Supplements; Double-Blind Method; Humans; Myocardial Infarction; Piperidines; Polyunsaturated Alkamides

Nonalcoholic fatty liver diseases (NAFLD) is a highly prevalent disease that is closely associated with several cardiometabolic complications. The potential anti-inflammatory role of curcuminoids that have already been reported to reduce hepatic steatosis, in patients with NAFLD was explored in this study.. This double-blind, randomized placebo-controlled trial was conducted for a period of 8 weeks in patients with NAFLD. Subjects (n = 55) were randomly allocated to receive either curcuminoids or placebo. The curcuminoids group received one capsule containing 500 mg curcuminoids (plus 5 mg piperine to increase intestinal absorption) per day for 8 weeks and the control group received matched placebo capsules for the same period. Liver ultrasonography was performed to assess the severity of hepatic steatosis at baseline and the study end. Serum levels of cytokines including interleukin-1α, interleukin-1β, interleukin-2, interleukin-4, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-α, monocyte chemoattractant protein-1, interferon γ, vascular endothelial growth factor and epidermal growth factor were measured before and after the intervention.. The two groups were comparable in demographic features at baseline. The results showed that supplementation with curcuminoids could decrease weight compared to the placebo group (p = 0.016) in patients with NAFLD. Curcuminoids supplementation improved the severity of NAFLD according to the ultrasound results (p = 0.002). Moreover, serum concentrations of TNF-α (p = 0.024), MCP-1 (p = 0.008) and EGF (p = 0.0001) were improved by curcuminoids in NAFLD patients.. The results of our study showed that curcumin supplementation can improve serum levels of inflammatory cytokines in subjects with NAFLD and this might be at least partly responsible for the anti-steatotic effects of curcuminoids.

Topics: Adolescent; Adult; Aged; Alkaloids; Benzodioxoles; Curcumin; Diarylheptanoids; Double-Blind Method; Female; Humans; Inflammation; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Piperidines; Polyunsaturated Alkamides; Young Adult

Previous studies have shown a beneficial effect of curcuminoids supplementation on serum concentrations of adipokines; however, there are no published studies that have examined this effect among critically ill patients. We aimed to assess the effects of supplementation with curcuminoids on serum concentrations of leptin and adiponectin in critically ill patients with traumatic brain injury (TBI). In this trial, 62 critically ill patients with TBI, aged 18-65 years, were randomly allocated to receive either 500 mg/day curcuminoids (co-administered with 5 mg/day piperine) or matched placebo for 7 days. Patients in both intervention groups received routine treatments for TBI as well as enteral nutrition. Serum concentrations of leptin and adiponectin were measured at baseline and at the end of trial. We found a significant reduction in serum levels of leptin in both curcuminoids (47.1%) and placebo (22.8%) groups; though the magnitude of reduction was greater in the former (p < .05). Supplementation with curcumioinds was not found to alter serum concentrations of adiponectin (p > .05). Supplementation with curcumioinds significantly reduced serum levels of leptin but had no significant effect on adiponectin levels in critically ill patients with TBI. Further clinical trials, particularly those with a long-term period, are needed to confirm our findings.

Topics: Adipokines; Adiponectin; Adolescent; Adult; Aged; Alkaloids; Benzodioxoles; Critical Illness; Curcumin; Diarylheptanoids; Dietary Supplements; Double-Blind Method; Female; Humans; Iran; Leptin; Male; Middle Aged; Piperidines; Placebos; Polyunsaturated Alkamides; Young Adult

This study aims to investigate the efficacy of curcumin-piperine co-supplementation on disease duration, severity and clinical symptoms, and inflammatory mediators in patients with coronavirus (COVID-19).. This is a randomized, placebo-controlled, double-blind, parallel arm clinical trial.. All patients aged 20-75 years with the diagnosis of Covid-19 based on the PCR test. The exclusion criteria will include an age less than 20 and more than 75 years, current use of warfarin or other anticoagulant drugs, and the presence of sensitivity to herbal products such as turmeric and pepper. This study will be conducted in academic hospitals affiliated to Isfahan University of Medical Sciences, Isfahan, Iran.. Fifty outpatients will be randomly allocated in a ratio of 1:1 to receive a capsule of curcumin-piperine containing 500 mg curcumin plus 5 mg piperine or matching placebo containing 505 mg maltodextrin twice a daily, after lunch and dinner, over a period of 2 weeks. Similarly, 50 inpatients who are admitted to hospital wards excluding intensive care unit (ICU) will be randomly assigned in a ratio of 1:1 to receive a capsule curcumin-piperine or matching placebo (provided by the Sami Labs company) twice a daily, after lunch and dinner, over a period of 2 weeks.. The main outcomes of this study are the efficacy of curcumin-piperine on coronavirus disease's clinical symptoms, duration, severity, and inflammatory mediators after 2 weeks of curcumin-piperine co-supplementation.. Randomization sequences will be generated with the use of a random-number table with a permuted block design (block size of 4) and stratification according to the gender variable (male vs. female). These sequences will be prepared by an independent statistician and will be kept in opaque, sealed, numbered envelopes which will be opened only at the time of enrollment. The allocation ratio in intervention and control groups is 1:1. Researchers and all patients will be unaware of the study-group assignment until the completion of data analyses.. This study is a double-blind clinical trial (participant, researcher). The curcumin-piperine and placebo supplements are packaged in similar numbered drug containers, and the researcher and all patients will be unaware of the study assignment until the end of the study.. The calculated total sample size is 100 patients, with 25 patients in each group.. The protocol is Version 2.0, May 24, 2020. Recruitment began May 4, 2020, and is anticipated to be completed by April 19, 2021.. This trial has been registered by the title of "Effect of curcumin-piperine co-supplementation on disease duration, severity and clinical signs, and inflammatory factors in patients with coronavirus (COVID-19): A randomized, double-blind, placebo-controlled clinical trial study" in the Iranian Registry of Clinical Trials (IRCT) with code "IRCT20121216011763N46", https://www.irct.ir/trial/47529 . The registration date is May 4, 2020.. The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Topics: Alkaloids; Benzodioxoles; COVID-19 Drug Treatment; Curcumin; Dietary Supplements; Double-Blind Method; Hospitalization; Humans; Iran; Piperidines; Polyunsaturated Alkamides; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome

Background The main causes of the progression of non-alcoholic fatty liver disease (NAFLD) are enhanced levels of reactive oxygen species and lipid peroxidation products. Therefore, the usage of antioxidant agents for the prevention and remedy of this disorder was recommended. Curcumin is proposed to treat NAFLD due to its high antioxidative activity. The aim of this study was to examine the effect of curcumin with piperine supplementation on oxidative stress in subjects with NAFLD. Methods In this double-blind, placebo-controlled trial, 55 subjects were randomly divided into two groups (curcumin with piperine and placebo). The participants received administrations of curcumin (500 mg) in combination with piperine (5 mg) and placebo daily for 8 weeks. Oxidative stress was assessed by measuring serum pro-oxidant and antioxidant balance (PAB) assay before and after the intervention. Results The serum PAB values did not significantly change between the treatment group vs. age and gender-matched placebo group after 8 weeks of supplementation. Also, curcumin in combination with piperine did not show a significant decrease (p = 0.06) in PAB levels compared to baseline. Conclusions The present study demonstrated that a dose of curcumin, co-supplied with piperine might be less than a dose in which curcumin can significantly decrease PAB values in these patients.

Topics: Adolescent; Adult; Aged; Alkaloids; Antioxidants; Benzodioxoles; Curcumin; Dietary Supplements; Double-Blind Method; Female; Humans; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Piperidines; Polyunsaturated Alkamides; Young Adult

Curcuminoids have been shown to reduce glycemia and related complications in diabetes. In the present study, we evaluated the impact of curcuminoids plus piperine administration on glycemic, hepatic and inflammatory biomarkers in type 2 diabetes (T2D) patients.. T2D patients aged 18-65 years were enrolled in a randomized double-blind placebo-controlled trial and randomly allocated to standard-of-care treatment and dietary advises plus either curcuminoids (daily dose of 500 mg/day co-administered with piperine 5 mg/day) or placebo for a period of 3 months. Glycemic, hepatic and inflammatory parameters were measured at baseline and final conditions.. A total of 100 subjects (50 in each group) completed the 3-month period of trial. A significant reduction was found in serum levels of glucose (-9±16 mg/dL vs. -3±11 mg/dL in curcuminoids and placebo groups, respectively; p=0.048), C-peptide (-0.6±0.8 ng/mL vs. 0.02±0.6 ng/mL; p<0.001) and HbA1c (-0.9±1.1% vs. -0.2±0.5%; p<0.001) after curcuminoids supplementation versus placebo group. Additionally, participants in the intervention group showed lower serum alanine aminotransferase (-2±6 vs. -1±5; p=0.032) and aspartate aminotransferase (-3±5 vs. -0.3±4; p=0.002) levels compared with the placebo group. Finally, no significant differences in high-sensitivity C-reactive protein (hs-CRP) concentrations were observed between curcuminoids and placebo groups (p>0.05).. The results of the present trial revealed a beneficial effect of curcuminoids plus piperine supplementation on glycemic and hepatic parameters but not on hs-CRP levels in T2D patients.

Topics: Adolescent; Adult; Aged; Alanine Transaminase; Alkaloids; Antioxidants; Aspartate Aminotransferases; Benzodioxoles; Biomarkers; Blood Glucose; C-Reactive Protein; Curcumin; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation; Male; Middle Aged; Oxidative Stress; Piperidines; Polyunsaturated Alkamides; Young Adult

Type 2 diabetes (T2D) is an established risk factor for cardiovascular disease (CVD) and is associated with disturbed metabolism of lipids and lipoproteins. Curcuminoids are natural products with anti-diabetic and lipid-modifying actions but their efficacy in improving dyslipidemia in diabetic individuals has not been sufficiently studied.. To investigate the efficacy of supplementation with curcuminoids, plus piperine as an absorption enhancer, in improving serum lipids in patients with T2D.. In this 12-week randomized double-blind placebo-controlled trial, subjects with T2D (n=118) were assigned to curcuminoids (1000mg/day plus piperine 10mg/day) or placebo plus standard of care for T2D. Serum concentrations of lipids including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), lipoprotein(a) [Lp(a)], and non-HDL-C were determined at baseline and at the end of trial.. Between-group comparison of change in the study parameters revealed significant reductions in serum levels of TC (-21.86±25.78 versus -17.06±41.51, respectively; p=0.023), non-HDL-C (-23.42±25.13 versus -16.84±41.42, respectively; p=0.014) and Lp(a) (-1.50±1.61 versus -0.34±1.73, respectively; p=0.001) and elevations in serum HDL-C levels (1.56±4.25 versus -0.22±4.62, respectively; p=0.048) in the curcuminoids group as compared with the placebo group (p<0.05). Serum TG and LDL-C changes did not show any significant difference between the study groups (p>0.05).. Curcuminoids supplementation can reduce serum levels of atherogenic lipid indices including non-HDL-C and Lp(a). Therefore, curcuminoids supplementation could contribute to a reduced risk of cardiovascular events in dyslipidemic patients with T2D.

Topics: Adult; Alkaloids; Benzodioxoles; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Dyslipidemias; Female; Humans; Lipids; Lipoprotein(a); Male; Middle Aged; Phytotherapy; Piperidines; Plant Extracts; Polyunsaturated Alkamides; Triglycerides

Curcumin is a naturally occurring polyphenol derived from tumeric that has been reported to have anti-inflammatory properties with effects on adipokine and ghrelin levels. Adiponectin, leptin and ghrelin modulate energy homeostasis but each has modulatory effects on inflammatory cytokines and the immune system. Therefore, this analysis was performed to investigate the effect of curcumin on adiponectin, leptin and ghrelin.. A double blind randomised control trial comparing curcumin 1000mg with 10mg of piperine daily to placebo over a 12 week period. 118 patients with type 2 diabetes were recruited out of which 50 control and 50 active subjects completed the trial. Adiponectin, leptin, ghrelin and tumor necrosis factor-α (TNF-α) were measured at baseline and 12 weeks.. Between group comparison of the magnitude of changes showed serum levels of leptin (p<0.001), TNF-α (p<0.001) and leptin:adiponectin ratio (p<0.001) to be significantly reduced while serum adiponectin levels were elevated in the curcuminoids versus placebo group (p=0.032). Changes in serum ghrelin levels did not differ between the study groups (p=0.135).. Curcumin supplementation increased adiponectin, whilst the the leptin:adiponectin ratio (a measure of atherosclerosis) and leptin levels were decreased independent of weight change and reflected a decrease in the inflammatory TNF-α levels.

Topics: Adipokines; Adiponectin; Adult; Alkaloids; Anti-Inflammatory Agents, Non-Steroidal; Benzodioxoles; Curcumin; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Ghrelin; Humans; Leptin; Male; Middle Aged; Piperidines; Polyunsaturated Alkamides; Tumor Necrosis Factor-alpha

Oxidative stress plays a key role in the development of chronic pulmonary complications of sulfur mustard (SM). Curcuminoids are polyphenols with documented safety and antioxidant activity. The present study aimed to investigate the efficacy of short-term supplementation with curcuminoids (co-administered with piperine to enhance the bioavailability of curcuminoids) in alleviating systemic oxidative stress and clinical symptoms, and improvement of health-related quality of life (HRQoL) in subjects suffering from chronic pulmonary complications due to SM exposure who are receiving standard respiratory treatments. Eighty-nine subjects were recruited to this randomized double-blind placebo-controlled trial, being randomly allocated to either curcuminoids (1500 mg/day) + piperine (15 mg/day) combination (n = 45) or placebo (n = 44) for a period of 4 weeks. High-resolution computed tomography suggested the diagnosis of bronchiolitis obliterans in all subjects. Efficacy measures were changes in serum levels of reduced glutathione (GSH) and malonedialdehyde (MDA). The severity and frequency of respiratory symptoms and HRQoL were also assessed using St. George respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT) indices. Serum levels of GSH were increased whilst those of MDA decreased by the end of trial in both groups. Likewise, there were significant improvements in the total as well as subscale (symptoms, activity and impact) SGRQ and CAT scores in both groups. However, comparison of magnitude of changes revealed a greater effect of curcuminoids-piperine combination compared to placebo in elevating GSH, reducing MDA and improving CAT and SGRQ (total and subscale) scores (p < 0.001). Regarding the promising effects of curcuminoids on the measures of systemic oxidative stress, clinical symptoms and HRQoL, these phytochemicals may be used as safe adjuvants in patients suffering from chronic SM-induced pulmonary complications who are receiving standard treatments.

Topics: Adult; Alkaloids; Antioxidants; Benzodioxoles; Bronchiolitis; Chronic Disease; Curcuma; Curcumin; Double-Blind Method; Glutathione; Humans; Male; Malondialdehyde; Middle Aged; Mustard Gas; Oxidative Stress; Phytotherapy; Piper; Piperidines; Plant Extracts; Polyphenols; Polyunsaturated Alkamides; Pulmonary Disease, Chronic Obstructive; Quality of Life; Respiratory Function Tests

Oxidative stress is implicated in the pathogenesis of osteoarthritis. Curcuminoids are natural polyphenols with strong antioxidant capacity and may thus be helpful in the treatment of osteoarthritis. The present randomized double-blind placebo-controlled trial investigated the efficacy of curcuminoids in reducing systemic oxidative burden in patients suffering from knee osteoarthritis. Forty patients with mild-to-moderate primary knee osteoarthritis were given curcuminoid capsules (1500 mg/day in 3 divided doses; n = 19) or matched placebo capsules (n = 21) for a period of 6 weeks. Curcuminoids were co-administered with piperine (15 mg/day) in order to improve the bioavailability. Serum activities of superoxide dismutase (SOD) and concentrations of reduced glutathione (GSH) and malonedialdehyde (MDA) were determined spectrophotometrically at baseline and at the end of the treatment period in both groups. Serum activities of SOD as well as GSH and MDA concentrations were comparable between the study groups at baseline (p > 0.05). There was a significant elevation in serum SOD activities (mean change: 2.94 ± 3.73 vs. -0.38 ± 1.33; p < 0.001), a borderline significant elevation in GSH concentrations (mean change: 1.39 ± 2.78 vs. -0.02 ± 1.62; p = 0.064) and a significant reduction in MDA concentrations (mean change: -5.26 ± 4.46 vs. -2.49 ± 3.81; p = 0.044) in the curcuminoids compared with the placebo group. Changes in serum activities of SOD and concentrations of GSH and MDA during the course of trial were significantly correlated. Short-term supplementation with curcuminoids attenuates systemic oxidative stress in patients with osteoarthritis. These antioxidant effects may account for the reported therapeutic effects of curcuminoids in relieving osteoarthritis symptoms.

Topics: Aged; Alkaloids; Antioxidants; Benzodioxoles; Biological Availability; Body Mass Index; Curcumin; Double-Blind Method; Female; Glutathione; Humans; Male; Malondialdehyde; Middle Aged; Osteoarthritis, Knee; Oxidative Stress; Piperidines; Polyunsaturated Alkamides; Superoxide Dismutase

Current medications have limited efficacy in controlling the symptoms of major depressive disorder (MDD), and are associated with several adverse events on long-term use. Curcuminoids are extremely safe and multifunctional phytopharmaceuticals that have been shown to alleviate depressive symptoms in a variety of experimental models. The present study aimed to investigate the efficacy of curcuminoids as an add-on to standard antidepressants in patients with MDD. One hundred and eleven subjects were assigned to standard antidepressive therapy plus curcuminoids-piperine combination (1000-10 mg/day; n=61) or standard antidepressive therapy alone (n=50) for a period of 6 weeks. Efficacy measures were changes in the psychological status on the basis of the Hospital Anxiety and Depression Scale (HADS) and Beck Depression Inventory II (BDI-II). The BDI-II and HADS total and subscale scores were reduced by the end of trial in both study groups. There were significantly greater reductions in total HADS score and subscales of anxiety and depression in the curcuminoids versus control group (p<0.001). Likewise, reductions in BDI-II total score and scores of somatic and cognitive subscales were found to be greater in the curcuminoids compared with control group (p<0.001). Co-administration of curcuminoids with piperine may be used as a safe and effective add-on to standard antidepressants in patients with MDD.

Topics: Adult; Alkaloids; Antidepressive Agents; Anxiety; Benzodioxoles; Biological Availability; Curcumin; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Piperidines; Polyunsaturated Alkamides; Psychiatric Status Rating Scales

Oxidative stress and inflammation have been proposed as emerging components of metabolic syndrome (MetS). Curcuminoids are natural polyphenols with strong antioxidant and anti-inflammatory properties.. To study the effectiveness of supplementation with a bioavailable curcuminoid preparation on measures of oxidative stress and inflammation in patients with MetS. Our secondary aim was to perform a meta-analysis of data from all randomized controlled trials in order to estimate the effect size of curcuminoids on plasma C-reactive protein (CRP) concentrations.. In this randomized double-blind placebo-controlled trial, 117 subjects with MetS (according to the NCEP-ATPIII diagnostic criteria) were randomly assigned to curcuminoids (n = 59; drop-outs = 9) or placebo (n = 58; drop-outs = 8) for eight weeks. Curcuminoids were administered at a daily dose of 1 g, and were co-supplemented with piperine (10 mg/day) in order to boost oral bioavailability. Serum activities of superoxide dismutase (SOD) and concentrations of malondialdehyde (MDA) and CRP were measured at baseline and at study end. Regarding the importance of CRP as a risk marker and risk factor of cardiovascular disease, a random-effects meta-analysis of clinical trials was performed to estimate the overall impact of curcuminoid therapy on circulating concentrations of CRP. The robustness of estimated effect size was evaluated using leave-one-out sensitivity analysis.. Supplementation with curcuminoid-piperine combination significantly improved serum SOD activities (p < 0.001) and reduced MDA (p < 0.001) and CRP (p < 0.001) concentrations compared with placebo. Quantitative data synthesis revealed a significant effect of curcuminoids vs. placebo in reducing circulating CRP concentrations (weighed mean difference: -2.20 mg/L; 95% confidence interval [CI]: -3.96, -0.44; p = 0.01). This effect was robust in sensitivity analysis.. Short-term supplementation with curcuminoid-piperine combination significantly improves oxidative and inflammatory status in patients with MetS. Curcuminoids could be regarded as natural, safe and effective CRP-lowering agents.

Topics: Adult; Alkaloids; Anti-Inflammatory Agents; Antioxidants; Benzodioxoles; Biological Availability; Blood Pressure; Body Mass Index; C-Reactive Protein; Curcumin; Databases, Factual; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation; Male; Malondialdehyde; Meta-Analysis as Topic; Metabolic Syndrome; Middle Aged; Oxidative Stress; Piperidines; Polyunsaturated Alkamides; Superoxide Dismutase

Dyslipidemia is an established feature of metabolic syndrome (MS) that is associated with an increased risk of atherosclerotic cardiovascular disease. Curcuminoids are natural products with anti-atherosclerotic and lipid-modifying effects but their efficacy in patients with MS has not yet been tested.. To investigate the effects of bioavailability-enhanced curcuminoids, as adjunctive to standard of care, on serum lipid concentrations in patients with MS.. Patients diagnosed with MS according to the NCEP-ATPIII criteria who were receiving standard of care were assigned to either curcuminoids (C3 complex(®); 1000 mg/day; n=50) or placebo (n=50; matched with drug capsules in shape and color) for 8 weeks. In order to improve the oral bioavailability, curcuminoids were co-administered with piperine (bioperine(®)) in a ratio of 100:1. Serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, small dense LDL (sdLDL), lipoprotein(a) [Lp(a)], and non-HDL-C were determined at baseline and at the end of 8-week treatment period.. Curcuminoids were more effective than placebo in reducing serum LDL-C, non-HDL-C, total cholesterol, triglycerides and Lp(a), and elevating HDL-C concentrations. However, changes in serum sdLDL levels were found to be comparable between the study groups. The effects of curcuminoids on triglycerides, non-HDL-C, total cholesterol and Lp(a) remained significant after adjustment for baseline values of lipids and body mass index.. Curcuminoids-piperine combination is an efficacious adjunctive therapy in patients with MS and can modify serum lipid concentrations beyond what is achieved with standard of care.

Topics: Adult; Alkaloids; Benzodioxoles; Curcumin; Female; Humans; Lipids; Male; Metabolic Syndrome; Middle Aged; Piperidines; Polyunsaturated Alkamides

Turmeric extract derived curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) are currently being evaluated for the treatment of cancer and Alzheimer's dementia. Previous in vitro studies indicate that curcuminoids and piperine (a black pepper derivative that enhances curcuminoid bioavailability) could inhibit human CYP3A, CYP2C9, UGT and SULT dependent drug metabolism. The aim of this study was to determine whether a commercially available curcuminoid/piperine extract alters the pharmacokinetic disposition of probe drugs for these enzymes in human volunteers.. A randomized placebo-controlled six way crossover study was conducted in eight healthy volunteers. A standardized curcuminoid/piperine preparation (4 g curcuminoids plus 24 mg piperine) or matched placebo was given orally four times over 2 days before oral administration of midazolam (CYP3A probe), flurbiprofen (CYP2C9 probe) or paracetamol (acetaminophen) (dual UGT and SULT probe). Plasma and urine concentrations of drugs, metabolites and herbals were measured by HPLC. Subject sedation and electroencephalograph effects were also measured following midazolam dosing.. Compared with placebo, the curcuminoid/piperine treatment produced no meaningful changes in plasma C(max), AUC, clearance, elimination half-life or metabolite levels of midazolam, flurbiprofen or paracetamol (α = 0.05, paired t-tests). There was also no effect of curcuminoid/piperine treatment on the pharmacodynamics of midazolam. Although curcuminoid and piperine concentrations were readily measured in plasma following glucuronidase/sulfatase treatment, unconjugated concentrations were consistently below the assay thresholds (0.05-0.08 μM and 0.6 μM, respectively).. The results indicate that short term use of this piperine-enhanced curcuminoid preparation is unlikely to result in a clinically significant interaction involving CYP3A, CYP2C9 or the paracetamol conjugation enzymes.

Topics: Acetaminophen; Alkaloids; Analgesics, Non-Narcotic; Area Under Curve; Benzodioxoles; Chromatography, High Pressure Liquid; Cross-Over Studies; Curcuma; Curcumin; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Double-Blind Method; Drug Interactions; Enzyme Inhibitors; Flurbiprofen; Half-Life; Humans; Hypnotics and Sedatives; Midazolam; Piperidines; Plant Extracts; Polyunsaturated Alkamides

The medicinal properties of curcumin obtained from Curcuma longa L. cannot be utilised because of poor bioavailability due to its rapid metabolism in the liver and intestinal wall. In this study, the effect of combining piperine, a known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the bioavailability of curcumin in rats and healthy human volunteers. When curcumin was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg increased the serum concentration of curcumin for a short period of 1-2 h post drug. Time to maximum was significantly increased (P < 0.02) while elimination half life and clearance significantly decreased (P < 0.02), and the bioavailability was increased by 154%. On the other hand in humans after a dose of 2 g curcumin alone, serum levels were either undetectable or very low. Concomitant administration of piperine 20 mg produced much higher concentrations from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the increase in bioavailability was 2000%. The study shows that in the dosages used, piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects.

Topics: Adult; Alkaloids; Animals; Area Under Curve; Benzodioxoles; Chromatography, High Pressure Liquid; Curcumin; Drug Interactions; Female; Humans; Male; Piperidines; Polyunsaturated Alkamides; Rats; Rats, Wistar; Spectrophotometry, Ultraviolet

Curcumin (CUR) and piperine (PIP) are very well-known phytochemicals that claimed to have many health benefits and have been widely used in foods and traditional medicines. This study investigated the therapeutic efficacy of these compounds to treat Alzheimer's disease (AD). However, poor oral bioavailability and permeability of curcumin are a major challenge for formulation scientists. In this research study, the researcher tried to enhance the bioavailability and permeability of curcumin by a nanotechnological approach. In this research study, we developed a CUR-PIP-loaded SNEDDS in various oils. Optimised formulation NF3 was subjected to evaluate its therapeutic effectiveness on AD animal model in comparison with untreated AD model and treated group (by market formulation donepezil). On the basis of characterisation results, it is confirmed that NF3 formulation is the best formulation. The optimised formulation shows a significant dose-dependent manner therapeutic effect on AD-induced model. Novel formulation CUR-PIP solid-SNEDDS was successfully developed and optimised. It is expected that the developed S-SNEDDS can be a potential, safe and effective carrier for the oral delivery of curcumin to the brain. To date, this article is the only study of CUR-PIP-loaded S-SNEDDS for the treatment of AD.

Topics: Alzheimer Disease; Animals; Biological Availability; Curcumin; Drug Delivery Systems; Emulsions; Nanoparticles; Particle Size; Piperidines

Use of natural polymer in the development of Drug Delivery Systems (DDS) has greatly increased in recent past because of their biocompatible, non-allergic and biodegradable nature. Natural polymers are usually hydrophilic supports, so in order to be a carrier of a hydrophobic drug their nature needs to be changed. Each developed system behaves differently towards different drugs in terms of loading and sustained release of the drug as well. In the present work we report differential binding of piperine & curcumin with cetyltrimethylammonium bromide (CTAB) modified cellulose, alginate and pectin. Difference in interaction between the piperine and curcumin with supports has been visualized using in-vitro as well as in-silico studies. Initial results obtained after in-silico studies have been validated via time dependent anti-trypsin, serum protein binding, anti-cathepsin, anti-oxidant, and anti-α-amylase activities. FT-IR, SEM, fluorescence and Particle size have been used to characterize the piperine loaded on CTAB-modified polymeric supports.

Topics: Alginates; Cellulose; Cetrimonium; Curcumin; Drug Carriers; Pectins; Polymers; Spectroscopy, Fourier Transform Infrared

Curcumin (CUR) and piperine (PP) are bioactive compounds with prominent pharmacological activities that have been investigated for the treatment of various diseases. The aim of the present study is to develop Bio-SNEDDS for CUR and PP as a combined delivery system for cancer therapy.. CUR and PP loaded Bio-SNEDDSs with varying compositions of bioactive lipid oils, surfactants, and cosolvents were prepared at room temperature. Bio-SNEDDSs were characterized using a Zetasizer Nano particle size analyzer and further examined by transmission electron microscopy (TEM) for morphology. The in vivo toxicity of the preparations of Bio-SNEDDS was investigated in wild-type zebrafish embryos and cytotoxicity in THP-1 (human leukemia monocytic cells), Jurkat (human T lymphocyte cells) and HUVEC (non-cancerous normal) cells.. Bio-SNEDDSs were successfully developed with black seed oil, Imwitor 988, Transcutol P and Cremophor RH40 at a ratio of 20/20/10/50 (%w/w). The droplet size, polydispersity index and zeta potential of the optimized Bio-SNEDDS were found to be 42.13 nm, 0.59, and -19.30 mV, respectively. Bio-SNEDDS showed a spherical structure evident by TEM analysis. The results showed that Bio-SNEDDS did not induce toxicity in zebrafish embryos at concentrations between 0.40 and 30.00 μg/mL. In TG (fli1: EGFP) embryos treated with Bio-SNEDDS, there was no change in the blood vessel structure. The O-dianisidine staining of Bio-SNEDDS treated embryos at 48 h post-fertilization also showed a significant reduction in the number of blood cells compared to mock (DMSO 0.1% V/V) treated embryos. Bio-SNEDDS induced significant levels of cytotoxicity in the hematological cell lines THP-1 and Jurkat, while low toxicity in normal HUVEC cell lines was observed with IC50 values of 18.63±0.23 μg/mL, 26.03 ± 1.5 μg/mL and 17.52 ± 0.22 μg/mL, respectively.. Bio-SNEDDS exhibited enhanced anticancer activity and could thus be an important new pharmaceutical formulation to treat leukemia.

Topics: Administration, Oral; Animals; Biological Availability; Curcumin; Drug Delivery Systems; Emulsions; Hematologic Neoplasms; Humans; Leukemia; Nanoparticles; Pharmaceutical Preparations; Solubility; Surface-Active Agents; Zebrafish

Poor bioavailability hampers the use of curcumin and piperine as biologically active agents. It can be improved by enhancing the solubility as well as by using bioenhancers to inhibit metabolic transformation processes. Obtaining an amorphous system of curcumin and piperine can lead to the overcoming of these limitations. Hot-melt extrusion successfully produced their amorphous systems, as shown by XRPD and DSC analyses. Additionally, the presence of intermolecular interactions between the components of the systems was investigated using the FT-IR/ATR technique. The systems were able to produce a supersaturation state as well as improve the apparent solubilities of curcumin and piperine by 9496- and 161-fold, respectively. The permeabilities of curcumin in the GIT and BBB PAMPA models increased by 12578- and 3069-fold, respectively, whereas piperine's were raised by 343- and 164-fold, respectively. Improved solubility had a positive effect on both antioxidant and anti-butyrylcholinesterase activities. The best system suppressed 96.97 ± 1.32% of DPPH radicals, and butyrylcholinesterase activity was inhibited by 98.52 ± 0.87%. In conclusion, amorphization remarkably increased the dissolution rate, apparent solubility, permeability, and biological activities of curcumin and piperine.

Topics: Alkaloids; Benzodioxoles; Biological Availability; Curcumin; Solubility; Spectroscopy, Fourier Transform Infrared

Curcumin is a pleiotropic molecule with well-known anti-inflammatory effects. This molecule has attracted attention due to its capacity to pass the blood-brain-barrier and modulate central nervous system (CNS) cells, such as astrocytes. Astrocytes are the most numerous CNS cells, and play a pivotal role in inflammatory damage, a common feature in neurodegenerative diseases such as Alzheimer's Disease. Although the actions of curcumin have been studied extensively in peripheral cells, few studies have investigated the effect of curcumin on astrocytes under basal and inflammatory conditions. The aim of this study was to characterize the effect of curcumin on astrocytic function (glutamatergic metabolism, GFAP and S100B), and investigate a possible synergic effect with another molecule, piperine. For this purpose, we used primary cultured astrocytes; our results showed that curcumin increases GSH and GFAP content, but decreases S100B secretion under basal conditions. Under inflammatory conditions, provoked by lipopolysaccharide (LPS), curcumin and piperine reversed the LPS-induced secretion of TNF-α, and piperine reverted the LPS-induced upregulation of GFAP content. Interestingly, curcumin decreases S100B secretion even more than LPS. These results highlight important context-dependent effects of curcumin and piperine on astrocytes. Although we did not observe synergic effects of co-treatment with curcumin and piperine, their effects were complementary, as piperine modulated GFAP content under inflammatory conditions, and curcumin modulated S100B secretion. Both curcumin and piperine had important anti-inflammatory actions in astrocytes. We herein provide new insights into the actions of curcumin in the CNS that may aid in the search for new molecular targets and possible treatments for neurological diseases.

Topics: Anti-Inflammatory Agents; Astrocytes; Curcumin; Lipopolysaccharides

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in the world. Poor prognosis of HCC patients is a major issue, thus, better treatment options for patients are required. Curcumin (Cur), hydrophobic polyphenol of the plant turmeric, shows anti-proliferative, apoptotic, and anti-oxidative properties. Boron is a trace element which is essential part of human nutrition. Sodium pentaborate pentahydrate (NaB), a boron derivative, is an effective agent against cancer. In the current study, we performed in vitro experiments and transcriptome analysis to determine the response of NaB, Cur, piperine (Pip) and their combination in two different HCC cell lines, HepG2 and Hep3B. NaB and Cur induced cytotoxicity in a dose and time dependent manner in HepG2 and Hep3B, whereas Pip showed no significant toxic effect. Synergistic effect of combined treatment with NaB, Cur and Pip on HCC cells was observed on cytotoxicity, apoptosis and cell cycle assay. Following in vitro studies, we performed RNA-seq transcriptome analysis on NaB, Cur and Pip and their combination on HepG2 and Hep3B cells. Transcriptome analysis reveals combined treatment of NaB, Cur and Pip induces anti-cancer activity in both of HCC cells.

Topics: Boron; Carcinoma, Hepatocellular; Cell Line; Curcumin; Humans; Liver Neoplasms

Limitations in the current clinical management of critical-sized osseous defects have driven the need for multifunctional bone constructs. The ideal bone scaffold should possess advanced microarchitecture, well-defined pore interconnectivity, and supply biological signals, which actively guide and control tissue regeneration while simultaneously preventing post-implantation complications. Here, a natural medicine-based localized drug delivery from 3D printed scaffold is presented, which offers controlled release of curcumin, piperine from nano-sized polymeric micelles, and burst release of antibacterial carvacrol from the coating endowing the scaffold with their distinct, individual biological properties. This functionalized scaffold exhibits improved osteoblast (hFOB) cell attachment, 4-folds higher hFOB proliferation, and 73% increased hFOB differentiation while simultaneously providing cytotoxicity towards osteosarcoma cells with 61% lesser viability compared to control. In vitro, early tube formation (p < 0.001) indicates that the scaffolds can modulate the endothelial cellular network, critical for faster wound healing. The scaffold also exhibits 94% enhanced antibacterial efficacy (p < 0.001) against gram-positive Staphylococcus aureus, the main causative bacteria for osteomyelitis. Together, the multifunctional scaffolds provide controlled delivery of natural biomolecules from the nano-sized micelle-loaded 3D printed matrix for significant improvement in osteoblast proliferation, endothelial formation, osteosarcoma, and bacterial inhibition, guiding better bone regeneration for post-traumatic defect repair.

Topics: Anti-Bacterial Agents; Bone Neoplasms; Bone Regeneration; Calcium Phosphates; Curcumin; Humans; Micelles; Osteogenesis; Osteosarcoma; Printing, Three-Dimensional; Tissue Engineering; Tissue Scaffolds

Based on the free drug hypothesis, we hypothesized that food compounds that bind stronger to BSA than CUR inhibit the binding between BSA and CUR, and that this results in an increase of the cellular uptake and physiological activities of CUR. To verify this hypothesis, food compounds that bind stronger to BSA than CUR were identified. When THP-1 monocytes were co-treated with the identified compounds (

Topics: Alkaloids; Benzodioxoles; Cell Survival; Curcumin; Endocytosis; Humans; Piperidines; Polyunsaturated Alkamides; Serum Albumin; THP-1 Cells

Piperine (PIP) was evaluated as a natural coformer in the preparation of multicomponent organic materials for enhancing solubility and dissolution rate of the poorly water-soluble drugs: curcumin (CUR), lovastatin (LOV), and irbesartan (IBS). A screening based on liquid assisted grinding technique was performed using 1:1 drug-PIP molar ratio mixtures, followed by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) analyses. Three eutectic mixtures (EMs) composed of CUR-PIP, LOV-PIP, and IBS-PIP were obtained. Therefore, binary phase and Tamman's diagrams were constructed for each system to obtain the exact eutectic composition, which was 0.41:0.59, 0.29:0.71, and 0.31:0.69 for CUR-PIP, LOV-PIP, and IBS-PIP, respectively. Further, bulk materials of each system were prepared to characterize them through DSC, PXRD fully, Fourier transform infrared spectroscopy (FT-IR), and solution-state nuclear magnetic resonance (NMR) spectroscopy. In addition, the contact angle, solubility, and dissolution rate of each system were evaluated. The preserved characteristic in the PXRD patterns and FT-IR spectra of the bulk material of each system confirmed the formation of EM mixture without molecular interaction in solid-state. The formation of EM resulted in improved aqueous solubility and dissolution rate associated with the increased wettability observed by the decrease in contact angle. In addition, solution NMR analyses of CUR-PIP, LOV-PIP, and IBS-PIP suggested no significant intermolecular interactions in solution between the components of the EM. Hence, this study concludes that PIP could be an effective coformer to improve the solubility and dissolution rate of CUR, LOV, and IBS.

Topics: Alkaloids; Benzodioxoles; Cardiovascular Diseases; Curcumin; Irbesartan; Lovastatin; Piperidines; Polyunsaturated Alkamides; Powders; Spectroscopy, Fourier Transform Infrared

Multiple myeloma (MM) is a hematological bone marrow malignancy that can be treated but is usually fatal. Medication resistance is the major cause of relapses due to cancer stem cells (CSCs). As a result, this study aimed to identify multiple myeloma cancer stem cells (MMCSCs) in the bone marrow of twelve MM patients with pathological complete response (pCR) after chemotherapy and to investigate the potential effect of Curcumin/Piperine (C/P) extract as an anti-MMCSCs treatment in twenty newly diagnosed patients.. This study included twenty bone marrow (BM) samples from newly diagnosed MM patients and twelve BM samples from pCR patients after a year of treatment. The MTT test was performed to assess the treatment's effective dosage. A flow cytometer was used to identify MMCSCs, cell cycle profile, extract's apoptotic activity, and proliferation marker in the selected samples. Also,  a colony formation test and stemness protein were investigated.. In newly diagnosed MM patients, the C/P extract suppressed MMCSCs by 64.71% for CD138-/CD19- and 38.31% for CD38++. In MM patients' samples obtained after one year of treatment, the MMCSCs inhibition percentage reached 44.71% (P < 0.008) for CD138-/CD19- and 36.94% (P < 0.221) for CD38++. According to cell cycle analyses, the number of cells treated with C/P extract was significantly reduced in the S and G0/G1 phases (87.38%: 35.15%, and 4.83%: 2.17% respectively), with a rapid increase in the G2/M phases (1.1%: 2.2%.). MMCSCs apoptosis was identified using a flow cytometer and Annexin-V. Multiple myeloma stem cell (MMCSC) proliferation was inhibited. Clonogenicity was suppressed by 60%, and stemness protein expression was reduced by 70%.. MMCSCs in the bone marrow of MM-pCR patients can be utilized as a prognostic tool to predict recurrent multiple myeloma incidence. Also, the therapeutic potential of C/P extract as a prospective anti-MM drug targeting MMCSCs.

Topics: Biomarkers; Curcumin; Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Neoplastic Stem Cells; Prognosis

Recently, studies conducted with astrocyte cells have drawn attention to neurodegeneration pathologies caused by aluminum exposure. In particular, investigating the potential of herbal therapeutic agents to prevent this effect of aluminum has gained importance. The purpose of this study was to investigate the therapeutic and preventive effects of piperine, curcumin, and the combination of these compounds on reactive primary astrocyte cells. In order to examine the preventive effect, certain concentrations of compounds were applied to the cells before the aluminum application, and to be able to determine the therapeutic effect, the compounds were examined after the aluminum application. The efficacy of the compounds was analyzed in terms of cell viability, apoptosis, necrosis, and cytokine release. In conclusion, the results of the study showed that the use of different concentrations of piperine, curcumin, and their combination had significantly higher % cell viability on aluminum-induced damage in astrocyte cells compared to the damaged control group. In addition, a decrease in the number of apoptotic and necrotic cells was observed in the same groups, which indicated that piperine increased curcumin activity. The decrease in the amount of IL-6 and TGF-β cytokines also supported that piperine increased the effectiveness of curcumin. Considering all these results, it can be said that in terms of aluminum damage in astrocyte cells, the bioavailability-enhancing property of piperine on curcumin was shown for the first time in the literature. In line with these results, it is inevitable to carry out further studies.

Topics: Alkaloids; Aluminum; Astrocytes; Benzodioxoles; Curcumin; Polyunsaturated Alkamides

Centell-S is a water-soluble extract of Centella asiatica containing more than 80% w/w triterpenoid glycosides. Madecassoside and asiaticoside are two major components of the extract and can be converted into active metabolites, triterpenic acids in large mammal species. In this study, the pharmacokinetic profiles and metabolomic changes generated by the bioactive triterpenoids of Centell-S alone, and in combination with the bioenhancers piperine and curcumin, were investigated in beagle dogs. The test substances were orally administered over multiple doses for 7 consecutive days. At day 1 and 7 after receiving the test compounds, the level of major bioactive triterpenoids and related metabolites were measured using triple quadrupole and high-resolution accurate mass orbitrap models of LCMS to determine pharmacokinetic and metabolomic profiles, respectively. Centell-S was well tolerated, alone and in all combination groups. The combination of Centell-S and piperine significantly increased (p < 0.05) the systemic exposure of madecassoside on day 1 and asiatic acid on day 7, by approximately 1.5 to 3.0-fold of C

Topics: Animals; Curcumin; Dogs; Mammals; Metabolome; Plant Extracts; Triterpenes

This study aimed to evaluate the role of spices/spice active principles on physical, biochemical, and molecular targets of bioaccessibility/bioavailability. Carotenoids-rich micellar fraction obtained through simulated digestion of green leafy vegetables (GLV) with individual or two/three combinations were correlated to their influence on bioaccessibility, cellular uptake, and basolateral secretion of carotenoids in Caco-2 cells. Results suggest that carotenoids' bioaccessibility depends on micelles physicochemical properties, which is affected due to the presence of co-treated dietary spices and their composition. Increased bioaccessibility of β-carotene (BC) and lutein (LUT) is found in GLV (spinach) digested with turmeric (TM) than red pepper (RP) and black pepper (BP). In contrast, enhanced cellular uptake and secretion of BC and LUT-rich triglyceride-rich lipoprotein is observed in the presence of RP and BP compared to the control group. In contrast, TM inhibited absorption, while retinol levels significantly reduced in the presence of TM and RP than BP. Control cells have indicated higher cleavage of β-carotene to retinol than the spice-treated group. Besides, spice active principles modulate facilitated transport of carotenoids by scavenger receptor class B type 1 (SR-B1) protein. The effect of spices on carotenoids' bioavailability is validated with active spice principles. Overall, carotenoids' bioavailability (cellular uptake and basolateral secretion) was found in the following order of treatments; piperine > capsaicin > piperine + capsaicin > curcumin + capsaicin + piperine > control > turmeric. These findings suggested that the interaction of specific dietary factors, including spice ingredients at the enterocyte level, could provide greater insight into carotenoid absorption. PRACTICAL APPLICATION: Spices/spice active principles play a role in the digestion process by stimulating digestive enzymes and bile acids secretion. Since carotenoids are lipid soluble and have low bioavailability, spice ingredients' influence on intestinal absorption of carotenoids is considered crucial. Hence, understanding the interaction of co-consumed spices on the absorption process of carotenoids may help to develop functional foods/formulation of nutraceuticals to improve their health benefits.

Topics: Alkaloids; Benzodioxoles; Biological Availability; Caco-2 Cells; Capsaicin; Capsicum; Carotenoids; Curcuma; Curcumin; Humans; Micelles; Piper nigrum; Piperidines; Polyunsaturated Alkamides

Bisphenol A (BPA) is a chemical agent which can exert detrimental effects on the male reproductive system, especially the prostate gland. In this study we described the efficacy of the dietary agent curcumin, alone or combined with piperine, to suppress the impact of BPA on the prostate. Adult gerbils were divided into nine experimental groups (n = 7 each group), regarding control (water and oil), exposed to BPA (50 μg/kg/day in water) or curcumin (100 mg/kg) and/or piperine (20 mg/kg). To evaluate the effects of the phytotherapic agents, the other groups received oral doses every two days, BPA plus curcumin (BCm), piperine (BP), and curcumin + piperine (BCmP). BPA promoted prostatic inflammation and morphological lesions in ventral and dorsolateral prostate lobes, associated with an increase in androgen receptor-positive cells and nuclear atypia, mainly in the ventral lobe. Curcumin and piperine helped to minimize these effects. BPA plus piperine or curcumin showed a reduction in nuclear atypical phenotype, indicating a beneficial effect of phytochemicals. Thus, these phytochemicals minimize the deleterious action of BPA in prostatic lobes, especially when administered in association. The protective action of curcumin and piperine consumption is associated with weight loss, anti-inflammatory potential, and control of prostate epithelial cell homeostasis.

Topics: Alkaloids; Animals; Benzhydryl Compounds; Benzodioxoles; Carcinogenesis; Curcumin; Endocrine Disruptors; Gerbillinae; Male; Phenols; Phytochemicals; Piperidines; Polyunsaturated Alkamides; Prostate; Prostatic Neoplasms; Protective Agents

The persistent activation of intestinal mechanistic target of rapamycin complex 1 (mTORC1) triggered by mucosal stress has been linked to deregulation of the gut immune response resulting in intestinal inflammation and cell death. The present study investigated the regulatory properties of food-derived mTORC1 modulators, curcumin, and piperine, toward the polarization of stimulated macrophages and the differentiation of monocytes at two mTORC1 activity levels (baseline and elevated). To that end, we created stable human THP-1 monocytes exhibiting normal or constitutively active mTORC1. Curcumin or its combination with piperine, but not piperine alone, suppressed mTORC1 kinase activity, curtailed lipopolysaccharide-mediated inflammatory response of THP-1 macrophages, and repressed macrophage activation by inhibiting signaling pathways involved in M1 (mTORC1) and M2 (mTORC2 and cAMP response element binding protein) polarization. The effects of piperine in the curcumin/piperine combination were modest overall, indicating it was curcumin that modulated differentiating monocytes into acquiring a M0 macrophage phenotype characterized by low inflammatory cytokine output.

Topics: Alkaloids; Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzodioxoles; Cell Differentiation; Cell Survival; Curcuma; Curcumin; Cytokines; Humans; Immunity; Lipopolysaccharides; Macrophage Activation; Macrophages; Mechanistic Target of Rapamycin Complex 1; Monocytes; Phenotype; Piper nigrum; Piperidines; Polyunsaturated Alkamides; Signal Transduction; THP-1 Cells

Curcumin, a molecule of immense pharmacological significance is also known to exhibit poor aqueous solubility and low bioavailability. Different strategies have been adopted to enhance the aqueous solubility of curcumin, but report on the effect of traditional excipients on curcumin solubility still stand in need of. Here, we presented the significance of different traditional excipients used in anti-inflammatory formulations on curcumin solubility. The endeavor has been undertaken with the hypothesis that "traditional formulation used since ages have a scientific basis". To meet the quest we encapsulated 28 different formulations containing varying concentrations of milk, sugar, cow milk fat, and black pepper in alginate hydrogels. After the characterization of formulations through FT-IR, solubility studies were conducted. Milk was found to be an essential component for improved curcumin availability. Individually, cow milk fat and piperine exhibited lesser effect but their synergistic effect was observed in the presence of milk. Dual behavior of sugar has been observed. Traditionally used excipients greatly enhanced the solubility of curcumin. The results have also been validated through anti-oxidant activities of different formulations. Intermolecular interactions have been explained using Molecular modeling studies.

Topics: Alginates; Alkaloids; Animals; Antioxidants; Benzodioxoles; Curcuma; Curcumin; Drug Liberation; Excipients; Hydrogels; Milk; Models, Molecular; Piperidines; Polyunsaturated Alkamides; Solubility; Sucrose

Widely accessible food phytochemicals such as curcumin have been reported to have anti-inflammatory and anticarcinogenic properties. However, curcumin has poor absorption in the gut, and piperine has been of interest as a dietary compound that can enhance curcumin bioavailability. The aim of this study was to develop and optimize a technique using reversed-phase chromatography with multi-wavelength detection for the simultaneous measurement of curcumin and piperine in various biological matrices. Emodin was used as an internal standard. Protein precipitation and liquid-liquid extraction based on acetonitrile provided good recovery of these analytes. A 150 mm × 4.6 mm I.D. Luna C18 column was used under isocratic conditions to separate curcumin, piperine, and emodin with baseline resolution, and with good separation from other sample components, in as little as 4 min. The detection limits for curcumin and piperine were 3 and 7 ng/mL, respectively. This method has been used to quantitate these compounds in samples such as human intestinal epithelial cell lysates and mouse plasma or GI tissues in research aimed at examining the bioavailability of curcumin in the presence of piperine.

Topics: Alkaloids; Animals; Benzodioxoles; Biological Availability; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Curcumin; Emodin; Humans; Limit of Detection; Linear Models; Male; Mice; Piperidines; Polyunsaturated Alkamides; Reproducibility of Results

COVID-19 is now pandemic throughout the world, and scientists are searching for effective therapies to prevent or treat the disease. The combination of curcumin and piperine is a potential option for the management of COVID-19 based on several mechanisms including antiviral, anti-inflammatory, immunomodulatory, antifibrotic, and antioxidant effects. Here, we describe the probable mechanism of curcumin-piperine against COVID-19. Administration of curcumin-piperine combination appears as a potential strategy to counterbalance the pathophysiological features of COVID-19 including inflammation. The optimal dose and duration of curcumin-piperine supplementation should be determined in the future.

Topics: Alkaloids; Benzodioxoles; COVID-19; Curcumin; Humans; Piperidines; Polyunsaturated Alkamides; SARS-CoV-2

Curcumin (CUR) is a natural polyphenol present in the rhizomes of Curcuma longa and possesses diverse pharmacological effects, especially anti-carcinogenic effects against several types of cancers. Unfortunately, this novel compound has poor aqueous solubility and bioavailability that limit its pharmaceutical effects. The use of polymeric nanocapsules has been applied in order to overcome such problems. Thus, our present study aimed at developing two novel polymeric nanoparticles (NPs) systems that encapsulate either curcumin alone (CURN) or with piperine (CURPN), which acts as a glucuronidation inhibitor and increases the bioavailability of CUR. The NPs were successfully designed by self-assembled nanoprecipitation method and their characteristics were identified by Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS), and Zeta potential analysis. The drug release profiles of NPs were monitored under different pH, and their cytotoxic effects were assessed in vitro against Caco-2 cells and in vivo against dimethylhydrazine-induced colon cancer in mice. The FTIR and XRD analyses and SEM images showed amorphous and spherical shaped CURN and CURPN of 80-100 nm sized diameter. In vitro drug release study showed that pH triggered the maximum release of CUR in basic medium compared to acidic and neutral media, and following Higuchi model. CUR nanoencapsulation enhanced its physiochemical properties and drug loading and release. In vitro and in vivo studies showed that CUR NPs exerted selective and potential cytotoxic effects against colon cancer cells. The addition of piperine facilitated the encapsulation and drug loading of CUR. Thus, CUR nanoencapsulation enhanced the solubility and bioavailability of curcumin rendering it more effective against colon cancer.

Topics: Alkaloids; Animals; Antineoplastic Agents; Benzodioxoles; Caco-2 Cells; Colonic Neoplasms; Curcumin; Female; Humans; Mice; Mice, Inbred BALB C; Nanocapsules; Piperidines; Polyamines; Polyunsaturated Alkamides

Breast cancer is the leading cause of cancer mortality in women worldwide. Conventional cancer treatment is costly and results in many side effects. Dietary bioactive compounds may be a potential source for breast cancer prevention and treatment. In this scenario, the aim of this study was to investigate the effects of the bioactive compounds resveratrol, curcumin and piperine (R-C-P) on MCF-7 breast cancer cells and to associate them to Glyoxalase 1 (GLO1) activity. The findings indicate that R-C-P exhibits cytotoxicity towards MCF-7 cells. R-C-P decreased mitochondrial membrane potential (ΔΨm) by 1.93-, 2.04- and 1.17-fold, respectively. Glutathione and N-acetylcysteine were able to reverse the cytotoxicity of the assessed bioactive compounds in MCF-7 cells. R-C-P reduced GLO1 activity by 1.36-, 1.92- and 1.31-fold, respectively. R-C-P in the presence of antimycin A led to 1.98-, 1.65- and 2.16-fold decreases in D-lactate levels after 2 h of treatment, respectively. Glyoxal and methylglyoxal presented cytotoxic effects on MCF-7 cells, with IC

Topics: Alkaloids; Benzodioxoles; Breast Neoplasms; Curcumin; Female; Humans; Lactoylglutathione Lyase; MCF-7 Cells; Membrane Potential, Mitochondrial; Piperidines; Polyunsaturated Alkamides; Resveratrol

The combinational therapy is often considered as a desire in chemotherapy despite some limitations. This study aimed to encapsulate two natural-based drugs, curcumin (CUR), and piperine (PIP) into highly biocompatible albumin nanoparticles for anticancer applications.. A simultaneous exertion of CUR and PIP in a biocompatible drug delivery system with the minimum side effects and no limitations was achievable in this work for cancer treatment.. Curcumin and piperine co-loaded human serum albumin nanoparticles (CUR-PIP-HSA-NPs) were synthesized by the self-assembly method. The effectiveness of the codelivery system was evaluated physically, chemically, and pharmaceutically. Moreover, the anticancer activity of CUR-PIP-HSA-NPs was studied on MCF-7 cells by MTT assay.. CUR-PIP-HSA-NPs showed appropriate stability with an average particle size of 154.7 ± 5.2 nm. Loading of drugs was demonstrated by Fourier transform infrared (FT-IR) and differential scanning calorimetry (DSC) analyses. The drug encapsulation efficiencies (DEEs) of CUR and PIP in NPs were 85.3% ± 1.46% and 81.7%, ± 1.67%, respectively. Furthermore, the drug loading efficiency (DLE) of CUR-PIP-HSA-NPs was 8.71% ± 0.24%. The circular dichroism (CD) examination of the NPs confirmed that the conformational structure of albumin remained unchanged during the synthesis. In addition, the cytotoxicity experiments demonstrated the high potential of CUR-PIP-HSA-NPs against breast cancer (MCF-7) cells in the presence of PIP as both bioenhancer and anticancer drug with the capability of suppressing the effect of multidrug resistance (MDR).. The results suggest that CUR-PIP-HSA-NPs can be employed as a practical drug delivery system in cancer treatment with synergistic effects of both CUR and PIP.

Topics: Alkaloids; Benzodioxoles; Curcumin; Drug Delivery Systems; Humans; Nanoparticles; Neoplasms; Particle Size; Piperidines; Polyunsaturated Alkamides; Serum Albumin, Human; Spectroscopy, Fourier Transform Infrared

The nutraceutical system of curcumin-piperine in 2-hydroxypropyl-β-cyclodextrin was prepared by using the kneading technique. Interactions between the components of the system were defined by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR). Application of hydroxypropyl-β-cyclodextrin as a carrier-solubiliser improved solubility of the curcumin-piperine system, its permeability through biological membranes (gastrointestinal tract, blood-brain barrier) as well as the antioxidant, antimicrobial and enzyme inhibitory activities against acetylcholinesterase and butyrylcholinesterase.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Acetylcholinesterase; Alkaloids; Anti-Infective Agents; Antioxidants; Benzodioxoles; Biological Transport; Blood-Brain Barrier; Butyrylcholinesterase; Cholinesterase Inhibitors; Curcumin; Dietary Supplements; Drug Carriers; Drug Compounding; Gastrointestinal Tract; Humans; Piperidines; Polyunsaturated Alkamides; Solubility

The present work aimed to accomplish a comparative and principled study on desolvation and self-assembly methods for synthesis of piperine-loaded human serum albumin nanoparticles (PIP-HSA-NPs). Among drugs, PIP was selected as the hydrophobic model drug. The response surface methodology (RSM)-central composite design (CCD) was employed to precisely study the processes and the interactions between the factors affecting the methods. Optimization was performed to obtain the best formulations for both procedures. Both optimized PIP-HSA-NPs prepared by the two methods were stable and semi-spherical with the size less than 200 nm. The self-assembled PIP-HSA-NPs which were prepared under the optimized conditions with drug encapsulation efficiency (DEE) of 76.8% ± 0.44%, and drug loading efficiency (DLE) of 8.92% ± 0.3% had significantly higher DEE and DLE than the optimized particles obtained from the desolvation method with DEE of 34.1% ± 0.32% and DLE of 1.68 ± 0.11%. The secondary structure of HSA did not change much in self-assembled PIP-HSA-NPs compared to desolvated PIP-HSA-NPs. The self-assembled PIP-HSA-NPs showed more cumulative drug release than desolvated NPs, causing them to have more cytotoxicity on MCF-7 cells at high concentrations. These findings introduce the self-assembly technique as the better chemical method to produce a practical cost-effective carrier for many hydrophobic drugs.

Topics: Alkaloids; Antineoplastic Agents; Benzodioxoles; Cell Proliferation; Cell Survival; Curcumin; Dose-Response Relationship, Drug; Drug Carriers; Drug Liberation; Drug Screening Assays, Antitumor; Humans; Hydrophobic and Hydrophilic Interactions; MCF-7 Cells; Nanoparticles; Particle Size; Piperidines; Polyunsaturated Alkamides; Serum Albumin, Human; Solubility; Structure-Activity Relationship; Surface Properties

Studies have documented the anti-inflammatory effects of spices, which may be related to treatment of chronic diseases. The purpose of this study was to evaluate the influence of curcumin and piperine and their association on experimental periodontal repair in rats.. Periodontitis was induced via the installation of a ligature around the first molar. After 15 days, the ligatures were removed, and the rats were separated into groups (12 animals per group): (i) curcumin, (ii) piperine, (iii) curcumin+piperine, (iv) corn oil vehicle, and (v) control group (animals had ligature-induced periodontitis but were not treated). The compounds were administered daily, for 15 days by oral gavage. Animals were euthanized at 5 and 15 days, and hemimaxillae and gingival tissues were harvested. Bone repair was assessed by μCT (microcomputer tomography). Histological sections were stained with hematoxylin/eosin (H/E) for the assessment of cellular infiltrate or picrosirius red for quantification of collagen content, and subjected to immunohistochemistry for detecting NF-ĸB. Gingival tissues were used to evaluate levels of TGF-β and IL-10 (ELISA).. Curcumin and piperine increased the TGF-β level, significantly improved the collagen repair, and decreased the cellularity and activation of NF-ĸB in the periodontal tissues, but only curcumin caused a significant increase in early bone repair.. Curcumin and piperine promoted a substantive effect on tissue repair; however, there was not synergistic effect of compounds administered in combination.. Curcumin and piperine stimulates the tissue repair and may be potential candidates for the treatment of periodontal disease.

Topics: Alkaloids; Animals; Benzodioxoles; Cats; Curcumin; Male; Periodontitis; Piperidines; Polyunsaturated Alkamides; Rats; Rats, Wistar

Curcumin (CUR) has gained increasing interest worldwide due to multiple biological activities. However, the therapeutic application remains limited because of its low aqueous solubility, intestinal metabolism and poor membrane permeability. In present study, an excipient-free CUR solid dispersion co-formed with piperine (PIP), the absorption enhancer involving metabolism-permeability, was successfully prepared by melting and quench cooling (co-amorphous CUR-PIP). The co-amorphous CUR-PIP exhibited superior performance in non-sink dissolution compared with crystalline and amorphous CUR, and showed physically stable at least 3 months, attributing to the strong molecular interactions between CUR and PIP as evaluated by FTIR spectra. Furthermore, the combination of PIP with CUR in the co-amorphous formulation could inhibit the glucuronidation of CUR, as exhibited in the in vitro assay of rat intestinal microsomes. The co-amorphous CUR-PIP would also exhibit higher gastrointestinal membrane permeability of CUR, as confirmed by P

Topics: Alkaloids; Animals; Benzodioxoles; Biological Availability; Cells, Cultured; Curcumin; Drug Delivery Systems; Drug Stability; Humans; Intestinal Absorption; Intestinal Mucosa; Piperidines; Polyunsaturated Alkamides; Rats; Solubility

Previous studies have demonstrated that different curcumin extracts are able to influence cell metabolic activity vitality in human papillary thyroid carcinoma TPC-1 cells. We continued the study using the most effective extract and adding other nutraceuticals such as piperine and vitamin E, in order to define the possible role of these in modulating the genetic expression of cell markers and to understand the effectiveness in modulating the regression of cancer phenotype. Cells were treated with one extract of curcumin (Naturex

Topics: Alkaloids; Apoptosis Regulatory Proteins; Benzodioxoles; Cell Cycle Checkpoints; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Cell Survival; Curcumin; Drug Synergism; Humans; Piperidines; Polyunsaturated Alkamides; Thyroid Cancer, Papillary; Vitamin E

Ginkgo biloba extract (GBE) is widely used as herbal medicine. Preventive effect of GBE against dementia, including Alzheimer's disease, has been reported. The bioactive compounds in GBE that impart these beneficial effects, flavonoids and terpene lactones, have poor bioavailability. Our previous study found distribution of bioactive compounds of sesame extract in mice brain after mixing it with turmeric oil. Here, we evaluate the distribution of bioactive compounds of GBE by combining it with the mixture of sesame extract and turmeric oil (MST). The content of terpene lactones in mice serum was significantly increased in a dose-dependent manner after administration of GBE. However, the contents of terpene lactones in mice brain were not significantly changed. Concentration of ginkgolide A in mice brain increased significantly when GBE was co-administrated with MST than when GBE was administered alone. These results suggest that MST may be effective in enhancing the bioavailability of ginkgolide A in GBE.

Topics: Alkaloids; Animals; Benzodioxoles; Biological Availability; Brain; Curcuma; Ginkgo biloba; Ginkgolides; Lactones; Male; Mice; Phytochemicals; Piper; Piperidines; Plant Extracts; Plant Oils; Polyunsaturated Alkamides; Sesamum

Deltamethrin (DLM) is a well-known pyrethroid insecticide which is widely used in the agriculture and home pest control due to restriction on the sale of organophosphate. DLM induced apoptosis is well known but its mechanism is still unclear. This study has been designed to find out its mechanism of apoptosis with the help of computational methods along with in vivo methods. The QikProp and ProTox results have shown that DLM has good oral absorption. The docking results reveal that DLM has a strong binding affinity toward the CD4, CD8, CD28 and CD45 receptors. Further, to understand the toxicity of DLM on lymphoid cells, a single dose of DLM (5 mg/kg, oral for seven days) has been administered to male Balb/c mice and cytotoxicity (MTT assay), oxidative stress indicators (glutathione, reactive oxygen species) and apoptotic markers (caspase-3 activity, DNA fragmentation) have been assessed in thymic and splenic single cell suspensions. Lowering of body weight, cellularity and loss in cell viability have been observed in DLM treated mice. The significant increase in ROS and GSH depletion in spleen and thymus, indicate the possible involvement of oxidative stress. The spleen cells appear more susceptible to the adverse effects of DLM than thymus cells. Further, for the amelioration of its effect, two structurally different bioactive herbal extracts, piperine and curcumin have been evaluated and have shown the cytoprotective effect by inhibiting the apoptogenic signaling pathways induced by DLM.

Topics: Alkaloids; Animals; Antioxidants; Apoptosis; Benzodioxoles; Caspase 3; Cell Survival; Curcumin; Cytoprotection; Glutathione; Insecticides; Male; Mice, Inbred BALB C; Molecular Docking Simulation; Nitriles; Oxidative Stress; Piperidines; Polyunsaturated Alkamides; Protein Binding; Protein Conformation; Pyrethrins; Reactive Oxygen Species; Receptors, Immunologic; Spleen; Structure-Activity Relationship; Thymus Gland; Time Factors

Persistent activation of the mechanistic target of rapamycin complex 1 (mTORC1) is linked to sustained inflammation and progression of colorectal cancer. Widely available dietary phenolics, curcumin and piperine are purported to have antiinflammatory and anticarcinogenic activities through yet-to-be-delineated multitarget mechanisms. Piperine is also known to increase the bioavailability of dietary components, including curcumin. The objective of the study was to determine whether curcumin and piperine have individual and combined effects in the setting of gut inflammation by regulating mTORC1 in human intestinal epithelial cells. Results show that curcumin repressed (a) mTORC1 activity (measured as changes in the phosphorylation state of p70 ribosomal protein S6 kinase B1 and 40S ribosomal protein S6) in a dose-dependent manner (2.5-20 μM, P<.007) and (b) synthesis of nascent proteins. Piperine inhibited mTORC1 activity albeit at comparatively higher concentrations than curcumin. The combination of curcumin + piperine further repressed mTORC1 signaling (P<.02). Mechanistically, curcumin may repress mTORC1 by preventing TSC2 degradation, the conserved inhibitor of mTORC1. Results also show that a functional mTORC1 was required for the transcription of TNFα as Raptor knockdown abrogated TNFα gene expression. Curcumin, piperine and their combination inhibited TNFα gene expression at baseline but failed to do so under conditions of mTORC1 hyperactivation. TNF∝-induced cyclooxygenase-2 expression was repressed by curcumin or curcumin + piperine at baseline and high mTORC1 levels. We conclude that curcumin and piperine, either alone or in combination, have the potential to down-regulate mTORC1 signaling in the intestinal epithelium with implications for tumorigenesis and inflammation.

Topics: Alkaloids; Benzodioxoles; Caco-2 Cells; Cell Differentiation; Curcumin; Cyclooxygenase 2; Drug Synergism; HT29 Cells; Humans; Mechanistic Target of Rapamycin Complex 1; Piperidines; Polyunsaturated Alkamides; Protein Synthesis Inhibitors; Signal Transduction; Tuberous Sclerosis Complex 2 Protein; Tumor Necrosis Factor-alpha

Allergic asthma is an inflammatory condition accompanied by inflammation as well as oxidative stress. Supplementation of an anti-inflammatory agent having antioxidant properties may have therapeutic effects against this disease. Over the recent decades, the interest in combination therapy as new alternative medication has increased and it offers numerous benefits along with noticeable lack of toxicity as well as side effects. In this study, protective effects of curcumin alone and in combination with piperine were evaluated in mouse model of allergic asthma. Balb/c mice were sensitized on days 0, 7, and 14 and challenged from days 16-30 on alternate days with ovalbumin (OVA). Mice were pretreated with curcumin (Cur; 10 and 20 mg/kg) and piperine (Pip; 5 mg/kg) alone and in combination via the intraperitoneal route on days 16-30 and compared with intranasal curcumin (5 mg/kg) treatment. Blood, bronchoalveolar lavage fluid (BALF), and lungs were collected after mice were sacrificed on day 31st. Mice immunized with OVA have shown significant increase in airway inflammation and oxidative stress as determined by oxidative stress markers. A significant suppression was observed with all the treatments, but intranasal curcumin treatment group has shown maximum suppression. So, among all the treatment strategies utilized, intranasal curcumin administration was most appropriate in reducing inflammation and oxidative stress and possesses therapeutic potential against allergic asthma. Present study may prove the possibility of development of curcumin nasal drops towards treatment of allergic asthma.

Topics: Alkaloids; Animals; Anti-Inflammatory Agents; Asthma; Benzodioxoles; Bronchoalveolar Lavage Fluid; Curcumin; Drug Administration Routes; Drug Therapy, Combination; Inflammation; Lung; Mice; Mice, Inbred BALB C; Ovalbumin; Oxidative Stress; Piperidines; Polyunsaturated Alkamides

Glutathione-S-transferase also referred as GST is one of the major detoxification enzymes in parasitic helminths. The crucial role played by GST in various chronic infections has been well reported. The dependence of nematodes on detoxification enzymes to maintain their survival within the host established the crucial role of GST in filariasis and other related diseases. Hence, this well-established role of GST in filariasis along with its greater nonhomology with its human counterpart makes it an important therapeutic drug target. Here in this study, we have tried to explore the inhibitory potential of some of the well-reported natural ant-filarial compounds against the GST from Wuchereria bancrofti (W.bancrofti) and Brugia malayi (B.malayi). In silico virtual screening, approach was used to screen the selected natural compounds against GST from W.bancrofti and B.malayi. On the basis of our results, here we are reporting some of the natural compounds which were found to be very effective against GSTs. Along with we have also revealed the characteristic of the active site of BmGST and WbGST and the role of important active site residues involve in the binding of natural compounds within the active site of GSTs. This information will oped doors for using natural compounds as anti-filarial therapy and will also be helpful for future drug discovery.

Topics: Alkaloids; Animals; Anthelmintics; Benzodioxoles; Biological Products; Brugia malayi; Capsaicin; Catalytic Domain; Curcumin; Drug Evaluation, Preclinical; Glutathione Transferase; Molecular Docking Simulation; Piperidines; Polyunsaturated Alkamides; Strychnine; Wuchereria bancrofti

Poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles are loaded with curcumin and piperine by in situ emulsion polymerization using dodecyl benzene sulfonic acid both as a stabilizer and a doping agent. The loaded drugs affect the morphology, size, and colloidal stability of the nanoparticles. Furthermore, kinetics studies of nonstimulated drug release have evidenced that polymer···drug interactions are stronger for curcumin than for piperine. This observation suggests that drug delivery systems based on combination of the former drug with PEDOT are much appropriated to show an externally tailored release profile. This is demonstrated by comparing the release profiles obtained in presence and absence of electrical stimulus. Results indicate that controlled and time-programmed release of curcumin is achieved in a physiological medium by applying a negative voltage of -1.25 V to loaded PEDOT nanoparticles.

Topics: Alkaloids; Benzodioxoles; Bridged Bicyclo Compounds, Heterocyclic; Curcumin; Drug Carriers; Drug Delivery Systems; Drug Liberation; Nanoparticles; Particle Size; Piperidines; Polymers; Polyunsaturated Alkamides; Thiophenes

The lipophilic phytocannabinoids cannabidiol (CBD) and Δ

Topics: Administration, Oral; Alkaloids; Animals; Benzodioxoles; Biological Availability; Cannabidiol; Curcumin; Dronabinol; Drug Delivery Systems; Emulsions; Excipients; Gastrointestinal Absorption; Lipids; Male; Nanoparticles; Piperidines; Polyunsaturated Alkamides; Rats, Wistar; Resveratrol; Stilbenes

Inhibition of cytochrome P450 (P450) enzymes (CYP) has been shown to lower the metabolism of drugs that are P450 substrates and to consequently alter their pharmacokinetic profiles. Curcumin (CUR), piperine (PIP), and capsaicin (CAP) are spice components (SC) that inhibit the activities of a range of P450 enzymes, but the selection of which SC to be prioritized for further development as an adjuvant will depend on the ranking order of the inhibitory potential of the SCs on specific P450 isozymes. We used common human recombinant enzyme platforms to provide a comparative evaluation of the inhibitory activities of CUR, PIP, and CAP on the principal drug-metabolizing P450 enzymes. SC-mediated inhibition of CYP3A4 was found to rank in the order of CAP (IC

Topics: Alkaloids; Benzodioxoles; Capsaicin; Curcumin; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Humans; Molecular Structure; Piperidines; Polyunsaturated Alkamides; Recombinant Proteins; Spices

6-hydroxy dopamine (6-OHDA) is a neurotoxin which on intranigral administration produces severe nigrostriatal damage with motor and cognitive deficit in animals. Curcumin (CMN) in combination with bioenhancer piperine (PP) in 6-hydroxydopamine-induced Parkinsonian rats was used to investigate the antioxidant, neuromodulatory and neuroprotective mechanisms.. Hemi-Parkinson's rat model was developed with intranigral infusion of 6-OHDA (8 μg/2 μl, once, unilaterally), treatment with CMN (25 and 50 mg/kg) and combination of PP (2.5 mg/kg) with CMN (25 mg/kg) was given daily for 21 days starting from the 7th day after 6-OHDA infusion. The behavioral (locomotor, grip strength, and narrow beam walk) parameters were studied on weekly basis. On 22nd day, isolated brain preparations were subjected to biochemical (lipid peroxidation, glutathione, and nitrite), neuroinflammatory (IL-1β, IL-6, and TNF- α), and neurochemical (DA, NE, 5- HT, GABA, Glutamate, DOPAC, HVA, and 5-HIAA) analysis.. Oral administration of CMN had significantly prevented behavioral, neuroinflammatory, and neurochemical changes and preserved the antioxidant potential of the nigrostriatum in rats treated with 6-OHDA.. In the present study, PP and CMN had afforded a better neuroprotective effect compared to alone treatment on behavior, biochemical, neuroinflammatory, and neurochemical parameters in rats.

Topics: Alkaloids; Animals; Benzodioxoles; Corpus Striatum; Curcumin; Drug Therapy, Combination; Hand Strength; Locomotion; Male; Motor Skills Disorders; Neuroprotective Agents; Oxidopamine; Piperidines; Polyunsaturated Alkamides; Random Allocation; Rats; Rats, Wistar

Curcumin (CUR) is known to exert numerous health-promoting effects in pharmacological studies, but its low bioavailability hinders the development of curcumin as a feasible therapeutic agent. Piperine (PIP) has been reported to enhance the bioavailability of curcumin, but the underlying mechanism remains poorly understood. In an attempt to find the mechanism by which piperine enhances the bioavailability of curcumin, the dosage ratio (CUR: PIP) and pre-treatment with piperine were hypothesized as key factors for improving the bioavailability in this combination. Therefore, combining curcumin with piperine at various dose ratios (1:1 to 100:1) and pre-dosing with piperine (0.5-8 h prior to curcumin) were designed to investigate their contributions to the pharmacokinetic parameters of curcumin in rats and their effects on the expression of UGT and SULT isoforms. It was shown that the C

Topics: Alkaloids; Animals; Arylsulfotransferase; Benzodioxoles; Biological Availability; Caco-2 Cells; Colon; Curcumin; Drug Interactions; Glucuronosyltransferase; Hep G2 Cells; Humans; Liver; Male; Piperidines; Polyunsaturated Alkamides; Rats, Sprague-Dawley

Quinolinic acid (QA) is an excitotoxin that induces Huntington's-like symptoms in animals and humans. Curcumin (CMN) is a well-known antioxidant but the major problem is its bioavailability. Therefore, the present study was designed to investigate the effect of CMN in the presence of piperine against QA-induced excitotoxic cell death in rats.. QA was administered intrastriatally at a dose of 200 nmol/2 µl saline, bilaterally. CMN (25 and 50 mg/kg/day, p.o.) and combination of CMN (25 mg/kg/day, p.o.) and with piperine (2.5 mg/kg/day, p.o.) was administered daily for the next 21 days. Body weight and behavioral parameters were observed on 1st, 7th, 14th and 21st day. On the 22nd day, animals were sacrificed and striatum was isolated for biochemical (LPO, nitrite and GSH), neuroinflammatory (interleukin (IL)-1β, IL-6 and TNF-α) and neurochemical (dopamine, norepinephrine, GABA, glutamate, 5-HT, 3,4-dihydroxyphenylacetic acid and homovanillic acid) estimation.. CMN treatment showed beneficial effect against QA-induced motor deficit, biochemical and neurochemical abnormalities in rats. Combination of piperine (2.5 mg/kg/day, p.o.) with CMN (25 mg/kg/day, p.o.) significantly enhanced its protective effect as compared to treatment with CMN alone.. This study has revealed that the combination of CMN and piperine showed strong antioxidant and protective effect against QA-induced behavioral and neurological alteration in rats.

Topics: Adenosine; Alkaloids; Animals; Antioxidants; Benzodioxoles; Brain; Catecholamines; Curcumin; Cytokines; Drug Therapy, Combination; gamma-Aminobutyric Acid; Glutamic Acid; Glutathione; Hand Strength; Huntington Disease; Lipid Peroxidation; Locomotion; Neuroprotective Agents; Nitrites; Piperidines; Polyunsaturated Alkamides; Quinolinic Acid; Rats, Wistar

The aim of the present study was to investigate the protective effects of curcumin alone and in combination with piperine against lipopolysaccharide (LPS)-induced neurobehavioral and neurochemical deficits in the mice hippocampus. Mice were treated with curcumin (100, 200, and 400 mg/kg, p.o.) and piperine (20 mg/kg, p.o.) for 7 days followed by LPS (0.83 mg/kg, i.p.) administration. Animals exhibited anxiety and depressive-like phenotype after 3 and 24 h of LPS exposure, respectively. LPS administration increased the oxido-nitrosative stress as evident by elevated levels of malondialdehyde, nitrite, and depletion of glutathione level in the hippocampus. Furthermore, we found raised level of pro-inflammatory cytokines (IL-1β and TNF-α) in the hippocampus of LPS-treated mice. Pretreatment with curcumin alleviated LPS-induced neurobehavioral and neurochemical deficits. Furthermore, co-administration of curcumin with piperine significantly potentiated the neuroprotective effect of curcumin. These results demonstrate that piperine enhanced the neuroprotective effect of curcumin against LPS-induced neurobehavioral and neurochemical deficits.

Topics: Alkaloids; Animals; Benzodioxoles; Curcumin; Drug Synergism; Hippocampus; Lipopolysaccharides; Mice; Neurodegenerative Diseases; Neuroprotective Agents; Piperidines; Polyunsaturated Alkamides

We combine quantum chemical and molecular docking techniques to provide new insights into how piperine molecule in various forms of pepper enhances bioavailability of a number of drugs including curcumin in turmeric for which it increases its bioavailability by a 20-fold. We have carried out docking studies of quantum chemically optimized piperine structure binding to curcumin, CYP3A4 in cytochrome P450, p-Glycoprotein and UDP-glucuronosyltransferase (UGT), the enzyme responsible for glucuronosylation, which increases the solubility of curcumin. All of these studies establish that piperine binds to multiple sites on the enzymes and also intercalates with curcumin forming a hydrogen bonded complex with curcumin. The conjugated network of double bonds and the presence of multiple charge centers of piperine offer optimal binding sites for piperine to bind to enzymes such as UDP-GDH, UGT, and CYP3A4. Piperine competes for curcumin's intermolecular hydrogen bonding and its stacking propensity by hydrogen bonding with enolic proton of curcumin. This facilitates its metabolic transport, thereby increasing its bioavailability both through intercalation into curcumin layers through intermolecular hydrogen bonding, and by inhibiting enzymes that cause glucuronosylation of curcumin.

Topics: Alkaloids; Benzodioxoles; Biological Availability; Curcumin; Drug Discovery; Molecular Docking Simulation; Piper; Piperidines; Polyunsaturated Alkamides; Protein Conformation; Quantum Theory

Topics: Alkaloids; Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Benzodioxoles; Biological Availability; Cell Survival; Chitosan; Curcumin; Drug Interactions; Drug Stability; Emulsions; Fibroblasts; HT29 Cells; Humans; Imidoesters; Male; Mice; Nanoparticles; NIH 3T3 Cells; Particle Size; Piperidines; Polyunsaturated Alkamides; Rats, Wistar; Surface Properties; Tissue Distribution

Curcumin is a potential agent for both the prevention and treatment of cancers. Curcumin treatment alone, or in combination with piperine, limits breast stem cell self-renewal, while remaining non-toxic to normal differentiated cells. We paired fluorescence-activated cell sorting with RNA sequencing to characterize the genome-wide changes induced specifically in normal breast stem cells following treatment with these compounds. We generated genome-wide maps of the transcriptional changes that occur in epithelial-like (ALDH+) and mesenchymal-like (ALDH-/CD44+/CD24-) normal breast stem/progenitor cells following treatment with curcumin and piperine. We show that curcumin targets both stem cell populations by down-regulating expression of breast stem cell genes including ALDH1A3, CD49f, PROM1, and TP63. We also identified novel genes and pathways targeted by curcumin, including downregulation of SCD. Transient siRNA knockdown of SCD in MCF10A cells significantly inhibited mammosphere formation and the mean proportion of CD44+/CD24- cells, suggesting that SCD is a regulator of breast stemness and a target of curcumin in breast stem cells. These findings extend previous reports of curcumin targeting stem cells, here in two phenotypically distinct stem/progenitor populations isolated from normal human breast tissue. We identified novel mechanisms by which curcumin and piperine target breast stem cell self-renewal, such as by targeting lipid metabolism, providing a mechanistic link between curcumin treatment and stem cell self-renewal. These results elucidate the mechanisms by which curcumin may act as a cancer-preventive compound and provide novel targets for cancer prevention and treatment.

Topics: Alkaloids; Antineoplastic Agents; Benzodioxoles; Breast Neoplasms; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Cell Separation; Curcumin; Female; Flow Cytometry; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; MCF-7 Cells; Piperidines; Polyunsaturated Alkamides; Sequence Analysis, RNA; Stearoyl-CoA Desaturase; Stem Cells

Curcumin is a nutraceutical obtained from the rhizomes of Curcuma longa with a significant medicinal value against numerous disorders. However, the potential cannot be completely exploited due to low in vivo bioavailability. Hence, in order to enhance the bioavailability of curcumin, we combined it with the bioavailability enhancers like piperine and quercetin.. The present study was targeted to explore the antidiabetic potential of combinatorial extract of curcumin with piperine and quercetin (CPQ) in streptozotocin- and nicotinamide-induced diabetic rats. Diabetes mellitus was induced by single intraperitoneal injection of streptozotocin (55 mg/kg) and nicotinamide (120 mg/kg-1). CPQ was orally administered at 100 mg kg-1 dose/day for a period of 28 days. At the end of 28 days, blood was analyzed for glucose, high density lipoprotein (HDL), low density lipoprotein (LDL) and total cholesterol level. Oral glucose tolerance test (OGTT) was also conducted at the end of 28 days.. Oral administration of CPQ at the dose of 100 mg kg-1 significantly (p<0.01) reduced plasma glucose at the end of 28 days, as compared to the diabetic control group. The reduction in the plasma glucose produced by the CPQ extract was equivalent to that of glibenclamide and significantly more compared to curcumin alone (p<0.01). Furthermore, a significant (p<0.01) reduction in the raised LDL, cholesterol and triglycerides and improvement was observed in the group fed with CPQ compared to diabetic control as well as the alone (p<0.05) curcumin group. There was a significant improvement in the body weight with CPQ compared to diabetes control group. OGTT revealed a significantly high glucose tolerance in CPQ fed rats compared to the diabetic control as well as the rats fed with curcumin alone.. Treatment with combinatorial extract of curcumin presented a significantly better therapeutic potential when compared with curcumin alone, which reveals that CPQ, with reduced dose of curcumin may serve as a therapeutic agent in the treatment of type 2 diabetes mellitus.

Topics: Alkaloids; Animals; Benzodioxoles; Biological Availability; Blood Glucose; Body Weight; Curcuma; Curcumin; Diabetes Mellitus, Experimental; Drug Combinations; Female; Glucose Tolerance Test; Hypoglycemic Agents; Lipids; Male; Mice; Phytotherapy; Piperidines; Plant Extracts; Polyunsaturated Alkamides; Quercetin; Rats, Wistar

Parkinson's disease (PD) is the most widespread form of dementia where there is an age related degeneration of dopaminergic neurons in the substantia nigra region of the brain. Accumulation of α-synuclein (αS) protein aggregate, mitochondrial dysfunction, oxidative stress, and neuronal cell death are the pathological hallmarks of PD. In this context, amalgamation of curcumin and piperine having profound cognitive properties, and antioxidant activity seems beneficial. However, the blood-brain barrier (BBB) is the major impediment for delivery of neurotherapeutics to the brain. The present study involves formulation of curcumin and piperine coloaded glyceryl monooleate (GMO) nanoparticles coated with various surfactants with a view to enhance the bioavailability of curcumin and penetration of both drugs to the brain tissue crossing the BBB and to enhance the anti-parkinsonism effect of both drugs in a single platform. In vitro results demonstrated augmented inhibition of αS protein into oligomers and fibrils, reduced rotenone induced toxicity, oxidative stress, and apoptosis, and activation of autophagic pathway by dual drug loaded NPs compared to native counterpart. Further, in vivo studies revealed that our formulated dual drug loaded NPs were able to cross BBB, rescued the rotenone induced motor coordination impairment, and restrained dopaminergic neuronal degeneration in a PD mouse model.

Topics: Alkaloids; alpha-Synuclein; Animals; Antiparkinson Agents; Benzodioxoles; Blood-Brain Barrier; Capillary Permeability; Curcumin; Drug Delivery Systems; Drug Therapy, Combination; Liposomes; Male; Mice, Inbred BALB C; Mice, Inbred C57BL; Nanoparticles; Neuroprotective Agents; Parkinsonian Disorders; PC12 Cells; Piperidines; Polyunsaturated Alkamides; Protein Aggregation, Pathological; Random Allocation; Rats; Rotenone; Surface-Active Agents

The therapeutic agents for dementia are limited due to the complex system underlying the mechanisms. Taking a preventive point of view, we focused on the inhibition of β-secretase and acetylcholinesterase (AChE). In addition, plant resources including herbs and spices have been widely consumed, and further, may be consumed for a long period over a lifetime. Considering this background, we screened β-secretase and AChE inhibitors from curry spices. Amongst them, curry leaf, black pepper, and turmeric extracts were effective to inhibit β-secretase. Furthermore, black pepper and turmeric extracts were also effective to inhibit AChE. Having these results in hand, we focused on the investigation of β-secretase inhibitors since the inhibitor of this enzyme has not previously been well investigated. As a result, α- and β-caryophyllene, β-caryophyllene oxide (from curry leaf), piperine (from black pepper), curcumin, demethoxycurcumin, and bisdemethoxycurcumin (from turmeric) were successfully identified as low molecular inhibitors. This is the first report to determine α- and β-caryophyllene, β-caryophyllene oxide, and piperine as β-secretase inhibitors. These compounds may pass through the blood brain barrier since their molecular weights are relatively low.

Topics: Acetylcholinesterase; Alkaloids; Amyloid Precursor Protein Secretases; Benzodioxoles; Cholinesterase Inhibitors; Curcuma; Curcumin; Diarylheptanoids; Murraya; Piper nigrum; Piperidines; Plant Extracts; Polycyclic Sesquiterpenes; Polyunsaturated Alkamides; Sesquiterpenes

Spices are rich in natural antioxidants and have been shown to be potent inhibitors of lipid peroxidation during cooking of meat. Turmeric contains unique conjugated curcuminoids with strong antioxidant activity. Piperine, one of the main constituents of black pepper, is known to increase the bioavailability of curcuminoids in mouse and human studies when consumed with turmeric. We investigated whether adding black pepper to turmeric powder may further inhibit lipid peroxidation when added to meat patties prior to cooking. The addition of black pepper to turmeric significantly decreased the lipid peroxidation in hamburger meat. When investigating the antioxidant activity of the main chemical markers, we determined that piperine did not exhibit any antioxidant activity. Therefore, we conclude that other black pepper ingredients are responsible for the increased antioxidant activity of combining black pepper with turmeric powder.

Topics: Alkaloids; Antioxidants; Benzodioxoles; Cooking; Curcuma; Curcumin; Food Handling; Humans; Lipid Peroxidation; Meat; Piper nigrum; Piperidines; Plant Extracts; Polyunsaturated Alkamides; Spices

Deltamethrin (DLM) being a potent immunotoxicant affects both humoral and cell mediated immunity. Thus, for the amelioration of its effects, two different bioactive herbal extracts piperine and curcumin are evaluated and their efficacy has been compared. The docking results demonstrated that curcumin has good binding affinity towards CD28 and CD45 receptors as compared to piperine but in vitro studies revealed that piperine is more effective. DLM induced apoptotic markers such as oxidative stress and caspase 3 have been attenuated more significantly by piperine as compared to curcumin. Phenotypic and cytokine changes have also been mitigated best with piperine. Thus, these findings strongly demonstrate that piperine displays the more anti-oxidative, anti-apoptotic and chemo-protective properties in the DLM induced splenic apoptosis as compared to curcumin. So, piperine can be considered the drug of choice under immunocompromised conditions.

Topics: Alkaloids; Animals; Apoptosis; Benzodioxoles; CD28 Antigens; Curcumin; Humans; Immunity; Leukocyte Common Antigens; Male; Mice; Mice, Inbred BALB C; Nitriles; Piperidines; Polyunsaturated Alkamides; Pyrethrins; Spleen

The rod outer segments (OS) of the retina are specialized organelles where phototransduction takes place. The mitochondrial electron transport complexes I-IV, cytochrome c and Fo F1 -ATP synthase are functionally expressed in the OS disks. Here, we have studied the effect of some polyphenolic compounds acting as inhibitors of mitochondrial ATPase/synthase activity on the OS ectopic Fo F1 - ATP synthase. The mechanism of apoptosis in the OS was also investigated studying the expression of cytochrome c, caspase 9 and 3 and Apaf-1.. We prepared OS from fresh bovine retinae. Semi-quantitative Western blotting, confocal and electron microscopy, and cytofluorimetry were used along with biochemical analyses such as oximetry, ATP synthesis and hydrolysis.. Resveratrol and curcumin plus piperine inhibited ATP synthesis and oxygen consumption in the OS. Epigallocatechin gallate and quercetin inhibited ATP hydrolysis and oxygen consumption in the OS. Malondialdehyde and hydrogen peroxide were produced in respiring OS in the presence of substrates. Cytochrome c was located inside the disk membranes. Procaspase 9 and 3, as well as Apaf-1 were expressed in the OS.. These polyphenolic phytochemicals modulated the Fo F1 -ATP synthase activity of the the OS reducing production of reactive oxygen intermediates by the OS ectopic electron transport chain. Polyphenols decrease membrane peroxidation and cytochrome c release from disks, preventing the induction of caspase-dependent apoptosis in the OS Such effects are relevant in the design of protection against functional impairment of the OS following oxidative stress from exposure to intense illumination.

Topics: Adenosine Triphosphate; Alkaloids; Animals; Benzodioxoles; Caspase 3; Caspase 9; Catechin; Cattle; Curcumin; Cytochromes c; Hydrogen Peroxide; Malondialdehyde; Oxidative Phosphorylation; Oxygen Consumption; Phytochemicals; Piperidines; Polyunsaturated Alkamides; Quercetin; Resveratrol; Rod Cell Outer Segment; Stilbenes

Curcumin (CUR) is a poorly water-soluble drug and its absorption is very low. In this study, CUR and piperine (PIP) were co-encapsulated into the nanoformulation called self-microemulsifying drug delivery system (SMEDDS) to improve the stability and water-solubility of CUR and enhance its anti-colitis activity. The formulation of CUR-PIP-SMEDDS was prepared to encapsulate two hydrophobic components CUR and PIP, and then was characterized by assessing appearance, morphology, particle size, zeta potential and drug encapsulation efficiency. The appearance of CUR-PIP-SMEDDS remained clarified and transparent, and the microemulsion droplets appeared spherical without aggregation. The mean size of microemulsion droplet formed from CUR-PIP-SMEDDS was 15.87 ± 0.76 nm, and the drug encapsulation efficiency of SMEDDS for CUR and PIP were (94.34 ± 2.18)% and (90.78 ± 2.56)%, respectively. The vitro stability investigation of CUR-PIP-SMEDDS in colon tissue suggested that using SMEDDS as a delivery vehicle and co-encapsulated with PIP, CUR was more stable than drug solution in colons site. Meanwhile, the anti-inflammatory activity of CUR-PIP-SMEDDS was evaluated on DSS-induced colitis model. The results showed that CUR-PIP-SMEDDS exhibited definite anti-colitis activity by directing CUR-PIP-SMEDDS to inflammatory colon tissue through retention enema administration. Our study illustrated that the developed CUR-PIP-SMEDDS formulation was a potential carrier for developing colon-specific drug delivery system of CUR for ulcerative colitis treatment.

Topics: Alkaloids; Animals; Benzodioxoles; Chemistry, Pharmaceutical; Colitis, Ulcerative; Curcumin; Drug Delivery Systems; Drug Stability; Emulsions; Male; Mice; Mice, Inbred BALB C; Particle Size; Piperidines; Polyunsaturated Alkamides; Solubility

3-Nitropropionic acid (3-NP) is a fungal toxin well established model used for inducing symptoms of Huntington's disease. Curcumin a natural polyphenol has been reported to possess neuroprotective activity by decreasing oxidative stress. The aim of present study was to investigate neuroprotective effect of curcumin with piperine (bioavailability enhancer) against 3-NP induced neurotoxicity in rats. Administration of 3-NP (10 mg/kg for 21 days) showed loss in body weight, declined motor function and changes in biochemical (LPO, nitrite and glutathione level), neuroinflammatory (TNF-α and IL-1β level) and neurochemical (DA, NE, 5-HT, DOPAC, 5-HIAA and HVA). Chronic treatment with curcumin (25 and 50 mg/kg) and curcumin (25 mg/kg) with piperine (2.5 mg/kg) once daily for 21 days prior to 3-NP administration. All the behavioral parameters were studied at 1st, 7th, 14th, and 21st day. On 22nd day all the animals was scarified and striatum was separated. Curcumin alone and combination (25 mg/kg) with piperine (2.5 mg/kg) showed beneficial effect against 3-NP induced motor deficit, biochemical and neurochemical abnormalities in rats. Piperine (2.5 mg/kg) with curcumin (25 mg/kg) significantly enhances its protective effect as compared with curcumin alone treated group. The results of the present study indicate that protective effect of curcumin potentiated in the presence of piperine (bioavailability enhancer) against 3-NP-induced behavioral and molecular alteration.

Topics: Alkaloids; Animals; Benzodioxoles; Curcumin; Drug Therapy, Combination; Male; Motor Activity; Neuroprotective Agents; Neurotransmitter Agents; Nitro Compounds; Oxidative Stress; Piperidines; Polyunsaturated Alkamides; Propionates; Rats; Rats, Wistar

Curcumin has been reported to suppress different types of clinical and experimentally-induced tumors, but due to less absorption and quick metabolism it show poor bioavailability. The present study was envisaged to investigate the possible synergistic effect of combined treatment of curcumin with piperine in suppression of diethylnitrosamine (DENA)-induced hepatocellular carcinoma (HCC) in rats, owing to permeability enhancing effect of latter. HCC was induced by supplying DENA (0.01%) in drinking water for 10 weeks. The rats were treated with curcumin (100mg/kg; p.o.) per se and curcumin along with piperine (20mg/kg; p.o.) for 4 weeks post HCC induction. The combined treatment significantly attenuated the morphological, histopathological, biochemical, apoptotic and proliferative changes in the liver and serum in comparison to curcumin per se and vehicle control group. The results of present study concluded that curcumin in combination with piperine shows better suppression of DENA-induced HCC in contrast to curcumin per se.

Topics: Alkaloids; Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Benzodioxoles; Carcinoma, Hepatocellular; Cell Proliferation; Curcumin; Diethylnitrosamine; Drug Administration Schedule; Drug Synergism; Lipid Peroxidation; Liver Neoplasms; Male; Neoplasms, Experimental; Piperidines; Polyunsaturated Alkamides; Rats

The dietary pigment curcumin is a natural polyphenol extracted from the Curcuma longa rhizomes native to South Asia. The antioxidative, antimicrobial, and anti-inflammatory activities besides its unknown side effects suggest that curcumin could be a promising antiresorptive agent to prevent replacement resorption in replanted teeth after traumatic avulsion. Piperine, an alkaloid present in black pepper, seems to enhance the bioavailability and activity of curcumin. Therefore, this study evaluated the biocompatibility of curcumin and piperine in cultures of periodontal ligament cells as well as their effects in an in vitro osteoclastogenesis model of RAW 264.7 macrophages.. The cytotoxicity in human periodontal ligament fibroblasts, human osteogenic sarcoma cells (SAOS-2), and murine osteoclastic precursors (RAW 264.7) was analyzed by using cell number determination and proliferation assays. The ability of curcumin and its conjugate to suppress the receptor activator of nuclear factor kappa B ligand-induced osteoclastogenesis was assessed by tartrate-resistant acid phosphatase (TRAP) staining and activity as well as real-time polymerase chain reaction.. Curcumin at concentrations ≥ 10 μmol/L was cytotoxic in all cell types tested, whereas piperine showed only slight cytotoxicity at 30 μmol/L in RAW and SAOS cultures. Although curcumin caused already significant effects, the combination with piperine completely suppressed the osteoclastogenesis by decreasing the TRAP activity and inhibiting the expression of the specific osteoclast markers TRAP, cathepsin K, and calcitonin receptor.. We demonstrated that curcumin combined with piperine suppressed the osteoclastogenesis in vitro without causing cytotoxic effects in periodontal ligament cells. These findings suggest its potential therapeutic application for the prevention and treatment of replacement resorption in replanted avulsed teeth.

Topics: Alkaloids; Animals; Benzodioxoles; Cells, Cultured; Curcumin; Fibroblasts; Humans; Mice; Osteogenesis; Periodontal Ligament; Piperidines; Polyunsaturated Alkamides; Postoperative Complications; RAW 264.7 Cells; Root Resorption; Tooth Avulsion; Tooth Replantation

A disruption of cholesterol homeostasis characterized by the physical-chemical imbalance of cholesterol solubility in bile often results in formation of cholesterol gallstones. Our earlier studies revealed that curcumin (1000 mg/kg) could prevent formation of gallstones. It has been proved that curcumin is poorly absorbed while piperine is a bioavailability-enhancer. Nevertheless, whether curcumin combined with piperine could enhance the effect of curcumin in preventing gallstones is still awaited.. C57BL6 mice were fed on a lithogenic diet concomitant with curcumin at 500 or 1000 mg/kg and/or piperine at 20 mg/kg for 4 weeks. The ratio of gallbladder stone formation was recorded and samples of blood, bile, gallbladder, liver and small intestine were also collected. The volume of gallbladder and weight of liver were calculated, and blood and bile samples were analyzed through biochemical methods. Intestinal NPC1L1 and SREBP2 mRNA and protein expression were detected by real-time PCR and Western blot.. Combining with piperine can significantly enhance the effect of curcumin, thus preventing the development of gallbladder stones, lowering the saturation of blood lipids and cholesterol in bile, as well as decreasing the expression of NPC1L1 and SREBP2 in both mRNA and protein levels.. Curcumin can prevent the formation of cholesterol gallstones induced by high fat diet in mice and SREBP2 and NPC1L1 may participate in this process. Piperine can increase curcumin's bioavailability, thereby enhancing the effect of curcumin.

Topics: Alkaloids; Animals; Anticholesteremic Agents; Benzodioxoles; Bile; Biological Availability; Cholesterol, Dietary; Curcumin; Diet; Drug Combinations; Drug Synergism; Gallbladder; Gallstones; Gene Expression; Intestinal Mucosa; Intestines; Liver; Male; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; Piperidines; Polyunsaturated Alkamides; Protective Agents; RNA, Messenger; Sterol Regulatory Element Binding Protein 2

The objective of this study was to develop the microspheres from gelatin (G) and silk fibroin (SF) aimed to be applied for the controlled release of curcumin and piperine. The glutaraldehyde-crosslinked G/SF microspheres at various weight blending ratios (100/0, 70/30, 50/50, and 30/70) were successfully fabricated by water in oil emulsion technique. The microspheres prepared from all compositions were in a round shape with homogeneous size distribution both in the dried (194-217 μm) and swollen states (297-367 μm). When subjected in collagenase solution at physiological condition, the G microspheres gradually degraded within 14 days while the blended G/SF microspheres, particularly at 50/50 and 30/70, were not degraded. For the release application, the microspheres were loaded with curcumin and/or piperine. It was found that the microspheres composed of SF tended to entrap curcumin and piperine with the high entrapment and loading efficiencies, possibly due to their hydrophobic interactions. The G/SF microspheres, particularly at the ratios of 50/50 and 30/70, released curcumin and piperine in a sustained manner both for the single and dual release systems. The controlled dual release of curcumin and piperine from the G/SF microspheres would prolong their half-life, provide the optimal concentrations for therapeutic effects at a target site, and improve the bioavailability of curcumin. These novel injectable microspheres dually releasing curcumin and piperine would be introduced for the treatment of diseases without the need of operation.

Topics: Alkaloids; Benzodioxoles; Biocompatible Materials; Curcumin; Drug Carriers; Fibroins; Gelatin; Microscopy, Electron, Scanning; Microspheres; Piperidines; Polyunsaturated Alkamides; Silk

In this study, curcumin was designed into the nanoformulation called cubosome with piperine in order to improve oral bioavailability and tissue distribution of curcumin.. The characteristic of the cubosome was studied by using scanning electron microscope (SEM), Infrared spectrum and small angle X-ray scattering (SAXS) techniques. Tissue distribution of cubosome was measured by liquid chromatography-mass spectrometry (LC-MS) method in mice.. The characteristic of the cubosome was demonstrated that the curcumin and piperine were encapsulated in the interior of the cubosome and the crystal form was Pn3m space. The pharmacokinetic test revealed that the cubosome could improve the oral bioavailability significantly compared to the suspension of curcumin with piperine and be mainly absorbed by the spleen.. These findings provide the reference to a preferable choice of the curcumin formulation and contribute to therapeutic application in clinical research.

Topics: Alkaloids; Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzodioxoles; Curcumin; Mice; Nanocapsules; Particle Size; Piperidines; Polyunsaturated Alkamides; Scattering, Small Angle; Spleen; Tissue Culture Techniques; X-Ray Diffraction

Encapsulation in lipid particles is often proposed as a solution to improve curcumin bioavailability. This bioactive molecule has low water solubility and rapidly degrades during digestion. In the present study, the uptake of curcumin from oil in water emulsions, prepared with two different emulsifiers, Tween 20 and Poloxamer 407, was investigated to determine the effect of interfacial composition on absorption. Piperine was added to the curcumin to limit the degradation of curcumin because it is known to inhibit β-glucuronidase activity. The emulsions were administered to Caco-2 cell cultures, which is used as a model for intestinal uptake, and the recovery of curcumin was measured. The curcumin uptake was significantly affected by the type of interface, and the extent of curcumin uptake improved significantly by piperine addition only in the case of oil-in-water emulsions stabilized by Poloxamer 407. This work provides further evidence of the importance of interfacial composition on the delivery of bioactives.

Topics: Alkaloids; Benzodioxoles; Biological Availability; Caco-2 Cells; Cell Survival; Chemical Phenomena; Curcumin; Drug Stability; Emulsifying Agents; Emulsions; Glucuronidase; Humans; Hydrophobic and Hydrophilic Interactions; Particle Size; Piperidines; Poloxamer; Polysorbates; Polyunsaturated Alkamides

Curcumin and piperine are proven for their potent medicinal benefits to treat various diseases and they are most commonly used combination in various Indian systems of medicine such as Ayurveda, Siddha and Unani. The objective of the present work is to develop a simultaneous estimation of curcumin and piperine by reverse phase Ultra-fast liquid chromatographic (RP-UFLC) method. The chromatographic separation was performed on a C8 column (250 x 4.6 mm, 5µ i.d.) stationary phase using a mobile phase of 25mM potassium dihydrogen ortho phosphate buffer (pH 3.5) and acetonitrile (30: 70 v/v) at a flow rate of lml/min at detection wave length of 280nm. The calibration curve was plotted in the concentration range of 0-2200ng/ml and found to be linear for both curcumin (r(2)=0.996) and piperine (r(2)=0.999). The method was validated for parameters such as accuracy, sensitivity, precision, linearity, specificity, ruggedness and robustness as per ICH guidelines. The developed simple, precise and specific method can be used as a quality control tool for qualitative and quantitative estimation of curcumin and piperine in various food products, herbal medicines and nutraceuticals.

Topics: Alkaloids; Benzodioxoles; Chromatography, Reverse-Phase; Curcumin; Limit of Detection; Piperidines; Polyunsaturated Alkamides

Knowing that curcumin has low bioavailability when administered orally, and that piperine has bioenhancer activity by inhibition of hepatic and intestinal biotransformation processes, the aim of this study was to investigate the antidiabetic and antioxidant activities of curcumin (90 mg/kg) and piperine (20 or 40 mg/kg), alone or co-administered, incorporated in yoghurt, in streptozotocin (STZ)-diabetic rats. The treatment for 45 days of STZ-diabetic rats with curcumin-enriched yoghurt improved all parameters altered in this experimental model of diabetes: the body weight was increased in association with the weight of skeletal muscles and white adipose tissues; the progressive increase in the glycemia levels was avoided, as well as in the glycosuria, urinary urea, dyslipidemia, and markers of liver (alanine and aspartate aminotransferases and alkaline phosphatase) and kidney (urinary protein) dysfunction; the hepatic oxidative stress was decreased, since the activities of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase were increased, and the levels of malondialdehyde and protein carbonyl groups were reduced. The dose of 20 mg/kg piperine also showed antidiabetic and antioxidant activities. The treatment of STZ-diabetic rats with both curcumin and 20 mg/kg piperine in yoghurt did not change the antidiabetic and antioxidant activities of curcumin; notably, the treatment with both curcumin and 40 mg/kg piperine abrogated the beneficial effects of curcumin. In addition, the alanine aminotransferase levels were further increased in diabetic rats treated with curcumin and 40 mg/kg piperine in comparison with untreated diabetic rats. These findings support that the co-administration of curcumin with a bioenhancer did not bring any advantage to the curcumin effects, at least about the antidiabetic and antioxidant activities, which could be related to changes on its biotransformation.

Topics: Alanine Transaminase; Alkaloids; Animals; Antioxidants; Benzodioxoles; Blood Glucose; Body Weight; Catalase; Curcumin; Diabetes Mellitus, Experimental; Drug Interactions; Glutathione Peroxidase; Hypoglycemic Agents; Lipid Peroxidation; Liver; Male; Malondialdehyde; Oxidative Stress; Piperidines; Polyunsaturated Alkamides; Rats, Wistar; Superoxide Dismutase; Treatment Outcome

The objective of the study was to prepare and evaluate the quality of curcumin-piperinedual drug loaded self-microemulsifying drug delivery system(Cur-PIP-SMEDDS). Simplex lattice design was constructed using optimal oil phase, surfactant and co-surfactant concentration as independent variables, and the curcumin and piperine were used as model drugs to optimize Cur-PIP-SMEDDS formulation. In the present study, the drug loadings of curcumin and piperine, mean particle size of Cur-PIP-SMEDDS were made as indicators, and the experiment design, model building and response surface analysis were established using Design Expert 8. 06 software to optimize and verify the composition of SMEDDS formulation. The quality of Cur-PIP-SMEDDS was evaluated by observing the appearance status, transmission electron microscope micrographs and determining particle diameter, electric potential, drug entrapment efficiency and drug loading of it. As a result, the optimal formulation of SMEDDS was CapryoL 90-Cremophor RH40-TranscutoL HP (10:60:30). The appearance of Cur-PIP-SMEDDS remained clarified and transparent, and the microemulsion droplets appeared spherical without aggregation with uniform particle size distribution. The mean size of microemulsion droplet formed from Cur-PIP-SMEDDS was 15.33 nm, the drug loading of SMEDDS for Cur and PIP were 40.90 mg · g(-1) and 0.97 mg · g(-1), respectively, the drug entrapment efficiency were 94.98% and 90.96%, respectively. The results show that Cur-PIP-SMEDDS can increase the solubility and stability of curcumin significantly, in the expectation of enhancing the bioavailability of it. Taken together, these findings can provide the reference to a preferable choice of the Cur formulation and contribute to therapeutic application in clinical research.

Topics: Alkaloids; Benzodioxoles; Chemistry, Pharmaceutical; Curcumin; Drug Carriers; Drug Combinations; Drug Delivery Systems; Drugs, Chinese Herbal; Emulsions; Methylmethacrylates; Particle Size; Piperidines; Polystyrenes; Polyunsaturated Alkamides

Cerebellar atrophy during ageing can produce neurobehavioural changes characterized by cognitive and motor impairment. Chronic exposure to D-galactose, a reducing sugar can accelerate ageing by producing an unprecedented rise in oxidative load. This can enhance neuronal damage by promoting the oxidation of protein and lipids. We perceived that the simultaneous administration of piperine and curcumin, two powerful antioxidants can exert neuroprotective effect by inhibiting damage caused by the chronic exposure to D-galactose. Young Wistar rats treated with D-galactose (150 mg/kg, s.c.) were simultaneously treated with piperine alone, curcumin separately; and in combination for a period of 56 days by the oral route. A vehicle control, D-galactose alone and naturally aged control were also evaluated. Cognitive changes, motor impairment, protein carbonyls, protein thiols, advanced oxidation protein products, 4 hydroxynonenol and nitric oxide levels were determined in the brain homogenate. In order to ascertain the impact of cerebellum on motor performance, histopathological changes in the cerebellum were also established. Results obtained from our studies reflect a marked improvement in memory, sensorimotor performance, reduced oxidative and nitrosative burden on simultaneous treatment with piperine and curcumin. Furthermore, alterations produced in the Purkinje cells were minimized on treatment with the combination. Our studies demonstrated the influence of protein and lipid oxidation products on behavioural changes in D-galactose induced ageing model. Incorporation of these antioxidants might reduce the risk of developing neurodegenerative disorders, an important counterpart of advancing age.

Topics: Aging; Alkaloids; Animals; Antioxidants; Benzodioxoles; Brain; Curcumin; Drug Combinations; Galactose; Lipid Peroxidation; Oxidation-Reduction; Oxidative Stress; Piperidines; Polyunsaturated Alkamides; Random Allocation; Rats; Rats, Wistar

Bilateral destruction of the olfactory bulbs is known to cause behavioral changes analogous to symptoms of depression. Curcumin, a traditional Indian spice is currently being investigated in different psychiatric problems including depression. Dietary phytochemicals are currently used as an adjuvant therapy to accelerate their therapeutic efficacy. Therefore, the present study is an attempt to elucidate the neuroprotective mechanism of curcumin and its co-administration with piperine against olfactory bulbectomy induced depression in rats.. Rats undergone olfactory bulbs ablations were analyzed after post-surgical rehabilitation period of 2 weeks. Animals were then treated with different doses of curcumin (100, 200 and 400 mg/kg; p.o.), piperine (20 mg/kg; p.o.) and their combination daily for another 2 weeks. Imipramine (10 mg/kg; i.p.) served as a standard control. Various behavioral tests like forced swim test (FST), open field behaviour and sucrose preference test (SPT) were performed, followed by estimation of biochemical, mitochondrial, molecular and histopathological parameters in rat brain.. Ablation of olfactory bulbs caused depression-like symptoms as evidenced by increased immobility time in FST, hyperactivity in open field arena, and anhedonic like response in SPT along with alterations in mitochondrial enzyme complexes, increased serum corticosterone levels and oxidative damage. These deficits were integrated with increased inflammatory cytokines (TNF-α) and apoptotic factor (caspase-3) levels along with a marked reduction in neurogenesis factor (BDNF) in the brain of olfactory bulbectomized (OBX) rats. Curcumin treatment significantly and dose-dependently restored all these behavioral, biochemical, mitochondrial, molecular and histopathological alterations associated with OBX induced depression. Further, co-administration of piperine with curcumin significantly potentiated their neuroprotective effects as compared to their effects alone.. The present study highlights that curcumin along with piperine exhibits neuroprotection against olfactory bulbectomy induced depression possibly by modulating oxidative-nitrosative stress induced neuroinflammation and apoptosis.

Topics: Alkaloids; Animals; Apoptosis; Benzodioxoles; Brain; Brain-Derived Neurotrophic Factor; Caspase 3; Corticosterone; Curcumin; Depression; Disease Models, Animal; Drug Therapy, Combination; Electron Transport Chain Complex Proteins; Food Preferences; Immobilization; Inflammation; Lipid Peroxidation; Male; Mitochondria; Olfactory Bulb; Piperidines; Polyunsaturated Alkamides; Rats; Rats, Wistar; Signal Transduction; Sucrose; Tumor Necrosis Factor-alpha

The antigenotoxic effects of curcumin alone and with piperine on benzo(a)pyrene-diol (BaP) epoxide DNA adducts (BaPDE-DNA adducts), and carcinogen biotransformation enzymes was investigated in liver and lung of mice. Male Swiss albino mice received curcumin (100 mgkg(-1) body weight) and piperine (20 mgkg(-1) body weight) separately as well as in combination orally in corn oil for 7 days as pretreatments and thereafter 2 h, BaP (125 mgkg(-1) body weight) was administered orally in corn oil. A single dose of BaP to normal mice increased the activities of ethoxyresorufin o-deethylase (EROD), pentoxyresorufin o-depentylase (PROD) and levels of BaPDE-DNA adducts in both the tissues. Quinone reductase (QR) activity was also elevated in the BaP-treated group in both liver and lung when compared with normal control group. Pretreatment of curcumin and curcumin plus piperine before administration of BaP significantly decreased the activities of EROD, PROD, and the level of BaPDE-DNA adducts with consequent increase in QR activities. The study clearly indicates that curcumin, when given in combination with piperine, is more effective in modulating BaPDE-DNA adducts (liver and lung), and activity of EROD (liver).

Topics: Alkaloids; Animals; Benzo(a)pyrene; Benzodioxoles; Biotransformation; Carcinogens; Curcumin; Cytochrome P-450 CYP1A1; DNA Adducts; Liver; Lung; Male; Mice; Piperidines; Polyunsaturated Alkamides

Aging is associated with progressive decline in mental abilities and functional capacities. Postmitotic tissues are most vulnerable to alteration due to oxidative damage leading to behavioral and biochemical changes. We hypothesized that the anatomical and functional facets of the brain could be protected with powerful antioxidants such as piperine and curcumin by examining their effects individually and in combination in delaying senescence induced by d-galactose. Young adult male Wistar rats were treated with piperine (12 mg/kg) alone, and curcumin (40 mg/kg) alone; and in combination for a period of 49 days by the oral route with treatment being initiated a week prior to d-galactose (60 mg/kg, i.p.). A control group, d-galactose alone and naturally aged control were also evaluated. Behavioral tests, hippocampal volume, CA1 neuron number, oxidative parameters, formation of lipofuscin like autofluorescent substances, neurochemical estimation, and histopathological changes in CA1 region of hippocampus were established. Our results suggest that the combination exerted a superior response compared to monotherapy as evidenced by improved spatial memory, reduced oxidative burden, reduced accumulation of lipofuscin; improvement in signaling, increase in hippocampal volume and protection of hippocampal neurons. We speculate that the powerful antioxidant nature of both, augmented response of curcumin in the presence of piperine and enhanced serotoninergic signaling was responsible for improved cognition and prevention in senescence.

Topics: Aging; Alkaloids; Animals; Antioxidants; Benzodioxoles; Brain; Catalase; Curcumin; Drug Synergism; Galactose; Glutathione; Male; Malondialdehyde; Maze Learning; Piperidines; Polyunsaturated Alkamides; Pyramidal Cells; Rats; Rats, Wistar; Serotonin; Superoxide Dismutase

To prepare curcumin-piperine (Cu-Pi) nanoparticles by various methods and to study the effect of various manufacturing parameters on Cu-Pi nanoparticles and to identify a suitable method for the preparation of Cu-Pi nanoparticles to overcome oral bioavailability and cancer cell targeting limitations in the treatment of cancer.. Cu-Pi nanoparticles were prepared by thin film hydration method, solid dispersion method, emulsion polymerization method and Fessi method. Optimization was carried out to study the effect of various manufacturing parameter on the Cu-Pi nanoparticles.. Out of four methods, Fessi method produced a minimum average particle size of 85.43 nm with a polydispersity index of 0.183 and zeta potential of 29.7 mV. Change of organic solvent (acetone or ethanol) did not have any significant effect on Cu-Pi nanoparticles. However, increase in sonication time, stirring speed, viscosity, use of 1:10:10 ratio of drug/polymer/surfactant, and use of anionic surfactant or combination of anionic surfactant with cationic polymer or combination of non-ionic surfactant with cationic polymer had a significant effect on Cu-Pi nanoparticles.. Cu-Pi nanoparticles coated with PEG containing copolymer produced by Fessi method had a minimum average particle size, excellent polydispersity index and optimal zeta potential which fall within the acceptable limits of the study. This dual nanoparticulate drug delivery system appears to be promising to overcome oral bioavailability and cancer cell targeting limitations in the treatment of cancer.

Topics: Alkaloids; Antineoplastic Agents; Benzodioxoles; Curcumin; Drug Carriers; Drug Combinations; Nanoparticles; Particle Size; Piperidines; Polyunsaturated Alkamides

The objective of the present study was to evaluate the effects of curcumin alone and with adjuvant piperine against benzo(a)pyrene (BaP) induced oxidative stress in lungs of male Swiss albino mice. Mice were pretreated either with curcumin (100 mg/kg body weight), or piperine (20 mg/kg body weight), and in combination of both for one week, followed by single dose of benzo(a)pyrene (125 mg/kg body weight) treatment. Treatment with benzo(a)pyrene resulted in increased levels of lipid peroxides (LPO), protein carbonyl content (PCC) and with consequent decrease in the levels of tissue antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and reduced glutathione (GSH), which however, were increased significantly following curcumin treatment, but the increase was more pronounced when piperine was used as an adjuvant. BaP treatment alone did not alter significantly the GST activity. Pretreatment with curcumin increased the GST activity in BaP treated group, which was enhanced further upon synergistic treatment with piperine and curcumin. Therefore, combined administration of curcumin and piperine shall prove to be more effective in attenuating BaP induced toxicity.

Topics: Alkaloids; Animals; Antioxidants; Benzo(a)pyrene; Benzodioxoles; Curcumin; Drug Synergism; Lipid Peroxides; Lung; Male; Mice; Oxidative Stress; Piperidines; Polyunsaturated Alkamides; Protein Carbonylation

Baicalein (B), a bioactive flavone isolated from the root of a traditional Chinese medicinal herb Scutellaria baicalensis Georgi, was found to undergo extensive intestinal Phase II metabolism during its absorption process. Compounds sharing the same metabolic pathways with B or being inhibitors of enzymes UGT and SULT are expected to interfere with the metabolism of B leading to alteration of the absorption of B. The present study aims to identify potential intestinal absorption and metabolism interactions between B and four selected compounds, namely acetaminophen (APAP), (-)-epicatechin (EC), piperine (PIP) and curcumin (CUR) using in vitro and in situ models.. Three in vitro and one in situ methods were employed to investigate the effect of selected compounds on the metabolism and absorption on B. Incubation studies using rat intestinal s9 and Caco-2 cell lysate were used to study the effect of selected compounds on glucuronidation and sulfation of B. Sigmoidal dose-response curves were plotted and IC(50) values were estimated. Apical to basolateral absorption study using Caco-2 cell monolayer model was also employed to study the effect of selected compounds on absorption of B. The most potent inhibitor identified was selected to further investigate its potential herb-drug interaction with B using in situ rat intestinal perfusion model. LC/MS/MS was used for the analysis of B and its metabolites in collected samples.. It was found that all the four selected compounds could produce a dose-dependent inhibition on the glucuronidation and sulfation of B. Moreover, the presence of CUR and high-dose EC demonstrated a subsequent increase in the absorption of B. In general, the order of potency on glucuronidation inhibition is: CUR>PIP>EC>APAP; while the potency order on sulfation inhibition is: CUR>EC>PIP>APAP. CUR was selected to further study its in vivo effect on B using in situ rat intestinal perfusion model. It was found that CUR could significantly increase the absorption of B via the inhibition on formation of its metabolites.. Our findings indicated that the intestinal metabolism of B could be inhibited by all the selected compounds with CUR being the most potent inhibitor, which could result in subsequent increase of absorption of B. The current study had significant implications for further investigation on the in vivo evaluations of the herb-drug and herb-herb interactions between B and selected compounds, especially CUR.

Topics: Acetaminophen; Administration, Oral; Alkaloids; Animals; Benzodioxoles; Biotransformation; Caco-2 Cells; Catechin; Chromatography, Liquid; Curcumin; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Flavanones; Glucuronides; Herb-Drug Interactions; Humans; Intestinal Absorption; Jejunum; Male; Medicine, Chinese Traditional; Perfusion; Piperidines; Plant Roots; Plants, Medicinal; Polyunsaturated Alkamides; Rats; Rats, Sprague-Dawley; Scutellaria baicalensis; Sulfates; Tandem Mass Spectrometry

A few common spices are known to stimulate secretion of bile with higher amount of bile acids which play a major role in digestion and absorption of dietary lipids. It would be appropriate to verify if these spices enable efficient digestion and absorption during high-fat intake. In this context, dietary ginger (0.05%), piperine (0.02%), capsaicin (0.015%), and curcumin (0.5%) were examined for their influence on bile secretion, digestive enzymes of pancreas and absorption of dietary fat in high-fat (30%) fed Wistar rats for 8 weeks.. These spices enhanced the activity of pancreatic lipase, amylase, trypsin and chymotrypsin by 22-57%, 32-51%, 63-81% and 12-38%, respectively. Dietary intake of spices along with high-fat enhanced fat absorption. These dietary spices increased bile secretion with higher bile acid content. Stimulation of lipid mobilisation from adipose tissue was suggested by the decrease in perirenal adipose tissue weight by dietary capsaicin and piperine. This was also accompanied by prevention of the accumulation of triglyceride in liver and serum in high-fat fed rats. Activities of key lipogenic enzymes in liver were reduced which was accompanied by an increased activity of hormone-sensitive lipase.. Thus, dietary ginger and other spice compounds enhance fat digestion and absorption in high-fat fed situation through enhanced secretion of bile salts and a stimulation of the activity pancreatic lipase. At the same time, the energy expenditure is facilitated by these spices to prevent the accumulation of absorbed fat.

Topics: Adiposity; Alkaloids; Animals; Benzodioxoles; Bile; Bile Acids and Salts; Capsaicin; Curcumin; Diet, High-Fat; Dietary Fats; Digestion; Hydrolases; India; Intestinal Absorption; Lipid Metabolism; Liver; Male; Pancreas; Piperidines; Polyunsaturated Alkamides; Rats, Wistar; Rhizome; Spices; Up-Regulation; Zingiber officinale

In the present study, the antioxidative and anticlastogenic effects of curcumin and piperine separately and in combination have been investigated against benzo(a)pyrene (BaP)-mediated toxicity in mice. Male Swiss albino mice were pretreated with curcumin (100 mg kg(-1) body weight) and piperine (20 mg kg(-1) body weight) separately as well as in combination orally in corn oil for 7 days; and subsequently, after 2 h of pretreatment, BaP was administered orally in corn oil (125 mg kg(-1) body weight). A single dose of BaP in normal mice increased the levels of lipid peroxidation (LPO), protein carbonyl content (PCC), and frequency of bone marrow micronucleated polychromatic erythrocytes (MNPCEs) but decreased significantly the levels of endogenous antioxidants such as superoxide dismutases (SODs), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT) and reduced glutathione (GSH) in the liver. Pretreatments with curcumin and curcumin plus piperine before administration of single dose of BaP significantly decreased the levels of LPO, PCC, and incidence of MNPCEs but elevated the level of GSH and enzyme activities of GPx, GR, SOD, CAT, and glutathione-S-transferase (GST) when compared to the BaP-treated group. The effect of curcumin plus piperine is more pronounced as compared to curcumin in attenuating BaP-induced oxidative insult and clastogenicity.

Topics: Alkaloids; Animals; Antimutagenic Agents; Antioxidants; Benzo(a)pyrene; Benzodioxoles; Carcinogens; Catalase; Curcumin; Drug Combinations; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Glutathione Transferase; Liver; Male; Mice; Micronuclei, Chromosome-Defective; Piperidines; Polyunsaturated Alkamides; Protein Carbonylation; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

Curcumin, a principal component from Curcuma longa, with antioxidant and anti-inflammatory activities was proposed as a potential candidate for the preventation and/or treatment of cancer and chronic diseases. However, curcumin could not achieve its expected therapeutic outcome in clinical trials due to its low solubility and poor bioavailability. The actual intestinal physiological barriers limiting curcumin absorption after oral administration have not been fully investigated. To identify the main barriers curtailing its absorption, in vitro permeability of curcumin and flux of its glucuronide were monitored in rat jejunum and Transwell grown Caco-2 cells. Curcumin was more permeable under acidic conditions, but the permeability was substantially below the permeability of highly permeable standards. Its efflux could not be inhibited by specific Pgp and MRP inhibitors. BCRP was found to participate in curcumin transport, but the Organic Anion Transporting Polypeptide (OATP) did not. The permeability of curcumin significantly increased when the structure of mucus was compromised. The inhibitor of curcumin metabolism, piperin, failed to act as a permeability enhancer. Piperin inhibited Pgp and MRP transporters and decreased the amount of glucuronide transported back into the intestine. Inclusion of piperin in curcumin-containing formulations is highly recommended as to inhibit curcumin glucuronidation and to increase the transport of formed glucuronides into the plasma, therefore increasing the probability of glucuronide distribution into target tissue and inter-convertion to curcumin. It would also be beneficial, if curcumin delivery systems could reversibly compromise the mucous integrity to minimize the non-specific binding of curcumin to its constituents.

Topics: Algorithms; Alkaloids; Animals; Benzodioxoles; Buffers; Caco-2 Cells; Chromatography, High Pressure Liquid; Curcumin; Drug Stability; Glucuronides; Humans; Hydrogen-Ion Concentration; Intestinal Absorption; Intestinal Mucosa; Jejunum; Mass Spectrometry; Membrane Potentials; Patch-Clamp Techniques; Permeability; Piperidines; Polyunsaturated Alkamides; Rats; Solubility

Life event stressors are the major vulnerability factors for the development of cognitive disorders. A vital therapeutic for stress related disorders is curcumin, derived from curry spice turmeric. Dietary phytochemicals are currently used as an adjuvant therapy to accelerate their therapeutic efficacy. Therefore, the present study was designed to investigate the effect of curcumin and its co-administration with piperine against chronic unpredictable stress (CUS)-induced cognitive impairment and oxidative stress in mice. Male Laca mice were subjected to undergo a battery of stressors for a period of 28 days. Vehicle/drugs were administered daily 30mins before CUS procedure. Chronic stress significantly impaired memory performance (delayed latency time to reach platform in Morris water maze as well as to reach closed arm in elevated plus maze test) and decreased locomotor activity along with sucrose consumption. Further, there was a significant impairment in oxidative parameters (elevated malondialdehyde, nitrite concentration and decreased reduced glutathione, catalase levels) and mitochondrial enzyme complex activities, along with raised acetylcholinesterase and serum corticosterone levels. Chronic treatment with curcumin (200 and 400mg/kg, p.o.) significantly improved these behavioral and biochemical alterations, restored mitochondrial enzyme complex activities and attenuated increased acetylcholinesterase and serum corticosterone levels. In addition, co-administration of piperine (20mg/kg; p.o.) with curcumin (100 and 200mg/kg, p.o.) significantly elevated the protective effect as compared to their effects alone. The results clearly suggest that piperine enhanced the bioavailability of curcumin and potentiated its protective effects against CUS induced cognitive impairment and associated oxidative damage in mice.

Topics: Alkaloids; Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzodioxoles; Chronic Disease; Cognition Disorders; Corticosterone; Curcumin; Cytochrome P-450 Enzyme Inhibitors; Dietary Sucrose; Drug Synergism; Food Preferences; Male; Maze Learning; Mice; Mice, Inbred Strains; Mitochondria; Motor Activity; Neuroprotective Agents; Oxidative Stress; Piperidines; Polyunsaturated Alkamides; Stress, Psychological; Uncertainty

Although spice compounds have several pharmacological and biochemical actions such as antioxidant activity, their physiological effects on neuropeptides related to feeding regulation are not well known. The aim of the present study was to identify the pharmacological activities of spice compounds on appetite regulation using a goldfish (Carassius auratus) model with emphasis on the role of neuropeptides. The spice compounds used in this study were curcumin, piperine, and ursolic acid. Goldfish were injected intraperitoneally with test solutions containing each spice or vehicle (including 10% dimethyl sulfoxide in saline), and the changes in food intake were measured every 15 min for 60 min. Among the tested spice compounds, curcumin was found to reduce cumulative food intake and was thus selected for further experiments. Pretreatment with capsaicin, a neurotoxin of afferent nerves, abolished the curcumin-induced decrease of food intake. Curcumin-induced anorexigenic action was also attenuated by intracerebroventricular injection of the corticotropin-releasing hormone (CRH) receptor antagonist α-helical CRH((9-41)). We also examined the expression levels of mRNA for CRH, which is a potent anorexigenic neuropeptide in goldfish, in the diencephalon at 1 h after treatment with curcumin, and found that they were increased. Therefore, the reduction of appetite induced by curcumin treatment in goldfish was suggested to be mediated by the vagal afferent and subsequently through the CRH/CRH receptor pathway.

Topics: Alkaloids; Animals; Appetite Depressants; Appetite Regulation; Benzodioxoles; Capsaicin; Corticotropin-Releasing Hormone; Curcumin; Eating; Enzyme Inhibitors; Feeding Behavior; Goldfish; Hormone Antagonists; Humans; Injections, Intraperitoneal; Molecular Structure; Peptide Fragments; Piperidines; Polyunsaturated Alkamides; Receptors, Corticotropin-Releasing Hormone; Sensory System Agents; Triterpenes; Ursolic Acid

Long-term treatment with haloperidol is associated with a number of extrapyramidal side effects, particularly the irregular movements of chorionic type. This limitation presents a marked therapeutic challenge. The present study investigates the molecular etiology of haloperidol neurotoxicity and the role of curcumin, a well-known anti-oxidant, in ameliorating these adverse effects. The redox status of haloperidol-treated brains along with NO, TNF-α, NF-kappaB p65 subunit, caspase-3, and monoamine neurotransmitters were measured in the striatum of rat brain. Chronic treatment with haloperidol (5 mg/kg, i.p., 21 days) produced orofacial dyskinetic movements which were coupled with marked increase in oxidative stress parameters, TNF-α, caspase-3 activity in cytoplasmic lysate and active p65 sub unit of NF-kappaB in nuclear lysates of the striatum. Neurochemically, chronic administration of haloperidol resulted in a significant decrease in the levels of norepinephrine, dopamine, and serotonin. The prototype atypical anti-psychotic, clozapine (10 mg/kg, i.p., 21 days) produced mild oxidative stress but did not alter any other parameters. Interestingly, co-administration of curcumin (25 and 50 mg/kg, i.p., 21 days) dose-dependently prevented all the behavioral, cellular, and neurochemical changes associated with the chronic administration of haloperidol. Curcumin per se (50 mg/kg) did not show any side effects. Co-administration of piperine significantly enhanced the effect of curcumin (25 mg/kg) but not of curcumin (50 mg/kg). Collectively, the data indicated the potential of curcumin as an adjunct to haloperidol treatment and provided initial clues to the underlying molecular mechanisms in haloperidol neurotoxicity. This study also provides a rationale for the combination of piperine and curcumin.

Topics: Alkaloids; Analysis of Variance; Animals; Apoptosis; Behavior, Animal; Benzodioxoles; Caspase 3; Colorimetry; Curcumin; Cytokines; Disease Models, Animal; Dopamine Antagonists; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Haloperidol; Inflammation; Male; Neuroprotective Agents; Neurotoxicity Syndromes; Neurotransmitter Agents; Piperidines; Polyunsaturated Alkamides; Rats; Rats, Wistar; Statistics as Topic; Thiobarbituric Acid Reactive Substances

The present study was planned to investigate the antigenotoxic effects of curcumin and piperine separately and in combination against benzo(a)pyrene (BaP) induced DNA damage in lungs and livers of mice. Male Swiss albino mice received curcumin (100 mg kg(-1) body weight) and piperine (20 mg kg(-1) body weight) separately as well as in combination orally in corn oil for 7 days as pretreatments and subsequently, 2h after, BaP was administered orally in corn oil (125 mg kg(-1) body weight). A single dose of BaP to normal mice increased the level of 8-oxo-2'-deoxyguanosine (8-oxo-dG) content and % DNA in the comet tail in the lungs and liver. Pretreatments of curcumin and curcumin plus piperine before administration of single dose of BaP significantly decreased the levels of 8-oxo-dG content and % DNA in the comet tail in both the tissues. Moreover, the genoprotective potential of curcumin plus piperine was significantly higher as compared to curcumin alone against BaP induced DNA damage.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Alkaloids; Animals; Benzo(a)pyrene; Benzodioxoles; Comet Assay; Curcumin; Deoxyguanosine; DNA Damage; Drug Synergism; Enzyme-Linked Immunosorbent Assay; Hepatocytes; Liver; Lung; Male; Mice; Piperidines; Polyunsaturated Alkamides

In this study we examined the antioxidant effect of curcumin on lipid oxidation in vitro and in vivo. In vitro, curcumin at 5 microgM concentration completely prevented low-density lipoprotein (LDL) oxidation by CuS0(4), indicating that curcumin is an effective antioxidant in vitro. In vivo, feeding a pure cholesterol (PC)-rich diet to rabbits significantly increased the plasma and liver lipids as well as thiobarbituric acid reactive substances (TBARS) levels. Addition of curcumin to the PC diet did not show any effect on either plasma lipid and TBARS or liver lipids. Liver TBARS tended to decrease but that decrease was not significant. Erythrocyte glutathione peroxidase (GSH-Px) activity was significantly decreased while catalase activity was significantly increased in rabbits fed a PC diet. The addition of curcumin to a PC diet did not show any significant effect on erythrocyte enzyme activities compared to the rabbits fed a PC diet. The liver GSH-Px and catalase activities were significantly decreased in rabbits fed a PC diet, but the addition of curcumin to the PC diet enhanced the liver GSH-Px activity, which became nonsignificantly different from the control group. These results were discussed considering that curcumin may not be well absorbed and it did not reach a level high enough in vivo to overcome the severe hypercholesterolemia and oxidative stress produced by the PC-rich diet.

Topics: Alkaloids; Animals; Antioxidants; Benzodioxoles; Catalase; Cholesterol, Dietary; Curcumin; Glutathione Peroxidase; Hypercholesterolemia; Lipid Peroxidation; Lipids; Lipoproteins, LDL; Liver; Male; Oxidation-Reduction; Oxidative Stress; Piperidines; Polyunsaturated Alkamides; Rabbits

The cancer stem cell hypothesis asserts that malignancies arise in tissue stem and/or progenitor cells through the dysregulation or acquisition of self-renewal. In order to determine whether the dietary polyphenols, curcumin, and piperine are able to modulate the self-renewal of normal and malignant breast stem cells, we examined the effects of these compounds on mammosphere formation, expression of the breast stem cell marker aldehyde dehydrogenase (ALDH), and Wnt signaling. Mammosphere formation assays were performed after curcumin, piperine, and control treatment in unsorted normal breast epithelial cells and normal stem and early progenitor cells, selected by ALDH positivity. Wnt signaling was examined using a Topflash assay. Both curcumin and piperine inhibited mammosphere formation, serial passaging, and percent of ALDH+ cells by 50% at 5 microM and completely at 10 microM concentration in normal and malignant breast cells. There was no effect on cellular differentiation. Wnt signaling was inhibited by both curcumin and piperine by 50% at 5 microM and completely at 10 microM. Curcumin and piperine separately, and in combination, inhibit breast stem cell self-renewal but do not cause toxicity to differentiated cells. These compounds could be potential cancer preventive agents. Mammosphere formation assays may be a quantifiable biomarker to assess cancer preventive agent efficacy and Wnt signaling assessment can be a mechanistic biomarker for use in human clinical trials.

Topics: Aldehyde Dehydrogenase; Alkaloids; Antineoplastic Combined Chemotherapy Protocols; Benzodioxoles; Breast; Breast Neoplasms; Cell Differentiation; Cell Proliferation; Cells, Cultured; Curcumin; Female; Humans; Immunoenzyme Techniques; Neoplastic Stem Cells; Piperidines; Polyunsaturated Alkamides; Signal Transduction; Wnt Proteins

Pentylenetetrazol (PTZ)-induced oxidative stress results in disturbance of the antioxidant enzyme status accompanied by neuronal injury and the development of epilepsy in rats. The present study evaluated the antioxidant effects of curcumin against PTZ-induced convulsions. Over a period of 30 days, i.p. injections of subconvulsive doses of PTZ on alternate days resulted in the development of a well-known kindling model of epilepsy. Spectrophotometric analysis revealed a markedly elevated activity of the antioxidant enzymes malondialdehyde (MDA), catalase and glutathione S-transferase (GST) in the cerebrum and cerebellum of epileptic rats due to PTZ-induced oxidative stress. Oral supplementation of curcumin at a dose of 2 g/kg for 30 days resulted in a transient decrease in MDA, catalase and GST levels in the rat cerebrum and cerebellum. Piperine (20 mg/kg orally) was administered along with curcumin to enhance the bioavailability of the latter up to 20-fold more. Combined treatment with curcumin and carbamazepine (3.6 mg/kg orally) also gave similar results, indicating that the potent antioxidant curcumin can be used as an adjuvant in antiepileptic therapy.

Topics: Alkaloids; Animals; Antioxidants; Benzodioxoles; Biological Availability; Carbamazepine; Catalase; Curcumin; Disease Models, Animal; Drug Therapy, Combination; Epilepsy; Glutathione Transferase; Injections, Intraperitoneal; Male; Malondialdehyde; Oxidative Stress; Pentylenetetrazole; Piperidines; Polyunsaturated Alkamides; Rats; Rats, Wistar

Curcumin, capsaicin and piperine--the bioactive compounds present in spices--turmeric (Curcuma longa), red pepper (Capsicum annuum) and black pepper (Piper nigrum) respectively, have a considerable portion of structural homology. Tissue distribution and elimination of these three structurally similar bioactive compounds was examined following their oral intake in rats.. Separate sets of animals (150-160 g) were orally administered the three spice principles at dosages of 30 mg (capsaicin), 170 mg (piperine) and 500 mg (curcumin) / kg body weight. The tissue concentrations of administered spice compounds were determined by HPLC.. Maximum distribution of 24.4 per cent of administered capsaicin was seen at 1 h, while no intact capsaicin was detectable after 4 days. Absorption of capsaicin was about 94 per cent and very rapid relative to other two compounds. A maximum of 10.8 per cent of administered piperine was seen in tissues at 6 h. Absorption of the administered piperine was about 96 per cent. Curcumin concentration was maximum in the intestine at 1 h; maximum in blood at 6 h and remained at significantly higher level even at 24 h. About 63.5 per cent of the curcumin dose was absorbed. Only a small portion of the administered dose of capsaicin (< 0.1%) and curcumin (0.173 %) was excreted in urine, whereas piperine was not detectable in urine. Enhanced bioavailability of curcumin was evidenced when the same was orally administered concomitant with piperine. Intestinal absorption of curcumin was relatively higher when administered concomitantly with piperine, and it stayed significantly longer in the body tissues. Intact curcumin was detected in brain at 24, 48 and 96 h with a maximum at 48 h.. Considerable difference exists in the bioavailability of the three test compounds. Curcumin could be traced in the brain following its administration. Bioavailability of curcumin can be improved by co-administration with piperine.

Topics: Administration, Oral; Alkaloids; Animals; Benzodioxoles; Biological Availability; Capsaicin; Chromatography, High Pressure Liquid; Curcumin; Male; Piperidines; Polyunsaturated Alkamides; Rats; Rats, Wistar; Spectrophotometry, Ultraviolet; Tissue Distribution

Dietary supplements have been extensively studied for their beneficial effects on cognition and AD neuropathology. The current study examines the effect of a medical food cocktail consisting of the dietary supplements curcumin, piperine, epigallocatechin gallate, α-lipoic acid, N-acetylcysteine, B vitamins, vitamin C, and folate on cognitive functioning and the AD hallmark features and amyloid-beta (Aβ) in the Tg2576 mouse model of the disease.. The study found that administering the medical food cocktail for 6 months improved cortical- and hippocampal- dependent learning in the transgenic mice, rendering their performance indistinguishable from non-transgenic controls. Coinciding with this improvement in learning and memory, we found that treatment resulted in decreased soluble Aβ, including Aβ oligomers, previously found to be linked to cognitive functioning.. In conclusion, the current study demonstrates that combination diet consisting of natural dietary supplements improves cognitive functioning while decreasing AD neuropathology and may thus represent a safe, natural treatment for AD.

Topics: Acetylcysteine; Alkaloids; Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Ascorbic Acid; Benzodioxoles; Brain; Catechin; Cerebral Cortex; Cognition; Curcumin; Dietary Supplements; Folic Acid; Hippocampus; Humans; Immunoblotting; Maze Learning; Memory; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Transgenic; Piperidines; Polyunsaturated Alkamides; Thioctic Acid; Vitamin B Complex; Vitamins

Curcumin, a yellow pigment extracted from rhizomes of the plant Curcuma longa (turmeric), has been widely used as food additive and also as a herbal medicine throughout Asia. The present study was designed to study the pharmacological, biochemical and neurochemical effects of daily administration of curcumin to rats subjected to chronic unpredictable stress. Curcumin treatment (20 and 40 mg/kg, i.p., 21 days) significantly reversed the chronic unpredictable stress-induced behavioral (increase immobility period), biochemical (increase monoamine oxidase activity) and neurochemical (depletion of brain monoamine levels) alterations. The combination of piperine (2.5 mg/kg, i.p., 21 days), a bioavailability enhancer, with curcumin (20 and 40 mg/kg, i.p., 21 days) showed significant potentiation of its anti-immobility, neurotransmitter enhancing (serotonin and dopamine) and monoamine oxidase inhibitory (MAO-A) effects as compared to curcumin effect per se. This study provided a scientific rationale for the use of curcumin and its co-administration with piperine in the treatment of depressive disorders.

Topics: Alkaloids; Animals; Antidepressive Agents; Behavior, Animal; Benzodioxoles; Biogenic Amines; Biological Availability; Biomarkers; Brain Chemistry; Chronic Disease; Cold Temperature; Curcumin; Depressive Disorder; Female; Light; Monoamine Oxidase; Motor Activity; Piperidines; Polyunsaturated Alkamides; Rats; Rats, Wistar; Stress, Psychological; Swimming

Oral carcinoma accounts for 40-50 percent of all cancers in India. Tobacco chewing, smoking and alcohol consumption are the major risk factors associated with the high incidence of oral cancer in India. Our aim was to investigate the chemopreventive potential of curcumin and piperine during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis.. Oral squamous cell carcinoma was developed in the buccal pouch of Syrian golden hamsters, by painting them with 0.5 percent DMBA in liquid paraffin, three times a week for 14 weeks. The tumour incidence, tumour volume and burden were determined in the buccal pouches. The status of phase II detoxification agents, lipid peroxidation and antioxidants were estimated by specific colorimetric methods.. We observed 100 percent tumour formation in DMBA-alone painted hamsters. Disturbances in the status of lipid peroxidation, antioxidants and phase II detoxification agents were noticed in DMBA-alone painted hamsters. Oral administration of curcumin (80 mg/kg body weight) and piperine (50 mg/kg body weight) to DMBA-painted hamsters on alternate days to DMBA painting for 14 weeks completely prevented the formation of oral carcinoma. Also, curcumin and piperine restored the status of lipid peroxidation, antioxidants and detoxifying agents in DMBA-painted hamsters.. The chemopreventive efficacy of curcumin and piperine is probably due to their antilipidperoxidative and antioxidant potential as well as their modulating effect on the carcinogen detoxification process.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Alkaloids; Animals; Anticarcinogenic Agents; Antioxidants; Benzodioxoles; Carcinogens; Carcinoma, Squamous Cell; Cheek; Colorimetry; Cricetinae; Curcumin; Humans; Lipid Peroxidation; Mesocricetus; Mouth Neoplasms; Piperidines; Polyunsaturated Alkamides

Curcumin, a derived product from common spice turmeric that is safe and beneficial in several aliments was formulated into biodegradable nanoparticles with a view to improve its oral bioavailability. The curcumin encapsulated nanoparticles prepared by emulsion technique were spherical in shape with particle size of 264nm (polydispersity index 0.31) and 76.9% entrapment at 15% loading. The curcumin encapsulated nanoparticles were able to withstand the International Conference on Harmonisation (ICH) accelerated stability test conditions for refrigerated products for the studied duration of 3 months. X-ray diffraction analysis revealed the amorphous nature of the encapsulated curcumin. The in vitro release was predominantly by diffusion phenomenon and followed Higuchi's release pattern. The in vivo pharmacokinetics revealed that curcumin entrapped nanoparticles demonstrate at least 9-fold increase in oral bioavailability when compared to curcumin administered with piperine as absorption enhancer. Together the results clearly indicate the promise of nanoparticles for oral delivery of poorly bioavailable molecules like curcumin.

Topics: Alkaloids; Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzodioxoles; Biological Availability; Curcumin; Drug Compounding; Electrochemistry; Excipients; Freeze Drying; Intestinal Absorption; Lactic Acid; Male; Microscopy, Atomic Force; Nanoparticles; Particle Size; Piperidines; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polyunsaturated Alkamides; Rats; Rats, Sprague-Dawley; Solubility; Tissue Distribution; X-Ray Diffraction

Spice active principles are reported to have anti-diabetic, anti-hypercholesterolemic, antilithogenic, anti-inflammatory, anti-microbial and anti-cancer properties. In our previous report we have shown that spices and their active principles inhibit 5-lipoxygenase and also formation of leukotriene C4. In this study, we report the modulatory effect of spice active principles viz., eugenol, capsaicin, piperine, quercetin, curcumin, cinnamaldehyde and allyl sulphide on in vitro human platelet aggregation. We have demonstrated that spice active principles inhibit platelet aggregation induced by different agonists, namely ADP (50microM), collagen (500microg/ml), arachidonic acid (AA) (1.0mM) and calcium ionophore A-23187 (20microM). Spice active principles showed preferential inhibition of arachidonic acid-induced platelet aggregation compared to other agonists. Among the spice active principles tested, eugenol and capsaicin are found to be most potent inhibitors of AA-induced platelet aggregation with IC50 values of 0.5 and 14.6microM, respectively. The order of potency of spice principles in inhibiting AA-induced platelet aggregation is eugenol>capsaicin>curcumin>cinnamaldehyde>piperine>allyl sulphide>quercetin. Eugenol is found to be 29-fold more potent than aspirin in inhibiting AA-induced human platelet aggregation. Eugenol and capsaicin inhibited thromboxane B2 (TXB2) formation in platelets in a dose-dependent manner challenged with AA apparently by the inhibition of the cyclooxygenase (COX-1). Eugenol-mediated inhibition of platelet aggregation is further confirmed by dose-dependent decrease in malondialdehyde (MDA) in platelets. Further, eugenol and capsaicin inhibited platelet aggregation induced by agonists-collagen, ADP and calcium ionophore but to a lesser degree compared to AA. These results clearly suggest that spice principles have beneficial effects in modulating human platelet aggregation.

Topics: Acrolein; Adenosine Diphosphate; Alkaloids; Allyl Compounds; Arachidonic Acid; Benzodioxoles; Calcimycin; Capsaicin; Collagen Type III; Curcumin; Eugenol; Humans; Malondialdehyde; Piperidines; Platelet Aggregation; Platelet Aggregation Inhibitors; Polyunsaturated Alkamides; Quercetin; Spices; Sulfides; Thromboxanes

Topics: Alkaloids; Anticarcinogenic Agents; Benzodioxoles; Breast; Breast Neoplasms; Clinical Trials as Topic; Curcumin; Diet; Estrogen Antagonists; Humans; Piperidines; Polyunsaturated Alkamides; Stem Cells

Cadmium (Cd), a well known environmental carcinogen, is a potent immunotoxicant. In rodents, it is primarily characterized by marked thymic atrophy and splenomegaly. Cadmium induces apoptosis in murine lymphocytes and alters the immune functions. Thus, for the amelioration of its effect, three structurally different bioactive herbal extracts such as piperine-alkaloid, picroliv-glycosides and curcumin-polyphenols were evaluated and their efficacy compared. For ascertaining their immunomodulatory role, various biochemical indices of cell damage such as cytotoxicity, oxidative stress (ROS, GSH), apoptosis (mitochondrial membrane potential, caspase-3 activity, phosphatidylserine externalization, apoptotic DNA) along with lymphocyte phenotyping, blastogenesis and cytokine secretion were assessed in thymic and splenic cell suspensions. Of the three herbals examined, piperine displayed maximum efficacy. All the three doses of piperine (1, 10 and 50 microg/ml) increased cell viability in a dose dependent manner, whereas curcumin and picroliv were also effective, but to a lesser degree. Only the two higher doses exhibited cell viability efficacy. The median doses ie 10 microg/ml, were therefore selected, for comparison of their antioxidant, anti-apoptotic and immune function modulation. Restoration of ROS and GSH was most prominent with piperine. The anti-apoptotic potential was directly proportional to their antioxidant nature. In addition, Cd altered blastogenesis, T and B cell phenotypes and cytokine release were also mitigated best with piperine. The ameliorative potential was in order of piperine > curcumin > picroliv and former could be considered the drug of choice under immunocompromised conditions.

Topics: Alkaloids; Animals; Apoptosis; B-Lymphocytes; Benzodioxoles; Cadmium Chloride; Caspase 3; Cell Survival; Cinnamates; Curcumin; DNA Damage; Glutathione; Glycosides; Interferon-gamma; Interleukin-2; Membrane Potential, Mitochondrial; Mice; Mice, Inbred BALB C; Oxidative Stress; Piperidines; Polyunsaturated Alkamides; Reactive Oxygen Species; Vanillic Acid

Curcumin is a major active principle of Curcuma longa, one of the widely used preparations in the Indian system of medicine. It is known for its diverse biological actions.. The present study was designed to investigate the involvement of monoaminergic system(s) in the antidepressant activity of curcumin and the effect of piperine, a bioavailability enhancer, on the bioavailability and biological effects of curcumin.. Behavioral (forced swim test), biochemical (monoamine oxidase (MAO) enzyme inhibitory activity), and neurochemical (neurotransmitter levels estimation) tests were carried out. Curcumin (10-80 mg/kg, i.p.) dose dependently inhibited the immobility period, increased serotonin (5-hydroxytryptamine, 5-HT) as well as dopamine levels (at higher doses), and inhibited the monoamine oxidase enzymes (both MAO-A and MAO-B, higher doses) in mice. Curcumin (20 mg/kg, i.p.) enhanced the anti-immobility effect of subthreshold doses of various antidepressant drugs like fluoxetine, venlafaxine, or bupropion. However, no significant change in the anti-immobility effect of imipramine and desipramine was observed. Furthermore, combination of subthreshold dose of curcumin and various antidepressant drugs resulted in synergistic increase in serotonin (5-HT) levels as compared to their effect per se. There was no change in the norepinephrine levels. The coadministration of piperine (2.5 mg/kg, i.p.), a bioavailability enhancing agent, with curcumin (20 and 40 mg/kg, i.p.) resulted in potentiation of pharmacological, biochemical, and neurochemical activities.. The study provides evidences for mechanism-based antidepressant actions of curcumin. The coadministration of curcumin along with piperine may prove to be a useful and potent natural antidepressant approach in the management of depression.

Topics: Alkaloids; Animals; Antidepressive Agents; Behavior, Animal; Benzodioxoles; Biogenic Monoamines; Biological Availability; Curcumin; Dopamine; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Immobility Response, Tonic; Injections, Intraperitoneal; Male; Mice; Mice, Inbred Strains; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Piperidines; Polyunsaturated Alkamides; Reserpine; Selegiline; Serotonin; Swimming; Time Factors; Tranylcypromine

Recent studies have proposed curcumin as a potential partner for artemisinin in artemisinin combination therapies to treat malaria infections. The efficacy of curcumin alone and in combination with artemisinin was evaluated on a clone of Plasmodium chabaudi selected for artemisinin resistance in vivo. The addition of piperine as an enhancer of curcumin activity was also tested. Results indicated that curcumin, both alone and in combination with piperine had only a modest antimalarial effect and was not able to reverse the artemisinin-resistant phenotype or significantly affect growth of the tested clone when used in combination with artemisinin. This is in contrast with previous in vivo work and calls for further experimental evaluation of the antimalarial potential of curcumin.

Topics: Administration, Oral; Alkaloids; Animals; Anti-Infective Agents; Artemisinins; Benzodioxoles; Biological Availability; Curcumin; Drug Resistance; Drug Therapy, Combination; Malaria; Male; Mice; Parasitemia; Piperidines; Plasmodium chabaudi; Polyunsaturated Alkamides

Curcuminoid extract and piperine are being evaluated for beneficial effects in Alzheimer's disease, among other intractable disorders. Consequently, we studied the potential for herb-drug interactions involving cytochrome P450 (P450), UDP-glucuronosyltransferase (UGT), and sulfotransferase (SULT) enzymes. The curcuminoid extract inhibited SULT > CYP2C19 > CYP2B6 > UGT > CYP2C9 > CYP3A activities with IC(50) values ranging from 0.99 +/- 0.04 to 25.3 +/- 1.3 microM, whereas CYP2D6, CYP1A2, and CYP2E1 activities were less affected (IC(50) values > 60 microM). Inhibition of CYP3A activity by curcuminoid extract was consistent with competitive inhibition (K(i) = 11.0 +/- 1.3 microM), whereas inhibition of both CYP2C9 and CYP2C19 activities were consistent with mixed competitive-noncompetitive inhibition (10.6 +/- 1.1 and 7.8 +/- 0.9 microM, respectively). Piperine was a relatively selective noncompetitive inhibitor of CYP3A (IC(50) 5.5 +/- 0.7 microM, K(i) = 5.4 +/- 0.3 microM) with less effect on other enzymes evaluated (IC(50) > 29 microM). Curcuminoid extract and piperine inhibited recombinant CYP3A4 much more potently (by >5-fold) than CYP3A5. Pure synthetic curcuminoids (curcumin, demethoxycurcumin, and bisdemethoxycurcumin) were also evaluated for their effects on CYP3A, CYP2C9, UGT, and SULT activities. All three curcuminoids had similar effects on CYP3A, UGT, and SULT activity, but demethoxycurcumin (IC(50) = 8.8 +/- 1.2 microM) was more active against CYP2C9 than either curcumin or bisdemethoxycurcumin (IC(50) > 50 microM). Based on these data and expected tissue concentrations of inhibitors, we predict that a p.o. administered curcuminoid/piperine combination is most likely to inhibit CYP3A, CYP2C9, UGT, and SULT metabolism within the intestinal mucosa.

Topics: Acetaminophen; Alkaloids; Benzodioxoles; Chromatography, High Pressure Liquid; Curcumin; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Glucuronosyltransferase; Humans; Liver; Piperidines; Polyunsaturated Alkamides; Recombinant Proteins; Spectrometry, Fluorescence; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Ultraviolet; Sulfotransferases

The effects of four alkaloids on the biosynthesis of ochratoxin A (OTA), ochratoxin B (OTB) and citrinin were examined on four OTA-producing aspergilli: Aspergillus auricomus, A. sclerotiorum and two isolates of A. alliaceus. Piperine and piperlongumine, natural alkaloids of Piper longum, significantly inhibited OTA production at 0.001% (w/v) for all aspergilli examined. Piperine and piperlongumine affected the polyketide synthesis step of OTA production and inhibited production of citrinin. Curcumin, a constituent of tumeric, completely inhibited mycelial growth of A. alliaceus isolate 791 at 0.1% (w/v) and decreased OTA production by approximately 70% at 0.01% (w/v). Sesamin, a constituent of sesame oil, inhibited OTA and OTB production by 60 and 45%, respectively, at 0.1% (w/v), showing its effect was on chloroperoxidase and polyketide synthase activity. The potential advantage of these natural products to reduce ochratoxin contamination of agricultural commodities is discussed.

Topics: Alkaloids; Antineoplastic Agents, Phytogenic; Antioxidants; Aspergillus; Benzodioxoles; Carcinogens; Citrinin; Culture Media; Curcuma; Curcumin; Dioxolanes; Dioxoles; Food Contamination; Lignans; Mycelium; Mycotoxins; Ochratoxins; Piper; Piperidines; Polyunsaturated Alkamides; Sesame Oil

A comparative evaluation of the absorbability of three structurally similar and physiologically active spice principles in an in vitro system consisting of everted rat intestinal sacs was made. When everted sacs of rat intestines were incubated with 50-1000 microg of curcumin in 10 ml incubation medium, absorption of the spice principle was maximum at 100 microg concentration. The amount of absorbed curcumin present in the serosal fluid was negligible. This and the comparatively lower recovery of the original compound suggested that curcumin to some extent undergoes a modification during absorption. For similar concentrations of added piperine, about 44-63% of piperine disappeared from the mucosal side. Absorption of piperine which was maximum at 800 microg per 10 ml was about 63%. The absolute amounts of piperine absorbed in this in vitro system exceeded the amounts of curcumin. The absorbed piperine could be traced in both the serosal fluid and in the intestinal tissue, indicating that piperine did not undergo any metabolic change during the process of absorption. 7-12% of the absorbed piperine was found in the serosal fluid. When everted sacs of rat intestines were incubated with 10-500 microg of capsaicin, a maximum of 82-88% absorption could be seen in the lower concentrations, and the amount of absorbed capsaicin did not proportionately increase at higher concentrations. A relatively higher percentage of the absorbed capsaicin could be seen in the serosal fluid as compared to curcumin or piperine. When these spice active principles were associated with mixed micelles, their in vitro intestinal absorption was relatively higher. Curcumin absorption in everted intestinal sac increased from 48.7% to 56.1% when the same was present in micelles. In the case of capsaicin and piperine, increase in absorption was 27.8-44.4% and 43.4-57.4%, respectively, when they were present in micelles as compared to its native form.

Topics: Alkaloids; Animals; Benzodioxoles; Capsaicin; Curcumin; In Vitro Techniques; Intestinal Absorption; Intestinal Mucosa; Male; Micelles; Piperidines; Polyunsaturated Alkamides; Rats; Rats, Wistar; Spices

The effect of dietary supplementation of spice-active principles, curcumin (0.2%), capsaicin (0.015%), and piperine (0.02%) on the activities of the liver drug-metabolizing enzyme system was examined. All the 3 dietary spice principles significantly stimulated the activity of aryl hydroxylase. A synergistic action of dietary curcumin and capsaicin with respect to stimulating the activity of aryl hydroxylase was also evidenced when fed in combination. The activity of N-demethylase essentially remained unaffected by dietary curcumin, capsaicin, or their combination, but was significantly lowered as a result of piperine feeding. Uridine dinucleotide phosphate (UDP)-glucuronyl transferase activity was decreased by dietary piperine and the combination of curcumin and capsaicin. NADPH-cytochrome c reductase activity was significantly decreased by dietary piperine. The levels of hepatic microsomal cytochrome P450 and cytochrome b5 were not influenced by any of the dietary spice-active principles. These spice-active principles were also examined for their possible in vitro influence on the components of the hepatic drug-metabolizing enzyme system in rat liver microsomal preparation. Piperine significantly decreased the activity of liver microsomal aryl hydroxylase activity when included in the assay medium at 1 x 10(-6) mol/L, 1 x 10(-5) mol/L, and 1x 10(-4) mol/L level. Lowered activity of N-demethylase was observed in presence of capsaicin or piperine at 1 x 10(-6) mol/L in the assay medium. Hepatic microsomal glucuronyl transferase activity was significantly decreased in vitro by addition of capsaicin or piperine. Capsaicin and piperine brought about significant decrease in liver microsomal cytochrome P450 when included at 1 x 10(-6) mol/L and 1 x 10(-5) mol/L, the effect being much higher in the case of piperine. The results suggested that whereas the 3 spice principles have considerable similarity in structure, piperine is exceptional in its influence on the liver drug-metabolizing enzyme system. The study also indicated that a combination of curcumin and capsaicin does not produce any significant additive effect on the liver drug-metabolizing enzyme system.

Topics: Alkaloids; Animals; Aryl Hydrocarbon Hydroxylases; Benzodioxoles; Capsaicin; Carrier Proteins; Curcumin; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drug Synergism; Enzyme Activation; Enzyme Inhibitors; Glucuronosyltransferase; Heme-Binding Proteins; Hemeproteins; In Vitro Techniques; Liver; Male; Microsomes, Liver; NADPH-Ferrihemoprotein Reductase; Oxidoreductases, N-Demethylating; Piperidines; Polyunsaturated Alkamides; Rats; Rats, Wistar

Spice components and their active principles are potential antioxidants. In this study we examined the effect of phenolic and non-phenolic active principles of common spices on copper ion-induced lipid peroxidation of human low density lipoprotein (LDL) by measuring the formation of thiobarbituric acid reactive substance (TBARS) and relative electrophoretic mobility (REM) of LDL on agarose gel. Curcumin, capsaicin, quercetin, piperine, eugenol and allyl sulfide inhibited the formation of TBARS effectively through out the incubation period of 12 h and decreased the REM of LDL. Spice phenolic active principles viz. curcumin, quercetin and capsaicin at 10 microM produced 40-85% inhibition of LDL oxidation at different time intervals while non-phenolic antioxidant allyl sulfide was less potent in inhibiting oxidation of LDL. However, allyl sulfide, eugenol and ascorbic acid showed pro-oxidant activity at lower concentrations (10 microM) and antioxidant activity at higher concentrations (50 microM) only. Among the spice principles tested quercetin and curcumin showed the highest inhibitory activity while piperine showed least antioxidant activity at equimolar concentration during initiation phase of oxidation of LDL. The inhibitory effect of curcumin, quercetin and capsaicin was comparable to that of BHA, but relatively more potent than ascorbic acid. Further, the effect of curcumin, quercetin, capsaicin and BHA on initiation and propagation phases of LDL oxidation showed that curcumin significantly inhibited both initiation and propagation phases of LDL oxidation, while quercetin was found to be ineffective at propagation phase. These data suggest that the above spice active principles, which constitute about 1-4% of above spices, are effective antioxidants and offer protection against oxidation of human LDL.

Topics: Alkaloids; Allyl Compounds; Ascorbic Acid; Benzodioxoles; Butylated Hydroxyanisole; Capsaicin; Curcumin; Eugenol; Humans; In Vitro Techniques; Lipoproteins, LDL; Oxidation-Reduction; Piperidines; Polyunsaturated Alkamides; Quercetin; Spices; Sulfides

Three spices, chili, black pepper, and turmeric, were tested for the effect of their aqueous extracts on the sensitivity of three bacteria, Escherichia coli, Bacillus megaterium, and Bacillus pumilusspores, to gamma-radiation. It was found that the extracts of the three spices offered protection to these organisms against inactivation by gamma-radiation. These spice extracts were also tested for their protection of naked plasmid DNA. Radiation-induced degradation of plasmid pUC18 DNA was reduced in the presence of the spice extracts. The maximum protection was offered by the chili extract followed by that of black pepper and turmeric. The two known antioxidants, curcumin and piperine from turmeric and black pepper, respectively, were shown to protect the plasmid DNA from the degradation by gamma-radiation. Experiments with the plasmid pUC18 DNA indicated that the spice extracts probably protected microorganisms by protecting their DNA. These studies indicated the importance of spices among ingredients in food as dose-modifying factors during radiation processing.

Topics: Alkaloids; Antioxidants; Bacillus; Bacillus megaterium; Benzodioxoles; Curcuma; Curcumin; Dose-Response Relationship, Radiation; Escherichia coli; Gamma Rays; Piperidines; Plant Extracts; Plasmids; Polyunsaturated Alkamides; Radiation Tolerance; Spices

1. The effects of some naturally occurring pungent substances, piperine, mustard oil, eugenol and curcumin, were compared to those of capsaicin in the rat isolated urinary bladder. 2. All test compounds dose-dependently contracted the rat bladder and produced desensitization toward capsaicin (1 mumol/l). Development of cross-tachyphylaxis among the natural pungent substances on one hand and capsaicin on the other, suggested a common site of action on visceral primary afferents. 3. Contractile responses to piperine, mustard oil and eugenol were partially tetrodotoxin and ruthenium red-sensitive, suggesting that activation of sensory terminals by these agents takes place indirectly, as well as by a direct action on sensory receptors. 4. The presence of the secondary acrylamide linkage (present in the backbone of capsaicin, but not in that of test compounds) does not appear to be essential to produce desensitization of sensory nerve terminals.

Topics: Alkaloids; Animals; Benzodioxoles; Capsaicin; Curcumin; Eugenol; In Vitro Techniques; Isothiocyanates; Male; Muscle Contraction; Mustard Plant; Nerve Endings; Neurons, Afferent; Piperidines; Plant Extracts; Plant Oils; Polyunsaturated Alkamides; Rats; Rats, Inbred Strains; Ruthenium Red; Tetrodotoxin; Thiocyanates