curcumin and Liver-Diseases

Metabolic-associated fatty liver disease (MAFLD), formerly non-alcoholic fatty liver disease (NAFLD), is characterized by excessive fat accumulation in hepatocytes. It is the most common chronic liver disease worldwide and is a significant public health problem. In the absence of pharmacological therapy, other treatments such as diet, physical activity, or supplementation are sought. Non-pharmacological therapies may include curcumin supplementation, which has been shown to have many health-promoting properties, including antioxidant, anti-inflammatory, and anti-cancer effects. For this reason, we reviewed available databases to analyze publications describing the effect of curcumin supplementation on biochemical parameters in MAFLD. Nine studies (eight RCTs and one CT) based solely on supplementation of patients with curcumin were included in this review. The results from the individual trials were varied and did not allow clear conclusions. Although they suggest that curcumin shows some potential in the treatment of MAFLD, further research is needed.

Topics: Curcumin; Databases, Factual; Dietary Supplements; Hepatocytes; Humans; Interleukins; Liver Diseases; Non-alcoholic Fatty Liver Disease

Topics: Alzheimer Disease; Animals; Curcuma; Curcumin; Disease Models, Animal; Heart Diseases; Humans; Liver Diseases; Lung Neoplasms; Medicine, Ayurvedic; Osteoarthritis; Phytotherapy

Liver ischemia/reperfusion (I/R) injury is a major complication of hepatic surgery and transplantation. It is one of the leading causes of morbidity and mortality because of post-surgery hepatic dysfunction. Several studies have suggested different mechanisms are involved in the pathogenesis of I/R injury in the liver that includes oxidative stress, inflammation, mitochondria dysfunction, liver Kupffer cells (KCs) activation, vascular cell adhesion molecule overexpression, and facilitation of polymorphonuclear neutrophil injury. Curcumin is a natural product extracted from Curcuma longa that is known to suppress these pathways and as a result reduces liver ischemia-reperfusion injury. This paper gives an overview of the protective effects of curcumin against I/R injury in the liver and discusses the studies that have linked biological functions of curcumin with liver I/R injury improvement.

Topics: Animals; Curcumin; Disease Models, Animal; Humans; Liver Diseases; Liver Transplantation; Protective Agents; Reperfusion Injury

Oxidative stress has been considered a key causing factor of liver damage induced by a variety of agents, including alcohol, drugs, viral infections, environmental pollutants and dietary components, which in turn results in progression of liver injury, non-alcoholic steatohepatitis, non-alcoholic liver disease, liver fibrosis and cirrhosis. During the past 30 years and even after the major progress in the liver disease management, millions of people worldwide still suffer from an acute or chronic liver condition. Curcumin is one of the most commonly used indigenous molecules endowed by various shielding functionalities that protects the liver. The aim of the present study is to comprehensively review pharmacological effects and molecular mechanisms, as well as clinical evidence, of curcumin as a lead compound in the prevention and treatment of oxidative associated liver diseases. For this purpose, electronic databases including “Scopus,” “PubMed,” “Science Direct” and “Cochrane library” were extensively searched with the keywords “curcumin or curcuminoids” and “hepatoprotective or hepatotoxicity or liver” along with “oxidative or oxidant.” Results showed that curcumin exerts remarkable protective and therapeutic effects of oxidative associated liver diseases through various cellular and molecular mechanisms. Those mechanisms include suppressing the proinflammatory cytokines, lipid perodixation products, PI3K/Akt and hepatic stellate cells activation, as well as ameliorating cellular responses to oxidative stress such as the expression of Nrf2, SOD, CAT, GSH, GPx and GR. Taking together, curcumin itself acts as a free radical scavenger over the activity of different kinds of ROS via its phenolic, β-diketone and methoxy group. Further clinical studies are still needed in order to recognize the structure-activity relationships and molecular mechanisms of curcumin in oxidative associated liver diseases.

Topics: Animals; Antioxidants; Curcumin; Humans; Liver; Liver Diseases; Oxidative Stress; Signal Transduction

Curcumin is a principal polyphenolic curcuminoid extracted from turmeric rhizome, which has been used for treating inflammation of joints, ulcers, jaundice and other disorders in Asian traditional medicine. In recent years, many studies have indicated that curcumin plays important roles in treatment of liver diseases. Curcumin attenuates liver injury and non-alcoholic fatty liver disease by lowering the release of inflammation cytokines, minimizing oxidative stress, enhancing the sensitivity of insulin and altering lipid metabolism. Curcumin shows potent anti-fibrosis activity, contributing to inhibit the activation of hepatic stellate cells and reduce the deposition of extracellular matrix by its regulation of PPAR-γ, NF-ΚB and TGF-β signaling pathways. Moreover, curcumin exhibits anti-cancer effect by inducing G2/M phase cell cycle arrest and apoptosis in several hepatoma cell lines. However, poor water solubility and low bioavailability of curcumin limit its clinical applications. To overcome its limited systemic bioavailability, many new approaches have been explored to deliver curcumin effectively. This article focuses on advances in the effects of curcumin and its derivatives for treatment of liver injury, non-alcoholic fatty liver disease, liver fibrosis and hepatocarcinoma.

Topics: Apoptosis; Cell Cycle Checkpoints; Cell Line, Tumor; Curcumin; Hepatic Stellate Cells; Humans; Inflammation; Liver Diseases; NF-kappa B; Oxidative Stress; PPAR gamma; Signal Transduction; Transforming Growth Factor beta

Type 2 diabetes is a chronic condition in which cells have reduced insulin signalling, leading to hyperglycemia and long-term complications, including heart, kidney and liver disease. Macrophages activated by dying or stressed cells, induce the transcription factor nuclear factor kappa-B leading to the production of pro-inflammatory cytokines including TNF and IL-6. These inflammatory macrophages in liver and adipose tissue promote insulin resistance, and medications which reduce inflammation and enhance insulin signalling improve glucose control. Curcumin is an anti-oxidant and nuclear factor kappa-B inhibitor derived from turmeric. A number of studies have shown that dietary curcumin reduces inflammation and delays or prevents obesity-induced insulin resistance and associated complications, including atherosclerosis and immune mediate liver disease. Unfortunately dietary curcumin is poorly absorbed by the digestive system and undergoes glucuronidation and excretion rather than being released into the serum and systemically distributed. This confounds understanding of how dietary curcumin exerts its beneficial effects in type 2 diabetes and associated diseases. New improved methods of delivering curcumin are being developed including nanoparticles and lipid/liposome formulations that increase absorption and bioavailability of curcumin. Development and refinement of these technologies will enable cell-directed targeting of curcumin and improved therapeutic outcome.

Topics: Adipose Tissue; Animals; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Disease Models, Animal; Drug Delivery Systems; Humans; I-kappa B Proteins; Inflammation; Insulin; Insulin Resistance; Liver; Liver Diseases; Nanoparticles; NF-kappa B; NF-KappaB Inhibitor alpha; Obesity; Randomized Controlled Trials as Topic

Since 1900 bc, several therapeutic activities have been attributed to the rhizomes of the plant Curcuma longa for a variety of diseases, including liver disorders. Curcumin, the main active compound obtained from this plant, was first isolated two centuries ago and its structure as diferuloylmethane was determined in 1910. Curcumin has shown anti-inflammatory, anti-oxidant, antifungal, antibacterial and anticancer activities. The pharmacological properties of curcumin were reviewed recently and focused mainly on its anticancer properties. However, its beneficial activity on liver diseases (known centuries ago, and demonstrated recently utilizing animal models) has not being reviewed in depth until now. The curcumin ability to inhibit several factors like nuclear factor-kappaB, which modulates several pro-inflammatory and profibrotic cytokines as well as its anti-oxidant properties, provide a rational molecular basis to use it in hepatic disorders. Curcumin attenuates liver injury induced by ethanol, thioacetamide, iron overdose, cholestasis and acute, subchronic and chronic carbon tetrachloride (CCl(4)) intoxication; moreover, it reverses CCl(4) cirrhosis to some extent. Unfortunately, the number of studies of curcumin on liver diseases is still very low and investigations in this area must be encouraged because hepatic disorders constitute one of the main causes of worldwide mortality.

Topics: Animals; Carbon Tetrachloride; Cholestasis; Curcuma; Curcumin; Humans; Iron; Liver; Liver Cirrhosis; Liver Cirrhosis, Biliary; Liver Diseases; Thioacetamide

The use of herbal drugs for the treatment of liver diseases has a long tradition in many eastern countries. The easy accessibility without the need for laborious pharmaceutical synthesis has drawn increased attention towards herbal medicines. Few herbal preparations exist as standardized extracts with major known ingredients or even as pure compounds. Some of the herbals, which show promising activity, are ellagic acid for antifibrotic treatment, phyllanthin for treating chronic hepatitis B, glycyrrhizin to treat chronic viral hepatitis and picroliv for liver regeneration. These compounds, which have proven antioxidant, antiviral or anticarcinogenic properties, can serve as primary compounds for further development as hepatoprotective drugs. This review provides the chemistry, pharmacology and future aspects of picroliv, ellagic acid and curcumin with focus on hepatoprotective properties. These phytochemicals may prove to be very useful in the treatment of hepatotoxicity induced by viral agents, toxic drugs and plant poisons. The high safety profile may be an added advantage. However, poor bioavailability and temperature and light sensitivity can reduce the efficacy of drugs like curcumin. In future, the derivatives or new combinations of these drugs may prove to be useful.

Topics: Animals; Cinnamates; Clinical Trials as Topic; Curcumin; Drug Discovery; Glycosides; Humans; Hydrolyzable Tannins; Liver; Liver Diseases; Plant Preparations; Protective Agents; Treatment Outcome; Vanillic Acid

Liver diseases are a major problem of worldwide proportions. However, the number of drugs actually used successfully in humans is very small. In this review some of the most promising/studied drugs utilized for liver diseases were chosen and analysed critically from the basic to the clinical point of view. Antiviral agents are not discussed because excellent reviews have appeared on this topic. The compounds/preparations described herein are, alphabetically: colchicine, corticosteroids, curcumin, glycyrrhizin, interferons (for their antifibrotic properties), Liv 52, nitric oxide, resveratrol, silymarin, sulfoadenosylmethionine, and thalidomide. Colchicine and corticosteroids have been studied extensively in animals and humans; most clinical studies suggest that these compounds are not useful in the treatment of liver diseases. Glycyrrhizin is an herbal medicine with several components that has interesting hepatoprotective properties in patients with subacute liver failure but deserves more prospective controlled trials. Interferon has shown interesting antifibrotic properties in animals and humans; prospective studies on their antifibrotic/fibrolytic activity are required. Curcumin, resveratrol and thalidomide are very attractive newly discovered protective and curative compounds on experimental hepatic diseases. Their mechanism of action is associated with the ability to down-regulate NF-kappaB and to decrease pronecrotic and profibrotic cytokines. Unfortunately, clinical studies are lacking. Sulfoadenosylmethionine and silymarin are also promising drugs utilized mainly in cholestasis but the benefits can be expanded if more controlled trials are performed. The future is to carry out controlled prospective double-blind multicenter studies with the newly discovered drugs with proven beneficial effects on animals. Fundamental hepatobiology should also be encouraged.

Topics: Adrenal Cortex Hormones; Animals; Colchicine; Curcumin; Disease Models, Animal; Drug Combinations; Glycyrrhizic Acid; Humans; Interferons; Liver Diseases; Nitric Oxide; Plant Extracts; Resveratrol; S-Adenosylmethionine; Silymarin; Stilbenes; Thalidomide

Medicinal plants have been traditionally used for treating liver diseases since centuries. Several leads from plant sources have been found as potential hepatoprotective agents with diverse chemical structures. Although, a big list of hepatoprotective phytomolecules was reported in the scientific literature, only a few were potent against various types of liver damages. Of which, silymarin, andrographolide, neoandrographolide, curcumin, picroside, kutkoside, phyllanthin, hypophyllanthin, and glycyrrhizin have largely attracted the scientific community. This review focuses discussion on the chemistry, biological activity, mode of action, toxicity, and future prospects of these leads.

Topics: Animals; Cinnamates; Curcumin; Cytokines; Diterpenes; Glucosides; Glycyrrhizic Acid; Humans; Lignans; Liver; Liver Diseases; Phytotherapy; Plant Extracts; Plants; Protective Agents; Silymarin; Tetrahydronaphthalenes

Curcumin (diferuloylmethane) is an orange-yellow component of turmeric (Curcuma longa), a spice often found in curry powder. In recent years, considerable interest has been focused on curcumin due to its use to treat a wide variety of disorders without any side effects. It is one of the major curcuminoids of turmeric, which impart its characteristic yellow colour. It was used in ancient times on the Indian subcontinent to treat various illnesses such as rheumatism, body ache, skin diseases, intestinal worms, diarrhoea, intermittent fevers, hepatic disorders, biliousness, urinary discharges, dyspepsia, inflammations, constipation, leukoderma, amenorrhea, and colic. Curcumin has the potential to treat a wide variety of inflammatory diseases including cancer, diabetes, cardiovascular diseases, arthritis, Alzheimer's disease, psoriasis, etc, through modulation of numerous molecular targets. This article reviews the use of curcumin for the chemoprevention and treatment of various diseases.

Topics: Antioxidants; Curcumin; Diabetes Mellitus; Humans; Inflammation; Liver Diseases; Neoplasms

Curcumin (U1) has a wide spectrum of therapeutic effects such as antitumor and anti-inflammatory effects, including antibacterial, antiviral, antifungal, and antispasmodic activities. By comparison of the structure-activity relationship, tetrahydrocurcumin (THU1), one of the major metabolites, showed the highest antioxidative activity in both in vitro and in vivo systems. U1 has been reported to have the nephroprotective effect to improve creatinine and urea clearance and also protected the chronic renal allograft nephropathy. These beneficial effects have been explained by the protection of oxidative stress and the induction of antioxidative enzymes. The protective effect of THU1 against ferric nitrilotriacetate (Fe-NTA)-induced oxidative renal damage using male ddY mice was greater than that of U1, by monitoring not only radical scavenging activity measured by ESR, and TBARS, 4-HNE-modified protein and 8-OHdG formation but also induction of anioxidative enzymes and detoxification enzymes. THU1 was also expected to improve redox regulation through glutathione and suppress the oxidative stress in diabetic nephropathy and neuropathy. Earlier studies reported that U1 reduced the iron-induced hepatic damage, aflatoxin- and benzo[a]pyrene- induced mutagenicity and hepatocarcinogenecity and also the formation of the DNA adduct by inhibiting cytochrome P450 in the liver. The hepatoprotective role of U1 has been examined using carbone terachloride-induced liver damage in rats and alcoholic liver disease model rats, but not examined using THU1. Our recent data suggests that THU1 is a more promising hepatprotective agent because of its strong induction activity of antioxidant and phase 2-metabolizing enzymes in liver compared to kidney, although more detaied examinations are required.

Topics: Animals; Curcumin; Kidney; Kidney Diseases; Liver; Liver Diseases

Botanical medicines have been used traditionally by herbalists and indigenous healers worldwide for the prevention and treatment of liver disease. Clinical research in this century has confirmed the efficacy of several plants in the treatment of liver disease, while basic scientific research has uncovered the mechanisms by which some plants provide their therapeutic effects. This article is Part Two in a review of botanicals used in the treatment of liver disease. Curcuma longa (turmeric), Camellia sinensis (green tea), and Glycyrrhiza glabra (licorice) are reviewed in this installment. Silybum marianum (milk thistle) and Picrorhiza kurroa (kutkin) were reviewed in Part One.

Topics: Antioxidants; Curcuma; Glycyrrhiza; Humans; Liver; Liver Diseases; Phytotherapy; Plant Extracts; Plants, Medicinal; Tea

Topics: Animals; Chemical and Drug Induced Liver Injury; Curcumin; Humans; Liver Diseases; Lung Diseases

Previous animal studies have shown that Curcuma longa (turmeric) improves liver function. Turmeric may thus be a promising ingredient in functional foods aimed at improving liver function. The purpose of the study is to investigate the hepatoprotective effect of fermented turmeric powder (FTP) on liver function in subjects with elevated alanine transaminase (ALT) levels.. A randomised, double-blind, placebo-controlled trial was conducted between November 2010 and April 2012 at the clinical trial center for functional foods of the Chonbuk National University Hospital. The trial included 60 subjects, 20 years old and above, who were diagnosed mild to moderate elevated ALT levels between 40 IU/L and 200 IU/L. Sixty subjects were randomised to receive FTP 3.0 g per day or placebo 3.0 g per day for 12 weeks. The treatment group received two capsules of FTP three times a day after meals, for 12 weeks. The primary efficacy endpoint was change in the ALT levels in the two groups. The secondary efficacy endpoints included its effect on aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TB), and lipid profiles. Safety was assessed throughout the study using ongoing laboratory tests. Adverse events (AEs) were also recorded.. Sixty subjects were randomised in the study (30 into the FTP group, 30 into the placebo group), and among them, twelve subjects were excluded from the analysis for protocol violation, adverse events or consent withdrawal. The two groups did not differ in baseline characteristics. After 12 weeks of treatment, 48 subjects were evaluated. Of the 48 subjects, 26 randomly received FTP capsules and 22 received placebo. The FTP group showed a significant reduction in ALT levels after 12 weeks of treatment compared with the placebo group (p = 0.019). There was also observed that the serum AST levels were significantly reduce in the FTP group than placebo group (p = 0.02). The GGT levels showed a tendency to decrease, while the serum alkaline phosphatase (ALP), TB, and lipids levels were not modified. There were no reported severe AEs during this study, or abnormalities observed on blood glucose, total protein, albumin, blood urea nitrogen (BUN), and creatinine levels.. The data of this trial indicate that FTP is effective and safe, generally well-tolerated without severe AEs, in the treatment of subjects with elevated ALT levels over a 12 weeks period.. ClinicalTrials.gov: NCT01634256

Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Bilirubin; Curcuma; Double-Blind Method; Female; Fermentation; gamma-Glutamyltransferase; Humans; Liver; Liver Diseases; Male; Middle Aged; Phytotherapy; Plant Preparations; Treatment Outcome

To evaluate the ability of Curcuma longa (CL) and Tinospora cordifolia (TC) formulation to prevent anti-tuberculosis (TB) treatment (ATT) induced hepatotoxicity.. Patients with active TB diagnosis were randomized to a drug control group and a trial group on drugs plus an herbal formulation. Isoniazid, rifampicin, pyrazinamide and ethambutol for first 2 mo followed by continuation phase therapy excluding Pyrazinamide for 4 mo comprised the anti-tuberculous treatment. Curcumin enriched (25%) CL and a hydro-ethanolic extract enriched (50%) TC 1 g each divided in two doses comprised the herbal adjuvant. Hemogram, bilirubin and liver enzymes were tested initially and monthly till the end of study to evaluate the result.. Incidence and severity of hepatotoxicity was significantly lower in trial group (incidence: 27/192 vs 2/316, P<0.0001). Mean aspartate transaminase (AST) (195.93+/-108.74 vs 85+/-4.24, P<0.0001), alanine transaminase (ALT) (75.74+/-26.54 vs 41+/-1.41, P<0.0001) and serum bilirubin (5.4+/-3.38 vs 1.5+/-0.42, P<0.0001). A lesser sputum positivity ratio at the end of 4 wk (10/67 vs 4/137, P=0.0068) and decreased incidence of poorly resolved parenchymal lesion at the end of the treatment (9/152 vs 2/278, P=0.0037) was observed. Improved patient compliance was indicated by nil drop-out in trial vs 10/192 in control group (P<0.0001).. The herbal formulation prevented hepatotoxicity significantly and improved the disease outcome as well as patient compliance without any toxicity or side effects.

Topics: Adult; Antitubercular Agents; Blood Sedimentation; Body Weight; Chemical and Drug Induced Liver Injury; Curcuma; Drug Therapy, Combination; Ethambutol; Female; Hemoglobins; Humans; Isoniazid; Liver Diseases; Male; Middle Aged; Patient Compliance; Plant Preparations; Pyrazinamide; Rifampin; Tinospora; Treatment Outcome; Tuberculosis

Abemaciclib (ABEM) is an important antitumor agent for breast cancer treatment. However, the side-effects of ABEM are unclear in the liver. This study investigated the protective effect of curcumin (CURC) on liver damage caused by ABEM. The rats were divided into five groups with eight animals in each group; Control, DMSO (150 µL for per rats), CURC, 30 mg/kg/day), ABE (26 mg/kg/day), and ABE + CURC (26 mg/kg/day ABE, 30 mg/kg/day) groups. Injections were administered daily for 28 days. The levels of AST, LDH, HDL, LDL, triglyceride, and total cholesterol in serum, and hepatic tissue fibrosis, caspase-3, Bax, and TNF-α expression were higher in the ABE group compared to the control group (

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Cholesterol; Curcumin; Fibrosis; Liver; Liver Diseases; Rats; Triglycerides; Tumor Necrosis Factor-alpha

Curcumin may have promising application in the prevention and amelioration of inflammatory bowel disease (IBD). However, the underlying mechanisms underpinning the ability of curcumin to interact with the gut and liver in IBD remains to be defined, which is the exploration aim of this study.. Curcumin supplementation not only prevented further loss of body weight and colon length in IBD mice but also improved diseases activity index (DAI), colonic mucosal injury, and inflammatory infiltration. Meanwhile, curcumin restored the composition of the gut microbiota, significantly increased Akkermansia, Muribaculaceae_unclassified, and Muribaculum, and significantly elevated the concentration of propionate, butyrate, glycine, tryptophan, and betaine in the intestine. For hepatic metabolic disturbances, curcumin intervention altered 14 metabolites, including anthranilic acid and 8-amino-7-oxononanoate while enriching pathways related to the metabolism of bile acids, glucagon, amino acids, biotin, and butanoate. Furthermore, SCC analysis revealed a potential correlation between the upregulation of intestinal probiotics and alterations in liver metabolites.. The therapeutic mechanism of curcumin against IBD mice occurs by improving intestinal dysbiosis and liver metabolism disorders, thus contributing to the stabilization of the gut-liver axis.

Topics: Animals; Chromatography, Liquid; Colitis; Colon; Curcumin; Dextran Sulfate; Disease Models, Animal; Dysbiosis; Inflammatory Bowel Diseases; Liver Diseases; Mice; Mice, Inbred C57BL; Tandem Mass Spectrometry

Cadmium chloride (Cd) and sodium arsenite (As) are two prominent examples of non-biodegradable substances that accumulate in ecosystems, pose a serious risk to human health and are not biodegradable. Although the toxicity caused by individual use of Cd and As is known, the toxicity of combined use (Cd+As) to mammals is poorly understood. The present study aims to investigate the hepatoprotective effect of curcumin (CUR), a naturally occurring bioactive component isolated from the root stem of Curcuma longa Linn., in preventing liver damage caused by a Cd+As mixture. A group of 30 Sprague-Dawley rats were subjected to intraperitoneal administration of Cd+As (0.44 mg/kg+5.55 mg/kg i.p.) and CUR (100 or 200 mg/kg) for a period of 14 days. The experimental results showed that the animals treated with Cd+As exhibited changes in liver biochemical parameters, inflammation and oxidative stress at the end of the experiment. Administration of CUR significantly reduced inflammation, oxidative stress and lipid peroxidation in the Cd+As plus CUR groups compared to the Cd+As group. Furthermore, histological examination of the liver tissue showed that administration of CUR had led to a significant reduction in the liver damage observed in the Cd+As group. The present study provides scientific evidence for the protective effects of CUR against lipid peroxidation, inflammation, oxidative stress and liver damage induced by Cd+As in the liver of rats. The results of our in vivo experiments were confirmed by those of our molecular modelling studies, which showed that CUR can enhance the diminished antioxidant capacity caused by Cd+As.

Topics: Animals; Antioxidants; Arsenic; Cadmium; Curcumin; Ecosystem; Humans; Inflammation; Interleukin-1beta; Liver; Liver Diseases; Mammals; NF-kappa B; Oxidative Stress; Rats; Rats, Sprague-Dawley

Curcumin has been demonstrated to exert anti-oxidant, anti-fibrotic, anti-inflammatory, and anti-cancer activities. This study was conducted to observe the effect and inner mechanism of curcumin in rats with radiation-induced liver damage (RILD).. Thirty SD rats were classified into Control, Radiation group and Curcumin (Cur) + Radiation group (n = 10 in each group). The changes in body weight of the rats were observed on the 3rd, 7th and 14th days after the treatment with curcumin. On the 14th day post treatment, the heart blood of the rats was drawn for measurement of liver function indices including total protein (TP), alanine aminotransfetase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) as well as aspartate aminotransfetase (AST). Subsequently, the rats were euthanized and liver tissues were taken to observe liver morphological changes using hematoxylin-eosin (HE), and to analyze apoptosis condition using transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assays. Meanwhile, the oxidative stress level in liver tissue homogenate was determined by biochemical analysis. The expression of nuclear factor kappa B (NF-κB) pathway-associated and apoptosis-associated proteins was detected using Western blot analysis, and the expression levels of inflammatory factors were measured by Enzyme-linked immunosorbent assay (ELISA).. The reduced body weight was observed in rats of the Radiation group compared to the Control and Cur + Radiation groups on day 14. In the Radiation group, hepatic cell edema and inflammatory cell infiltration could be visible under the light microscope, and the hepatocytes presented with vacuolar degeneration. In the Cur + Radiation group, the hepatocytes swelled under the microscope, but the pathological changes were alleviated in comparison with the Radiation group. RILD rats with curcumin treatment presented with decreased ALT, AST, ALP, LDH, and maleicdialdehyde (MDA) levels, and elevated TP, superoxide dismutase (SOD), caspase activated DNase (CAD) and glutathione (GSH) levels. Apoptosis and inflammation in rats with RILD were up-regulated, and the NF-κB pathway was activated, but they were reversed after continuously intragastric administration of curcumin for 14 days.. Our study highlights that curcumin treatment reduces the liver damage caused by radiation through the inhibition of the NF-κB pathway.

Topics: Animals; Curcuma; Curcumin; Liver; Liver Diseases; Male; NF-kappa B; Oxidative Stress; Phytotherapy; Plant Extracts; Radiation Injuries, Experimental; Rats, Sprague-Dawley; Signal Transduction

Liver ischemia-reperfusion (I/R) injury is a common clinical pathological phenomenon, which is accompanied by the occurrence in liver transplantation. However, the underlying mechanism is not yet fully understood. MicroRNAs (miRNAs) play an important role in liver I/R injury. Therefore, the study of miRNAs function will contribute a new biological marker diagnosis of liver I/R injury. This study aims to evaluate effects of miR-497-5p in liver I/R injury in mice. The related regulatory factors of miR-497-5p in liver I/R injury were predicted by bioinformatics analysis. Vascular occlusion was performed to establish the liver I/R injury animal models. Hypoxia/reoxygenation (H/R) was performed to establish the in vitro models. Hematoxylin-eosin (HE) staining was conducted to assess liver injury. The inflammatory factors were evaluated by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was adopted to assess the cell apoptosis. The expression of miR-497b-5p was increased in liver I/R injury. Knockdown of miR-497b-5p inhibited the production of inflammatory factors and cell apoptosis. Overexpression of mediator complex subunit 1 (MED1) and tissue inhibitor of metalloproteinase 2 (TIMP2) inhibited cell apoptosis to alleviate liver I/R injury. miR-497b-5p could activate the nuclear factor kappa-B (NF-κB) pathway by inhibiting the MED1/TIMP-2 axis to promote liver I/R injury. This study may provide a new strategy for the treatment of liver I/R injury.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Gene Expression Regulation; Hepatocytes; Kupffer Cells; Liver Diseases; Male; Mediator Complex Subunit 1; Mice; Mice, Inbred C57BL; MicroRNAs; NF-kappa B; Oxygen; Reperfusion Injury; Tissue Inhibitor of Metalloproteinase-2

Reusing deep-fried vegetable oils multiple times is a common practice to save costs, and their chronic consumption may cause hepatic dysfunction. In this investigation, we assessed the modulatory effects of ginger and turmeric lipid-solubles that may migrate to oils during heating on the hepatic inflammatory response in rats.. Male Wistar rats were fed with; 1) control {native canola (N-CNO) or native sunflower (N-SFO)} oil, 2) heated (heated canola {(H-CNO) or heated sunflower (H-SFO)} oil, and 3) heated oil with ginger or turmeric {heated canola with ginger (H-CNO + GI) or heated canola oil with turmeric (H-CNO + TU), heated sunflower oil with ginger (H-SFO + GI) or heated sunflower oil with turmeric (H-SFO + TU)} for 120 days. Hepatic inflammatory response comprising eicosanoids, cytokines, and NF-kB were assessed.. Compared to respective controls, feeding heated oils significantly (p < 0.05); 1) increased eicosanoids (PGE. Consumption of repeatedly heated oil may cause hepatic dysfunction by inducing inflammatory stress through NF-kB upregulation. Lipid-solubles from ginger and turmeric that may migrate to oil during heating prevent the hepatic inflammatory response triggered by heated oils in rats.

Topics: Animals; Curcuma; Cytokines; Down-Regulation; Eicosanoids; Hot Temperature; Inflammation; Lipids; Liver Diseases; Male; NF-kappa B; Rapeseed Oil; Rats; Rats, Wistar; Sunflower Oil; Zingiber officinale

Ageing is an unavoidable, universal, biological phenomenon affecting all organisms, which involves variable declines of individuals motor and memory capabilities. This study aimed to investigate the potential ameliorating effects of curcumin C3 complex, Astragalus membranaceus and blueberry on certain age-related biochemical alterations in rat liver. Four groups of rats, aged 12 months-old, were used. The first group; aged control group in which rats were left without any treatment until the age of 17 months. The other three groups received daily by oral gavage for 5 months the following supplements; curcumin C3 complex (110 mg/kg), Astragalus membranaceus (100 mg/kg) and blueberry (100 mg/kg) respectively. Additionally, a fifth group of rats, aged 5 months-old, was used as an adult control group. Our supplements alleviated ageing-induced redox state imbalance and inflammation as evidenced by reduction of hepatic thiobarbituric acid reactive substances and 8-hydroxydeoxyguanosine levels, restoration of total antioxidant capacity and nitric oxide contents, and lessening of lipofuscin deposition. All supplements decreased hepatic interlukin-6 gene expression and serum levels. Notably, Astragalus membranaceus and blueberry upregulated hepatic telomerase reverse transcriptase gene expression and increased telomere length. Our findings recommend the use of these natural hepatoprotective supplements for the elderly to promote healthy ageing and minimize the risk of age-related liver diseases.

Topics: Animals; Astragalus propinquus; Blueberry Plants; Curcumin; Liver Diseases; Rats

Blood stasis syndrome (BSS) is characterized by blood retardation and is the major cause of some deadly diseases. Some factors that affect BSS have been identified. However, the small molecule that related to BSS is still largely unknown. Traditional Chinese Medicine (TCM), such as Sanleng and Ezhu, has been used for a long time in treating BSS and promising outcomes have been achieved. However, the mechanism of how they work is unclear. Thus, we constructed the Rat BSS model and treated them with Sanleng and Ezhu. Then, the liver dialysis of those rats was collected and the small molecule metabolites were analyzed by GC-MS based metabolomics approach. Our results showed after Sanleng and Ezhu treatment, several small molecule metabolites were significantly changed metabolites (VIP>1 and P<0.05). Pathway enrichment analysis also showed that Sanleng and Ezhu share the similar mechanism in treating BSS, such as regulating Glyoxylate and dicarboxylate metabolism pathway and energy metabolism. Besides, we also identified some key metabolites that were significantly correlated with BSS. In conclusion, those findings uncover the mechanism of Sanleng and Ezhu in treating BSS.

Topics: Animals; Curcuma; Drugs, Chinese Herbal; Gas Chromatography-Mass Spectrometry; Liver; Liver Diseases; Male; Medicine, Chinese Traditional; Metabolomics; Rats; Rats, Sprague-Dawley; Rhizome

Liver diseases are classified as acute and chronic hepatic failures. In particular, chronic pathologies are the most common diseases in the World. Chronic pathologies of liver disease are the most common diseases in the world. There are many causes that induce a progressive and irreversible degeneration of the hepatic parenchyma, but, in general, they lead to the destruction of the normal balance between reactive oxygen stress (ROS) formation and ROS degradation within the liver. The prevalence of disabling diseases, including the hepatic diseases, is increasingly widespread, and it is important to find a safe, inexpensive, accessible and effective way to face this condition. Many recent studies have focused on different natural antioxidants, which could restore the physiological hepatic environment, thereby allowing the normal functioning of this organ. Natural products have been used to discover new leads for treating several diseases; among them, it is important to emphasize curcumin, which is a polyphenol obtained from

Topics: Curcumin; Humans; Liver Diseases; Oxidative Stress

Acetaminophen (APAP) hepatotoxicity is characterised by an extensive oxidative stress due to depletion of glutathione (GSH), which results in massive lipid peroxidation and subsequent liver injury. The current paradigm suggests that mitochondria are the main source of reactive oxygen species (ROS), which impair mitochondrial function and are responsible for cell signalling resulting in cell death. This study was designed to compare the potential impact of thymoquinone (THQ), and/or curcumin (CURC) on liver injury induced by APAP toxicity in rats.. Serum levels of alanine transaminase, aspartate transaminase, total bilirubin, and total protein were measured. In addition, liver nitric oxide (NO), malondialdehyde, reduced glutathione (GSH), and superoxide dismutase (SOD) were estimated. Moreover, these biochemical parameters were confirmed by histopathological and immunohistochemical investigations for the expression of thioredoxin, iNOS and caspase 3.. Acetaminophen toxicity elevated most of the above-mentioned parameters but decreased GSH, SOD, and total protein levels. Histologically, liver sections demonstrated liver injury characterised by hepatocellular necrosis with nuclear pyknosis, karyorrhexis and karyolysis. Immunohistochemical study revealed increased expression of iNOS and caspase 3 proteins, while the thioredoxin protein expression was decreased.. Treatment with the THQ and CURC regulated the biochemical and histopathological alterations induced by APAP toxicity. It was concluded that the combination strategy of THQ and CURC might be considered as a potential antidote in combating liver injury induced by APAP with minimal side effects.

Topics: Acetaminophen; Alanine Transaminase; Animals; Aspartate Aminotransferases; Benzoquinones; Bilirubin; Caspase 3; Curcumin; Glutathione; Immunohistochemistry; Liver; Liver Diseases; Male; Malondialdehyde; Nitric Oxide; Nitric Oxide Synthase Type II; Rats; Superoxide Dismutase; Thioredoxins

Curcuma zedoaria (dry stenophora of

Topics: Acetic Acid; Apoptosis; Biomarkers; Curcuma; Liver Diseases; Oxidative Stress; Plant Extracts; Protective Agents; Reactive Oxygen Species; Solvents

Rats with a normal birth weight (NBW) or intra-uterine growth retardation (IUGR) were fed basic diets (NBW and IUGR groups) or basic diets supplemented with curcumin (NC and IC groups) from 6 to 12 weeks. The body weight of IUGR rats was lower (P<0·05) than that of the controls. Rats with IUGR showed higher (P<0·05) concentrations of TNF-α, IL-1β and IL-6; higher (P<0·05) activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in their serum; and increased (P<0·05) concentrations of malondialdehyde (MDA), protein carbonyl (PC) and 8-hydroxy-2'-deoxyguanosine (8-OHDG) in the liver compared with the NBW rats. The livers of IUGR rats exhibited a lower (P<0·05) superoxide dismutase activity and decreased (P<0·05) metabolic efficiency of the hepatic glutathione redox cycle compared with those of the NBW rats. In response to dietary curcumin supplementation, concentrations of inflammatory cytokines and activities of AST and ALT in the serum and MDA, PC and 8-OHDG in the liver were lower (P<0·05), and the hepatic glutathione redox cycle in the liver was improved (P<0·05) in the IC group than in the IUGR group. These results were associated with lower (P<0·05) phosphorylated levels of the NF-κB pathway and Janus kinase 2 (JAK2) and higher (P<0·05) mRNA expression of genes involved in the nuclear factor, erythroid 2-like 2 (Nfe2l2)/antioxidant response element (ARE) pathway in the liver of the IC rats than that of the IUGR rats. Maternal undernutrition decreased birth weight and led to inflammation, oxidative damage and injury in rats. Curcumin appeared to be beneficial in preventing IUGR-induced inflammation, oxidative damage and injury by activating the expression of the NF-κB, JAK/STAT and Nfe2l2/ARE pathways in the liver.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Alanine Transaminase; Animals; Animals, Newborn; Aspartate Aminotransferases; ATP-Binding Cassette Transporters; Birth Weight; Caenorhabditis elegans Proteins; Curcumin; Cytokines; Deoxyguanosine; Dietary Supplements; Disease Models, Animal; Female; Fetal Growth Retardation; Gene Expression; Inflammation; Liver; Liver Diseases; Oxidation-Reduction; Oxidative Stress; Pregnancy; Rats

New evidence has proven the hepatoprotective activity of curcumin; however, its underlying mechanisms remain to be elucidated. The aim of this study was to investigate the protective effect of curcumin on hepatic damage by measuring the antioxidant capacity and expression level of Rho-related C3 botulinum toxin substrate (Rac1), Rac1-Guanosine triphosphate (Rac1-GTP), and NADPH oxidase 1(NOX1) in biliary duct-ligated (BDL)-fibrotic rat model.. Wistar rats weighing 200 to 250 g were divided into four groups (n = 8 for each): sham group, sham+Cur group (received curcumin 100 mg/kg daily), BDL+Cur group, and BDL group. The mRNA and protein expression levels of Rac1, Rac1-GTP, and NOX1 were measured by real-time polymerase chain reaction and Western blotting, respectively.. Curcumin treatment of BDL rats reduced liver injury, as verified by improvement of hepatic cell histologic alterations, and by reduction of hepatic enzymes. Moreover, the increase in the expression of Rac1, Rac1-GTP, and NOX1 observed in BDL rats was precluded and reversed back toward normalcy by curcumin treatment (P < 0.05). We also observed an escalation of protein thiol groups, increased enzyme activity of serum antioxidant markers (e.g., superoxide dismutase) and a decrease of carbonylation in curcumin-treated BDL rats compared with BDL rats (P < 0.05).. Curcumin attenuated liver damage through the downregulation of Rac1, Rac1-GTP, and NOX1 as well as reduced oxidative stress in the serum and liver tissue of BDL rats.

Topics: Animals; Antioxidants; Bile Ducts; Curcumin; Down-Regulation; Hepatocytes; Ligation; Liver; Liver Diseases; Liver Function Tests; Male; NADH, NADPH Oxidoreductases; NADPH Oxidase 1; Oxidative Stress; rac1 GTP-Binding Protein; Rats; Rats, Wistar; Superoxide Dismutase

This study aimed to evaluate the protective effects of curcumin on angiotensin-converting enzyme (ACE) gene expression, oxidative stress and anti-oxidant status in thioacetamide (TAA)-induced hepatotoxicity in rats.. Total 32 albino Wistar rats (male, 200-250 g) were divided into six groups (n=8). Group 1: untreated controls; Group 2: received TAA (200 mg/kg body weight (b.w.); i.p.) for 12 weeks; Group 3: received curcumin (75 mg/kg b.w.) for 24 weeks; Group 4: received TAA (200 mg/kg b.w.; i.p.) for 12 weeks+curcumin (75 mg/kg b.w.) for 12 weeks.. A significantly higher ACE gene expression was observed in TAA-induced groups as compared with control, indicating more synthesis of ACE proteins. Treatment with curcumin suppressed ACE expression in TAA liver and reversed the toxicity produced. TAA treatment results in higher lipid peroxidation and lower GSH, SOD and CAT than the normal, and this produces oxidative stress in the liver. Cirrhotic conditions were confirmed by serum enzymes (ALT, AST and ALP) as well as histopathological observations.. Curcumin treatment reduced oxidative stress in animals by scavenging reactive oxygen species, protecting the anti-oxidant enzymes from being denatured and reducing the oxidative stress marker lipid peroxidation. Curcumin treatment restores hepatocytes, damaged by TAA, and protects liver tissue approaching cirrhosis.

Topics: Animals; Antioxidants; Curcumin; Gene Expression Regulation, Enzymologic; Lipid Peroxidation; Liver; Liver Diseases; Male; Oxidative Stress; Peptidyl-Dipeptidase A; Rats, Wistar; Thioacetamide

Curcumin, an established pleiotropic agent, has potential for hepatoprotection owing to its powerful antioxidant, anti-inflammatory, and antifibrogenic properties. However, its poor bioavailability limits its use in therapeutics. In this study, we aimed to package curcumin into solid lipid nanoparticles (C-SLNs) to improve its bioavailability and compare the efficacy of C-SLNs with that of free curcumin and silymarin, a well-established hepatoprotectant in clinical use, against carbon tetrachloride (CCl4)-induced hepatic injury in rats, post-induction. A self-recovery group to which no treatment was given was also employed for quantifying self-healing of hepatic tissue, if any.. C-SLNs (particle size 147.6 nm), prepared using a microemulsification technique, were administered to rats post-treatment with CCl4 (1 ml/kg body weight [BW] twice weekly for 2 weeks, followed by 1.5 ml/kg BW twice weekly for the subsequent 2 weeks). The extent of liver damage and repair in terms of histopathology and levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), oxidative stress markers (malondialdehyde, superoxide dismutase, and reduced glutathione) and a pro-inflammatory response marker, tumor necrosis factor (TNF)-α, were determined in both the CCl4 group and the treatment groups.. C-SLNs (12.5 mg/kg) significantly (p < 0.001-0.005) attenuated histopathological changes and oxidative stress, and also decreased induction of ALT, AST, and TNF-α in comparison with free curcumin (100 mg/kg), silymarin (25 mg/kg), and self-recovery groups.. Curcumin could be used as a therapeutic agent for hepatic disorders, provided it is loaded into a suitable delivery system.

Topics: Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Carbon Tetrachloride; Curcumin; Glutathione; Lipids; Liver; Liver Diseases; Male; Malondialdehyde; Nanoparticles; Oxidative Stress; Rats; Rats, Wistar; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Acute respiratory distress syndrome (ARDS) is a common scenario associated with hepatic warm ischemia and reperfusion (I/R) injury after shock or hemorrhage. Inflammation of lung parenchyma and increase in matrix metalloprotease 9 (MMP-9) activity have been implicated in ARDS. In this study, we aimed to investigate the protective efficacy of curcumin treatment against hepatic I/R-induced lung function impairment.. Thirty Sprague-Dawley male rats were evenly divided into 3 groups: a sham group, a hepatic I/R group, and a group treated with curcumin (15 mg/kg/d) 15 minutes before ischemia and every 24 hours for the next 48 hours. Ischemia was induced by occluding the hepatic artery and portal vein for 30 minutes. The clamps were then released and the abdominal incision was closed. Pulmonary function test was conducted after 48 hours of reperfusion. We also examined serum alanine transaminase (ALT) level and degrees of tumor necrosis factor α (TNF-α) and MMP-9 activity in the lung tissue.. Hepatic I/R injury decreased the ratio of residual volume to total lung capacity (RV/TLC), chord compliance (Cchord), and maximum midexpiratory flow (MMEF; P < .05), and increased inspiratory resistance (RI; P < .05), characterized as combined obstructive and restrictive lung disease. Treatment with curcumin markedly improved RV/TLC, Cchord, and MMEF and decreased RI (P < .05). In addition, curcumin treatment reduced serum ALT level and degrees of TNF-α level and MMP-9 activity in the lungs.. Curcumin attenuated hepatic I/R-induced combined restrictive and obstructive lung disease by reducing lung inflammation and MMP-9 activity.

Topics: Alanine Transaminase; Animals; Biomarkers; Curcumin; Cytoprotection; Disease Models, Animal; Liver; Liver Diseases; Lung; Lung Diseases, Obstructive; Lung Injury; Male; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Rats, Sprague-Dawley; Reperfusion Injury; Time Factors; Tumor Necrosis Factor-alpha; Warm Ischemia

The objective of this study is to develop a nanostructured parenteral delivery system, laden with curcumin (CUR), for the therapeutic intervention of sepsis and associated pathologies.. Nanoemulsions were fabricated using sonication and speed homogenization. Size and zeta potential were evaluated by dynamic light scattering and transmission electron microscopy analysis. Pharmacodynamic and pharmacokinetic studies were performed on a rat model of lipopolysaccharide (LPS)-induced sepsis.. The drug content of optimized nanoemulsion (F5) formulation (particle size 246 ± 08 nm, polydispersity index (PDI) of 0.120, zeta potential of -41.1 ± 1.2 mV) was found to be 1.25 mg/ml. In vitro release studies demonstrated that F5 was able to sustain the release of CUR for up to 24 h. Minimal hemolysis and cellular toxicity demonstrated its suitability for intravenous administration. Significant reduction of inflammatory mediator levels was mediated through enhanced uptake by in RAW 264.7 and THP-1 in absence/presence of LPS. Nanoemulsion resulted in an improvement of plasma concentration (AUCF5/AUC CUR = 8.80) and tissue distribution of CUR in rats leading to a reduction in LPS-induced lung and liver injury due to less neutrophil migration, reduced TNF-α levels and oxidative stress (demonstrated by levels of lipid peroxides as well as carbonylated proteins) as confirmed by histopathological studies.. The findings suggest that the therapeutic performance (i.e., reduction in oxidative damage in tissues) of CUR can be enhanced by employing tocol acetate nanoemulsions (via improving pharmacokinetics and tissue distribution) as a platform for drug delivery in sepsis-induced organ injury.

Topics: alpha-Tocopherol; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Curcumin; Cytokines; Disease Models, Animal; Drug Carriers; Drug Delivery Systems; Emulsions; Enzyme-Linked Immunosorbent Assay; Escherichia coli; Flow Cytometry; Infusions, Parenteral; Lipid Peroxides; Lipopolysaccharides; Liver Diseases; Male; Nanoparticles; Pulmonary Edema; Rats; Rats, Sprague-Dawley; Sepsis; Tissue Distribution; Vitamins

In this study, we investigated the protective effect and mechanism of curcumin on a rat model of intestinal ischemia/reperfusion (I/R), which induces an acute liver lesion.. Curcumin was injected into rats in the curcumin groups through left femoral vein. The same volume of vehicle (0.9% normal saline) was injected into sham and I/R groups. Blood and liver tissue were gathered for serological and histopathological determination.. Intestinal I/R led to severe liver injury manifested as a significant increase in serum AST and ALT levels; all of those were reduced by treatment with curcumin. Simultaneously, the activity of SOD in liver decreased after intestinal I/R, which was increased by curcumin treatment. On the other hand, curcumin reduced MPO activity of liver tissue, as well as serum IL-6 and TNF-α levels observably. This is in parallel with the decreased level of liver intercellular cell adhesion molecule-1 (ICAM-1) and nuclear factor-κB (NF-κB) expression.. Our findings suggest that curcumin treatment attenuates liver lesion induced by intestinal I/R, attributable to the antioxidative and anti-inflammatory effect via inhibition of the NF-κB pathway.

Topics: Acute Disease; Alanine Transaminase; Animals; Aspartate Aminotransferases; Curcumin; Disease Models, Animal; Intercellular Adhesion Molecule-1; Interleukin-6; Liver; Liver Diseases; Male; NF-kappa B; Peroxidase; Protective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction; Superoxide Dismutase

Reperfusion of the ischemic liver results in the generation of oxidative and nitrosative stresses and reaction product of peroxynitrite, which induce rapid cytotoxicity and liver injury. In this study we demonstrated that curcumin, an antioxidant, attenuated ischemia/reperfusion (I/R)-induced liver injury.. Ischemia was induced by clamping the common hepatic artery and portal vein of rats for 30 minutes. Thereafter, flow was restored and the liver was reperfused for 80 minutes. Blood samples collected prior to ischemia and after reperfusion were analyzed for methyl guanidine (MG), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and adenosphate triphosphate (ATP). Blood levels of serum glutamic oxaloacetic transaminase (sGOT), serum glutamate pyruvate transaminase (sGPT), and lactic dehydrogenase (LDH), which served as indexes of liver injury, were measured.. The protocol resulted in elevation of blood NO (P < .001), TNF-α (P < .001), and MG (P < .001). sGOT, sGPT, and LDH were elevated significantly (P < .001), whereas ATP was significantly diminished (P < .001). Pretreatment with curcumin (25 mg/kg) significantly attenuated the reperfusion liver injury, while the ATP content reversed. In addition, MG, TNF-α, and NO release were attenuated.. These results indicated that curcumin exerted potent anti-inflammatory effects in I/R-induced liver injury due to its antioxidant effects.

Topics: Adenosine Triphosphate; Alanine Transaminase; Animals; Anti-Inflammatory Agents; Antioxidants; Aspartate Aminotransferases; Biomarkers; Curcumin; Cytoprotection; Disease Models, Animal; Inflammation Mediators; L-Lactate Dehydrogenase; Liver; Liver Diseases; Male; Methylguanidine; Nitric Oxide; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Time Factors; Tumor Necrosis Factor-alpha

Acetaminophen is one of the most popular analgesic and antipyretic drugs and its overdose, which can cause severe damage to liver and kidneys, is one of the most common reasons of emergency admissions. In this study we investigated the effects of curcumin, derived from plant Curcuma longa, on acetaminophen toxicity, and the possibility of combining therapy of curcumin and N-acetyl cysteine (NAC) to treat this toxicity. The experiments were conducted on 72 male Sprague-Dawley rats randomly divided into 12 groups. Control group was left without treatment, and the other groups were treated with different combinations of acetaminophen, curcumin and NAC. 15min after intraperitoneal injection, the blood level of curcumin was measured using HPLC. Blood levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), blood urea nitrogen and creatinine were determined 18 and 42h after acetaminophen injection. One week later, the left kidney and the caudate lobe of the liver were harvested to assay glutathione peroxidase, catalase and malondialdehyde. The right kidney and the remaining lobes of the liver were used for histopathology. Analysis of organ function and oxidation parameters showed that curcumin significantly reduced toxic effects of acetaminophen on the liver and kidneys in a dose-dependent manner and significantly potentiated the protective effects of NAC. These findings were confirmed by histopathology. It is concluded that curcumin can protect the liver and kidney from the damage caused by acetaminophen overdose. Moreover, curcumin has the potential to be used in a combination therapy with NAC, significantly decreasing the therapeutic dose of NAC and therefore its side-effects.

Topics: Acetaminophen; Acetylcysteine; Animals; Biomarkers; Catalase; Curcumin; Drug Synergism; Glutathione Peroxidase; Kidney; Kidney Diseases; Liver; Liver Diseases; Male; Malondialdehyde; Oxidative Stress; Rats; Rats, Sprague-Dawley; Serologic Tests

Activated hepatic stellate cells (HSCs), the major source of the collagens involved in fibrosis and non-alcoholic fatty liver disease (NAFLD), undergo a profound loss of lipid and vitamin A storage capacity, as a consequence of a decline in expression of 'adipogenic' transcription factors such as peroxisome proliferator-activated receptor-gamma (PPARgamma). By contrast, hepatocytes undergo a micro- and macro-vesicular steatosis, reflecting the accumulation of triacylglycerol, and associated with chronic inflammation and fibrosis. These paradoxical findings are extended in this issue: Kang and Chen demonstrate that while low-density lipoproteins (LDL) can activate HSCs, curcumin can inhibit this process by activation of PPARgamma, which not only represses gene expression of SREBP-2 and LDLR, but via induction of expression of SREBP-1c, restores the lipid storage capacity characteristic of quiescent HSCs, suggesting that curcumin may be of therapeutic usage in protecting against liver steatosis and fibrosis.

Topics: Animals; Cell Differentiation; Cell Proliferation; Curcumin; Hepatic Stellate Cells; Lipid Metabolism; Lipoproteins, LDL; Liver Diseases; PPAR gamma; Sterol Regulatory Element Binding Proteins

Curcumin and saikosaponin a, the bioactive phytochemicals of turmeric and Bupleurum, act as antioxidants. This study investigated the effects of supplementation with curcumin and/or saikosaponin a on hepatic lipids and antioxidant status in rats with CCl(4)-induced liver injury. Male Sprague-Dawley rats were randomly divided into control, CCl(4), CCl(4) + curcumin (0.005%; CU), CCl(4) + saikosaponin a (0.004%; SS), and CCl(4) + curcumin + saikosaponin a (0.005% + 0.004%; CU+SS) groups. CCl(4) (40% in olive oil) was injected intraperitoneally at a dose of 0.75 mL/kg once a week. Curcumin and/or saikosaponin a was administered orally 1 week before CCl(4) injection for 8 weeks. The pathological results showed that liver fibrosis was ameliorated in the SS and CU+SS groups. After 8 weeks, supplementation with curcumin and/or saikosaponin a significantly decreased plasma alanine aminotransferase and aspartate aminotransferase activities, as well as plasma and hepatic cholesterol and triglyceride levels. The CU+SS group showed reversal of the impaired hepatic superoxide dismutase activity and an increase in total glutathione level. Supplementation with curcumin and/or saikosaponin a significantly improved hepatic antioxidant status and suppressed malondialdehyde formation. Therefore, supplementation with curcumin and/or saikosaponin a protects against CCl(4)-induced liver injury by attenuating hepatic lipids and lipid peroxidation and enhancing antioxidant defense. Curcumin and saikosaponin a had no additive effects on hepatoprotection except for greater improvement in the total glutathione level and antioxidant status.

Topics: Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Curcumin; Glutathione; Lipids; Liver; Liver Diseases; Male; Oleanolic Acid; Rats; Rats, Sprague-Dawley; Saponins; Superoxide Dismutase

Topics: Anesthetics; Animals; Anthocyanins; Antioxidants; Carbon Monoxide; Curcumin; Cytoprotection; Disease Models, Animal; Flavonoids; Glucosides; Heme Oxygenase-1; Hepatocytes; Humans; Isoflurane; Liver; Liver Diseases; Liver Transplantation; Phenols; Polyphenols; Propofol; Reperfusion Injury

Hepatolenticular degeneration (Wilson disease, WD) is an autosomal recessive disorder of copper metabolism. The clinical manifestations are dominated by the neuropsychiatric and hepatic symptoms due to copper deposition. Investigation of mechanism of copper injury should be helpful for elucidating the pathogenesis and treatment of WD. Curcumin, a plant-derived polyphenol, exhibits the properties of anti-oxidant, anti-inflammation and has no evident side effects, therefore, today curcumin is studied by more and more researchers in pharmacologic action and clinical application especially for its protective effect on liver diseases. The present study was designed to investigate the lipid peroxidation and apoptotic liver injury in copper-overloaded rats, and to explore the protective effects of curcumin.. Wistar rats, male, were randomly divided by copper-overloaded groups and curcumin treatment groups and control group. Copper-overloaded rat model was established by feeding with forage containing 1 g/kg copper sulfate and water with 0.185% copper sulfate for 8 weeks or 12 weeks. In the treatment groups, curcumin was administered orally either 50 mg/kg or 200 mg/kg for 2 weeks and 4 weeks and 8 weeks and fed with copper sulfate at the same time until the 12th week. Malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) in liver homogenates were measured to reflect the copper induced lipid peroxidation. The apoptosis of liver cell was detected by electron microscope (EM) and TUNEL assay. The expressions of TNF-alpha mRNA and IL-8 mRNA were observed by RT-PCR. Contents of TNF-alpha and IL-8 in liver homogenates were measured by ELISA.. The MDA concentrations were significantly increased and the GSH and SOD levels were decreased in the copper-overloaded rats. The apoptosis index displayed from (2.2 +/- 1.2)% in control rats to (16.7 +/- 2.5)% in the copper treated animals. Expression of TNF-alpha mRNA and IL-8 mRNA were enhanced in the copper-overloaded rats. Curcumin significantly attenuated the increase of MDA concentrations and recovered the GSH and SOD levels. The apoptosis index decreased to (10.4 +/- 1.2)% in the copper-overloaded rats with curcumin treatment. Curcumin down-regulated the expressions of TNF-alpha mRNA and IL-8 mRNA and content of TNF-alpha and IL-8. Histological changes induced by copper in liver, such as mitochondrial swelling and endoplasmic reticulum distention and increased lysosomal granules in the model rats, were also improved significantly by curcumin treatment as evidenced by EM examination.. Copper-overloading caused lipid peroxidatic injury and induced significant apoptosis in liver. TNF-alpha and IL-8 might be involved in liver injury in this model. Curcumin exhibited protective effects and possibly acted through its antioxidant and anti-apoptotic properties.

Topics: Animals; Copper; Curcumin; Glutathione; Interleukin-8; Lipid Peroxidation; Liver Diseases; Male; Malondialdehyde; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Effect of drug praziquantel (PZQ) and C. longa extract on S. mansoni infected mice is reported. The level of glycogen, alkaline and acid phosphatases (ALP and ACP respectively), and body weight, liver weight and liver weight/body weight ratio were studied in mice infected with S. mansoni. ALP level was increased after infection. C. longa treated mice showed marked reduction in ALP level more than after PZQ-treatment. C. longa enhanced the concentration of glycogen after being reduced by infection, while PZQ-treatment revealed more reduction. C. longa caused enhancement in body weight while PZQ treatment had no effect. The formation of granuloma around schistosome eggs in the liver produced inflammation. C. longa extract and PZQ were effective in reducing granuloma size in infected mice.

Topics: Alkaline Phosphatase; Animals; Body Weight; Curcuma; Liver Diseases; Male; Mice; Organ Size; Phytotherapy; Plant Extracts; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni

Tetrahydrocurcumin (THC) is an antioxidative substance, which is derived from curcumin, the component of turmeric. In the present investigation, the effect of THC and curcumin against chloroquine (CQ) induced hepatotoxicity were studied in female Wistar rats.. On single oral administration of CQ (970 mg/kg body weight) the activities of serum marker enzymes namely aspartate transaminase, alanine transaminase and alkaline phosphatase and the levels of bilirubin were significantly increased with significant alterations of lipids in serum and lipidperoxidation markers such as thiobarbituric acid reactive substances (TBARS) and hydroperoxides in plasma and liver were also elevated in CQ treated rats. The levels of non-enzymic antioxidants (vitamin C, vitamin E and reduced glutathione) and enzymic antioxidants (superoxide dismutase, catalase and glutathione peroxidase) were also decreased in CQ treated rats. Administration of THC (80 mg/kg body weight) and curcumin (80 mg/kg body weight) for 8 days before and 7 days after single administration of CQ significantly decreased the activities of serum markers and lipids in serum. In addition, the level of TBARS and hydroperoxides were significantly decreased with significant increase in non-enzymic and enzymic antioxidants on treatment with THC and curcumin. The biochemical observation was supplemented by histopathological examination of liver section. The results of the study reveal that THC shows more pronounced protective effect than curcumin against CQ induced toxicity.

Topics: Animals; Chemical and Drug Induced Liver Injury; Chloroquine; Curcuma; Curcumin; Female; Liver Diseases; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances

To Study the protective effect of curcumin on three models of experimental liver injury in mice.. The experimental models of live injury were induced by carbon tetrachloride (CCl4), D-galactosamine (D-Gal N), and Bacillus Calmette-Guerin (BCG) Plus lipolysaccharides (LPS), respectively, in mice. The serum ALT, AST, NO and liver MDA were measured to evaluate the protective effect of curcumin on experimental injury in mice.. Curcumin (50 mg.kg-1, 100 mg.kg-1, 150 mg.kg-1), like biophenyldicarboxylate, were shown to significantly inhibit the increase of serum ALT, AST, NO and liver molondialdehyde (MDA) content induced by CCl4, D-Gal N, BCG + LPS.. Curcumin showed protective effect against liver injury induced by CCl4, D-Gal N, BCG plus LPS.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Curcumin; Galactosamine; Lipopolysaccharides; Liver; Liver Diseases; Male; Malondialdehyde; Mice; Nitric Oxide; Protective Agents

This study was carried out to investigate the protective effects of curcumin on acute or subacute carbon tetrachloride-induced liver damage in rats. Acute hepatotoxicity was induced by intraperitoneal injection of carbon tetrachloride after 4 consecutive days of curcumin treatment. Subacute hepatotoxicity was induced by oral administration of carbon tetrachloride twice a week during 4 weeks of curcumin treatment. In rats with acute liver injury, curcumin (100 and 200 mg kg(-1)) lowered the activity of serum alanine aminotransferase to 52-53% (P < 0.05) and aspartate aminotransferase to about 62% (P < 0.05) those of control rats. In rats with subacute liver injury, curcumin (100 mg kg(-1)) lowered the activity of serum alanine aminotransferase to 34% (P < 0.01) and alkaline phosphatase to 53% (P < 0.05) of control rats. The liver hydroxyproline content in the curcumin (100 mg kg(-1))-treated group was reduced to 48% of the carbon tetrachloride control group (P < 0.01). Malondialdehyde levels in curcumin (100 mg kg(-1)) treated rat liver was decreased to 67% of the control rat liver (P < 0.01) in subacute injury. It was concluded that curcumin improved both acute and subacute liver injury induced by carbon tetrachloride in rats.

Topics: Alanine Transaminase; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspartate Aminotransferases; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Curcumin; Dose-Response Relationship, Drug; Hydroxyproline; Liver; Liver Diseases; Male; Malondialdehyde; Rats; Rats, Sprague-Dawley

Topics: Bile; Biliary Tract; Curcumin; Humans; Liver Diseases; Pancreas; Pancreatic Juice; Plant Extracts; Plants, Medicinal; Secretory Rate

Topics: Biliary Tract; Biliary Tract Diseases; Curcuma; Humans; Liver Diseases; Plant Extracts