piperine and gingerol

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

Pungent spice constituents such as piperine, capsaicin and [6]-gingerol consumed via daily diet or traditional Chinese medicine, have been reported to possess various pharmacological activities. These dietary phytochemicals have also been reported to inhibit P-glycoprotein (P-gp) in vitro and act as an alternative to synthetic P-gp modulators. However, the in vivo effects on P-gp inhibition are currently unknown. This study aimed to test the hypothesis that phytochemical P-gp inhibitors, i.e., piperine, capsaicin and [6]-gingerol, modulate the in vivo tissue distribution of doxorubicin, a representative P-gp substrate. Mice were divided into four groups and each group was pretreated with intraperitoneal injections of control vehicle, piperine, capsaicin, or [6]-gingerol and doxorubicin (1 mg/kg) was administered via the penile vein. The concentrations of the phytochemicals and doxorubicin in the plasma and tissues were determined by LC-MS/MS. The overall plasma concentration-time profiles of doxorubicin were not significantly affected by piperine, capsaicin, or [6]-gingerol. In contrast, doxorubicin accumulation was observed in tissues pretreated with piperine or capsaicin. The tissue to plasma partition coefficients, K

Topics: Alkaloids; Animals; Antibiotics, Antineoplastic; ATP Binding Cassette Transporter, Subfamily B, Member 1; Benzodioxoles; Biological Transport; Capsaicin; Catechols; Doxorubicin; Fatty Alcohols; Mice; Phytochemicals; Piperidines; Polyunsaturated Alkamides; Tissue Distribution

Benjakul, a Thai traditional herbal preparation, comnprises five plants: Piper chaba, Piper sarmentosum, Piper interruptum, Plumbago indica, and Zingiber officinale. It has widely been used to treat cancer patients in folk medicine in Thailand. Benjakul extract, and its isolated compounds should be investigated for cytotoxic activity and analysis isolated compounds from chemical fingerprinting.. To study cytotoxicity ofBenjakul extract and its isolatedpure compounds against human small cell lung cancer cell line (NCI-HI 688) and in normal human lungfibroblast cell line (MRC-5) and analysis the content ofisolated compounds for quality control of Benjakul extract.. Bioassay-guided fractionation was used for isolated active compounds from ethanolic extract of Benjakul. Cytotoxic activity was carried using the SRB assay. HPLC method was applied to analyze six isolated compound contentfrom Benjakul extract.. The ethanolic extract ofBenjakul showed cytotoxicity against NCI-H1688 with IC50 value = 36.15±4.35 μg/ml. Hexane fraction as semi-separation by VLC showed the best cytotoxic activity (21.1 7±7.42 μg/ml). Six isolated compounds were identified as myristicin, plumbagin, methyl piperate, 6-shogaol, 6-gingerol and piperine. Plumbagin exhibited the highest cytotoxic activity and 6-shogaol was the second most effective cytotoxic constituent (IC50 values = 1.41±0.01 and 6.45±0.19 μg/ml, respectively). Piperine showed the highest content in both ofHPLC analysis and column chromatography separation.. Benjakul extract exhibited cytotoxicity against NCI-HI 688. Plumbagin and 6-shogaol are bioactive markers for cytotoxicity against this small cell lung cancer cell line. Chromatographic fingerprinting can be used to analyze six cytotoxic compounds isolatedfrom the ethanolic extract ofBenjakul.

Topics: Alkaloids; Benzodioxoles; Catechols; Cell Line, Tumor; Chromatography, High Pressure Liquid; Drug Screening Assays, Antitumor; Ethanol; Fatty Alcohols; Humans; Lung Neoplasms; Medicine, Traditional; Naphthoquinones; Piper; Piperidines; Plant Extracts; Plumbaginaceae; Polyunsaturated Alkamides; Small Cell Lung Carcinoma; Thailand; Zingiber officinale

Benjakul [BEN], a Thai Traditional medicine preparation, is composed of five plants: Piper chaba fruit [PC], Piper sarmentosum root [PS], Piper interruptum stem [PI], Plumbago indica root [PL] and Zingiber officinale rhizome [ZO]. From selective interviews of folk doctors in Southern Thailand, it was found that Benjakul has been used for cancer patients.. To investigate cytotoxicity activity of Benjakul preparation [BEN] and its ingredients against three human cancer cell lines, large lung carcinoma cell line (COR-L23), cervical cancer cell line (Hela) liver cancer cell line (HepG2) as compared with normal lungfibroblast cell (MRC-5) by using SRB assay.. The extraction as imitated the method used by folk doctors was done by maceration in ethanol and boiling in water Bioassay guided isolation was used isolated cytotoxic compound.. The ethanolic extracts of PL, ZO, PC, PS, BEN and PS showed specific activity against lung cancer cell (IC50 = 3.4, 7.9, 15.8, 18.4, 19.8 and 32.91 microg/ml) but all the water extracts had no cytotoxic activity. Three active ingredients [6-gingerol, plumbagin and piperine as 0.54, 4.18 and 7.48% w/w yield of crude extract respectively] were isolated from the ethanolic extract of BEN and they also showed cytotoxic activity with plumbagin showing the highest cytotoxic activity against COR-L23, HepG2, Hela and MRC-5 (IC50 = 2.55, 2.61, 4.16 and 11.54 microM respectively).. These data results may support the Thai traditional doctors who are using Benjakul to treat cancer patients and three of its constituents (6-gingerol, plumbagin and piperine) are suggested to be used as biomarkers for standardization of this preparation.

Topics: Alkaloids; Benzodioxoles; Catechols; Cell Line, Tumor; Fatty Alcohols; Female; Humans; Liver Neoplasms; Lung Neoplasms; Medicine, East Asian Traditional; Naphthoquinones; Phytotherapy; Piper; Piperidines; Plant Extracts; Plants, Medicinal; Plumbaginaceae; Polyunsaturated Alkamides; Thailand; Uterine Cervical Neoplasms; Zingiber officinale