Oral intake of curcumin markedly activated CYP 3A4: in vivo and ex-vivo studies

Hsieh, Ying‐Hen; Huang, Chang Jen; Yang, Shih-ying; Peng, Yu‐Hsuan; Yu, Chung-Ping; Chao, Pei‐Dawn Lee; Hou, Yu‐Chi

doi:10.1038/srep06587

Cited by 50 publications

(38 citation statements)

References 35 publications

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“…The serum gliclazide levels obtained in the study were comparable to previous studies in rabbits with similar dose 3,18. Curcumin is reported in vitro to have the ability to induce drug-metabolizing enzyme CYP3A4 in liver microsomes and p-glycoprotein in intestinal cells 33. Similar results are obtained in vivo, where drugs such as celiprolol (p-glycoprotein substrate), midazolam,34 and norfloxacin35 (CYP3A4 substrate) when given in combination with curcumin resulted in increased C max and area under the curve of these drugs as they share a common substrate.…”

Section: Discussionsupporting

confidence: 62%

Influence of curcumin on the pharmacodynamics and pharmacokinetics of gliclazide in animal models

Vatsavai¹,

Kilari²

2016

JEP

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PurposePatients suffering from obesity-related diseases use multiple prescription drugs to control their condition, and it is therefore essential to determine the safety and efficacy of any combination. Gliclazide is one of the most commonly used drug of choice for treatment of type 2 diabetes, and curcumin is a widely used herbal supplement to counter obesity condition. The objective of this study was to investigate the effect of oral administration of curcumin on pharmacodynamics and pharmacokinetics of gliclazide in rats and rabbits to further evaluate the safety and effectiveness of this combination.MethodsInfluence of curcumin on the activity of gliclazide was determined by conducting single- and multiple-dose interaction studies in rats (normal and diabetic) and rabbits. Blood samples collected at predetermined time intervals from experimental animals were used for the estimation of glucose and insulin levels by using automated clinical chemistry analyzer and radioimmunoassay method, respectively. The insulin resistance and β-cell function were determined by homeostasis model assessment. Additionally, serum gliclazide levels in rabbits were analyzed by high-performance liquid chromatography.ResultsGliclazide showed peak reduction in blood glucose levels at 2 and 8 hours in rats and at 3 hours in rabbits. This activity of gliclazide was not altered by single-dose treatment with curcumin. However, in multiple-dose interaction studies, samples analyzed from all time points showed subtle but significantly greater reduction in percent blood glucose ranging from 23.38% to 42.36% in normal rats, 27.63% to 42.27% in diabetic rats, and 16.50% to 37.88% in rabbits. The pharmacokinetics of gliclazide was not altered by single- or multiple-dose curcumin treatments in rabbits.ConclusionThe interaction of curcumin with gliclazide up on multiple-dose treatment was pharmacodynamic in nature, indicating the need for periodic monitoring of glucose levels and dose adjustment as necessary when this combination is prescribed to obese patients.

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Section: Discussionsupporting

confidence: 62%

Influence of curcumin on the pharmacodynamics and pharmacokinetics of gliclazide in animal models

Vatsavai¹,

Kilari²

2016

JEP

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“…In this study, we investigated the co-treatment of MCF-7 resistant breast cancer cells with Dox and the chemosensitizer curcumin (Cur). Cur is a natural compound that inhibits the MDR protein family-member P-glycoprotein (P-gp) and blocks the transport of anti-cancer drugs out of cancer cells (Hsieh et al 2014;Neerati et al 2013;Peng et al 2018;Sahu et al 2016;Umsumarng et al 2015;Vinod et al 2013;Wang et al 2016;Zhang et al 2016). Both the drugs were encapsulated into ANPs and co-administered to cells both sequentially and simultaneously.…”

Section: Introductionmentioning

confidence: 99%

Co-encapsulation of curcumin and doxorubicin in albumin nanoparticles blocks the adaptive treatment tolerance of cancer cells

et al. 2019

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The adaptive treatment tolerance (ATT) of cancer cells is the main encumbrance to cancer chemotherapy. A potential solution to this problem is to treat cancer cells with multiple drugs using nanoparticles (NPs).In this study, we tested the co-administration of curcumin (Cur) and doxorubicin (Dox) to MCF-7 resistant breast cancer cells to block the ATTand elicit efficient cell killing. Drugs were co-administered to cells both sequentially and simultaneously. Sequential drug co-administration was carried out by pre-treating the cells with albumin nanoparticles (ANPs) loaded with Cur (Cur@ANPs) followed by treatment with Dox-loaded ANPs (Dox@ANPs). Simultaneous drug co-administration was carried out by treating the cells with ANPs loaded with both the drugs (Cur/Dox@ANPs). We found that the simultaneous drug co-administration led to a greater intra-cellular accumulation of Dox and cell killing with respect to the sequential drug co-administration. However, the simultaneous drug co-administration led to a lower intracellular accumulation of Cur with respect to the sequential drug co-administration. We showed that this result was due to the aggregation and entrapment of Cur in the lysosomes as soon as it was released from Cur@ANPs, a phenomenon called lysosomotropism. In contrast, the simultaneous release of Dox and Cur from Cur/Dox@ANPs into the lysosomes led to lysosomal pH elevation, which, in turn, avoided Cur aggregation, led to lysosome swelling and drug release in the cytosol, and finally provoked efficient cell killing. Our study shed the light on the molecular processes driving the therapeutic effects of anti-cancer drugs co-administered to cancer cells in different manners. Biophysics ReportsRESULTS AND DISCUSSION Preparation and characterization of albumin nanoparticles loaded with Cur and/or Dox Bovine serum albumin (BSA) nanoparticles (ANPs) loaded with Cur (Cur@ANPs), Dox (Dox@ANPs), or both RESEARCH ARTICLE S. M. Motevalli et al.

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“…Notably, as different CYP450 isozymes catalyze AFB 1 to various metabolites, including the highly toxic AFBO and the less- or non-toxic aflatoxicol, AFM 1 , AFP 1 , and AFQ 1 , examination of the regulation of the proportions of CYP450 isozymes by CM would be valuable [10,23]. Previous studies have described that CM can alter various CYP450 isozymes in vivo and in vitro [24,25,26,27]. Moreover, CM inhibition of AFB 1 toxicity has been reported by modulating CYP450 function [14], while the knowledge of which crucial CYP450 isozymes are involved in this process remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Curcumin Prevents Aflatoxin B1 Hepatoxicity by Inhibition of Cytochrome P450 Isozymes in Chick Liver

Zhang

Zhao

et al. 2016

Toxins

113

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This study was designed to establish if Curcumin (CM) alleviates Aflatoxin B1 (AFB1)-induced hepatotoxic effects and to determine whether alteration of the expression of cytochrome P450 (CYP450) isozymes is involved in the regulation of these effects in chick liver. One-day-old male broilers (n = 120) were divided into four groups and used in a two by two factorial trial in which the main factors included supplementing AFB1 (< 5 vs. 100 μg/kg) and CM (0 vs. 150 mg/kg) in a corn/soybean-based diet. Administration of AFB1 induced liver injury, significantly decreasing albumin and total protein concentrations and increasing alanine aminotransferase and aspartate aminotransferase activities in serum, and induced hepatic histological lesions at week 2. AFB1 also significantly decreased hepatic glutathione peroxidase, catalase, and glutathione levels, while increasing malondialdehyde, 8-hydroxydeoxyguanosine, and exo-AFB1-8,9-epoxide (AFBO)-DNA concentrations. In addition, the mRNA and/or activity of enzymes responsible for the bioactivation of AFB1 into AFBO—including CYP1A1, CYP1A2, CYP2A6, and CYP3A4—were significantly induced in liver microsomes after 2-week exposure to AFB1. These alterations induced by AFB1 were prevented by CM supplementation. Conclusively, dietary CM protected chicks from AFB1-induced liver injury, potentially through the synergistic actions of increased antioxidant capacities and inhibition of the pivotal CYP450 isozyme-mediated activation of AFB1 to toxic AFBO.

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Oral intake of curcumin markedly activated CYP 3A4: in vivo and ex-vivo studies

Cited by 50 publications

References 35 publications

Influence of curcumin on the pharmacodynamics and pharmacokinetics of gliclazide in animal models

Influence of curcumin on the pharmacodynamics and pharmacokinetics of gliclazide in animal models

Co-encapsulation of curcumin and doxorubicin in albumin nanoparticles blocks the adaptive treatment tolerance of cancer cells

Curcumin Prevents Aflatoxin B1 Hepatoxicity by Inhibition of Cytochrome P450 Isozymes in Chick Liver

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