Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study

Wu, Xiaochun; Li, Qing; Xin, Hua‐Wen; Ai-rong, YU; Mingyuan, Zhong

doi:10.1007/s00228-005-0952-3

Cited by 78 publications

(53 citation statements)

References 20 publications

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“…Considerable overlap in the substrate selectivity, tissue localization, and coinducibility of CYP3A4 and P-gp underscores the importance of assessing the effects of goldenseal and kava kava on human P-gp activity in vivo. The appropriateness of such an investigation was heightened by a recent report citing markedly elevated blood concentrations of cyclosporine (a CYP3A4 and P-gp substrate) in renal transplant recipients after berberine administration (Wu et al, 2005). In light of our current findings, it would appear that goldenseal's mechanism for producing herb-drug interactions lies more with its ability to inhibit P450 isoforms than its effect on P-gp.…”

Section: Discussionmentioning

confidence: 71%

Effect of Goldenseal (Hydrastis canadensis) and Kava Kava (Piper methysticum) Supplementation on Digoxin Pharmacokinetics in Humans

et al. 2006

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ABSTRACT:Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may give rise to many herb-drug interactions. Serial plasma concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo. Twenty healthy volunteers were randomly assigned to receive a standardized goldenseal (3210 mg daily) or kava kava (1227 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin, 0.5 mg) was administered p.o. before and at the end of each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC) (0-3) , AUC (0-24) , C max, CL/F, and elimination half-life were used to assess the effects of goldenseal, kava kava, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p < 0.01) in AUC (0-3) , AUC (0-24) , CL/F, t 1/2 , and C max , whereas clarithromycin increased these parameters significantly (p < 0.01). With the exception of goldenseal's effect on C max (14% increase), no statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava. When compared with rifampin and clarithromycin, supplementation with these specific formulations of goldenseal or kava kava did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo.

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Section: Discussionmentioning

confidence: 71%

Effect of Goldenseal (Hydrastis canadensis) and Kava Kava (Piper methysticum) Supplementation on Digoxin Pharmacokinetics in Humans

et al. 2006

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“…In human liver microsomes, berberine inhibits CYP2D6 and CYP3A4 activities, in mice, berberine inhibits CYP3A11 and CYP3A25 expression while induces CYP1A2 expression (Guo et al, 2011a;Guo et al, 2011b). In renaltransplant recipients, berberine was reported to markedly elevate the blood concentration of cyclosporine A, a drug metabolized by CYP3A4 (Wu et al, 2005). Prior to our work, little has been reported about the effects of berberine on estrogen-metabolizing enzymes CYP1A1 and CYP1B1 in human breast cells.…”

Section: Introductionmentioning

confidence: 82%

Preferential Induction of CYP1A1 over CYP1B1 in Human Breast Cancer MCF-7 Cells after Exposure to Berberine

Wen

Wu²,

Fu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Estrogens are considered the major breast cancer risk factor, and the carcinogenic potential of estrogens might be attributed to DNA modification caused by derivatives formed during metabolism. 17β-estradiol (E 2 ), the main steroidal estrogen present in women, is metabolized via two major pathways: formation of 2-hydroxyestradiol (2-OH E 2 ) and 4-hydroxyestradiol (4-OH E 2 ) through the action of cytochrome P450 (CYP) 1A1 and 1B1, respectively. Previous reports suggested that 2-OH E 2 has putative protective effects, while 4-OH E 2 is genotoxic and has potent carcinogenic activity. Thus, the ratio of 2-OH E 2 /4-OH E 2 is a critical determinant of the toxicity of E 2 in mammary cells. In the present study, we investigated the effects of berberine on the expression profile of the estrogen metabolizing enzymes CYP1A1 and CYP1B1 in breast cancer MCF-7 cells. Berberine treatment produced significant induction of both forms at the level of mRNA expression, but with increased doses produced 16~ to 52~fold greater induction of CYP1A1 mRNA over CYP1B1 mRNA. Furthermore, berberine dramatically increased CYP1A1 protein levels but did not influence CYP1B1 protein levels in MCF-7 cells. In conclusion, we present the first report to show that berberine may provide protection against breast cancer by altering the ratio of CYP1A1/CYP1B1, could redirect E 2 metabolism in a more protective pathway in breast cancer MCF-7 cells.

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“…37 In contrast to this observation, a report on concurrent use of berberine with cyclosporine A in renal transplant patient showed significant increase in Area Under the Curve (AUC) (by 34.50%), t max (by 1.7 hours), t 1/2 (by 2.7 hours) and decrease of apparent oral clearance (by 40.40%). 38 The suggested speculative mechanism of these interactions could be attributed to decreased liver or intestinal metabolism through CYP3A4 inhibition leading to increase in cyclosporine A bioavailability. These observations advocate the need for more reliable screening tools to predict metabolic clinical herb-drug interactions during disease conditions.…”

Section: Discussionmentioning

confidence: 99%

Effect of Botanical Immunomodulators on Human CYP3A4 Inhibition

et al. 2013

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Purpose. Many botanical immunomodulators are used as adjuvants along with cancer chemotherapy. However, information on the impact of concurrent administration of such botanicals on pharmacokinetics of chemotherapy agents is inadequate. This study investigates inhibitory activities of 3 popular botanical adjuvants: Asparagus racemosus (root aqueous extract; ARE), Withania somnifera (root aqueous extract; WSE), and Tinospora cordifolia (stem aqueous extract, TCE) on human CYP3A4 isoenzyme, responsible for metabolism of several chemotherapy agents. Experimental design. Testosterone 6-β hydroxylation was monitored using high-performance liquid chromatography as an indicator of CYP3A4 catalytic activities. Ketoconazole (positive control) and extracts were studied at their in vivo-relevant concentrations. Results. TCE showed mild inhibition while no significant inhibitory activities were observed in WSE and ARE. TCE was further fractionated to obtain polar and nonpolar fractions. The nonpolar fraction showed significant CYP3A4 inhibition with IC 50 13.06 ± 1.38 µg/mL. Major constituents of nonpolar fraction were identified using HPLC-DAD-MS profiling as berberine, jatrorrhizine, and palmatine, which showed IC 50 values as 6.25 ± 0.30, 15.18 ± 1.59, and 15.53 ± 1.89 µg/mL, respectively. Conclusion. Our findings suggest that constituents of TCE extract especially protoberberine alkaloids have the potential to interact with cancer chemotherapy agents that are metabolized by CYP3A4 in vivo.

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Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study

Cited by 78 publications

References 20 publications

Effect of Goldenseal (Hydrastis canadensis) and Kava Kava (Piper methysticum) Supplementation on Digoxin Pharmacokinetics in Humans

Effect of Goldenseal (Hydrastis canadensis) and Kava Kava (Piper methysticum) Supplementation on Digoxin Pharmacokinetics in Humans

Preferential Induction of CYP1A1 over CYP1B1 in Human Breast Cancer MCF-7 Cells after Exposure to Berberine

Effect of Botanical Immunomodulators on Human CYP3A4 Inhibition

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