Glycyrrhizin accelerates the metabolism of triptolide through induction of CYP3A in rats

Tai, Ting; Huang, Xin; Y, Su; Ji, Jin-Zi; Su, Yijing; Jiang, Zhenzhou; Zhang, Luyong

doi:10.1016/j.jep.2014.01.026

Cited by 52 publications

(29 citation statements)

References 34 publications

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“…When CsA was co-administered with a single dose of 150 mg/kg GZ to rats, the C max and AUC 0-t of CsA decreased by 49.0 and 45.6%, respectively (Hou et al, 2012). Also, the AUC, MRT and t 1/2 of triptolide were significantly altered by GZ pretreatment (Tai et al, 2014). All together, these findings indicate that treatment with GZ results in an induction of CYP3A in vivo.…”

Section: Interactions Of Gz and Ga With Cyp450smentioning

confidence: 74%

“…For example, a clinical trial performed by Tu et al showed that oral administration of 150 mg twice daily of monopotassium glycyrrhizinate tablets for 14 days resulted in a 20 and 12% decrease in the AUC 0-1 and C max , respectively, of a probe for CYP3A called midazolam (Tu et al, 2010a). Similar experiments found that pretreatment of rats with GZ notably increased the AUC of 1'-hydroxymidazolam and the ratio of AUC of 1'hydroxymidazolam to midazolam (Tai et al, 2014). Together, these two studies demonstrate that the hydroxylation of midazolam catalyzed by CYP3A is induced by treatment with GZ.…”

Section: Interactions Of Gz and Ga With Cyp450smentioning

confidence: 95%

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Potential drug interactions associated with glycyrrhizin and glycyrrhetinic acid

Feng

Ding

Qiu

2015

Drug Metabolism Reviews

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Glycyrrhizin (GZ), the main active component of licorice, is a widely used therapeutic in the clinic. Depending on the disease, the treatment may involve a long course of high dose GZ. Another component of licorice, glycyrrhetinic acid (GA), is the main active metabolite of GZ and is thought to be responsible for the majority of the pharmacological properties of GZ. Therefore, GZ and GA are both used for therapeutic purposes. In addition, GZ and GA are also widely used to sweeten and flavor foods. Due to this widespread, multifaceted use of these substances, potential drug interactions with GZ and GA have recently gained attention. Along these lines, this review covers the known effects of GZ and GA on drug-metabolizing enzymes and efflux transporters. We conclude that both GZ and GA may have an effect on the activity of CYPs. For example, GZ may induce CYP3A activity through activation of PXR. Also, GZ and GA may affect glucuronidation in rats and humans. Furthermore, 18β-GA is a potent inhibitor of P-gp, while GZ and GA are inhibitors of MRP1, MRP2 and BCRP. The pharmacokinetics and pharmacodynamics of many medications may be altered when used concurrently with GZ or GA, which is also covered in this review. Overall, GZ, GA or related products should be taken with caution when taken with additional medications due to the possible drug interactions.

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Section: Interactions Of Gz and Ga With Cyp450smentioning

confidence: 74%

Section: Interactions Of Gz and Ga With Cyp450smentioning

confidence: 95%

Potential drug interactions associated with glycyrrhizin and glycyrrhetinic acid

Feng

Ding

Qiu

2015

Drug Metabolism Reviews

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“…Another reason our fertility control bait has low risk is that the active ingredients have blood half-lives of less than 15 minutes. Each active ingredient is inactivated by liver enzymes: VCD by microsomal epoxide hydrolase (Flaws et al 1994) and T by P450 CYP3A (Tai et al 2014). Over 90% of the inactive metabolites from each active ingredient are excreted in urine and there is less than 1% of each active ingredient excreted in the urine.…”

Section: Discussionmentioning

confidence: 99%

Sprague Dawley Female Rat Consumption of a Liquid Bait Containing Vinylcyclohexene Diepoxide and Triptolide Leads to Subfertility

Dyer¹,

Mayer²

2014

vertebrate_pest_conference

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Worldwide, Norway rats cause significant infrastructure damage, agricultural losses, and carry zoonotic diseases.Due to rat fecundity, killing them by mechanical and/or poison does not lead to sustainable management of their populations. Our biotechnology company, SenesTech, Inc, has developed an environmentally safe oral bait taken by rats, causing them to produce fewer rat pups and take longer to deliver, without any observable adverse effects. The fertility control bait is an emulsion and contains two chemicals that cause ovarian follicle elimination; vinylcyclohexene diepoxide (VCD) targets the finite pool of primordial/primary follicles, and triptolide (T) targets growing follicles. Female Sprague Dawley rats were 33 days old when provided bait with 0.1% VCD and increasing amounts of T with unlimited chow and water for 15 days (n = 8 rats per group). The rats consumed >5% of their body weight of bait and thrived during their rapid growth phase. The day after the end of baiting, female rats were bred with untreated, proven male breeders for 21 days, then litter size and time to delivery was tracked over the next 25 days. The control group that consumed bait without active ingredients had an average litter size of 11.5 pups, treatment groups that consumed bait with T at 400, 800, or 1200 μg/kg body weight had average litter sizes respectively of 9.6, 8.3, and 3.6, and pup production per treatment group compared to control group was 83.5%, 72.2%, and 29.6% respectively with increasing T doses. Time to delivery increased significantly as T dose increased: control rats took 26.0 days versus 31.5, 38.9, and 38.2 days to delivery. We conclude our fertility control bait is a palatable liquid readily consumed by growing female rats that causes subfertility, with significantly fewer pups/litter taking 1.5 times longer to deliver. Fertility control bait effects on rat population dynamics are currently being tested in field locations. Proc. 26 th Vertebr. Pest Conf. (R. M. Timm and J. M. O'Brien, Eds.) Published at Univ. of Calif., Davis. 2014. Pp. 386-390.

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“…Recently, GLY has been reported to inhibit the metabolism of CYP2C9, 2C19, and 3A4 substrates in human liver microsomes (HLM) (Zhao et al , ). Moreover, chronic repeated glycyrrhizin doses caused a moderate induction of CYP3A activity in rats and human (Tai et al , ; Tu et al , ). However, there are few studies on the CYP inhibition mechanism and in vivo pharmacokinetic consequences of a single GLY dose in rats.…”

Section: Introductionmentioning

confidence: 99%

Modulation of Cytochrome P450 Activity by 18β‐Glycyrrhetic Acid and its Consequence on Buspirone Pharmacokinetics in Rats

Kim

Cho

Kim

et al. 2015

Phytotherapy Research

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The aim of this study was to elucidate the inhibition mechanism of 18β-glycyrrhetic acid (GLY) on cytochrome P450 (CYP) activity and in vivo pharmacokinetic consequences of single GLY dose in rats. An in vitro CYP inhibition study in rat liver microsomes (RLM) was conducted using probe substrates for CYPs. Then, an in vivo pharmacokinetics of intravenous and oral buspirone (BUS), a probe substrate for CYP3A, was studied with the concurrent administration of oral GLY in rats. In the in vitro CYP inhibition study, CYP3A was involved in the metabolism of GLY. Moreover, GLY inhibited CYP3A activity with an IC50 of 20.1 ± 10.7 μM via a mixed inhibition mechanism. In the in vivo rat pharmacokinetic study, single oral GLY dose enhanced the area under plasma concentration-time curve (AUC) of intravenous and oral BUS, but the extent of increase in AUC was only minimal (1.12-1.45 fold). These results indicate that GLY can inhibit the in vitro CYP3A-mediated drug metabolism in RLM via a mixed inhibition mechanism. However, the impact of single oral GLY dose on the pharmacokinetics of BUS in rats was limited, showing that GLY could function as merely a weak inhibitor for CYP3A-mediated drug metabolism in vivo. Copyright © 2015 John Wiley & Sons, Ltd.

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Glycyrrhizin accelerates the metabolism of triptolide through induction of CYP3A in rats

Cited by 52 publications

References 34 publications

Potential drug interactions associated with glycyrrhizin and glycyrrhetinic acid

Potential drug interactions associated with glycyrrhizin and glycyrrhetinic acid

Sprague Dawley Female Rat Consumption of a Liquid Bait Containing Vinylcyclohexene Diepoxide and Triptolide Leads to Subfertility

Modulation of Cytochrome P450 Activity by 18β‐Glycyrrhetic Acid and its Consequence on Buspirone Pharmacokinetics in Rats

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