18beta-glycyrrhetinic acid protects against pyrrolizidine alkaloid-induced hepatotoxicity by inhibition of CYPs-mediated metabolic activation
Refereed conference paper presented and published in conference proceedings


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摘要Pyrrolizidine alkaloids (PAs) are phytotoxins present in a variety of herbs and may cause liver damage. PAs are metabolic activated by hepatic cytochrome P450 (CYPs) to generate toxic metabolites, which can form pyrrole-protein adducts leading to hepatotoxicity. Liquorice is commonly used concurrently with PA-containing herbs in the traditional Chinese medicine practice. Until now, no PA-induced hepatotoxicity has been reported with such combinational use. Therefore, we hypothesized that liquorice may prevent and/or reduce the hepatotoxicity of PAs. The present study investigated the protective effect of 18β-glycyrrhetinic acid (GA), the major bioactive constituent of liquorice, against PA-induced hepatotoxicity and delineated the underlying mechanism, using retrorsine (RTS) as a model toxic PA.
Morphological and biochemical assessments demonstrated a hepato-protective effect of GA against RTS-induced liver damage. The pre-treatment, co-treatment and post-treatment of GA all significantly alleviated the RTS-induced elevation of alanine aminotransferase (ALT) and bilirubin level, and prevented the increase of malondialdehyde (MDA) caused by RTS. Furthermore, GA reduced hepatic metabolic activation by inhibiting the activity of rat CYP3A1, which was evidenced by an decrease of pyrrole-protein adducts in rats treated with GA prior to RTS. The in vitro study of GA in rat liver microsomes demonstrated that GA significantly and dose-dependently inhibited the formation of pyrrole-GSH conjugates, confirming the inhibitory effect of GA on metabolic activation of RTS. In addition, a molecular docking prediction model indicated a potential interaction between GA and the catalytic sites of human CYP3A4.
In conclusion, our study demonstrated that GA exhibited a significant protective effect against PA-induced hepatotoxicity. The inhibition of CYPs-mediated metabolic activation of PA might be involved in this protective mechanism
著者ZT WANG, J MA, L ZHU, Y YE, G LIN
會議名稱The 13th international Postgraduate Symposium on Chinese Medicine
會議開始日17.08.2017
會議完結日17.08.2017
會議地點Hong Kong
會議國家/地區香港
出版年份2017
月份8
日期17
語言美式英語

上次更新時間 2018-30-11 於 10:55