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A hepatoprotection study of Radix Bupleuri on acetaminophen-induced liver injury based on CYP450 inhibition

查看全文 作  者:WANG Yu-[1,3]Xin;DU [2]Yi;LIU Xia-[2]Fei;YANG Fang-[2]Xiu;WU [2]Xiao;TAN [3]Li;LU Yi-[2,3]Hong;ZHANG Jing-[1]Wei;ZHOU [1]Fang;WANG Guang-[1]Ji 高影响力作者 机构地区:[1]Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China;[2]Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China;[3]Jiangsu Institute for Food and Drug Control, Nanjing 210019, China高影响力机构 出  处:《Chinese Journal of Natural Medicines》索引2019年第17卷第7期,共8页高影响力期刊 基  金:supported by State Project for Essential Drug Research and Development of China(No.20152X09303001) 摘  要:We investigated the potential hepatoprotective effect of Radix Bupleuri(RB) by inducing acute liver injury(ALI) in an animal model using acetaminophen(APAP) after pretreatment with RB aqueous extract for three consecutive days. Compared to those of the APAP group, the biochemical and histological results of the RB pretreatment group showed lower serum aspartate transaminase(AST) and alanine transaminase(ALT) levels as well as less liver damage. Pharmacokinetic study of the toxicity related marker acetaminophen-cysteine(APC) revealed a lower exposure level in rats, suggesting that RB alleviated APAP-induced liver damage by preventing glutathione(GSH) depletion. The results of cocktail approach showed significant inhibition of CYP2 E1 and CYP3 A activity. Further investigation revealed the increasing of CYP2 E1 and CYP3 A protein was significantly inhibited in pretreatment group,while no obvious effect on gene expression was found. Therefore, this study clearly demonstrates that RB exhibited significant protective action against APAP-induced acute live injury via pretreatment, and which is partly through inhibiting the increase of activity and translation of cytochrome P450 enzymes, rather than gene transcription. 关 键 词:HEPATOPROTECTION RADIX Bupleuri ACETAMINOPHEN Acute liver injury CYTOCHROME P450 enzymes
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