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 Liu Mubo,Gao Jianmei,Shi Jingshan,et al.Effects of icariside II on hepatic cytochrome P450 expression in mice[J].Journal of Zunyi Medical University,2019,42(05):481-487.





Effects of icariside II on hepatic cytochrome P450 expression in mice
(1.遵义医科大学 基础药理教育部重点实验室暨特色民族药教育部国际合作联合实验室,贵州 遵义 563099; 2.遵义医科大学 药学院,贵州 遵义 563099; 3.遵义医科大学附属医院 神经内科,贵州 遵义 563099)
Liu Mubo12Gao Jianmei12Shi Jingshan1Yu Changyin3Gong Qihai1
(1.Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education,Zunyi Medical University,Zunyi Guizhou 563099,China; 2.Department of Clinical Pharmacotherapeutics,School of Pharmacy,Zunyi Medical University,Zunyi Guizhou 563099,China; 3.Department of Neurology,Affiliated Hospital of Zunyi Medical University,Zunyi Guizhou 563099,China)
淫羊藿次苷II 细胞色素P450 黄酮 肝脏毒性
icariside II CYP450 flavonoids liver toxicity
目的 探究淫羊藿次苷II(ICS II)对小鼠细胞色素P450(CYP450)总酶及其主要亚型的影响。方法 雄性C57BL/6小鼠随机分为6组:空白对照组(Normal saline,NS)、ICS II(5、10、 20 mg/kg组)、地塞米松(Dexamethasone,DEX)80 mg/kg和红霉素(Erythromycin,ERY)200 mg/kg组(n=12)。连续灌胃给药14 d,每天1次,空白对照组给予同等体积的生理盐水。同种方式给予DEX和ERY选择性诱导和抑制小鼠CYP3A11作为对照。采用酶联免疫试剂盒(Elisa kit)检测CYP450总酶的变化情况,血清生化指标(ALT、AST)与HE染色观察ICS II对小鼠的肝脏毒性。蛋白免疫印迹(WB)检测CYP450主要亚型的表达情况。结果 ICS II显著抑制CYP450总酶; WB结果显示ICS II显著抑制CYP3A11和诱导CYP1A2亚型的表达; ALT、AST与HE结果显示ICS II无明显肝脏毒性。结论 本研究表明ICS II可降低小鼠肝脏微粒体CYP450总酶含量,并抑制其亚型CYP3A11和诱导CYP1A2的表达。
ObjectiveTo investigate the effects of icariside II(ICS II)on the contents of hepatic cytochrome P450(CYP450)enzymes and its major isoforms expressions in mice.Methods Male C57BL/6 mice were randomly divided into six groups:normal saline(NS),ICS II(5,10 and 20 mg/kg)groups,dexamethasone(DEX,80 mg/kg)and erythromycin(ERY,200 mg/kg)groups(n=12).Mice were treated with different doses of ICS II by gavage daily for 14 days,and the NS group was administered with volume-matched saline.To induce and inhibit selectively certain CYP3A11,mice were oral gavage with either DEX and ERY,respectively.The contents of CYP450 enzymes in liver were detected by Elisa kits.Liver injury were evaluated by analyzing the histopathological changes and the level of serum biochemical parameters was detected by hematoxylin and eosin staining and Elisa kits.Western blot assay was used to analyze the expression of major CYP450 isoforms.Results ICS II decreased the content of liver CYP450 enzymes.Furthermore,ICS II decreased CYP3A11 and induced CYP1A2 protein expression.No obvious changes in serum and liver tissue biochemical parameters were found and no significant pathological changes were observed in liver tissues after ICS II treatment.Conclusion The present study indicates that ICS II could decrease the content of liver CYP450 enzymes and decrease the expression of CYP3A11 and increase the expression of CYP1A2.


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[基金项目]贵州省科技创新人才团队资助项目(NO:20154023); 贵州省百级高层次创新人才项目(NO:QKHRCPT 20165684); 石京山药理学导师工作室(NO:GZS-201607); 中国高校长江学者与创新研究团队项目(NO:IRT_17R113); 遵义医科大学优秀青年人才项目(NO:15zy-002)。 [通信作者]龚其海,男,博士,教授,博士生导师,研究方向:神经药理学,E-mail:gqh@zmu.edu.com。
更新日期/Last Update: 2019-10-25