基于体外实验技术评价芫花素肝毒性风险

Evaluation of Genkwanin Hepatotoxicity Risk Based on in Vitro Experimental Techniques

目的:考察芫花素对UGT1A1酶活性的影响,为阐明其肝毒性作用机制提供依据。方法:采用计算机分子对接技术考察芫花素与UGT1A1酶的结合方式及亲和作用强弱;采用体外人肝微粒体抑制实验评价芫花素对人源UGT1A1酶抑制作用强弱。结果:分子对接显示芫花素对接进入UGT1A1酶蛋白F活性区,亲和作用较强,体外抑制实验提示芫花素对UGT1A1酶具有较强抑制作用,抑制类型为竞争型抑制,与分子对接结果一致。结论:芫花素可与胆红素竞争性结合UGT1A1酶,抑制酶活性,具有潜在肝毒性风险。

Objective:To investigate the inhibition of genkwanin on UGT1A1 activities of human liver microsomes,and predict the toxicity mechanism of genkwanin. Methods:The binding mode and affinity of genkwanin to UGT1A1 enzyme was studied by using computer molecular docking technology.The inhibitory effect of genkwanin on human UGT1A1 enzyme was evaluated by using in vitro human liver microsome inhibition test. Results:Molecular docking showed that genkwanin docked into the active region F of UGT1A1 enzyme protein,and the affinity was strong.The inhibition experiments indicated that genkwanin had strong inhibitory effect on UGT1A1 enzyme,and the inhibition type was competitive,which was consistent with molecular docking results. Conclusion:Genkwanin can compete with bilirubin for UGT1A1 enzyme in order to inhibit enzyme activity,so it prompted genkwanin has potential hepatotoxicity and it should be pay a close attention.