基于网络药理学研究兖州卷柏对酒精性肝病小鼠的保护作用

The study of the protective effect of Selaginella involven against alcoholic liver disease in mice based on network pharmacology

目的利用网络药理学和动物实验研究兖州卷柏治疗酒精性肝病(alcoholic liver disease,ALD)的分子机制。方法2022年2-10月通过查阅文献和中药系统药理学数据库与分析平台(TCMSP)预测兖州卷柏有效成分及作用靶点,并通过靶点富集分析和分子对接预测兖州卷柏治疗ALD的作用机制。构建急性ALD小鼠模型,验证网络药理学预测结果。结果网络靶点分析结果显示,从兖州卷柏中共筛选出治疗ALD的有效成分20个,其中黄酮类化合物是治疗ALD的关键化合物。从兖州卷柏治疗ALD的65个靶点中筛选出6个核心靶点,核心靶点中除血管内皮生长因子A(VEGFA)外,均富集在白细胞介素-17(IL-17)信号通路。分子对接结果显示,黄酮类关键化合物与核心靶点均具有较好的结合活性。动物实验结果显示,模型组小鼠血清天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)活性[(240.16±15.77)U/L,(168.01±8.26)U/L]显著高于正常组[(112.43±6.88)U/L,(85.02±5.77)U/L],差异有统计学意义(P<0.05)。与模型组比较,低、中、高浓度兖州卷柏总黄酮AST[(201.39±9.63)U/L,(165.86±12.00)U/L,(151.72±9.07)U/L]和ALT[(147.51±6.61)U/L,(133.09±5.88)U/L,(111.52±8.00)U/L]活性均显著下降(P<0.05)。此外,兖州卷柏总黄酮能改善酒精引起的肝组织损伤,抑制IL-17信号通路关键基因mRNA表达。结论黄酮类化合物是兖州卷柏治疗ALD的主要成分,可通过多靶点、多途径实现治疗ALD的作用,其治疗机制可能与抑制IL-17信号通路有关。

Objective To explore the mechanism of Selaginella involven in the treatment of alcoholic liver disease(ALD)based on network pharmacology and animal experiment.Methods From February to October 2022,the active compounds and relative targets of Selaginella involven were predicted through literature review and Traditional Chinese Medicine Systems Pharmacology(TCMSP)database,and the mechanism of Selaginella involven against ALD was analyzed by targets enrichment analysis and molecular docking.The network predictions were validated by establishing acute alcoholic liver injury mice model.Results Based on the prediction results,20 chemical compounds in the treatment of ALD were identified from Selaginella involven,and flavonoids compounds were the main compounds in the treatment of ALD.Six core targets were screened from 65 ALD-related targets of Selaginella involven,and the core targets were enriched in interleukin 17(IL-17)signaling pathway except vascular endothelial growth factor A(VEGFA).Molecular docking indicated that the main flavonoids compounds from Selaginella involven showed good binding properties with the core targets.The results of animal experiments showed that the activities of serum aspartate aminotransferase(AST)and alanine aminotransferase(ALT)in the model group mice[(240.16±15.77)U/L,(168.01±8.26)U/L]were significantly elevated compared to those in the normal group[(112.43±6.88)U/L,(85.02±5.77)U/L],respectively(P<0.05).In comparison to the model group,the activities of AST[(201.39±9.63)U/L,(165.86±12.00)U/L,(151.72±9.07)U/L]and ALT[(147.51±6.61)U/L,(133.09±5.88)U/L,(111.52±8.00)U/L]were significantly reduced by the administration of total flavonoids from Selaginella involventis at low,medium,and high concentrations,respectively(P<0.05).Furthermore,total flavones of Selaginella involventis significantly alleviated pathological changes of liver tissues,and significantly inhibited the mRNA expression of core genes enrichment in IL-17 signaling pathway.Conclusion Flavonoid compounds were the main active compounds of Selaginella involventis in the treatment of ALD through multiple targets and multiple pathways,and its mechanisms maybe involved in inhibiting the IL-17 signaling pathway.