基于肝氣虛證與網絡藥理學探討黃芪柴胡干預肝炎的作用機制

周怡馳　晏軍　李玲　冉云　胡世平　黨志博　蘇曉鵬

摘要目的：從肝氣虛證角度并通過網絡藥理學探討黃芪柴胡干預肝炎的作用機制。方法：檢索中藥系統藥理學數據庫與分析平臺（TCMSP）等數據庫，篩選黃芪柴胡干預肝炎的活性成分和作用靶點。構建化合物靶點疾病網絡和蛋白質蛋白質相互作用（PPI） 網絡，進行拓撲學分析，篩選關鍵藥效分子和核心靶點。對作用靶點進行基因本體（GO）富集分析和京都基因和基因組百科全書（KEGG）富集分析，并用Cytoscape軟件構建化合物靶點通路網絡。結果：黃芪柴胡通過升補肝氣治療肝炎患者肝氣虛證。經網絡藥理學分析，篩選出黃芪柴胡14個關鍵藥效分子，19個核心作用靶點與其干預肝炎密切相關。分子對接結果顯示，度值前10的核心靶點能與黃芪柴胡的關鍵活性成分形成較穩定的構象，具有良好的結合活性。GO和KEGG結果主要涉及炎癥、氧化應激、細胞增殖等生物學過程。結論：黃芪柴胡或通過槲皮素、山柰酚、芒柄花素等活性成分作用于Toll樣受體、Th17細胞分化、Th1和Th2細胞分化、PI3K/AKT、MAPK、IL17等信號通路，參與調節氧化應激反應、肝臟炎癥反應、細胞增殖等生物學過程，發揮干預肝炎的作用。

關鍵詞黃芪;柴胡;肝氣虛證;肝炎;網絡藥理;分子對接;槲皮素;氧化應激

Mechanisms of Astragalusradix Bupleuri in Intervening Hepatitis Based

on Liver Qi Deficiency Syndrome and Network Pharmacology

ZHOU Yichi，YAN Jun，LI Ling，RAN Yun，HU Shiping，DANG Zhibo，SU Xiaopeng

（1 Dongzhimen Hospital，Beijing University of Chinese Medicine，Beijing 100020，China; 2 Shenzhen

Hospital，Beijing University of Chinese Medicine，Shenzhen 518172，China）

AbstractObjective：Investigating the theoretical foundation of AstragalusRadix bupleuri in treating patients with hepatitis from liver qi deficiency syndrome and exploring the possible mechanisms of AstragalusRadix bupleuri in intervening hepatitis by using the method of network pharmacology.Methods：Effective components and targets of AstragalusRadix bupleuri in intervening hepatitis were obtained from TCMSP and other databases.Then，“componenttargetdisease” network and proteinprotein interaction（PPI） network were established in Cytoscape and STRING database respectively，to ascertain the key efficacy components and targets.Molecular docking simulations were evaluated through Autodock vina software.Finally，GO and KEGG enrichment analysis were performed，and “compoundtargetsignaling pathway” network was also established in Cytoscape.Results：AstragalusRadix bupleuri can treat patients with hepatitis of liver qi deficiency by lifting and tonifying liver qi.The fourteen core active components and nineteen key targets of AstragalusRadix bupleuri were closely related to the intervention of hepatitis.Molecular docking results indicated that the top 10 key targets of degree values can form stable conformations with key compounds of RB and had favorable binding activities.Go and KEGG analysis revealed that the targets of AstragalusRadix bupleuri in intervening hepatitis significantly enriched in biological processes such as inflammation，oxidative stress，cell proliferation and TLR signaling pathway.Conclusion：AstragalusRadix bupleuri acts on Tolllike receptors，Th17 cell differentiation，Th1 and Th2 cell differentiation，PI3K/AKT，MAPK，IL17 and other signaling pathways through active components such as quercetin，kaempferol，and formononetin.It participates in the regulation of oxidative stress response，liver inflammatory response，cell proliferation and other biological processes，and plays a role in intervening hepatitis.

KeywordsAstragalus; Radix bupleuri; Syndrome of liver qi deficiency; Hepatitis; Network pharmacology; Molecular docking; Quercetin; Oxidative stress

中圖分類號：R285文獻標識碼：Adoi：10.3969/j.issn.1673-7202.2022.04.001

流行病學資料顯示，肝炎發病率較高，提高肝炎的治愈率和防治慢性肝炎、肝硬化和肝癌的發展是醫學研究的重要方向。在肝炎的治療中，中醫藥具有較大的優勢和前景。……