摘要
目的 通过网络药理学和蛋白芯片研究鳖甲煎口服液抗肝纤维化的潜在机制。方法 鳖甲煎口服液的化学成分、潜在靶点及肝纤维化相关基因均来自开放源数据库。然后,利用Autodock vina对目标蛋白和化合物进行分子对接。利用PyMOL对对接构象进行可视化。随后用蛋白芯片比较AngⅡ诱导的人肝星状细胞(HSC-LX2)和鳖甲煎口服液处理的HSC-LX2磷酸化蛋白(DEPs),以验证上述结果。结果 鳖甲煎口服液抗肝纤维化的网络药理学GO和KEGG通路富集分析结果表明,关键信号通路为PI3K/Akt、MAPK和Ras信号通路。分子对接的结论表明,活性物质(β-谷甾醇、槲皮素、山柰酚)对关键靶点(TNF、AKT1、IL6)具有较高的亲和力。同时网络药理学的结果与蛋白芯片的结果相吻合。结论 鳖甲煎口服液治疗肝纤维化主要抑制Ras信号通路的活性,进而抑制MAPK和PI3K/Akt信号通路,包括抑制TNF、AKT1和IL6。上述通路蛋白还与鳖甲煎口服液具有活血化瘀、软坚散结的作用有关。这些途径可作为肝纤维化的治疗靶点。
Objective To study the potential mechanism of Biejiajian Oral Liquid against hepatic fibrosis by network pharmacology and protein chip.Methods The chemical compounds,potential targets of Biejiajian Oral Liquid,and related genes of liver fibrosis were available from open-source databases.Then,target proteins and compounds were selected for docking by Autodock vina.PyMOL was used to visualize the docked conformations.Thereafter,protein chip was used to compare human hepatic stellate cells(HSC-LX2)induced by AngⅡand the phosphorylated proteins(DEPs)of HSC-LX2 treated by Biejiajian Oral Liquid to verify the above results.Results GO and KEGG pathway enrichment analysis indicated that the key signaling pathways were PI3K/Akt,MAPK and Ras signaling pathways.The conclusions of molecular docking demonstrated that the primary active substances(Beta-sitosterol,quercetin,kaempferol)have a high affinity for the representative targets(TNF,AKT1,IL6).We discovered that the results of network pharmacology matched those of protein chips.Conclusion As a result,we deduced that Biejiajian Oral Liquid for the treatment of liver fibrosis inhibits the activity of Ras signaling pathway primarily and further inhibits MAPK and PI3K/Akt signaling pathways,including TNF,AKT1,and IL6.The above pathway proteins are also related to Biejiajian Oral Liquid on promoting blood circulation,removing blood stasis,and softening hard mass.These pathways could be exploited as therapeutic targets for liver fibrosis.
作者
谢泽宇
许一笑
郑梦圆
郑静茹
姚立
XIE Zeyu;XU Yixiao;ZHENG Mengyuan;ZHENG Jingru;YAO Li(School of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou 310053 Zhejiang,China)
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2023年第1期78-90,共13页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
国家自然科学基金项目(81173640)。
关键词
鳖甲煎口服液
肝纤维化
机制
网络药理学
蛋白芯片
Biejiajian Oral Liquid
liver fibrosis
mechanism
network pharmacology
protein chip
