[关键词]
[摘要]
目的 探讨铁包金Berchemia lineata (Linn.) DC.抗肝纤维化的作用机制,为临床应用提供科学依据。方法 采用UPLC-Q-TOF-MS/MS技术快速鉴定壮药铁包金的化学成分,运用Swiss ADME平台、中国知网、万方数据、维普数据库筛选活性成分,借助Swiss Target Prediction、GeneCard等平台预测铁包金成分靶点及疾病靶点,构建“药物-活性成分-靶点”网络。通过String数据库构建蛋白相互作用(PPI)网络,Cytoscape 3.7.0软件进行拓扑分析筛选核心靶点,David数据库进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析,分子对接技术验证活性成分与核心靶点的结合。结果 鉴定出铁包金100个活性成分,筛选出72个活性成分及152个药物-疾病靶点。PPI网络筛选出信号传导和转录激活因子3(STAT3)、肿瘤坏死因子(TNF)、半胱氨酸蛋白酶3(CASP3)、蛋白激酶B1(Akt1)、肿瘤抑癌蛋白p53(TP53)、白蛋白(ALB)、B淋巴细胞瘤-2基因(Bcl-2)等核心靶点,主要涉及细胞外基质分解、受体复合物、酶结合等生物过程、细胞组分和分子功能,以及低氧诱导分子-1信号通路、凋亡脂质与动脉粥样硬化、乙型肝炎、癌症中的通路、磷酯酰肌醇3-激酶(PI3K)/Akt信号通路等。分子对接显示活性成分与核心靶点结合能越低,提示结合越稳定。结论 铁包金主要活性成分(如柚皮素、异鼠李素等)通过核心靶点(如STAT3、CASP3等),调控低氧诱导分子-1信号通路、乙型肝炎、PI3K/Akt信号通路等,发挥抗肝纤维化作用,为壮药铁包金抗肝纤维化的研究提供了参考依据。
[Key word]
[Abstract]
Objective To explore the underlying mechanism of Berchemia lineata in its anti-hepatic fibrosis effects, thereby furnishing a scientific rationale for its potential clinical utilization. Methods To identify the chemical constituents of Berchemia lineata by using UPLC-Q-TOF-MS/MS technology. To screen the active components through Swiss ADME platform, CNKI, Wanfang Data, and VIP databases, predict the component targets and disease targets by using platforms such as Swiss Target Prediction and GeneCards, and construct a “drug–active component–target”. To establish the PPI network by using the STRING database, and screen core targets through Cytoscape 3.7.0 software. GO functional and KEGG pathway enrichment analyses were performed using the DAVID database. Molecular docking technology was employed to validate the binding of active components to core targets. Results 100 Active ingredients of Berchemia lineata were identified, 72 active ingredients and 152 drug-disease targets were screened. PPI network screened the core targets of STAT3, TNF, CASP3, Akt1, TP53, ALB, Bcl-2, etc. It mainly involves biological processes such as extracellular matrix decomposition, receptor complex, enzyme binding, cell components and molecular functions, as well as hypoxa-induced molecule-1 signaling pathway, apoptotic lipids and atherosclerosis, hepatitis B, cancer pathways, and PI3K/Akt signaling pathway. Molecular docking showed that the lower the binding energy between the active ingredient and the core target, the more stable the binding. Conclusion Main active components of Berchemia lineata (such as naringenin, isorhamnetin, etc.) exert anti-hepatic fibrosis effects by regulating core targets (including STAT3, CASP3, etc.) and modulating signaling pathways such as hypoxia-inducible factor-1, hepatitis B, and PI3K/Akt. These findings provide a scientific basis for further research on the anti- hepatic fibrosis mechanisms of Berchemia lineata.
[中图分类号]
R285.5
[基金项目]
国家重点研发计划项目(2022YFC3502200);广西中医药重点学科建设项目(GZXK-Z-20-62);国家中医药管理局高水平中医药重点学科建设项目(zyyzdxk-2023164);全国名中医黄汉儒学术思想及临床经验传承推广中心(2022V004);广西中医外治法示范基地项目(桂中医药医发〔2019〕14号);广西高校壮医毒病研究重点实验室(桂教科研[2022]10号)