Liu Fangzhou, Li Meng, Li Yuanbai, Du Yu, Li Yihao, Yang Yang
Institute of Information on Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
Medicine (Baltimore). 2025 Jan 3;104(1):e41089. doi: 10.1097/MD.0000000000041089.
This study aims to explore the mechanism of the iridoid glycosides from Fructus Gardeniae (IGFG) in treating hepatic encephalopathy (HE) by combining network pharmacology and molecular docking technology.
Firstly, we collected the targets of IGFG and HE. The targets of IGFG were predicted through the CTD, SWISS and TCMSP database and the targets of HE were screened through the DisGeNET database. Then the targets of IGFG and HE were mapped to attain the common target of IGFG in treating HE. Then, chemicals-target-disease network was constructed. Secondly, we constructed protein-protein interactions (PPI) network using STRING database and Cytoscape software. Moreover, we screened the core targets according to the degree value. Thirdly, the mechanism of IGFG in treating HE was revealed by Gene ontology and KEGG enrichment analysis. Meanwhile, chemicals-target-pathway network was constructed. Finally, to further verify the analysis results, molecular docking study was conducted.
Network pharmacology indicates that there are 12 common targets between IGFG and HE. Eleven core targets were identified by the construction of PPI network. Association for core targets, and related pathways was analyzed, implying that core targets related to these pathways are AKT1, tumor necrosis factor, MTOR, CHUK, PPP2CA, IKBKB, AKT2, IKBKG, IL1B, NFKBIA, and CASP8. The main mechanism of IGFG in treating HE is closely related to inhibit inflammatory reaction, regulate immunity, promote hepatocyte regeneration, reduce hepatocyte apoptosis, maintain liver function homeostasis and antiviral function. Finally, the results of molecular docking showed that the binding free energy of geniposide with the core target was less than -5 kJ/mol, which indicated that geniposide could spontaneously bind to the receptor protein and had strong binding force.
IGFG can achieve simultaneous intervention of HE by inhibit inflammatory reaction, regulate immunity, promote hepatocyte regeneration, reduce hepatocyte apoptosis, maintain liver function homeostasis and antiviral function. It presents the network regulation mechanism of mutual influence and complex correlation. This study provides a scientific basis for IGFG in the treatment of patients with HE.
本研究旨在结合网络药理学和分子对接技术，探讨栀子果实中环烯醚萜苷（IGFG）治疗肝性脑病（HE）的机制。
首先，我们收集了IGFG和HE的靶点。通过CTD、SWISS和TCMSP数据库预测IGFG的靶点，并通过DisGeNET数据库筛选HE的靶点。然后将IGFG和HE的靶点进行映射，以获得IGFG治疗HE的共同靶点。接着构建化学物质-靶点-疾病网络。其次，我们使用STRING数据库和Cytoscape软件构建蛋白质-蛋白质相互作用（PPI）网络。此外，根据度值筛选核心靶点。第三，通过基因本体论和KEGG富集分析揭示IGFG治疗HE的机制。同时构建化学物质-靶点-通路网络。最后，为进一步验证分析结果，进行了分子对接研究。
网络药理学表明，IGFG和HE之间存在12个共同靶点。通过构建PPI网络鉴定出11个核心靶点。对核心靶点及其相关通路进行了分析，表明与这些通路相关的核心靶点有AKT1、肿瘤坏死因子、MTOR、CHUK、PPP2CA、IKBKB、AKT2、IKBKG、IL1B、NFKBIA和CASP8。IGFG治疗HE的主要机制与抑制炎症反应、调节免疫、促进肝细胞再生、减少肝细胞凋亡、维持肝功能稳态和抗病毒功能密切相关。最后，分子对接结果表明，栀子苷与核心靶点的结合自由能小于-5 kJ/mol，这表明栀子苷可以自发地与受体蛋白结合，且结合力较强。
IGFG可通过抑制炎症反应、调节免疫、促进肝细胞再生、减少肝细胞凋亡、维持肝功能稳态和抗病毒功能，实现对HE的同时干预。它呈现出相互影响和复杂关联的网络调节机制。本研究为IGFG治疗HE患者提供了科学依据。
