Department of Digestion, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University (Hangzhou Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, China.
PLoS One. 2022 Feb 23;17(2):e0264398. doi: 10.1371/journal.pone.0264398. eCollection 2022.
Chinese medicine formulae possess the potential for cholestasis treatment. This study aimed to explore the underlying mechanisms of San-Huang-Chai-Zhu formula (SHCZF) against cholestasis.
The major chemical compounds of SHCZF were identified by high-performance liquid chromatography. The bioactive compounds and targets of SHCZF, and cholestasis-related targets were obtained from public databases. Intersected targets of SHCZF and cholestasis were visualized by Venn diagram. The protein-protein interaction and compound-target networks were established by Cytoscape according to the STRING database. The biological functions and pathways of potential targets were characterized by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. The biological process-target-pathway network was constructed by Cytoscape. Finally, the interactions between biological compounds and hub target proteins were validated via molecular docking.
There 7 major chemical compounds in SHCZF. A total of 141 bioactive compounds and 83 potential targets were screened for SHCZF against cholestasis. The process of SHCZF against cholestasis was mainly involved in AGE-RAGE signaling pathway in diabetic complications, fluid shear stress and atherosclerosis, and drug metabolism-cytochrome P450. ALB, IL6, AKT1, TP53, TNF, MAPK3, APOE, IL1B, PPARG, and PPARA were the top 10 hub targets. Molecular docking showed that bioactive compounds of SHCZF had a good binding affinity with hub targets.
This study predicted that the mechanisms of SHCZF against cholestasis mainly involved in AGE-RAGE signaling pathway in diabetic complications, fluid shear stress and atherosclerosis, and drug metabolism-cytochrome P450. Moreover, APOE, AKT1, and TP53 were the critical hub targets for bioactive compounds of SHCZF.
中药方剂具有治疗胆汁淤积的潜力。本研究旨在探讨三黄柴术方（SHCZF）抗胆汁淤积的潜在机制。
采用高效液相色谱法鉴定 SHCZF 的主要化学成分。从公共数据库中获取 SHCZF 的生物活性化合物和靶点，以及胆汁淤积相关靶点。通过 Venn 图可视化 SHCZF 和胆汁淤积的交叉靶点。根据 STRING 数据库，使用 Cytoscape 建立蛋白质-蛋白质相互作用和化合物-靶点网络。通过基因本体论和京都基因与基因组百科全书富集分析对潜在靶点的生物学功能和途径进行特征描述。使用 Cytoscape 构建生物过程-靶点-途径网络。最后，通过分子对接验证生物化合物和枢纽靶蛋白之间的相互作用。
SHCZF 中有 7 种主要化学成分。共筛选出 141 种生物活性化合物和 83 个潜在靶点用于 SHCZF 抗胆汁淤积。SHCZF 抗胆汁淤积的过程主要涉及糖尿病并发症中的 AGE-RAGE 信号通路、流体剪切应激和动脉粥样硬化以及药物代谢-细胞色素 P450。ALB、IL6、AKT1、TP53、TNF、MAPK3、APOE、IL1B、PPARG 和 PPARA 是前 10 个枢纽靶标。分子对接表明，SHCZF 的生物活性化合物与枢纽靶标具有良好的结合亲和力。
本研究预测，SHCZF 抗胆汁淤积的机制主要涉及糖尿病并发症中的 AGE-RAGE 信号通路、流体剪切应激和动脉粥样硬化以及药物代谢-细胞色素 P450。此外，APOE、AKT1 和 TP53 是 SHCZF 生物活性化合物的关键枢纽靶标。
