Department of Health Informatics and Management, School of Health Humanities, Peking University, Beijing, 100191, China.
School of Statistics, Beijing Normal University, Beijing, 100875, China.
Comb Chem High Throughput Screen. 2024;27(7):959-968. doi: 10.2174/1386207326666230810094557.
Houshiheisan (HSHS) has been effective in the treatment of ischemic stroke (IS) for centuries. However, its mechanisms are still underexplored.
The objective of this study is to identify the active ingredients and mechanisms of HSHS in treating IS.
We searched the main active compounds in HSHS and their potential targets, and key targets related to IS. Based on the common targets of HSHS and IS, we further expanded genes by KEGG database to obtain target genes and related genes, as well as gene interactions in the form of A→B, and then constructed a directed network including traditional Chinese medicines (TCMs), active compounds and genes. Finally, based on enrichment analysis, independent cascade (IC) model, and molecular docking, we explored the mechanisms of HSHS in treating IS.
A directed network with 6,348 nodes and 64,996 edges was constructed. The enrichment analysis suggested that the AGE pathway, glucose metabolic pathway, lipid metabolic pathway, and inflammation pathway played critical roles in the treatment of IS by HSHS. Furthermore, the gene ontologies (GOs) of three monarch drugs in HSHS mainly involved cellular response to chemical stress, blood coagulation, hemostasis, positive regulation of MAPK cascade, and regulation of inflammatory response. Several candidate drug molecules were identified by molecular docking.
This study advocated potential drug development with targets in the AGE signaling pathway, with emphasis on neuroprotective, anti-inflammatory, and anti-apoptotic functions. The molecular docking simulation indicated that the ligand-target combination selection method based on the IC model was effective and reliable.
厚樸三味散（HSHS）在治疗缺血性中风（IS）方面已有数百年的历史。然而，其机制仍未得到充分探索。
本研究旨在确定 HSHS 治疗 IS 的活性成分和机制。
我们搜索了 HSHS 中的主要活性化合物及其潜在靶点，以及与 IS 相关的关键靶点。基于 HSHS 和 IS 的共同靶点，我们进一步通过 KEGG 数据库扩展基因，获得靶基因和相关基因，以及 A→B 的基因相互作用，并构建了一个包含传统中药（TCM）、活性化合物和基因的有向网络。最后，基于富集分析、独立级联（IC）模型和分子对接，我们探讨了 HSHS 治疗 IS 的机制。
构建了一个包含 6,348 个节点和 64,996 条边的有向网络。富集分析表明，AGE 通路、葡萄糖代谢通路、脂质代谢通路和炎症通路在 HSHS 治疗 IS 中发挥着关键作用。此外，HSHS 三种君药的基因本体（GO）主要涉及细胞对化学应激的反应、血液凝固、止血、MAPK 级联的正调控以及炎症反应的调节。通过分子对接鉴定了几种候选药物分子。
本研究提倡以 AGE 信号通路为靶点进行潜在药物开发，重点关注神经保护、抗炎和抗细胞凋亡功能。分子对接模拟表明，基于 IC 模型的配体-靶标组合选择方法是有效和可靠的。
