基于机器学习和分子动力学探究侧柏叶治疗 雄激素脱发作用机制

Investigation on the Mechanism of Platycladus orientalis in the Treatment of Androgenetic Alopecia Based on Machine Learning and Molecular Dynamics

摘要: 目的：本研究旨在揭示中药侧柏叶(Platycladus orientalis, PO)治疗雄激素性脱发(Androgenetic Alopecia, AGA)的潜在活性成分、核心靶点及分子机制。方法：整合GEO数据库筛选差异表达基因，机器学习筛选特征基因并验证。采用CIBERSORT算法进行免疫浸润及相关性分析。整合TCMSP、SymMap、ccTCM等数据库，构建“药物–成分–靶点”网络，分子对接和分子动力学验证活性成分与核心靶点的结合活性。结果：在186个差异基因中锁定CYP1A1为核心枢纽。AGA病灶区存在T细胞浸润上调等特征，PO显著富集类固醇激素生物合成、脂质代谢等通路。共筛选出槲皮素、芹菜素、雪松醇等8种活性成分，均与CYP1A1形成稳定复合物。结论：本研究系统揭示了侧柏叶通过“多成分–多靶点–多通路”干预AGA，其核心在于调控“激素–代谢–炎症”环节，为开发以CYP1A1为轴心的AGA治疗提供理论依据。

Abstract: Objective: This study aims to reveal the potential active components, core targets, and molecular mechanisms of the traditional Chinese medicine Platycladus orientalis (PO) in the treatment of androgenetic alopecia (AGA). Methods: Differentially expressed genes were screened by integrating the GEO database, feature genes were identified using machine learning, and validation was performed. Immune infiltration and correlation analyses were conducted using the CIBERSORT algorithm. Databases including TCMSP, SymMap, and ccTCM were integrated to construct a “drug-component-target” network, and molecular docking and molecular dynamics were used to verify the binding activity of active components with core targets. Results: Among 186 differentially expressed genes, CYP1A1 was identified as a central hub. AGA lesions exhibited characteristics such as upregulated T cell infiltration, and PO was significantly enriched in pathways including steroid hormone biosynthesis and lipid metabolism. Eight active components, including quercetin, apigenin, and cedrol, were screened, all forming stable complexes with CYP1A1. Conclusion: This study systematically demonstrates that PO intervenes in AGA through a “multi-component, multi-target, multi-pathway” mechanism, primarily by regulating the “hormone-metabolism-inflammation” axis, providing a theoretical basis for developing AGA treatments centered on CYP1A1.