基于网络药理学和分子对接研究马齿苋治疗痤疮的作用机制

Study on Mechanism of Portulaca oleracea L. in Treating Acne Based on Network Pharmacology and Molecular Docking

摘要: 为系统解析马齿苋治疗痤疮的潜在分子机制，本研究基于计算模型预测其临床应用及天然抗痤疮药物研发的可行性。研究采用网络药理学结合分子对接、分子动力学模拟的in silico方法开展相关分析。首先从TCMSP数据库筛选马齿苋活性成分，通过Swiss Target Prediction预测其潜在靶点，同时从OMIM、GeneCards数据库获取痤疮相关靶点，取两者交集后借助STRING平台构建蛋白–蛋白相互作用(PPI)网络，筛选核心靶点并进行GO功能和KEGG通路富集分析；选取核心通路中的关键靶点雄激素受体(AR)、芳香化酶(CYP19A1)与马齿苋活性成分进行分子对接，对结合亲和力较高的复合物开展100 ns分子动力学模拟验证其结合稳定性。结果显示，共筛选出马齿苋10个活性成分，得到马齿苋–痤疮交集靶点102个，进一步筛选出核心靶点26个；GO功能富集分析表明靶点主要参与类固醇激素信号转导、炎症反应、细胞增殖调控等生物过程；KEGG通路富集分析显示靶点显著富集于卵巢类固醇生成、类固醇激素合成、IL-17、TNF等通路。分子对接结果显示，β-胡萝卜素与AR的结合能达−10.8 kcal/mol、环木菠萝烯醇与CYP19A1的结合能达−9.9 kcal/mol，为所有成分中结合亲和力最高的组合；100 ns分子动力学模拟证实，β-胡萝卜素-AR、环木菠萝烯醇-CYP19A1复合物在模拟过程中构象稳定，RMSD、RMSF均处于合理波动范围。基于上述计算数据，我们预测马齿苋可能通过“多成分–多靶点–多通路”的网络调控模式发挥抗痤疮作用，并提出假设：其活性成分β-胡萝卜素、环木菠萝烯醇可能分别通过靶向结合AR、CYP19A1调控体内性激素平衡，改善激素紊乱介导的皮脂过度分泌、毛囊角化异常等痤疮核心病理过程，同时通过调控炎症相关通路缓解痤疮炎症反应。综上，本研究构建的计算模型预测了马齿苋抗痤疮的潜在作用机制，该假设有待后续实验验证。

Abstract: To systematically elucidate the potential molecular mechanism of Portulaca oleracea L. against acne, this study predicted its feasibility for clinical application and natural anti-acne drug development based on computational models. An in silico approach combining network pharmacology, molecular docking, and molecular dynamics simulation was employed. Firstly, active ingredients of P. oleracea were screened from the TCMSP database, and their potential targets were predicted using Swiss Target Prediction. Acne-related targets were retrieved from OMIM and Gene Cards databases. After obtaining the intersection of these targets, a protein-protein interaction (PPI) network was constructed via the STRING platform to screen core targets, followed by GO functional and KEGG pathway enrichment analyses. Key targets from core pathways—androgen receptor (AR) and aromatase (CYP19A1)—were selected for molecular docking with active ingredients, and complexes with high binding affinity were subjected to 100 ns molecular dynamics simulations to verify binding stability. The results showed that 10 active ingredients and 102 common targets related to both P. oleracea and acne were identified, among which 26 core targets were further screened. GO analysis indicated that these targets were mainly involved in biological processes such as steroid hormone signaling, inflammatory response, and cell proliferation regulation. KEGG analysis revealed significant enrichment in pathways including ovarian steroidogenesis, steroid hormone biosynthesis, IL-17, and TNF. Molecular docking results demonstrated that β-carotene bound to AR with a binding energy of −10.8 kcal/mol, and cycloartenol bound to CYP19A1 with −9.9 kcal/mol, representing the highest affinities among all components. 100 ns molecular dynamics simulations confirmed that the conformations of both the β-carotene-AR and cycloartenol-CYP19A1 complexes remained stable throughout the simulation, with RMSD and RMSF values fluctuating within reasonable ranges. Based on the computational data, we predict that P. oleracea may exert anti-acne effects through a “multi-component, multi-target, multi-pathway” regulatory network. We hypothesize that its active ingredients, β-carotene and cycloartenol, may regulate sex hormone balance by targeting AR and CYP19A1, respectively, thereby improving sebum overproduction and follicular hyperkeratosis mediated by hormonal disorders, while also alleviating inflammatory responses by modulating related pathways. In conclusion, the computational model constructed in this study predicts the potential mechanism of P. oleracea against acne, and this hypothesis warrants further experimental validation.