Department of Rheumatology, The No.1 Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, 650021, PR China; Yunnan Provincial Clinical Medicine Research Center of Rheumatism in TCM, Yunnan Provincial Hospital of Traditional Chinese Medicine, Yunnan, 650021, PR China.
Department of Rheumatology and Immunology, The First People's Hospital of Yunnan Province and The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650034, PR China.
Comput Biol Med. 2023 Sep;163:107160. doi: 10.1016/j.compbiomed.2023.107160. Epub 2023 Jun 8.
Orthosiphon stamineus Benth is a dietary supplement and traditional Chinese herb with widespread clinical applications, but a comprehensive understanding of its active compounds and polypharmacological mechanisms is lacking. This study aimed to systematically investigate the natural compounds and molecular mechanisms of O. stamineus via network pharmacology.
Information on compounds from O. stamineus was collected via literature retrieval, while physicochemical properties and drug-likeness were evaluated using SwissADME. Protein targets were screened using SwissTargetPrediction, while the compound-target networks were constructed and analyzed via Cytoscape with CytoHubba for seed compounds and core targets. Enrichment analysis and disease ontology analysis were then carried out, generating target-function and compound-target-disease networks to intuitively explore potential pharmacological mechanisms. Lastly, the relationship between active compounds and targets was confirmed via molecular docking and dynamics simulation.
A total of 22 key active compounds and 65 targets were identified and the main polypharmacological mechanisms of O. stamineus were addressed. The molecular docking results suggested that nearly all core compounds and their targets possess good binding affinity. In addition, the separation of receptor and ligands was not observed in all dynamics simulation processes, whereas complexes of orthosiphol Z-AR and Y-AR performed best in simulations of molecular dynamics.
This study successfully identified the polypharmacological mechanisms of the main compounds in O. stamineus, and predicted five seed compounds along with 10 core targets. Moreover, orthosiphol Z, orthosiphol Y, and their derivatives can be utilized as lead compounds for further research and development. The findings here provide improved guidance for subsequent experiments, and we identified potential active compounds for drug discovery or health promotion.
罗勒是一种药食同源的植物，具有广泛的临床应用，但对其活性成分和多靶点作用机制的认识还不够全面。本研究旨在通过网络药理学系统研究罗勒的天然化合物和分子机制。
通过文献检索收集罗勒中的化合物信息，利用 SwissADME 评估其理化性质和类药性。使用 SwissTargetPrediction 筛选蛋白靶点，通过 Cytoscape 构建化合物-靶点网络，并利用 CytoHubba 分析种子化合物和核心靶点。然后进行富集分析和疾病本体分析，生成靶点-功能和化合物-靶点-疾病网络，直观地探讨潜在的药理机制。最后，通过分子对接和动力学模拟验证活性化合物与靶点的关系。
共鉴定出 22 种关键活性化合物和 65 个靶点，阐明了罗勒的主要多靶点作用机制。分子对接结果表明，几乎所有核心化合物及其靶点都具有良好的结合亲和力。此外，在所有动力学模拟过程中均未观察到受体和配体分离，而 orthosiphol Z-AR 和 Y-AR 的复合物在分子动力学模拟中表现最佳。
本研究成功鉴定了罗勒中主要化合物的多靶点作用机制，预测了 5 种种子化合物和 10 个核心靶点。此外，orthosiphol Z、orthosiphol Y 及其衍生物可作为进一步研究和开发的先导化合物。本研究为后续实验提供了改进的指导，并为药物发现或健康促进提供了潜在的活性化合物。
