Cai Aiyuan, Ye Huishi, Lin Yuanhong, Shi Meiping, Li Zhiwei, Li Jinyun, Luo Guangliang, Huang Yanfang, Lai Ciai
Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong Province, China.
Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan, Guangdong Province, China.
Medicine (Baltimore). 2025 Aug 29;104(35):e44163. doi: 10.1097/MD.0000000000044163.
This study aims to identify the primary active components of Danshen (Salvia miltiorrhiza) and explore the potential mechanisms underlying its therapeutic effect on Kawasaki disease (KD). Active components of Danshen and their action targets were screened using traditional Chinese medicine systems pharmacology and SwissTargetPrediction databases. KD-related targets were retrieved from Online Mendelian Inheritance in Man, Pharmacogenomics Knowledge Base, and GeneCards databases. Intersection targets between KD-related genes and the main active components of Danshen were identified. The protein-protein interaction network for intersecting targets of Danshen and KD was constructed using Search Tool for the Retrieval of Interacting Genes/Proteins database and Cytoscape software, and core genes were identified. Gene ontology functions and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of Danshen-KD intersecting targets were performed using database for annotation, visualization, and integrated discovery database. Molecular docking was conducted using Autodock software. A total of 65 active components of Danshen and 219 drug-related target proteins were identified, establishing 1308 KD-related human genes. The intersection yielded 70 potential drug targets associated with KD. Construction of the protein-protein interaction network for these common targets revealed 7 core genes: IL6, TNF, AKT1, BCL2, STAT3, CASP3, and TP53. Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that these targets were primarily enriched in pathways such as Pathways in Cancer, Lipid and Atherosclerosis, and Fluid Shear Stress and Atherosclerosis. Molecular docking results demonstrated that core active components of Danshen, including luteolin, tanshinone IIA, NSC 122421, (Z)-3-[2-[(E)-2-(3,4-dihydroxyphenyl)vinyl]-3,4-dihydroxy-phenyl]acrylic acid, and cryptotanshinone, could regulate the 7 core genes within these pathways. Danshen treats Kawasaki disease through a multicomponent, multi-target approach, potentially involving anti-inflammatory, antiapoptotic, antitumor, and anti-atherosclerotic mechanisms. This study provides scientific evidence for the use of Danshen in treating Kawasaki disease and offers new clues for targeting in the treatment of KD with traditional Chinese medicine.
本研究旨在确定丹参（Salvia miltiorrhiza）的主要活性成分，并探索其对川崎病（KD）治疗作用的潜在机制。利用中药系统药理学和瑞士靶点预测数据库筛选丹参的活性成分及其作用靶点。从人类孟德尔遗传在线、药物基因组学知识库和基因卡片数据库中检索KD相关靶点。确定KD相关基因与丹参主要活性成分之间的交集靶点。利用检索相互作用基因/蛋白质的搜索工具数据库和Cytoscape软件构建丹参与KD交集靶点的蛋白质-蛋白质相互作用网络，并确定核心基因。使用注释、可视化和综合发现数据库对丹参-KD交集靶点进行基因本体功能和京都基因与基因组百科全书通路富集分析。使用Autodock软件进行分子对接。共鉴定出65种丹参活性成分和219种药物相关靶蛋白，建立了1308个KD相关人类基因。交集产生了70个与KD相关的潜在药物靶点。构建这些共同靶点的蛋白质-蛋白质相互作用网络，揭示了7个核心基因：IL6、TNF、AKT1、BCL2、STAT3、CASP3和TP53。京都基因与基因组百科全书富集分析表明，这些靶点主要富集在癌症通路、脂质与动脉粥样硬化、流体剪切应力与动脉粥样硬化等通路中。分子对接结果表明，丹参的核心活性成分，包括木犀草素、丹参酮IIA、NSC 122421、（Z）-3-[2-[(E)-2-(3,4-二羟基苯基)乙烯基]-3,4-二羟基苯基]丙烯酸和隐丹参酮，可以调节这些通路中的7个核心基因。丹参通过多成分、多靶点方法治疗川崎病，可能涉及抗炎、抗凋亡、抗肿瘤和抗动脉粥样硬化机制。本研究为丹参治疗川崎病提供了科学依据，并为中药治疗KD的靶点研究提供了新线索。
