基于数据挖掘和网络药理学分析中医方药保护血管内皮细胞抗动脉粥样硬化的配伍规律和药理作用机制

Analysis on Compatibility Patterns and Mechanisms of Traditional Chinese Medicine against Atherosclerosis by Protecting Vascular Endothelial Cells Based on Data Mining and Network Pharmacology

目的基于数据挖掘和网络药理学分析中医方药保护血管内皮细胞(VECs)抗动脉粥样硬化(As)的配伍规律和药理作用机制。方法检索中国知网、万方、维普、SinoMed、PubMed、Cochrane Library、Embase、Elsevier数据库中明确指出中药方剂可以保护VECs抗As的相关文献,检索时间为建库至2022年7月28日。通过数据挖掘分析药物出现频率、性味归经、功效,配伍规律,找出核心角药组合(三味中药的组合)。在网络药理学研究中找出中药和疾病相同靶点,制作蛋白-蛋白间相互作用网络,分析靶点基因本体富集和信号通路预测。结果成功纳入64篇文献,纳入研究处方46首,收录115味药材。以补虚类、活血化瘀类、清热类药材居多,五味属性多集中在甘、苦、辛,在归经方面多属肝、脾、心经,确定核心角药组合是“桃仁-红花-川芎”。核心角药通过保护内皮细胞抗As的主要活性成分包括β-谷固醇、豆固醇、常春藤皂苷元、槲皮素等,作用的关键靶点主要位于SRC、促分裂原活化的蛋白激酶1、丝氨酸/苏氨酸蛋白激酶(AKT)1等。核心角药可能在调节磷脂酰肌醇-3-激酶/AKT通路、白细胞介素(IL)-4/IL-13、IL-10信号通路中发挥治疗效果。结论保护VECs抗As的核心角药在机制上呈现多靶点、多通路的特点,可能通过调节动脉内皮细胞迁移、修复损伤细胞、维持一氧化氮的正常释放发挥抗As的作用。

Objective To explore the compatibility patterns and pharmacological mechanisms of Traditional Chinese medicine(TCM)formulas in protecting vascular endothelial cells(VECs)and combating atherosclerosis(As)based on data mining and network pharmacology analysis.Methods The relevant literature was retrieved from databases such as China National Knowledge Infrastructure(CNKI),Wanfang Database,SinoMed,and VIP Database,as well as PubMed,Cochrane Library,Embase,and Elsevier Database from database establishment up to July 282022.The included literature should specifically indicate the protective effect of TCM formulas on VECs against As.Cata mining was employed to analyze the frequency of drug occurrence,their taste,property,meridian attribution,and effects.The compatibility patterns and core triangle drug combinations(the combination of three Chinese herbal medicines)were identified.Network pharmacology was utilized to identify overlapping targets between TCM compounds and the disease,and protein-protein interaction networks were constructed to perform analyses on target gene ontology enrichment and signaling pathway predictions.Results A total of 64 papers were included,including 46 research prescriptions and 115 herbs.The majority of included medicinal ingredients belong to the categories of tonifying deficiency,promoting blood circulation and removing blood stasis,and clearing heat.The five taste attributes are mainly concentrated in sweet,bitter,and acrid tastes.In terms of meridian attribution,they predominantly correspond to the Liver,Spleen,and Heart meridians.The core triangle drug combination is"Tao Ren-Hong Hua-Chuan Xiong".The main active components responsible for protecting endothelial cells against As in the core triangle drugs includeβ-sitosterol,stigmasterol,hederagenin,quercetin,etc.The key target proteins involved in the mechanism of action are mainly SRC,mitogen-activated protein kinase 1,and serine/threonine kinase(AKT)1.The core triangle drugs may exert therapeutic effects by modulating the phosphoinositide-3-kinase/AKT pathway,interleukin(IL)-4/IL-13,and IL-10 signaling pathways.Conclusion The core triangle drugs responsible for protecting VECs against As exhibit a multi-target,multi-pathway mechanism,which may exert their anti-As effects by regulating arterial endothelial cell migration,promoting repair of damaged cells,and maintaining normal release of the nitric oxide.