基于网络药理学分析荷丹片与他汀类药物的协同降脂作用

目的采用网络药理学的方法,筛选荷丹片组方的活性成分和与高脂血症疾病相关的作用靶点,通过生物过程与通路富集预测其作用机制,从而获得荷丹片与他汀类药物协同作用的依据。方法利用中药系统药理学分析平台(TCMSP,https:∥tcmspw.com/tcmsp.php)等数据库及文献筛选荷丹片的活性成分及靶点,利用Geen Card数据库(https:∥www.genecards.org/)获取高脂血症疾病靶点,筛选出荷丹片降脂的主要靶点,通过Cytoscape软件和STRING数据库进行作用靶点的蛋白互作分析、生物功能分析和通路富集,预测荷丹片降脂作用的机制,并根据预测得到的降脂机制,探讨荷丹片与他汀类药物的协同作用。结果经过筛选,共获得荷丹片的活性成分163个,在荷丹片的成分靶点与高脂血症的疾病靶点两者间取得交集,获得荷丹片对高脂血症的潜在作用靶点52个,蛋白相互作用网络分析表明,AKT1、ALB、INS、GAPDH和IL6可能是荷丹片治疗高脂血症的关键靶点,KEGG通路富集表明在荷丹片涉及的通路中,与疾病的治疗相关性较大的通路有脂肪细胞因子信号通路、非酒精性脂肪肝信号通路、胰岛素抵抗和胰高血糖素信号通路、花生四烯酸代谢通路和脂肪酸生物合成等。这与他汀类药物降脂作用的机制相似,证明荷丹片与他汀类药物在降脂作用上具有一致的作用通路和靶点,为其协同作用提供了可能。结论研究预测了荷丹片的降脂机制,体现了中药多成分、多靶点的作用特点,荷丹片能够有效的调节机体内脂肪酸生物过程、糖代谢过程和脂质代谢过程,为荷丹片与他汀类药物协同作用增加降脂疗效提供了依据。

Mechansim Analyse of the Synergistic Lipid-lowering Effect of HeDan Tablet and Statins Based on Network Pharmacology

OBJECTIVE Based on the network pharmacology,the active compounds and targets related to hyperlipidemia of HeDan tablet were searched,and the lipid-lowering mechanism were predicted by biological process and pathway enrichment,to provide the theory basis of synergistic lipid-lowering effect of HeDan tablet and statins. METHODS The active constituents and targets were acquired from online databases including TCMSP,and the main disease targets were obtained from OMIM online database. The effective lipid-lowering targets in HeDan tablet were screened,and the Protein-Protein interaction,biological process analysis and pathway enrichment were constructed by Cytoscape and String online database. The lipid lowering mechanism of HeDan tablet was proved and the possibility of synergism between HeDan tablet and statins were explored. RESULTS 163 active compounds of HeDan tablet and 52 targets related to hyperlipidemia were acquired from screening. Protein-Protein interaction network showed that AKT1,ALB,INS,GAPDH and IL6 were the key targets totreat hyperlipidemia. KEGG pathway enrichment showed that adipocytokine signaling pathway,non-alcoholic fatty liver signaling pathway,insulin resistance and glucagon signaling pathway,arachidonic acid metabolism pathway and fatty acid biosynthesis were significantly associated with the treatment of hyperlipidemia,similar to statins. This work proved the synergistic lipid-lowering effect of HeDan tablet and statins. CONCLUSION The study predicted the lipid-lowering mechanism of HeDan tablet based on network pharmacology,reflected the characteristics of multi-component and multi-target of traditional Chinese medicine,provided theoretical basis for the synergistic lipid-lowering effect between HeDan tablet and statin.