关键词: 芒果苷钠盐, 动脉粥样硬化, 网络药理学, 分子对接

Abstract: This work explores the mechanism of mangiferin sodium salt(MF-Na)in the treatment of atherosclerosis(AS)based on network pharmacology, molecular docking and in vitro validation. The target of MF-Na was screened by TCMSP, STITCH, SWISS and SEA databases. OMIM, GAD and Genecards databases were used to screen out the related targets of AS disease. The interaction network diagrams- DOI:10.3969/j.issn.1000-1565.2023.03.006基于网络药理学和实验验证探究芒果苷钠盐对动脉粥样硬化的作用机制蒲泽江¹,赵川平¹,闫子涵¹,王乾²,周程艳¹(1.河北大学 药学院,河北省药物质量分析控制重点实验室,河北 保定 071002;2.河北大学附属医院 神经内科,河北 保定 071000)摘 要:基于网络药理学、分子对接和细胞实验验证的方法探究芒果苷钠盐(MF-Na)治疗动脉粥样硬化(atherosclerosis, AS)的作用机制.利用TCMSP、STITCH、SWISS、SEA数据库筛选出MF-Na的作用靶点,利用OMIM、GAD、Genecards数据库筛选出AS疾病作用的相关靶点,分别绘制药物靶点、疾病靶点的相互作用网络图.利用Cytoscape3.6.1软件,绘制“化合物-靶标-通路-疾病”关系网络并进行分析.对筛选出的靶点基因进行GO分析和KEGG分析,采用AutoDock Vina软件进行分子对接,评估筛选靶标.最后采用酶联免疫吸附测定法(ELISA)检测了体外TNF-α、NF-κB、IL-6、CCL2和CXCL1的含量,并用免疫细胞化学检测了NF-κB p65和NF-κB p50的表达.筛选出MF-Na相关靶点119个,AS相关靶点433个,药物-疾病共同靶点23个,富集到通路46条.细胞实验证明:MF-Na能显著降低TNF-α、NF-κB、IL-6、CCL2和CXCL1的表达水平,并经过TNF-α/NF-κB/CCL2通路发挥作用.利用网络药理学筛选了MF-Na抗AS的潜在靶点,经实验验证发现MF-Na可能是经过TNF-α/NF-κB/CCL2途径降低炎症因子表达,进而发挥治疗AS的作用.关键词:芒果苷钠盐;动脉粥样硬化;网络药理学;分子对接中图分类号:R593.21 文献标志码:A 文章编号:1000-1565(2023)03-0263-11Mechanism of mangiferin sodium salt on arteriosclerosis based on network pharmacology and experimental verificationPU Zejiang¹, ZHAO Chuanping¹, YAN Zihan¹, WANG Qian², ZHOU Chengyan¹(1.Key Laboratory of Pharmaceutical Quality Control of Hebei Province,College of Pharmacy,Hebei University,Baoding 071002,China;2.Department of Neurology,Affiliated Hospital of Hebei University,Baoding 071000,China)Abstract: This work explores the mechanism of mangiferin sodium salt(MF-Na)in the treatment of atherosclerosis(AS)based on network pharmacology, molecular docking and in vitro validation. The target of MF-Na was screened by TCMSP, STITCH, SWISS and SEA databases. OMIM, GAD and Genecards databases were used to screen out the related targets of AS disease. The interaction network diagrams- 收稿日期:2022-04-16 基金项目:河北省自然科学基金资助项目(H2020201291);贵州医科大学省部共建药用植物功效与利用国家重点实验室资助项目(FAMP202006K);河北省创新能力提升计划项目(20567605H) 第一作者:蒲泽江(1998—),男,四川泸州人,河北大学在读硕士研究生,主要从事药理学、生物信息学、药物代谢分析方面的研究.E-mail:905139321@qq.com 通信作者:周程艳(1976—),女,河北唐山人,河北大学副教授,主要从事药理作用机制、多组学、中药药效和有效成分筛选的研究.E-mail:xuefanone@163.com王乾(1989—),男,河北沧州人,河北大学附属医院主治医师,主要从事重症脑血管疾病的治疗.E-mail:wq342robin@sina.com第3期蒲泽江等:基于网络药理学和实验验证探究芒果苷钠盐对动脉粥样硬化的作用机制of drug targets and disease targets were drawn respectively. Using Cytoscape 3.6.1 software, the relationship network of “compound target pathway disease was drawn and analyzed”. The screened target genes were analyzed by GO and KEGG, and the molecular docking was carried out by AutoDock Vina software to evaluate the screening targets. Finally, the contents of TNF-α, NF-κB, IL-6, CCL2 and CXCL1 in vitro were determined by enzyme linked immunosorbent assay(ELISA). The expression of NF-κB p65 and NF-κB P50 were detected by immunocytochemistry. 119 MF-Na related targets, 433 as related targets and 23 drug disease common targets were screened, and 46 pathways were enriched. Cell experiments showed that MF-Na could significantly reduce the expression of TNF-α、NF-κB. Levels of IL-6, CCL2 and CXCL1, and TNF-α/NF-κB/CCL2 pathway works. The potential targets of MF-Na were screened by network pharmacology, and it was found that MF-Na may be through TNF-α/NF-κB/CCL2 pathway to reduce the expression of inflammatory factors and play a role in the treatment of AS.

Key words: mangiferin sodium salt, atherosclerosis, network pharmacology, molecular docking