摘要
目的 借助网络药理学方法对逍遥散治疗慢性乙型肝炎(chronic hepatitis B,CHB)合并代谢相关脂肪性肝病(metabolic associated fatty liver disease,MAFLD)药效成分以及作用机制进行了预测和分析,为下一步实验验证研究提供思路和方向.方法 通过TCMSP获取逍遥散中中药的主要化学成分及活性物,在Uniprot蛋白质数据库将化合物作用的蛋白质靶点进行规范.通过GeneCards数据库获取CHB和MAFLD的主要靶点,利用韦恩分析工具绘制韦恩图,并得到三者交集靶点.随后在 STRING 11.5 数据库及 CytoScape 3.9.1 构建 PPI 网络模型.利用Metascape数据平台对潜在的靶点进行富集分析.结果 逍遥散干预CHB合并MAFLD的核心活性成分为山奈酚、槲皮素、木犀草素、β-谷甾醇等化合物.核心靶点有:RELA、MAPK1、MAPK3、AKT1、IL6 等靶点.逍遥散干预CHB合并MAFLD的生物学通路主要作用于Relaxin信号通路、IL-17 信号通路、HIF-1信号通路等信号通路,起到抗炎、抗氧化、抑制胶原蛋白的沉积等作用,从而减少肝脏的炎症损伤,改善肝纤维化.结论 逍遥散治疗CHB合并MAFLD可能通过Relaxin信号通路、IL-17 信号通路、HIF-1 信号通路等信号通路作用于RELA、MAPK1、MAPK3、AKT1、IL6 等靶蛋白的表达,起到抗炎、抗氧化、抑制胶原蛋白的沉积等作用,从而减少肝脏的炎症损伤,改善肝纤维化.
Abstract
Objective To predict and analyze the pharmacological components and mechanism of action of Xiaoyao San in the treatment of chronic hepatitis B(CHB)combined with metabolic associated fatty liver disease(MAFLD)using network pharmacology methods,providing ideas and directions for further experimental verification research.Methods TCMSP was used to obtain the main chemical components and active ingredients of traditional Chinese medicine in Xiaoyao San,and the protein targets of the compounds were standardized in the Uniprot protein database.Retrieve the main targets of CHB and MAFLD from the GeneCards database,draw a Venn diagram using Venn analysis tools,and obtain the intersection targets of the three.Subsequently,a PPI network model was constructed in the STRING 11.5 database and CytoScape 3.9.1.Perform enrichment analysis on potential targets using the Metascape data platform.Results The core active ingredients of Xiaoyao San in the intervention of CHB combined with MAFLD are compounds such as kaempferol,quercetin,luteolin,and β-sitosterol.The core targets include RELA,MAPK1,MAPK3,AKT1,IL6,and other targets.Xiaoyao San intervenes in the biological pathways of CHB combined with MAFLD,mainly acting on signaling pathways such as Relaxin,IL-17,HIF-1,etc.It has anti-inflammatory,antioxidant,and collagen deposition inhibiting effects,thereby reducing liver inflammation damage and improving liver fibrosis.Conclusion Xiaoyao San may act on the expression of target proteins such as RELA,MAPK1,MAPK3,AKT1,and IL6 through signaling pathways such as Relaxin,IL-17,and HIF-1 in the treatment of CHB combined with MAFLD.It has anti-inflammatory,antioxidant,and collagen deposition inhibiting effects,thereby reducing liver inflammation and improving liver fibrosis.