摘要
目的 探讨六味地黄汤治疗原发性干燥综合征(primary sjogren’s syndrome, pSS)的作用机制。方法 使用公共数据库平台TCMSP、GeneCards、DrugBank、PHARMGKB、OMIM和TTD对六味地黄汤组成药物的活性成分、作用靶点及PSS的疾病靶标进行检索,将药物成分靶点与疾病靶标取交集得到六味地黄汤治疗pSS的潜在靶点;使用STRING 11.5数据库获得六味地黄汤治疗PSS的蛋白互作网络(PPI),并通过Cytoscape 3.7.2软件分析得到核心靶点;通过基因本体(GO)富集分析、基因组百科全书(KEGG)通路富集分析筛选差异生物过程及靶点通路;使用Auto Dock 1.5.6及Pymol 2.2.0软件进行分子对接,验证核心靶点与活性成分之间的亲和力。结果 筛选得到六味地黄汤的药物活性成分74个,作用靶点184个,PSS疾病相关靶点1161个,药物-疾病交集靶点69个。数据分析显示,六味地黄汤的主要活性成分包括槲皮素、山柰酚、豆甾醇、海风藤酮和薯蓣皂苷元,六味地黄汤治疗pSS的8个核心靶点包括AKT1、CASP3、JUN、MMP9、NFKBIA、TP53、VEGFA。GO富集主要涉及脂多糖、氧化应激、活性氧代谢等生物过程。KEGG富集主要涉及抗炎、氧化应激等相关通路。分子对接结果显示,8个核心靶点与相应的活性成分的结合能均≤-5 kcal/mol,其中槲皮素与8个核心靶点均能较好地结合,可能是六味地黄汤干预pSS的主要有效成分。结论 六味地黄汤可能通过作用于AKT1、CASP3、JUN、MMP9、NFKBIA、TP53、VEGFA、IL-1β等关键靶点,通过“IL-17信号通路”“Th17细胞分化”“HIF-1信号通路”等发挥抗炎、免疫调节、抗氧化应激的作用,其中槲皮素可能是其发挥作用的主要有效成分。
Objective To investigate the therapeutic mechanism of Liuwei Dihuang Decoction(六味地黄汤,LWDHD)on primary Sjogren's Syndrome(PSS).Methods Public database platform(TCMSP、GeneCards、DrugBank、PHARMGKB、OMIM and TTD)were used to search the active ingredients and action targets of LWDHD,and disease targets of pSS were achieved.We intersected the drug ingredient targets and disease targets to obtain the potential targets of LWDHD for the treatment of pSS.The protein interaction network(PPI)of LWDHD for pSS treatment was obtained using STRING 11.5 database,and the core targets were obtained by Cytoscape 3.7.2 software.Differential biological processes and target pathways were screened by GO and KEGG analysis.Molecular docking was performed using Auto Dock 1.5.6 and PyMOL 2.2.0 software to verify the affinity between core target and active ingredient.Result The screening resulted in 74 pharmaceutically active components,184 action targets,1161 pSS disease-related targets,and 69 drug disease intersection targets of LWDHD.Data analysis revealed that main effective component of LWDHD included quercetin,kaempferol,stigmasterol,kaempferone and diosgenin,and the eight core targets of LWDHD in the treatment of pSS included AKT1,CASP3,Jun,MMP9,NFKBIA,TP53,VEGFA.Go analyses mainly involved the biological processes such as lipopolysaccharide,oxidative stress,and reactive oxygen species metabolism.KEGG analyses mainly involved in anti-inflammatory,oxidative stress and other related pathways.The molecular docking results showed that the binding energies of the eight core targets and the corresponding active ingredients were all≤-5 kcal/mol,among which quercetin bound better to all eight core targets,and might be the main effective ingredients of LWDHD in the treatment of pSS.Conclusion LWDHD may treat pSS by acting on core targets AKT1,CASP3,JUN,MMP9,NFKBIA,TP53,VEGFA and IL-1β.It can exert anti-inflammatory,immunoregulatory,antioxidant stress effects through"IL-17 signaling pathway""Th17 cell differentiation""HIF-1 s
作者
孙文婷
王琬茹
陈璐
孔维萍
阎小萍
SUN Wenting;WANG Wanru;CHEN Lu;KONG Weiping;YAN Xiaoping(China Academy of Chinese Medical Sciences,Beijing 100091,China;Aviation General Hospital,Beijing 100012,China;China-Japan Friendship Hospital,100029,Beijing,China)
出处
《实用中医内科杂志》
2024年第5期93-97,I0005-I0008,共9页
Journal of Practical Traditional Chinese Internal Medicine
基金
北京中医药管理局“薪火传承3+3工程”项目(2015-SZ-C-57)。
关键词
原发性干燥综合征
六味地黄汤
网络药理学
分子对接
primary sjogren's syndrome
Liuwei Dihuang Decoction(六味地黄汤)
network pharmacology
molecular docking
