Yang Jinfei, Li Siying
Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Front Pharmacol. 2023 Jun 8;14:1118804. doi: 10.3389/fphar.2023.1118804. eCollection 2023.
To determine the bioactive components of Hedyotis Diffusae Herba (HDH) and the targets in treating lupus nephritis (LN), and so as to elucidate the protective mechanism of HDH against LN. An aggregate of 147 drug targets and 162 LN targets were obtained from online databases, with 23 overlapped targets being determined as potential therapeutic targets of HDH against LN. Through centrality analysis, TNF, VEGFA and JUN were screened as core targets. And the bindings of TNF with stigmasterol, TNF with quercetin, and VEGFA with quercetin were further validated by molecular docking. By conducting Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses for drug targets, disease targets and the shared targets, TNF signaling pathway, Toll-like receptor signaling pathway, NF-kappa B signaling pathway and HIF-1 signaling pathway, etc., were found in all these three lists, indicating the potential mechanism of HDH in the treatment of LN. HDH may ameliorate the renal injury in LN by targeting multi-targets and multi-pathways, including TNF signaling pathway, NF-kappa B signaling pathway, HIF-1 signaling pathway and so on, which provided novel insights into further researches of the drug discovery in LN.
确定白花蛇舌草的生物活性成分及其治疗狼疮性肾炎(LN)的靶点,以阐明白花蛇舌草对LN的保护机制。从在线数据库中获得了147个药物靶点和162个LN靶点,确定了23个重叠靶点作为白花蛇舌草抗LN的潜在治疗靶点。通过中心性分析,筛选出肿瘤坏死因子(TNF)、血管内皮生长因子A(VEGFA)和Jun蛋白作为核心靶点。并通过分子对接进一步验证了TNF与豆甾醇、TNF与槲皮素以及VEGFA与槲皮素的结合。通过对药物靶点、疾病靶点和共同靶点进行京都基因与基因组百科全书(KEGG)和基因本体论(GO)富集分析,在这三个列表中均发现了TNF信号通路、Toll样受体信号通路、核因子κB信号通路和缺氧诱导因子-1信号通路等,表明白花蛇舌草治疗LN的潜在机制。白花蛇舌草可能通过靶向多靶点和多途径改善LN的肾损伤,包括TNF信号通路、核因子κB信号通路、缺氧诱导因子-1信号通路等,这为LN药物研发的进一步研究提供了新的见解。