Jin M A, Zhen-Wan L I, Yue-Zhong Luo, Yong Jiang, Zhong-Sheng Kuang, Yu-Hui Xie
the First Clinical Medical College of Guangzhou University of Chinese Medicine Guangzhou 510405, China.
Zhongguo Zhong Yao Za Zhi. 2020 Sep;45(17):4120-4128. doi: 10.19540/j.cnki.cjcmm.20200615.401.
As a prescription for promoting blood circulation and removing blood stasis, Taohong Siwu Decoction(THSWD) has certain effects in delaying the progression of renal fibrosis. However, as a traditional Chinese medicine compound containing many monomer components, it has been a research hotspot in the field of exploring the research methods and targets for the complex pathological process. The method of activating blood circulation and removing blood stasis has certain clinical effect in retarding the process of IgA nephropathy(IgAN) fibrosis, but the mechanism of action is still unclear. In this study, the network pharmacology method was used to investigate the active ingredients, targets and molecular mechanisms of THSWD in the intervention of IgAN fibrosis. On this basis, in vitro experiments were conducted to verify the effect of THSWD on the expression of ERK factor in BALB/c 3 T3 cells. The active ingredients and targets in THSWD were collected through the TCMSP. Sixty-one active ingredients and 240 targets including luteolin and quercetin were screened, and 185 targets were obtained by intersecting with CTD database to search IgAN related targets. Cytoscape software and STRING database were used to construct "THSWD-active ingredients-targets" network and protein-protein interaction network, and 69 core targets were screened. In DAVID's GO enrichment analysis and KEGG pathway analysis of the core targets and cell experiments, the results showed that ERK was an important factor for THSWD to interfere with IgAN fibrosis, and THSWD intervention could significantly decrease cell activity, ERK1/2 mRNA expression, and p-ERK1/2 protein expression. This study preliminarily revealed that THSWD may delay the growth of fibroblasts by affecting ERK factor and its phosphorylation level.
作为一种活血化瘀的方剂，桃红四物汤（THSWD）在延缓肾纤维化进展方面具有一定作用。然而，作为一种含有多种单体成分的中药复方，它一直是探索复杂病理过程研究方法和靶点领域的研究热点。活血化瘀法在延缓IgA肾病（IgAN）纤维化进程方面具有一定临床疗效，但其作用机制尚不清楚。本研究采用网络药理学方法探讨桃红四物汤干预IgAN纤维化的活性成分、靶点及分子机制。在此基础上，进行体外实验验证桃红四物汤对BALB/c 3T3细胞中ERK因子表达的影响。通过中药系统药理学数据库与分析平台（TCMSP）收集桃红四物汤中的活性成分和靶点。筛选出包括木犀草素和槲皮素在内的61种活性成分和240个靶点，并与比较毒理基因组学数据库（CTD）进行交集以搜索IgAN相关靶点，得到185个靶点。利用Cytoscape软件和STRING数据库构建“桃红四物汤-活性成分-靶点”网络和蛋白质-蛋白质相互作用网络，筛选出69个核心靶点。对核心靶点进行DAVID基因本体（GO）富集分析和京都基因与基因组百科全书（KEGG）通路分析以及细胞实验，结果表明ERK是桃红四物汤干预IgAN纤维化的重要因素，桃红四物汤干预可显著降低细胞活性、ERK1/2 mRNA表达和p-ERK1/2蛋白表达。本研究初步揭示桃红四物汤可能通过影响ERK因子及其磷酸化水平来延缓成纤维细胞生长。
