Ji Enhui, Wang Tingting, Xu Jing, Fan Jianwei, Zhang Yi, Guan Yongxia, Yang Hongjun, Wei Junying, Zhang Guimin, Huang Luqi
School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
Front Pharmacol. 2020 Aug 31;11:1337. doi: 10.3389/fphar.2020.01337. eCollection 2020.
The aim of this study was to investigate the precise clinical use of Sinitang decoction (SNT) in ulcerative colitis (UC). Network pharmacology-based analysis of the drug components-targets-diseases-pathways was used to predict the possible clinical applications of SNT. Next, 2,4,6-trinitrobenzenesulfonic acid (TNBS) was used to establish a rat model of UC, and the efficacy of SNT against UC was tested, followed by a proteomic analysis of the specific signatures regulated by SNT against UC. SNT was predicted to be effective in inflammatory bowel disease, UC, and several other diseases. In the rats with UC, SNT decreased the disease activity index and colon mucosal damage index compared to the untreated UC model rats. Additionally, SNT reversed the upregulated levels of serum tumor necrosis factor (TNF)-α, prostaglandin E (PGE), interleukin (IL)-6, and nitric oxide (NO) in UC model rats. The proteomic analysis identified 78 proteins that were differentially regulated by SNT in the rats with UC, which were associated with the Gene Ontology terms sulfur compound binding, calcium ion binding, and Toll-like receptor (TLR)-4 binding. Among these differentially regulated proteins, C-reactive protein (CRP) and collagen alpha-1(XII) chain (COL12A1) were found to be signature proteins associated with the efficacy of SNT against UC. This study represents the first precise investigation of the efficacy and mechanisms of SNT against UC, and shows that SNT is a promising candidate for personalized management of UC.
本研究旨在探讨四逆汤(SNT)在溃疡性结肠炎(UC)中的精准临床应用。采用基于网络药理学的药物成分-靶点-疾病-通路分析方法,预测SNT可能的临床应用。接下来,使用2,4,6-三硝基苯磺酸(TNBS)建立UC大鼠模型,检测SNT对UC的疗效,随后对SNT调控的UC特异性标志物进行蛋白质组学分析。预测SNT对炎症性肠病、UC及其他几种疾病有效。在UC大鼠中,与未治疗的UC模型大鼠相比,SNT降低了疾病活动指数和结肠黏膜损伤指数。此外,SNT逆转了UC模型大鼠血清肿瘤坏死因子(TNF)-α、前列腺素E(PGE)、白细胞介素(IL)-6和一氧化氮(NO)水平的上调。蛋白质组学分析鉴定出78种在UC大鼠中受SNT差异调控的蛋白质,这些蛋白质与基因本体术语硫化合物结合、钙离子结合和Toll样受体(TLR)-4结合相关。在这些差异调控的蛋白质中,发现C反应蛋白(CRP)和胶原蛋白α-1(XII)链(COL12A1)是与SNT治疗UC疗效相关的标志性蛋白质。本研究首次对SNT治疗UC的疗效和机制进行了精准研究,表明SNT是UC个性化治疗的有前景的候选药物。