基于网络药理学和实验验证的水黄连-黄连治疗溃疡性结肠炎的作用机制。
The Mechanism of Polygonum Hydropiper L-Coptis Chinensis in the Treatment of Ulcerative Colitis Based on Network Pharmacology and Experimental Validation.
机构信息
Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Key Laboratory for Research and Development of Tropical Herbs, Haikou Key Laboratory of Li Nationality Medicine, School of Pharmacy, Hainan Medical University, 571199 Haikou, Hainan, China.
Department of Pathology, The First Affiliated Hospital of Hainan Medical University, 570102 Haikou, Hainan, China.
出版信息
Front Biosci (Landmark Ed). 2024 Mar 8;29(3):93. doi: 10.31083/j.fbl2903093.
BACKGROUND
(PH) was widely used to treat dysentery, gastroenteritis, diarrhea and other diseases. (CC) had the effects of clearing dampness-heat, purging fire, and detoxifying. Study confirmed that flavonoids in PH and alkaloids in CC alleviated inflammation to inhibit the development of intestinal inflammation. However, how PH-CC affects UC was unclear. Therefore, the aim of this study is to analyze the mechanism of PH-CC on ulcerative colitis (UC) through network pharmacology and experiments.
METHODS
The active ingredients and targets of PH-CC and targets of UC were screened based on related databases. The core targets of PH-CC on UC was predicted by protein-protein interaction network (PPI), and then the Gene Ontology-biological processes (GO-BP) function enrichment analysis was conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. The binding activity between pyroptosis proteins, core targets and effective ingredients were verified based on molecular docking technology. Finally, combined with the results of network pharmacology and literature research, the mechanism of PH-CC against UC was verified by experiments.
RESULTS
There were 23 active components and 191 potential targets in PH-CC, 5275 targets in UC, and 141 co-targets. GO-BP functional analysis of 141 co-targets showed that the first 20 biological processes were closely related to inflammation and lipopolysaccharide (LPS) stimulation. Furthermore, core targets had good binding activity with the corresponding compounds. Animal experiment indicated that PH-CC effectively prevented weight loss in UC mice, reduced the disease activity index (DAI) score, maintained colon length, suppressed myeloperoxidase (MPO) activity, inhibited pyroptosis protein expression, and downregulated the levels of IL-18 and IL-1β to alleviate intestinal inflammation.
CONCLUSIONS
The results of network pharmacology and animal experiments showed that PH-CC suppressed the inflammatory response, restored colon morphology, and inhibited pyroptosis in UC mice. Thus, PH-CC may improve UC by regulating the NOD-like receptor protein domain 3 (NLRP3)/Caspase-1 signaling pathway.
背景
（PH）被广泛用于治疗痢疾、肠胃炎、腹泻等疾病。（CC）具有清热燥湿、泻火解毒的功效。研究证实 PH 中的类黄酮和 CC 中的生物碱能减轻炎症，抑制肠道炎症的发展。然而，PH-CC 如何影响 UC 尚不清楚。因此，本研究旨在通过网络药理学和实验分析 PH-CC 对溃疡性结肠炎（UC）的作用机制。
方法
基于相关数据库筛选 PH-CC 的活性成分和靶点以及 UC 的靶点。通过蛋白质-蛋白质相互作用网络（PPI）预测 PH-CC 治疗 UC 的核心靶点，然后使用数据库 for Annotation, Visualization and Integrated Discovery（DAVID）数据库进行基因本体论-生物过程（GO-BP）功能富集分析。基于分子对接技术验证细胞焦亡蛋白、核心靶点与有效成分的结合活性。最后，结合网络药理学和文献研究结果，通过实验验证 PH-CC 治疗 UC 的机制。
结果
PH-CC 中有 23 种活性成分和 191 个潜在靶点，UC 中有 5275 个靶点，有 141 个共同靶点。对 141 个共同靶点的 GO-BP 功能分析表明，前 20 个生物学过程与炎症和脂多糖（LPS）刺激密切相关。此外，核心靶点与相应化合物具有良好的结合活性。动物实验表明，PH-CC 能有效预防 UC 小鼠体重减轻，降低疾病活动指数（DAI）评分，维持结肠长度，抑制髓过氧化物酶（MPO）活性，抑制细胞焦亡蛋白表达，下调白介素-18（IL-18）和白介素-1β（IL-1β）水平，从而缓解肠道炎症。
结论
网络药理学和动物实验结果表明，PH-CC 抑制 UC 小鼠的炎症反应，恢复结肠形态，抑制细胞焦亡。因此，PH-CC 可能通过调节 NOD 样受体蛋白结构域 3（NLRP3）/半胱天冬酶-1 信号通路改善 UC。
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