Integrated network pharmacology and bioinformatics to identify therapeutic targets and molecular mechanisms of Huangkui Lianchang Decoction for ulcerative colitis treatment,BMC Complementary Medicine and Therapies

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Integrated network pharmacology and bioinformatics to identify therapeutic targets and molecular mechanisms of Huangkui Lianchang Decoction for ulcerative colitis treatment
BMC Complementary Medicine and Therapies ( IF 3.3 ) Pub Date : 2024-07-23 , DOI: 10.1186/s12906-024-04590-3
Zongqi He ₁ , Xiang Xu ₂ , Yugen Chen ₃ , Yuyu Huang ₁ , Bensheng Wu ₁ , Zhizhong Xu ₁ , Jun Du ₁ , Qing Zhou ₃ , Xudong Cheng _{1,

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Affiliation

Background

Huangkui Lianchang Decoction (HLD) is a traditional Chinese herbal formula for treating ulcerative colitis (UC). However, its mechanism of action remains poorly understood. The Study aims to validate the therapeutic effect of HLD on UC and its mechanism by integrating network pharmacology, bioinformatics, and experimental validation.

Methods

UC targets were collected by databases and GSE19101. The active ingredients in HLD were detected by ultra-performance liquid chromatography-tandem mass spectrometry. PubChem collected targets of active ingredients. Protein–protein interaction (PPI) networks were established with UC-related targets. Gene Ontology and Kyoto Encyclopedia (KEGG) of Genes and Genomes enrichment were analyzed for the mechanism of HLD treatment of UC and validated by the signaling pathways of HLD. Effects of HLD on UC were verified using dextran sulfate sodium (DDS)-induced UC mice experiments.

Results

A total of 1883 UC-related targets were obtained from the GSE10191 dataset, 1589 from the database, and 1313 matching HLD-related targets, for a total of 94 key targets. Combined with PPI, GO, and KEGG network analyses, the signaling pathways were enriched to obtain IL-17, Toll-like receptor, NF-κB, and tumor necrosis factor signaling pathways. In animal experiments, HLD improved the inflammatory response of UC and reduced UC-induced pro-inflammatory factors such as Tumor Necrosis Factor Alpha (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6). HLD suppressed proteins TLR4, MyD88, and NF-κB expression.

Conclusions

This study systematically dissected the molecular mechanism of HLD for the treatment of UC using a network pharmacology approach. Further animal verification experiments revealed that HLD inhibited inflammatory responses and improved intestinal barrier function through the TLR4/MyD88/NF-κB pathway.

中文翻译：

整合网络药理学和生物信息学确定黄葵连肠汤治疗溃疡性结肠炎的治疗靶点和分子机制

背景

黄葵连肠汤（HLD）是治疗溃疡性结肠炎（UC）的传统中药配方。然而，其作用机制仍知之甚少。该研究旨在通过整合网络药理学、生物信息学和实验验证来验证HLD对UC的治疗效果及其机制。

方法

UC 目标由数据库和 GSE19101 收集。采用超高效液相色谱-串联质谱法检测HLD中的活性成分。 PubChem 收集了活性成分的目标。蛋白质-蛋白质相互作用 (PPI) 网络是通过 UC 相关靶标建立的。基因本体论和京都基因和基因组百科全书（KEGG）富集分析了HLD治疗UC的机制，并通过HLD的信号通路进行了验证。使用葡聚糖硫酸钠 (DDS) 诱导的 UC 小鼠实验验证了 HLD 对 UC 的影响。

结果

从GSE10191数据集中总共获得了1883个UC相关目标，从数据库中获得了1589个，以及1313个匹配的HLD相关目标，总共94个关键目标。结合PPI、GO、KEGG网络分析，对信号通路进行富集，获得IL-17、Toll样受体、NF-κB、肿瘤坏死因子信号通路。在动物实验中，HLD改善了UC的炎症反应，并减少了UC诱导的促炎因子，如肿瘤坏死因子α（TNF-α）、白细胞介素1β（IL-1β）和白细胞介素6（IL-6）。 HLD 抑制 TLR4、MyD88 和 NF-κB 蛋白的表达。