Wu Yizhan, Guo Fei, Xu Xiaoxia, Liu Ya, Liu Jiangwei
Department of Graduate School, Xinjiang Medical University, Urumqi 830000, Xinjiang Uygur Autonomous Region, China.
Department of Emergency Trauma Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China.
Mediators Inflamm. 2025 Jul 23;2025:7748351. doi: 10.1155/mi/7748351. eCollection 2025.
Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by abdominal pain and altered bowel habits. Despite its high prevalence, the etiology of IBS remains elusive, and there is an unmet need for targeted therapeutic interventions. We initiated our study by conducting a causal analysis of proteomics data from 2941 proteins associated with IBS. Following this, we performed enrichment analysis to identify pathways and processes that may be implicated in the etiology of IBS. Subsequently, we utilized network pharmacology to explore the active compounds in traditional Chinese medicine that target the core proteins identified in our analysis. Molecular docking and molecular dynamics (MD) simulation are used to assess the stability of compound-protein binding. Our research has identified 169 proteins that have a positive causal relationship with IBS. We found that pathways linked to viruses, immune cells, and cytokines might play a role in IBS. Two traditional Chinese medicines, Phellodendri Amurensis Cortex (PAC) and Achyranthis Bidentatae Radix (ABR), showed potential in treating IBS, possibly through active compounds like quercetin, berberine, and evodiamine, targeting proteins Tumor Protein p53 (TP53), 5'(3')-Deoxyribonuclease (NT5E), Jun Proto-Oncogene (JUN), and major histocompatibility complex (MHC), Class II Invariant Chain (CD74). Additionally, we conducted molecular docking and MD simulations, and the results indicated that each protein has good binding stability with its corresponding compound. These findings not only deepen our understanding of the pathophysiological mechanisms of IBS but also indicate potential molecular targets for the development of innovative treatment strategies while highlighting the broad application prospects of traditional Chinese medicine in the field of IBS treatment.
肠易激综合征（IBS）是一种慢性功能性胃肠疾病，其特征为腹痛和排便习惯改变。尽管IBS患病率很高，但其病因仍不明确，靶向治疗干预仍存在未满足的需求。我们通过对2941种与IBS相关蛋白质的蛋白质组学数据进行因果分析来启动我们的研究。在此之后，我们进行了富集分析，以确定可能与IBS病因相关的途径和过程。随后，我们利用网络药理学探索中药中靶向我们分析中确定的核心蛋白质的活性化合物。分子对接和分子动力学（MD）模拟用于评估化合物 - 蛋白质结合的稳定性。我们的研究确定了169种与IBS呈正因果关系的蛋白质。我们发现与病毒、免疫细胞和细胞因子相关的途径可能在IBS中起作用。两种中药，黄柏（PAC）和牛膝（ABR），显示出治疗IBS的潜力，可能是通过槲皮素、小檗碱和吴茱萸碱等活性化合物，靶向肿瘤蛋白p53（TP53）、5'（3'） - 脱氧核糖核酸酶（NT5E）、原癌基因Jun（JUN）和主要组织相容性复合体（MHC）II类恒定链（CD74）等蛋白质。此外，我们进行了分子对接和MD模拟，结果表明每种蛋白质与其相应化合物具有良好的结合稳定性。这些发现不仅加深了我们对IBS病理生理机制的理解，还指出了创新治疗策略开发的潜在分子靶点，同时突出了中药在IBS治疗领域的广阔应用前景。
