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目的：应用网络药理学与分子对接研究肠安康对溃疡性结肠炎的疗效及机理。方法：基于TCMSP数据库，对肠道安康的药效物质基础进行筛选，采用Pubchem、 Swisstarget prediction及Uniprot等数据库，获得药效物质基础。利用Genecards, DisGeNET, OMIM等数据库获得UC相关靶基因。使用String及Cytoscape3.9.1构建肠安康治疗溃疡性结肠炎的蛋白-蛋白相互作用网络，通过GO、 KEGG等生物信息学分析，利用Autodock软件对其关键靶标进行分子对接，预测其作用机制。建立小鼠溃疡性结肠炎模型，通过HE染色检测肠安康对溃疡性结肠炎的影响，并验证网络药理学信号通路预测结果。结果：本研究共筛选出93个活性成分、227个作用靶点、2 545个疾病相关靶点，“药物-活性成分-作用靶点”共有333个节点和1 078条边。利用GO、 KEGG等方法，对上述20个基因进行了初步的生物学功能及信号途径的筛选。分子对接结果表明，核心组分与核心靶标之间存在良好的结合能。结论：肠安康有效改善溃疡性结肠炎形态学结构。肠安康通过其主要活性成分槲皮素，刺芒柄花素，山柰酚等，调节RXRA,AR,RB1,IL6等靶基因的表达。尤其在调节细胞自噬、炎症反应和巨噬细胞极化等生物学过程上发挥关键作用，从而发挥治疗溃疡性结肠炎的作用。
Abstract：Objective: To investigate the therapeutic effect and mechanism of ChangAnKang in treating ulcerative colitis. Methods: Using TCMSP database, we identified the active components of ChangAnKang. Using Pubchem, Swisstarget forecast and Uniprot database, we got the potential action targets of TCM active ingredients.Target genes of ulcerative colitis were acquired by Genecards, DisGeNET and OMIM. Using STRING and Cytoscape 3.9.1, the protein-protein interaction network for treating ulcerative colitis was constructed, and then analyzed with GO and KEGG. Finally, by using Autodock, the binding probability of the core chemical composition with the core target was predicted. A model of ulcerative colitis was established to detect the effect of intestinal health on ulcerative colitis by HE staining and to verify the prediction results of the network pharmacological signaling pathway. Results: A total of 93 active ingredients, 227 targets and 2 545 disease-related targets were identified in this study, and the "drug-active ingredient target" network had 333 nodes and 1 078 edges.The enrichment of GO and KEGG was used to identify the first 20 biological functions and signaling pathways. It was found that there was good binding probability of the core chemical composition with the core target. Conclusion: ChangAnKang effectively improves the morphological structure of ulcerative colitis. ChangAnKang may regulate cancer pathway, hepatitis B, MAPK signaling pathway, PI3K-AKT signaling pathway, human cytomegalovirus infection, chemical carcinogenesis-receptor-initiated, Toll-like receptor signaling pathway through the main active ingredients, quercetin, prickly aristolochicin, kaempferol and other signaling pathways, exerting a therapeutic effect on ulcerative colitis.
1 Shi X,Yu J,Lu C,et al. Screening of the shared pathogenic genes of ulcerative colitis and colorectal cancer by integrated bioinformatics analysis[J]. J Cell Mol Med,2023,28(5):e17878.
2 Truta B. The impact of inflammatory bowel disease on women′s lives[J]. Curr Opin Gastroenterol,2021,37(4):306-312.
3 Facanali CBG,Sobrado Junior CW,Fraguas Junior R,et al. The relationship of major depressive disorder with Crohn′s disease activity[J]. Clinics(Sao Paulo),2023,78:100188.
4 Nakase H,Sato N,Mizuno N,et al.The influence of cytokines on the complex pathology of ulcerative colitis[J].Autoimmunity Rev,2021,21(3):103017.
5 Neurath MF. Targeting immune cell circuits and trafficking in inflammatory bowel disease[J]. Nature Immunol,2019,20(8):970-979.
6 Nakase H. Treatment of inflammatory bowel disease from the immunological perspective[J]. Immunol Med,2020,43(2):79-86.
7 Porter RJ,Kalla R,Ho GT. Ulcerative colitis:Recent advances in the understanding of disease pathogenesis[J]. F1000Res,2020,9:F1000 Faculty Rev-294.
8 Lopetuso LR,Corbi M,Scaldaferri F,et al. Characterization of mucosal cytokine profile in ulcerative colitis patients under conventional and anti-TNF-a treatment[J].Eur J Gastroenterol Hepatol,2020,32(12):1527-1532.
9 Bertani L,Baglietto L,Antonioli L,et al.Assessment of serum cytokines predicts clinical and endoscopic outcomes to vedolizumab in ulcerative colitis patients[J].British J Clin Pharmacol,2020,86(7):1296-1305.
10 Hong S, Wang H, Chan S, et al. Identifying macrophage-related genes in ulcerative colitis using weighted coexpression network analysis and machine learning[J]. Med Inflamm,2023,2023:4373840.
11 Eftychi C,Schwarzer R,Vlantis K,et al.Temporally distinct functions of the cytokines IL-12 and IL-23 drive chronic colon inflammation in response to intestinal barrier impairment[J]. Immunity,2019,51(2):367-380.
12 Mirsepasi-Lauridsen HC,Vallance BA,Krogfelt KA,et al. Escherichia coli pathobionts associated with inflammatory bowel disease[J].Clinical Microbiol Rev, 2019, 32(2):e00060-18.
13 Vallabhapurapu S,Karin M. Regulation and function of NF-kappaB transcription factors in the immune system[J]. Annu Rev Immunol,2019,27(5):693-733.
14 Bidere N,Ngo VN. Casein kinase 1alpha governs antigen-receptor-induced NF-kappaB activation and human lymphoma cell survival[J]. Nature,2019,458(7234):92-96.
15 Xin P,Xu X,Deng C,et al.The role of JAK/STAT signaling pathway and its inhibitors in diseases[J].Int Immunopharmacol, 2020,80:106 210.
16 Zhang M,Ding X,Song W,et al.Correlation of IL-6 and JAK2/STAT3 signaling pathway with prognosis of nasopharyngeal carcinoma patients[J]. Aging(Albany NY),2021,13(12):16667-16683.
17 Abdel-Hamid AAM,Mesbah Y,Soliman MFM,et al.Dominance of pro-inflammatory cytokines over anti-inflammatory ones in placental bed of creta cases[J].J Microsc Ultrastruct,2022,12(1):14-20.
18 Jee SH,Chu CY,Chiu HC,et al. Interleukin-6 induced basic fibroblast growth actor-dependent angiogenesis in basal cell carcinoma cell line via JAK/STAT3 and PI3-ki-nase/Akt pathways[J]. J Invest Dermatol,2019,123(6):1169-1175.
19 Sabat R,Grutz G,Bamba S,et al. Biology of intedeukin-10 cytokine growth factor[J]. Rev,2019,21(5):331.
20 吕银娟，张玮珩，陈思易，等.基于TLR4/NF-κB p65信号通路研究左归丸防治产前应激子代大鼠卵巢储备功能下降的分子机制[J].中国实验方剂学杂志，1-12.Lv YJ, Zhang WH, Chen SY, et al. Study on the molecular mechanism of Zuogui pill in preventing and treating decreased ovarian reserve function in rats with prenatal stress based on TLR4/NF-κB p65 signaling pathway[J]. Chin J Exp Pharmaceut,1-12.
21 陶斯雨，李亚，陈锴，等.基于NF-κB信号通路的急性肺损伤病理机制及中医药干预研究进展[J].中药药理与临床，1-22.Tao SY, Li Y, Chen K, et al. Research progress on the pathological mechanism of acute lung injury based on NF-κB signaling pathway and the intervention of traditional Chinese medicine[J]. Pharmacol Clin Med Tradit Chin Med,1-22.
22 陈振东，田旭东.溃疡性结肠炎中医微观辨证研究进展[C].中国中西医结合学会，中国中西医结合学会消化内镜学专业委员会.2019中国中西医结合学会消化内镜学专业委员会第一届第四次学术交流会摘要集.2019:107-115.Chen ZD, Tian XD. Research progress on microscopic syndrome differentiation in traditional Chinese medicine for ulcerative colitis[C]. Chinese Association of Integrative Medicine,Digestive Endoscopy Professional Committee of Chinese Association of Integrative Medicine. 2019 Abstract Collection of the First Fourth Academic Exchange Meeting of the Digestive Endoscopy Professional Committee of Chinese Association of Integrative Medicine,2019:107-115.
基本信息:
DOI：10.13210/j.cnki.jhmu.20241205.001
中图分类号:R285
引用信息:
[1]陆振华,张国帅,范明明,等.肠安康治疗溃疡性结肠炎的作用机制研究[J].海南医科大学学报,2025,31(15):1172-1181.DOI:10.13210/j.cnki.jhmu.20241205.001.
基金信息:
黑龙江省中医药科研项目(ZHY2020-050)~~
2024-12-06
2024-12-06
2024-12-06