Qin Yan, Zhang Rui-Ya, Zhang Yu, Zhao Yi-Qing, Hao Hai-Feng, Wang Jun-Ping
Department of Gastroenterology, Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University, Taiyuan 030012, Shanxi Province, China.
Department of Urology, The First Hospital of Shanxi Medical University, Taiyuan 030012, Shanxi Province, China.
World J Gastroenterol. 2025 Mar 7;31(9):100271. doi: 10.3748/wjg.v31.i9.100271.
Ulcerative colitis (UC), a chronic and challenging condition, necessitates the development of more effective treatments owing to the unsatisfactory efficacy and side effects associated with current medications. Traditional Chinese medicine (TCM), known for its multi-stage and multi-targeted approach, has a long history in treating gastrointestinal diseases and offering a promising alternative UC treatment. (), a commonly used remedy for UC in TCM, exemplifies this potential, although the specific components and mechanisms through which its therapeutic effects are exerted remain to be fully elucidated, highlighting the need for further research to unlock its full potential as a treatment option.
To investigate the key constituents and biological pathways through which exerts therapeutic effects on UC.
Network pharmacology investigated the UC-alleviating mechanism of , including "active ingredient-target-disease" network analysis, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Panaxadiol (PD; active ingredient of ) was tested in a mouse model of 3% dextran sulfate sodium-induced UC, with assessments of body weight, Disease Activity Index scores, and colon length. Colitis and intestinal barrier integrity were analyzed hematoxylin-eosin and Alcian blue and periodic acid-Schiff staining, immunohistochemistry, real time-quantitative PCR, and western blotting.
By integrating and analyzing the targets of and UC, 15 critical hub genes were discovered. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed the mechanisms involved to be linked to MAPK and PI3K-Akt signaling. Among the 10 main active ingredients identified as potentially effective, PD was most abundant and was validated to mitigate weight loss, reduce Disease Activity Index scores, and prevent colon shortening. PD also reduced inflammation and suppressed expression of pro-inflammatory cytokines and mediators. In addition, PD increased expression of mucin and tight junction proteins. Ultimately, PD counteracted effects of dextran sulfate sodium by inhibiting phosphorylation of NF-кB and MAPK, while increasing phosphorylation of AMPK and expression of NRF2 and NQO1.
PD alleviates colitis and aids intestinal barrier repair, partly modulation of the MAPK/NF-кB and AMPK/NRF2/NQO1 pathways. These findings also suggest new research methods for treatment of UC with TCM.
溃疡性结肠炎（UC）是一种慢性且具有挑战性的疾病，由于目前药物的疗效不尽人意且存在副作用，因此需要开发更有效的治疗方法。中医以其多阶段、多靶点的治疗方法而闻名，在治疗胃肠道疾病方面有着悠久的历史，并为UC治疗提供了一种有前景的替代方案。（）是中医治疗UC常用的药物，体现了这种潜力，尽管其发挥治疗作用的具体成分和机制仍有待充分阐明，这突出了进一步研究以挖掘其作为治疗选择的全部潜力的必要性。
研究（）对UC发挥治疗作用的关键成分和生物学途径。
网络药理学研究了（）缓解UC的机制，包括“活性成分-靶点-疾病”网络分析以及基因本体论和京都基因与基因组百科全书富集分析。在3%葡聚糖硫酸钠诱导的UC小鼠模型中测试了人参二醇（PD；（）的活性成分），评估了体重、疾病活动指数评分和结肠长度。通过苏木精-伊红染色、阿尔辛蓝和过碘酸-希夫染色、免疫组织化学、实时定量PCR和蛋白质印迹法分析结肠炎和肠屏障完整性。
通过整合和分析（）与UC 的靶点，发现了15个关键的枢纽基因。京都基因与基因组百科全书通路分析显示其涉及的机制与丝裂原活化蛋白激酶（MAPK）和磷脂酰肌醇-3-激酶/蛋白激酶B（PI3K-Akt）信号传导有关。在确定的10种潜在有效主要活性成分中，PD含量最高，并经证实可减轻体重减轻、降低疾病活动指数评分并防止结肠缩短。PD还减轻了炎症并抑制了促炎细胞因子和介质的表达。此外，PD增加了粘蛋白和紧密连接蛋白的表达。最终，PD通过抑制核因子κB（NF-κB）和MAPK的磷酸化，同时增加腺苷酸活化蛋白激酶（AMPK）的磷酸化以及核因子E2相关因子2（NRF2）和醌氧化还原酶1（NQO1）的表达，抵消了葡聚糖硫酸钠的作用。
PD减轻结肠炎并有助于肠屏障修复，部分是通过调节MAPK/NF-κB和AMPK/NRF2/NQO1途径实现的。这些发现也为中医治疗UC提供了新的研究方法。
