<i>Craterellus cornucopioides</i>（灰喇叭菌）水提取物减轻结肠炎并通过网络药理学和分子对接探索其潜在机制

夏娟娟; 王鑫; 徐瑞祥; 夏紫微; 钟卫红; 刘婧; 肖雄; 付小梅

doi:10.13386/j.issn1002-0306.2025040175

Craterellus cornucopioides（灰喇叭菌）水提取物减轻结肠炎并通过网络药理学和分子对接探索其潜在机制

Craterellus cornucopioides Water Extracts Attenuate Colitis and Explore Underlying Mechanisms Via Network Pharmacology and Molecular Docking

摘要

摘要: 目的：本研究探讨Craterellus cornucopioides（灰喇叭菌）水提取物（CCWE）对大鼠溃疡性结肠炎（UC）模型的保护作用。方法：使用三硝基苯磺酸（TNBS）诱导大鼠溃疡性结肠炎（UC）模型。通过监测体重变化、疾病活动指数（DAI）评分和结肠组织苏木精-伊红（HE）染色来评估病理损伤。检测结肠组织中髓过氧化物酶（MPO）活性、一氧化氮（NO）、超氧化物歧化酶（SOD）活性、丙二醛（MDA）和促炎细胞因子（IL-1β、TNF-α、IL-6）水平，评价CCWE对UC的治疗效果。采用网络药理学筛选CCWE针对UC的活性成分、靶点和通路，然后对关键相互作用进行分子对接验证，以阐明其物质基础和作用机制。结果：TNBS组的DAI评分显著高于对照组（P<0.05）。与TNBS组相比，CCWE显著降低DAI评分（P<0.05）并改善宏观和组织学损伤。此外，与TNBS组相比，CCWE还显著降低了MPO、NO、MDA、IL-1β、TNF-α和IL-6水平（P<0.01），同时显著提高了SOD水平（P<0.01）。通过网络药理学预测CCWE治疗UC的核心靶点为 stat3、src、mapk3、pik3r1和akt1。作用机制包括HIF-1、relaxin和PI3K/Akt信号通路。CCWE治疗UC的主要成分是illudin T，quercetin（槲皮素），4-hydroxy-4-isopropenylcyclohexanemethanol acetate（4-羟基-4-异丙烯基环己烷甲醇乙酸酯），4-oxo-hex-5-enyl acetate（乙酸-4-氧代-5-己烯酯），craterellins B，ferulic acid（阿魏酸），craterellins A，caffeic acid（咖啡酸），4-oxohex-1,6-diyl diacetate（4-氧代己-1,6-二基二乙酸酯），and illudin M（隐陡头菌素M）。分子对接结果表明，CCWE的活性成分与这五个核心靶点表现出良好的结合亲和力，其中quercetin（槲皮素）和4-oxo-hex-5-enyl acetate（乙酸-4-氧代-5-己烯酯）显示出最显著的对接分数。结论：结果表明，CCWE的活性成分quercetin（槲皮素）和4-oxo-hex-5-enyl acetate（乙酸-4-氧代-5-己烯酯）可调节包括stat3、src、mapk3、pik3r1和akt1等基因表达，最终激活HIF-1、relaxin和PI3K/Akt通路治疗溃疡性结肠炎（UC）。

Abstract: Objective: The protective effects of Craterellus cornucopioides water extracts (CCWE) on rat model of UC were investigated in this study. Methods: Trinitrobenzene sulfonic acid (TNBS) was used to induce an ulcerative colitis (UC) model in rats. Pathological injury was assessed by monitoring body weight changes, disease activity index (DAI) scores, and hematoxylin-eosin (HE) staining of colonic tissues. The levels of myeloperoxidase (MPO) activity, nitric oxide (NO), superoxide dismutase (SOD) activity, malondialdehyde (MDA), and pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) in colon tissues were examined to evaluate the therapeutic effects of CCWE on UC. Network pharmacology was employed to screen active ingredients, targets, and pathways of CCWE against UC, followed by molecular docking validation of key interactions to elucidate its material basis and mechanism of action. Results: The results indicated that the DAI score of the TNBS group was significantly higher than that of the control group (P<0.05). Compared with the TNBS group, CCWE significantly reduced the DAI score (P<0.05) and improved macroscopic and histological damage. In addition, compared with the TNBS group, CCWE also significantly decreased the levels of MPO, NO, MDA, IL-1β, TNF-α and IL-6 (P<0.01), while significantly increasing the level of SOD (P<0.01). The core targets of CCWE in treating UC were predicted to be stat3、src、mapk3、pik3r1 and akt1 by network pharmacology. The mechanisms of action encompass the HIF-1, relaxin, and PI3K/Akt signaling pathway. The main components of CCWE for treating UC might be illudin T, quercetin, 4-hydroxy-4-isopropenylcyclohexanemethanol acetate, 4-oxo-hex-5-enyl acetate, craterellins B, ferulic acid, craterellins A, caffeic acid, 4-oxohex-1,6-diyl diacetate, and illudin M. Molecular docking results indicate that the active components of CCWE exhibit good binding affinity with these five core targets, with quercetin and 4-oxo-hex-5-enyl acetate showing the most significant docking scores. Conclusion: The results indicate that CCWE's active constituents, quercetin and 4-oxo-hex-5-enyl acetate, could modulate gene expression, including stat3、src、mapk3、pik3r1 and akt1, ultimately activating HIF-1, relaxin, and PI3K/Akt pathways for UC treatment.

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