阿片忍冬通过调节AHR/IL-22/STAT3信号轴减轻溃疡性结肠炎的炎症并重建肠屏障
Osbeckia opipara attenuates inflammation and reconstructs the intestinal barrier in ulcerative colitis by modulating the AHR/IL-22/STAT3 signaling axis.
摘要(中文译文)
溃疡性结肠炎（UC）因持续的上皮屏障功能障碍而成为治疗难题。传统苗药金锦香（Osbeckia opipara，O. opipara）具有临床疗效，但其作用机制尚不明确。本研究旨在通过整合药理学与实验方法阐明金锦香治疗UC的作用机制。研究采用从临床到基础的转化研究框架，结合多组学分析、遗传因果推断、分子模拟及临床前模型中的实验验证。采用超高效液相色谱-串联质谱法表征活性成分。药物靶点孟德尔随机化（DTMR）确定芳香烃受体（AHR）和信号转导与转录激活因子3（STAT3）为关键遗传靶点。分子动力学模拟评估配体-受体相互作用。在葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠及脂多糖刺激的肠上皮细胞中评估疗效。分别通过16S核糖体RNA测序和RNA测序分析肠道菌群及宿主转录组的变化。在临床前模型中，金锦香至少部分通过调控AHR/IL-22/STAT3信号轴减轻DSS诱导的结肠炎。没食子酸和鞣花酸被鉴定为核心AHR激动剂。治疗显著抑制炎症反应、恢复肠道菌群稳态，并通过上调紧密连接蛋白重建肠道屏障完整性。AHR抑制可消除上述治疗效应，证实该机制依赖于AHR激活。金锦香作为天然AHR激动剂，在临床前UC模型中调节炎症、菌群失调及屏障功能障碍以促进黏膜愈合，为其传统治疗应用提供了机制证据。
Abstract
Ulcerative colitis (UC) poses a therapeutic challenge due to persistent epithelial barrier dysfunction. The traditional Miao medicine Osbeckia opipara (O. opipara) shows clinical efficacy, yet its mechanism remains unclear. To elucidate the therapeutic mechanism of O. opipara in UC through integrated pharmacological and experimental approaches. A bedside to bench translational framework was employed combining multiomics analysis, genetic causal inference, molecular simulation and experimental validation in preclinical models. Active constituents were characterized using ultra high performance liquid chromatography tandem mass spectrometry. Drug target Mendelian randomization (DTMR) identified aryl hydrocarbon receptor (AHR) and signal transducer and activator of transcription 3 (STAT3) as pivotal genetic targets. Molecular dynamics simulations assessed ligand receptor interactions. Efficacy was evaluated in dextran sulfate sodium (DSS) induced colitis mice and lipopolysaccharide stimulated intestinal epithelial cells. Alterations in gut microbiota and host transcriptome were profiled by 16S ribosomal RNA sequencing and RNA sequencing respectively. O. opipara alleviated DSS-induced colitis, at least in part, through modulation of the AHR/IL-22/STAT3 signaling axis in preclinical models. Gallic acid and Ellagic acid were identified as core AHR agonists. Treatment significantly suppressed inflammatory responses, restored gut microbiota homeostasis, and reconstructed intestinal barrier integrity by upregulating tight junction proteins. AHR inhibition abolished these therapeutic effects, confirming the mechanism's dependence on AHR activation. O. opipara acts as a natural AHR agonist that modulates inflammation, microbiota dysbiosis, and barrier dysfunction to promote mucosal healing in preclinical UC models, providing mechanistic evidence supporting its traditional therapeutic application.
如何引用
AMA
Qiang Su, Qiuhong Yao, Tinghui Yue, Run Shi, Yuhao Xie, Chuang Liu, et al. Osbeckia opipara attenuates inflammation and reconstructs the intestinal barrier in ulcerative colitis by modulating the AHR/IL-22/STAT3 signaling axis.. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2026; doi:10.1016/j.phymed.2026.158554.
APA
Qiang Su, Qiuhong Yao, Tinghui Yue, Run Shi, Yuhao Xie, Chuang Liu, et al (2026). Osbeckia opipara attenuates inflammation and reconstructs the intestinal barrier in ulcerative colitis by modulating the AHR/IL-22/STAT3 signaling axis.. Phytomedicine : international journal of phytotherapy and phytopharmacology. https://doi.org/10.1016/j.phymed.2026.158554
GB/T 7714
Qiang Su, Qiuhong Yao, Tinghui Yue, Run Shi, Yuhao Xie, Chuang Liu, et al. Osbeckia opipara attenuates inflammation and reconstructs the intestinal barrier in ulcerative colitis by modulating the AHR/IL-22/STAT3 signaling axis.[J]. Phytomedicine : international journal of phytotherapy and phytopharmacology, 2026 doi:10.1016/j.phymed.2026.158554.
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