Therapeutic Effects of Valeriana jatamansi on Ulcerative Colitis: Insights into Mechanisms of Action through Metabolomics and Microbiome Analysis

Ulcerative colitis (UC), belonging to inflammatory bowel disease (IBD), is a chronic and relapsing inflammatory disorders of the gastrointestinal tract, which is not completely cured so far. Valeriana jatamansi is a Chinese medicine used clinically to treat "diarrhea", which is closely related to UC. This study was to elucidate the therapeutic effects of V. jatamansi extract (VJE) on dextran sodium sulfate (DSS)-induced UC in mice and its underlying mechanism. In this work, VJE effectively ameliorate the symptoms, histopathological scores and reduce the production of inflammatory factors of UC mice. The colon untargeted metabolomics analysis and 16S rDNA sequencing showed remarkable differences in colon metabolite profiles and intestinal microbiome composition between the control and DSS groups, and VJE intervention can reduce these differences. Thirty-two biomarkers were found and modulated the primary pathways including pyrimidine metabolism, arginine biosynthesis and glutathione metabolism. Meanwhile, twelve significant taxa of gut microbiota were found. Moreover, there is a close relationship between endogenous metabolites and intestinal flora. These findings suggested that VJE ameliorates UC by inhibiting inflammatory factors, recovering intestinal maladjustment, and regulating the interaction between intestinal microbiota and host metabolites. Therefore, the intervention of V. jatamansi is a potential therapeutic treatment for UC.

溃疡性结肠炎（Ulcerative Colitis, UC）隶属于炎症性肠病（Inflammatory Bowel Disease, IBD）范畴，是一类慢性复发性胃肠道炎症性疾病，目前尚无法完全治愈。蜘蛛香（Valeriana jatamansi）是一种临床用于治疗“泄泻”的中药材，其与溃疡性结肠炎的发病机制密切相关。本研究旨在阐明蜘蛛香提取物（Valeriana jatamansi Extract, VJE）对葡聚糖硫酸钠（Dextran Sodium Sulfate, DSS）诱导的小鼠溃疡性结肠炎的治疗作用及其潜在分子机制。
本研究结果显示，VJE可有效改善溃疡性结肠炎模型小鼠的临床症状与组织病理学评分，并降低其炎症因子的产生水平。通过结肠非靶向代谢组学分析与16S核糖体DNA（16S rDNA）测序发现，对照组与DSS模型组小鼠的结肠代谢物谱及肠道菌群组成存在显著差异，而VJE干预可显著缩小此类差异。研究共筛选得到32种差异生物标志物，其调控的核心通路包括嘧啶代谢、精氨酸生物合成与谷胱甘肽代谢；同时鉴定出12种具有显著差异的肠道菌群类群。此外，内源性代谢物与肠道菌群之间存在紧密的相互关联。
上述研究结果表明，VJE可通过抑制炎症因子释放、纠正肠道代谢失衡、调控肠道菌群与宿主代谢物之间的互作关系，从而改善溃疡性结肠炎病症。因此，蜘蛛香干预有望成为溃疡性结肠炎的潜在治疗策略。