Magnoflorine alleviates colitis-induced anxiety-like behaviors by regulating gut microbiota and microglia-mediated neuroinflammation

作者：Lei Wang, Mengfan Li, Yue Dong, Jingyi Wang, Siqi Qin, Liying Li, Bingqing Li, Bangmao Wang, Hailong Cao · 发表于：Microbiome · 年份：2025 · DOI：10.1186/s40168-025-02158-y · 被引用次数：6 · 研究领域：Ziziphus Jujuba Studies and Applications、Gut microbiota and health、Gastrointestinal motility and disorders

BACKGROUND: Inflammatory bowel disease (IBD) and anxiety are often comorbid and are interconnected through the microbiota-gut-brain axis. Therapeutic medications for anxiety are often constrained by adverse effects that limit their long-term use. Therefore, recent research has focused on identifying natural, safe drugs for anxiety, and elucidating the precise mechanisms underlying the interplay between drugs and the gut-brain axis in modulating mood. RESULTS: We revealed a significant association between active ulcerative colitis (UC) and anxiety. The results of Mendelian randomization analysis suggested that UC has a causal relationship with anxiety, but not depression. We identified Ziziphus jujuba, a natural plant, as a dual therapeutic agent for both UC and anxiety using the Batman database. Magnoflorine, the predominant compound found in Ziziphus jujuba, exhibits promising therapeutic properties for the treatment of UC and anxiety disorders. We found that magnoflorine not only alleviated colitis but also reduced colitis-induced anxiety behaviors through the gut microbiota. Mechanistically, magnoflorine increased the abundance of Odoribacteraceae and Ruminococcus and regulated bile acid metabolism, especially hyodeoxycholic acid (HDCA) in mice with colitis. HDCA supplementation alleviated both colitis and colitis-induced anxiety. HDCA inhibited the binding of lipopolysaccharide to the TLR4/MD2 complex, thereby inhibiting microglial activation and alleviating neuroinflamma...