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Published on: June 2, 2022
Magnoflorine alleviates colitis-induced anxiety-like behaviors by regulating gut microbiota and microglia-mediated
Lei Wang1,2, Mengfan Li1, Yue Dong1
1Department of Gastroenterology and Hepatology, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, General Hospital, Tianjin Medical University, Tianjin, 300052, China.
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 neuroinflammation.
Conclusion:
Our study revealed that magnoflorine alleviated colitis-induced anxiety-like behaviors by regulating the gut microbiota and microglia-mediated neuroinflammation, which has the potential to treat patients with IBD and anxiety disorders. Video Abstract.
Insights
Ziziphus jujuba
Area of Science:
- Microbiology
- Neuroscience
- Pharmacology
Background:
- Inflammatory bowel disease (IBD) and anxiety frequently co-occur, linked via the microbiota-gut-brain axis.
- Current anxiety medications have limitations due to adverse effects, driving research into natural alternatives.
- Understanding drug mechanisms within the gut-brain axis is crucial for mood modulation.
Purpose of the Study:
- To investigate the potential of natural compounds for treating comorbid IBD and anxiety.
- To elucidate the gut-brain axis mechanisms involved in the therapeutic effects of Ziziphus jujuba.
- To identify specific gut microbiota and metabolic pathways influenced by Ziziphus jujuba.
Main Methods:
- Mendelian randomization analysis to establish causality between ulcerative colitis (UC) and anxiety.
- Utilized the Batman database to identify Ziziphus jujuba as a potential therapeutic agent.
- Investigated the effects of magnoflorine (a Ziziphus jujuba compound) on colitis and anxiety behaviors in mice.
- Analyzed changes in gut microbiota composition and bile acid metabolism.
- Examined the impact of hyodeoxycholic acid (HDCA) on inflammation and anxiety.
Main Results:
- Ulcerative colitis (UC) showed a causal link with anxiety, not depression.
- Ziziphus jujuba, specifically its compound magnoflorine, demonstrated dual therapeutic potential for UC and anxiety.
- Magnoflorine treatment reduced colitis and associated anxiety behaviors by modulating gut microbiota (increasing Odoribacteraceae and Ruminococcus) and bile acid metabolism.
- Hyodeoxycholic acid (HDCA) supplementation alleviated colitis and anxiety.
- HDCA inhibited TLR4/MD2 complex activation, reducing microglial activation and neuroinflammation.
Conclusions:
- Magnoflorine effectively alleviates colitis-induced anxiety-like behaviors.
- The mechanism involves regulating gut microbiota and inhibiting microglia-mediated neuroinflammation.
- Magnoflorine shows promise as a dual therapeutic agent for patients with IBD and anxiety disorders.
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