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.

Microbiome
|July 27, 2025
PubMed
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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