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Published on: January 16, 2013
Lycium barbarum polysaccharides alleviate experimental autoimmune prostatitis by putrescine/TRAF/JAK/STAT-mediated
Xu Wang1, Shao-Yu Yue1, Lei Chen1
1Department of Urology, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, PR China; Institute of Urology, Anhui Medical University, Hefei, Anhui, PR China; Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, PR China.
Background:
Due to its often refractory nature, chronic prostatitis (CP) is a prevalent disorder that notably impacts the quality of life of 20-40-year-old men worldwide. Lycium barbarum polysaccharides (LBPs) have a broad spectrum of biological activities, such as immune modulation and the ability to reduce blood glucose and lipid levels. However, whether they modulate the gut microbiota and metabolites to exert their anti-inflammatory effects remains to be explored.
Methods:
Oral administration of LBPs was used to treat experimental autoimmune prostatitis (EAP) model mice. To investigate the alterations in the gut flora and its metabolites in EAP model mice, mass spectrometry-based metabolomics and 16S rRNA sequencing were conducted. A series of functional experiments was subsequently conducted to investigate the mechanisms by which gut flora metabolites modulate Th17 cell immunity and influence the pathogenesis of EAP.
Results:
Oral administration of LBPs alleviated EAP in mice. Pathway enrichment analysis of the metabolomics data revealed notable enrichment of pathways associated with putrescine synthesis and metabolism. This finding was subsequently validated by measuring serum, gut, and prostate putrescine levels. Both cell and animal model studies demonstrated that putrescine alleviates EAP and inhibits Th17 cell differentiation. Further mechanistic studies revealed that putrescine suppresses Th17 cell differentiation and inflammation-driven cytokine synthesis by inhibiting the JAK2-STAT3 pathway via TRAF6.
Conclusions:
Overall, we conducted the first study on the therapeutic effect of LBPs on CP, demonstrating that LBPs mediate the influence of the gut microbiota and its metabolic products on EAP in mice. Putrescine is a key metabolite that contributes to the anti-inflammatory effects of LBPs in vivo. This provides a possible option for the development of LBPs as clinical drugs.

