枸杞多糖通过腐胺/肿瘤坏死因子受体相关因子/ Janus激酶/信号转导子和转录激活子介导的辅助性T细胞17分化减轻实验性自身免疫性前列腺炎。

Lycium barbarum polysaccharides alleviate experimental autoimmune prostatitis by putrescine/TRAF/JAK/STAT-mediated Th17 differentiation.

作者信息

Wang Xu, Yue Shao-Yu, Chen Lei, Chen Jia, Li Chun, Wei Sheng-Ao, Hu Chao-Jie, Li Rong-Rong, Xu Ling-Fan, Cheng An-Dong, Meng Qing-Wei, Niu Di, Wang Hui, Liang Chao-Zhao

机构信息

Department 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.

The Second Clinical Medical College, Anhui Medical University, Hefei, Anhui, PR China.

出版信息

Phytomedicine. 2025 Aug 27;147:157210. doi: 10.1016/j.phymed.2025.157210.

DOI:10.1016/j.phymed.2025.157210

PMID:40896864

Abstract

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.

摘要

背景

由于其通常具有难治性，慢性前列腺炎（CP）是一种普遍存在的疾病，显著影响着全球20至40岁男性的生活质量。枸杞多糖（LBPs）具有广泛的生物活性，如免疫调节以及降低血糖和血脂水平的能力。然而，它们是否通过调节肠道微生物群及其代谢产物来发挥抗炎作用仍有待探索。

方法

采用口服枸杞多糖治疗实验性自身免疫性前列腺炎（EAP）模型小鼠。为了研究EAP模型小鼠肠道菌群及其代谢产物的变化，进行了基于质谱的代谢组学和16S rRNA测序。随后进行了一系列功能实验，以研究肠道菌群代谢产物调节Th17细胞免疫并影响EAP发病机制的机制。

结果

口服枸杞多糖可减轻小鼠的EAP。代谢组学数据的通路富集分析显示，与腐胺合成和代谢相关的通路显著富集。随后通过测量血清、肠道和前列腺中的腐胺水平验证了这一发现。细胞和动物模型研究均表明，腐胺可减轻EAP并抑制Th17细胞分化。进一步的机制研究表明，腐胺通过TRAF6抑制JAK2-STAT3通路，从而抑制Th17细胞分化和炎症驱动的细胞因子合成。