Celastrol Ameliorates Experimental Autoimmune Prostatitis Associated With Gut Microbiota Modulation and Regulatory B Cell Responses
Ziqiang Yu, Weilong Yao, Guangfeng Zhang, Mingfeng Shao, Siming Yang, Hexi DuBackground
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urological disorder with limited effective treatments. Celastrol (CEL) has been widely reported to exhibit anti-inflammatory and immunomodulatory properties. However, its therapeutic potential and underlying mechanisms in experimental autoimmune prostatitis remain largely unexplored.
Materials and Methods
An experimental autoimmune prostatitis (EAP) mouse model was established to mimic CP/CPPS. Celastrol (CEL) was orally administered for two weeks. Histological analysis, tactile allodynia testing, flow cytometry, ELISA, and 16S rRNA sequencing were employed to evaluate inflammatory responses, pelvic pain, Breg cell differentiation, IL-10 expression, and gut microbiota composition. Fecal and serum short-chain fatty acids (SCFAs) were quantified using GC–MS.
Results
CEL treatment significantly alleviated prostate inflammation and reduced pelvic pain in EAP mice. Gut microbiota analysis revealed that CEL reshaped microbial composition and notably increased butyric acid levels. Elevated butyric acid promoted the differentiation of regulatory B cells (Bregs) and enhanced IL-10 expression in prostate tissues. These immunomodulatory effects were closely associated with microbiota-derived metabolic changes.
Conclusion
CEL is associated with anti-inflammatory effects in EAP, potentially involving modulation of the gut microbiota–butyrate–Breg axis. These findings provide pharmacological evidence supporting the traditional use of CEL in managing chronic prostatitis and highlight the therapeutic potential of microbiota-targeting herbal interventions.