Obacunone alleviates chronic pelvic pain and pro-inflammatory depolarization of macrophage induced by experimental autoimmune prostatitis in mice

黄柏酮减轻小鼠实验性自身免疫性前列腺炎引起的慢性盆腔痛和巨噬细胞的促炎去极化

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作者:Yadong Wang, Zhaohui Dang, Xu Wang, Yuanyuan Chen, Peng Dong, Gang Liu, Weibin Tan, Zhong Gui, Fan Bu, Feng Lin, Chaozhao Liang

Abstract

Chronic pelvic pain syndrome (CPPS) is a common complication of prostatitis, which was associated with the pathological depolarization of macrophage and the neuroinflammation. However, its underlying reason is far from clear and few effective treatments is applicable. In this study, we tested the effect of obacunone (Oba), a highly oxygenated triterpenoid, on CPPS. The experimental autoimmune prostatitis (EAP) was induced by subcutaneous injection of heterologous prostate homogenate in mice. We found that EAP led to prostatodynia, neuronal activation of spinal dorsal horn, and the pro-inflammatory depolarization of macrophage within prostate, which was significantly alleviated by oral administration of Oba in a dose-dependent manner. Mechanistically, EAP-induced production of IL-6 on prostatic macrophage was suppressed by Oba. Moreover, co-administration of Oba and MIF inhibitor ISO-1 did not lead to additive effect when compared with either alone. In summary, we conclude that Oba prevents the production of macrophage-derived pro-inflammatory factors by inhibiting MIF, which eventually alleviates CPPS after prostatitis.

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