Effect of Eriocalyxin B on prostatic inflammation and pelvic pain in a mouse model of experimental autoimmune prostatitis.
Effect of Eriocalyxin B on prostatic inflammation and pelvic pain in a mouse model of experimental autoimmune prostatitis.
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Eriocalyxin B 对实验性自身免疫性前列腺炎小鼠模型前列腺炎症和盆腔疼痛的影响。
DOI：
10.1002/pros.24065
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发表时间：
2020
期刊：
影响因子：
2.8
通讯作者：
Chaozhao Liang
中科院分区：
文献类型：
--
作者：
Ligang Zhang;Ziqiang Yu;Cheng Yang;Jing Chen;Changsheng Zhan;Xianguo Chen;Li Zhang;Zongyao Hao;Chaozhao Liang
慢性前列腺炎/慢性骨盆疼痛综合征（CP/CPPS）是男性常见病、多发病。毛萼香茶菜素B（EriB）是从疏花毛萼香茶菜中提取的一种天然二萜类化合物，具有多种免疫相关的抗肿瘤作用。在这项研究中，我们研究了EriB对CP/CPPS使用小鼠模型的实验性自身免疫性前列腺炎（EAP）的影响，并探讨其潜在的mechanism.MethodsThe EAP模型建立在非肥胖糖尿病小鼠皮内注射前列腺抗原和完全弗氏佐剂的混合物在0和28天。然后，从第28天至第42天，EAP小鼠接受每天腹膜内注射EriB（5或10 mg/kg/d），持续14天（EAP+ EriB 5或EAP+ EriB 10组）。评价前列腺组织的组织病理学外观。慢性盆腔疼痛的发展评估皮肤异常性疼痛。通过酶联免疫吸附试验测定炎性细胞因子。然后，我们通过研究PI 3 K抑制剂wortmannin（EAP+ EriB 10 +Wort组）和NF-κB抑制剂SC 75741（EAP+ EriB 10 +SC组）对前列腺炎症和盆腔疼痛的影响，探讨EriB的抗炎潜在机制。在EAP小鼠中检测到骨盆疼痛显著增加（P<0.05）。与EAP+Veh组相比，EriB通过上调PI 3 K/Akt/mTOR通路和下调NF-κB通路，以剂量依赖方式减轻EAP的严重程度。进一步的机制研究表明，wortmannin可阻断PI 3 K/AKT/mTOR通路，而SC 75741对PI 3 K/AKT/mTOR通路无影响。此外，与EAP+ EriB 10 +Veh组相比，SC 75741可以进一步抑制NF-κB途径。然而，wortmannin可以重新激活NF-κB通路，表明在EriB治疗过程中，PI 3 K/AKT/mTOR通路负性调节NF-κB通路。结论本研究的结果表明，EriB可以减轻EAP小鼠模型前列腺炎症和盆腔疼痛的严重程度。这些发现可能扩大EriB作为治疗CP/CPPS的有希望的候选者的价值。
BackgroundChronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disease in males. Eriocalyxin B (EriB), a natural diterpenoid purified fromIsodon eriocalyxvar.laxiflora, was previously reported to have antitumor effects via multiple immune‐related pathways. In this study, we investigated the effect of EriB on CP/CPPS using a mouse model of experimental autoimmune prostatitis (EAP) and explored its potential mechanisms.MethodsThe EAP model was established in nonobese diabetic mice by intradermal injecting a mixture of prostate antigens and Complete Freund's Adjuvant on days 0 and 28. Then, EAP mice received daily intraperitoneal injections of EriB (5 or 10 mg/kg/d) for 14 days, from days 28 to 42 (EAP+EriB5 or EAP+EriB10 groups). The histopathological appearance of the prostate tissues was evaluated. Chronic pelvic pain development was assessed by cutaneous allodynia. Inflammatory cytokines were measured by enzyme‐linked immunosorbent assay tests. We then explored anti‐inflammatory potential mechanisms of EriB by studying the effects of PI3K inhibitor wortmannin (EAP+EriB10+Wort group) and NF‐κB inhibitor SC75741 (EAP+EriB10+SC group) on prostate inflammation and pelvic pain using this model.ResultsHistological analyses revealed significant prostate inflammation in EAP mice compared with control mice. Significantly increased pelvic pain was detected in EAP mice (P< .05). Compared with the EAP+Veh group, chronic pain development, histological appearance, and cytokine levels demonstrated that EriB could alleviate the severity of EAP in a dose‐dependent manner though upregulation of the PI3K/Akt/mTOR pathway and downregulation of the NF‐κB pathway. Further mechanism research demonstrated that the PI3K/AKT/mTOR pathway could be blocked by wortmannin, but was not affected by SC75741. In addition, the NF‐κB pathway could be further inhibited by SC75741 compared with the EAP+EriB10+Veh group. However, wortmannin could reactivate the NF‐κB pathway, indicating that the PI3K/AKT/mTOR pathway negatively regulates the NF‐κB pathway during EriB treatment.ConclusionsThe results of the present study suggested that EriB could alleviate the severity of prostatic inflammation and pelvic pain in an EAP mouse model. These findings may broaden the value of EriB as a promising candidate for the treatment of CP/CPPS.