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异甘草素通过促进 Nrf2 激活和抑制 NLRP3 炎性小体途径减轻实验性自身免疫性前列腺炎。

Isoliquiritigenin reduces experimental autoimmune prostatitis by facilitating Nrf2 activation and suppressing the NLRP3 inflammasome pathway.

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 Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, Anhui, PR China.

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 Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, Anhui, PR China.

出版信息

Mol Immunol. 2024 May;169:37-49. doi: 10.1016/j.molimm.2024.03.002. Epub 2024 Mar 16.

DOI:10.1016/j.molimm.2024.03.002
PMID:38493580
Abstract

BACKGROUND

Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) lead to severe irritation and impaired sperm quality in males. However, current therapeutic options often fail to achieve satisfactory effects. Consequently, the investigation of novel treatment strategies or remedies holds substantial clinical importance. As a flavonoid monomer, isoliquiritigenin (ISL) has been shown to possess anti-inflammatory activity, especially in several chronic nonspecific-inflammatory conditions. Thus, an exploration of the possible anti-inflammatory effects of ISL on CP/CPPS, a chronic aseptic inflammation of the prostate, has significant potential.

METHODS

An experimental autoimmune prostatitis (EAP) model was used for the evaluation of the anti-inflammatory effects of ISL. It was found that ISL treatment could reduce the secretion and invasion of pro-inflammatory cytokines in prostate tissue. In EAP mice, ISL treatment also reduced oxidative stress (OS) and activation of the NLRP3 inflammasome. In vitro, ISL upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and inhibited NLRP3 inflammasome activation in RAW264.7 macrophages exposed to lipopolysaccharide (LPS).

RESULTS

Treatment with ISL treatment relieved prostate inflammation and pelvic pain in EAP mice. Both in vivo and in vitro, ISL treatment activated Nrf2/HO-1 signaling, which in turn inhibited oxidative stress and activation of the NLRP3 inflammasome. Blockade of Nrf2/HO-1 signaling abolished the inhibitory effects of ISL on oxidative stress and NLRP3 inflammasome activation.

CONCLUSIONS

Isoliquiritigenin reduced experimental autoimmune prostatitis by facilitating Nrf2 activation and suppressing the NLRP3 inflammasome pathway.

摘要

背景

慢性前列腺炎和慢性骨盆疼痛综合征(CP/CPPS)会导致男性前列腺严重刺激和精子质量受损。然而,目前的治疗选择往往无法达到令人满意的效果。因此,研究新的治疗策略或治疗方法具有重要的临床意义。作为一种类黄酮单体,甘草素(ISL)已被证明具有抗炎活性,尤其是在几种慢性非特异性炎症疾病中。因此,探索 ISL 对 CP/CPPS(一种前列腺的慢性无菌性炎症)的可能抗炎作用具有重要意义。

方法

采用实验性自身免疫性前列腺炎(EAP)模型评价 ISL 的抗炎作用。结果发现,ISL 治疗可减少前列腺组织中促炎细胞因子的分泌和侵袭。在 EAP 小鼠中,ISL 治疗还可减轻氧化应激(OS)和 NLRP3 炎性小体的激活。在体外,ISL 上调了核因子红细胞 2 相关因子 2(Nrf2)的表达,并抑制了脂多糖(LPS)作用下 RAW264.7 巨噬细胞中 NLRP3 炎性小体的激活。

结果

ISL 治疗可缓解 EAP 小鼠的前列腺炎症和骨盆疼痛。体内和体外实验均表明,ISL 治疗激活了 Nrf2/HO-1 信号通路,从而抑制了氧化应激和 NLRP3 炎性小体的激活。阻断 Nrf2/HO-1 信号通路可消除 ISL 对氧化应激和 NLRP3 炎性小体激活的抑制作用。

结论

甘草素通过促进 Nrf2 激活和抑制 NLRP3 炎性小体途径减轻实验性自身免疫性前列腺炎。

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