Department of Pharmacology, College of Korean Medicine, Sangji University, 83 Sangjidae-gil, Wonju-si, Gangwon-do, 26339, Republic of Korea.
Department of Agroindustrial Technology, Lambung Mangkurat University, Banjarbaru, Indonesia.
Biomed Pharmacother. 2021 Mar;135:111197. doi: 10.1016/j.biopha.2020.111197. Epub 2021 Feb 1.
Prostatitis, defined as a pathological inflammatory change in the prostate tissue, is one of the most prevalent urological conditions in men. However, optimal management of prostatitis remains unclear, and treatment outcomes are unsatisfactory owing to adverse effects. Carica papaya leaf extract (PAL) is known for its antioxidant, immunomodulatory, and anticancer properties; however, evidence of its anti-inflammatory effect in prostatic tissues remains elusive. In this study, the therapeutic effects and underlying molecular mechanisms of PAL in mice with experimental autoimmune prostatitis (EAP) and a prostatic cell line (RWPE-1 cells) exposed to inflammatory conditioned medium were investigated. PAL suppressed pathological alterations in EAP and markedly reduced prostate weight in EAP mice. Histological analysis revealed that PAL alleviates prostatic hyperplasia. Furthermore, PAL significantly reduced cyclooxygenase-2 mRNA and protein expression; production of inflammatory cytokines, including interleukin-6, tumor necrosis factor-α, and transforming growth factor-β; and TRAF6/TAK1/MEK/ERK and NF-κB pathway-related protein expression. TRAF6/TAK1/MEK/ERK and NF-κB pathway-related proteins were upregulated in inflammatory conditioned medium-stimulated RWPE-1 cells, but PAL reduced the expression of these markers. Particularly, PAL treatment suppressed the nuclear translocation of NF-κB p65 and phosphorylation of p65 in RWPE-1 cells exposed to the inflammatory conditioned medium. Collectively, the results demonstrate the anti-proliferative and anti-inflammatory effects of PAL in the experimental prostatitis model, which highlights the potential of PAL as a new therapeutic agent in the treatment of prostatic disease.
前列腺炎是一种前列腺组织的病理性炎症改变，是男性最常见的泌尿科疾病之一。然而，前列腺炎的最佳治疗方法仍不明确，且由于不良反应，治疗效果并不令人满意。番木瓜叶提取物（PAL）具有抗氧化、免疫调节和抗癌特性；然而，其在前列腺组织中的抗炎作用的证据仍然难以捉摸。在这项研究中，研究了 PAL 在实验性自身免疫性前列腺炎（EAP）小鼠和前列腺细胞系（RWPE-1 细胞）中暴露于炎症条件培养基时的治疗效果和潜在的分子机制。PAL 抑制了 EAP 的病理改变，并显著降低了 EAP 小鼠的前列腺重量。组织学分析表明，PAL 缓解了前列腺增生。此外，PAL 显著降低了环氧合酶-2 mRNA 和蛋白表达；产生了包括白细胞介素-6、肿瘤坏死因子-α 和转化生长因子-β在内的炎症细胞因子；以及 TRAF6/TAK1/MEK/ERK 和 NF-κB 通路相关蛋白表达。在炎症条件培养基刺激的 RWPE-1 细胞中，TRAF6/TAK1/MEK/ERK 和 NF-κB 通路相关蛋白表达上调，但 PAL 降低了这些标志物的表达。特别是，PAL 处理抑制了暴露于炎症条件培养基的 RWPE-1 细胞中 NF-κB p65 的核易位和 p65 的磷酸化。总之，这些结果表明 PAL 在实验性前列腺炎模型中具有抗增殖和抗炎作用，这突出了 PAL 作为治疗前列腺疾病的新治疗剂的潜力。
