Zhang Jiong, Wang Jipeng, Wang Xinhao, Yan Zehao, Meng Lingfeng, Zhang Yaoguang
Peking University Fifth School of Clinical Medicine, Beijing 100730, China.
Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Beijing 100730, China.
Int J Mol Sci. 2025 Jun 8;26(12):5490. doi: 10.3390/ijms26125490.
Interstitial cystitis/bladder pain syndrome (IC/BPS) causes significant discomfort in patients and impairs the quality of urination. Pterostilbene (PTE), a natural polyphenol antioxidant, has demonstrated beneficial effects in mitigating inflammation, enhancing antioxidant capacity, and ameliorating organ dysfunction in various chronic nonspecific inflammatory conditions. The aim of this study was to evaluate the efficacy of PTE in IC/BPS and elucidate its underlying mechanisms using a rat model of cyclophosphamide (CYP)-induced interstitial cystitis. In comparison, chronic pain progression, histopathological features, and cytokine levels demonstrated that PTE mitigated the severity of symptoms in CYP-induced rats by inhibiting the NLRP3 inflammasome in a dose-dependent manner. Further mechanistic investigations indicated that PTE intervention alleviated oxidative stress in CYP-induced IC in rats via activation of the signaling pathway. Moreover, inhibitors of the pathway effectively blocked PTE-mediated attenuation of oxidative stress. The suppression of NLRP3 inflammasome activation by PTE could also be reversed by inhibition of the pathway. In vitro studies revealed that PTE enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and suppressed NLRP3 inflammasome activation in SV-HUC-1 cells exposed to lipopolysaccharide (LPS) and Adenosine Triphosphate (ATP). These findings collectively suggest that PTE treatment inhibits oxidative stress and suppresses NLRP3 inflammasome activation through modulation of the pathway.
间质性膀胱炎/膀胱疼痛综合征（IC/BPS）给患者带来极大不适，并损害排尿质量。紫檀芪（PTE）是一种天然多酚抗氧化剂，在减轻多种慢性非特异性炎症性疾病中的炎症、增强抗氧化能力及改善器官功能障碍方面已显示出有益作用。本研究旨在评估PTE对IC/BPS的疗效，并使用环磷酰胺（CYP）诱导的间质性膀胱炎大鼠模型阐明其潜在机制。相比之下，慢性疼痛进展、组织病理学特征和细胞因子水平表明，PTE通过以剂量依赖方式抑制NLRP3炎性小体减轻了CYP诱导大鼠的症状严重程度。进一步的机制研究表明，PTE干预通过激活 信号通路减轻了CYP诱导的大鼠IC中的氧化应激。此外， 通路抑制剂有效阻断了PTE介导的氧化应激减轻。抑制 通路也可逆转PTE对NLRP3炎性小体激活的抑制作用。体外研究表明，PTE增强了暴露于脂多糖（LPS）和三磷酸腺苷（ATP）的SV-HUC-1细胞中核因子红细胞2相关因子2（Nrf2）的表达，并抑制了NLRP3炎性小体激活。这些发现共同表明，PTE治疗通过调节 通路抑制氧化应激并抑制NLRP3炎性小体激活。
