Li Wenshuang, Luo Ruixiang, Liu Zheng, Li Xiaoyang, Zhang Chi, Huang Junlong, Wang Ziqiao, Chen Jialiang, Ding Honglu, Zhou Xiangfu, Liu Bolong
Department of Urology, The Third Affiliated Hospital, Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, People's Republic of China.
Department of Urology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, 511500, People's Republic of China.
Mol Divers. 2025 Jun;29(3):2489-2497. doi: 10.1007/s11030-024-11004-6. Epub 2024 Oct 14.
This study aims to investigate the anti-inflammatory effects of Resveratrol (RES) in the treatment of Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) by integrating network pharmacology, molecular docking, and experimental validation. Potential targets of RES were identified using DrugBank and SwissTargetPrediction, while IC/BPS-related targets were obtained from DisGeNET and Genecards. Molecular docking was performed using UCSF Chimera and SwissDock to validate the binding affinity of RES to key targets. Experimental validation involved treating TNF-α induced urothelial cells with RES, followed by assessments using RT-qPCR, ELISA, and Western blotting. A total of 86 drug targets and 211 disease targets were analyzed, leading to the identification of 8 key therapeutic targets for RES in IC/BPS treatment. Molecular docking revealed a strong affinity of RES for ESR2, with notable interactions also observed with SHBG, PTGS2, PPARG, KIT, PI3KCA, and AKT1. In vitro experiments confirmed that RES significantly alleviated the inflammatory response in TNF-α-induced urothelial cells, normalizing the expression levels of ESR2, SHBG, PPARG, and AKT1. RES can modulate critical pathways involving ESR2, SHBG, PPARG, and AKT1, highlighting its potential as a therapeutic agent for IC/BPS. This study provides a theoretical foundation for the clinical application of RES in treating IC/BPS.
本研究旨在通过整合网络药理学、分子对接和实验验证，探讨白藜芦醇（RES）在治疗间质性膀胱炎/膀胱疼痛综合征（IC/BPS）中的抗炎作用。利用DrugBank和SwissTargetPrediction确定RES的潜在靶点，同时从DisGeNET和Genecards获取IC/BPS相关靶点。使用UCSF Chimera和SwissDock进行分子对接，以验证RES与关键靶点的结合亲和力。实验验证包括用RES处理肿瘤坏死因子-α（TNF-α）诱导的尿路上皮细胞，随后使用实时定量聚合酶链反应（RT-qPCR）、酶联免疫吸附测定（ELISA）和蛋白质免疫印迹法进行评估。共分析了86个药物靶点和211个疾病靶点，从而确定了RES在IC/BPS治疗中的8个关键治疗靶点。分子对接显示RES与雌激素受体2（ESR2）具有很强的亲和力，同时也观察到与性激素结合球蛋白（SHBG）、前列腺素内过氧化物合酶2（PTGS2）、过氧化物酶体增殖物激活受体γ（PPARG）、原癌基因c-Kit（KIT）、磷脂酰肌醇-3激酶催化亚基α（PI3KCA）和蛋白激酶B（AKT1）有显著相互作用。体外实验证实，RES显著减轻了TNF-α诱导的尿路上皮细胞中的炎症反应，使ESR2、SHBG、PPARG和AKT1的表达水平恢复正常。RES可以调节涉及ESR2、SHBG、PPARG和AKT1的关键信号通路，突出了其作为IC/BPS治疗药物的潜力。本研究为RES在治疗IC/BPS中的临床应用提供了理论基础。
