Anti-inflammatory Effects of Resveratrol in Treating Interstitial Cystitis/bladder Pain Syndrome: a Multi-faceted Approach Integrating Network Pharmacology, Molecular Docking, and Experimental Validation

Overview

Journal Mol Divers

Date 2024 Oct 14

PMID 39400868

Authors

Wenshuang Li

Ruixiang Luo

Zheng Liu

Xiaoyang Li

Chi Zhang

Junlong Huang

Ziqiao Wang

Jialiang Chen

Honglu Ding

Xiangfu Zhou

Bolong Liu

Affiliations

Soon will be listed here.

Abstract

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.

References

Clemens J, Erickson D, Varela N, Lai H . Diagnosis and Treatment of Interstitial Cystitis/Bladder Pain Syndrome. J Urol. 2022; 208(1):34-42. DOI: 10.1097/JU.0000000000002756. View

Gonzalez G, Vaculik K, Khalil C, Zektser Y, Arnold C, Almario C . Experiences of Women With Interstitial Cystitis/Bladder Pain Syndrome: What Can We Learn From Women's Online Discussions?. J Urol. 2022; 209(1):208-215. DOI: 10.1097/JU.0000000000002955. View

Homma Y, Akiyama Y, Tomoe H, Furuta A, Ueda T, Maeda D . Clinical guidelines for interstitial cystitis/bladder pain syndrome. Int J Urol. 2020; 27(7):578-589. DOI: 10.1111/iju.14234. View

Su F, Meng L, Zhang W, Liu X, Liu X, Chen M . Multimodal Single-Cell Analyses Outline the Immune Microenvironment and Therapeutic Effectors of Interstitial Cystitis/Bladder Pain Syndrome. Adv Sci (Weinh). 2022; 9(18):e2106063. PMC: 9218658. DOI: 10.1002/advs.202106063. View

Nanjan M, Betz J . Resveratrol for the Management of Diabetes and its Downstream Pathologies. Eur Endocrinol. 2018; 10(1):31-35. PMC: 5983094. DOI: 10.17925/EE.2014.10.01.31. View

Meng T, Xiao D, Muhammed A, Deng J, Chen L, He J . Anti-Inflammatory Action and Mechanisms of Resveratrol. Molecules. 2021; 26(1). PMC: 7796143. DOI: 10.3390/molecules26010229. View

Shaito A, Posadino A, Younes N, Hasan H, Halabi S, Alhababi D . Potential Adverse Effects of Resveratrol: A Literature Review. Int J Mol Sci. 2020; 21(6). PMC: 7139620. DOI: 10.3390/ijms21062084. View

Kerimoglu G, Arici T, Biyik A, Kulaber A, Turkmen Alemdar N, Demir S . Protective potential of pterostilbene against cyclophosphamide-induced nephrotoxicity and cystitis in rats. Int Urol Nephrol. 2023; 55(12):3077-3087. DOI: 10.1007/s11255-023-03735-6. View

Keles I, Bozkurt M, Cemek M, Karalar M, Hazini A, Alpdagtas S . Prevention of cyclophosphamide-induced hemorrhagic cystitis by resveratrol: a comparative experimental study with mesna. Int Urol Nephrol. 2014; 46(12):2301-10. DOI: 10.1007/s11255-014-0833-8. View

10.

Zhang H, Zhang Y, Li Y, Wang Y, Yan S, Xu S . Bioinformatics and Network Pharmacology Identify the Therapeutic Role and Potential Mechanism of Melatonin in AD and Rosacea. Front Immunol. 2021; 12:756550. PMC: 8657413. DOI: 10.3389/fimmu.2021.756550. View

11.

Han Q, Li Z, Fu Y, Liu H, Guo H, Guan X . Analyzing the research landscape: Mapping frontiers and hot spots in anti-cancer research using bibliometric analysis and research network pharmacology. Front Pharmacol. 2023; 14:1256188. PMC: 10512719. DOI: 10.3389/fphar.2023.1256188. View

12.

Chen Q, Li Y, Tan K, Qiao Y, Pan S, Jiang T . Network-based methods for gene function prediction. Brief Funct Genomics. 2021; 20(4):249-257. DOI: 10.1093/bfgp/elab006. View

13.

Wang W, Yuan G, Wan S, Zheng Z, Liu D, Zhang H . A granularity-level information fusion strategy on hypergraph transformer for predicting synergistic effects of anticancer drugs. Brief Bioinform. 2024; 25(1). PMC: 10796255. DOI: 10.1093/bib/bbad522. View

14.

Kuret T, Peskar D, Kreft M, Erman A, Veranic P . Comprehensive transcriptome profiling of urothelial cells following TNFα stimulation in an interstitial cystitis/bladder pain syndrome model. Front Immunol. 2022; 13:960667. PMC: 9421144. DOI: 10.3389/fimmu.2022.960667. View

15.

Rooney P, Srivastava A, Watson L, Quinlan L, Pandit A . Hyaluronic acid decreases IL-6 and IL-8 secretion and permeability in an inflammatory model of interstitial cystitis. Acta Biomater. 2015; 19:66-75. DOI: 10.1016/j.actbio.2015.02.030. View

16.

Knox C, Wilson M, Klinger C, Franklin M, Oler E, Wilson A . DrugBank 6.0: the DrugBank Knowledgebase for 2024. Nucleic Acids Res. 2023; 52(D1):D1265-D1275. PMC: 10767804. DOI: 10.1093/nar/gkad976. View

17.

Daina A, Michielin O, Zoete V . SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res. 2019; 47(W1):W357-W364. PMC: 6602486. DOI: 10.1093/nar/gkz382. View

18.

Pinero J, Ramirez-Anguita J, Sauch-Pitarch J, Ronzano F, Centeno E, Sanz F . The DisGeNET knowledge platform for disease genomics: 2019 update. Nucleic Acids Res. 2019; 48(D1):D845-D855. PMC: 7145631. DOI: 10.1093/nar/gkz1021. View

19.

Safran M, Dalah I, Alexander J, Rosen N, Iny Stein T, Shmoish M . GeneCards Version 3: the human gene integrator. Database (Oxford). 2010; 2010:baq020. PMC: 2938269. DOI: 10.1093/database/baq020. View

20.

Sherman B, Hao M, Qiu J, Jiao X, Baseler M, Lane H . DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res. 2022; 50(W1):W216-W221. PMC: 9252805. DOI: 10.1093/nar/gkac194. View