The protective effect of resveratrol on lupus nephritis mice by up-regulating Sirt1

Document Type : Original Article

Authors

1 Department of Rheumatology, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, P.R. China

2 Department of Nephrology, Ningbo Yinzhou No.2 Hospital, Ningbo, Zhejiang Province, P.R. China

10.22038/ijbms.2025.90231.19451

Abstract

Objective(s): To investigate the therapeutic effect and protective mechanism of resveratrol (Res) on mice with lupus nephritis (LN).
Materials and Methods: We used Res to intervene in MRL/lpr mice and employed biochemical techniques to assess kidney function, inflammation levels, and oxidative stress. We also evaluated changes in immune function and used immunohistochemistry to assess Sirt1 protein and mRNA expression.
Results: Res improved the kidney function, alleviated proteinuria, and renal pathological damage in MRL/lpr mice. Res also ameliorated spleen weight and spleen index, and inhibited urinary protein/creatinine levels. Moreover, Res inhibited the expression of circulating inflammatory factors, oxidative stress levels, and kidney cell apoptosis in MRL/lpr mice. Res effectively promoted Sirt1 protein and mRNA expression in the kidneys of MRL/lpr mice. 
Conclusion: Res has a protective effect on MRL/lpr mice, and its mechanism may involve activation of the Sirt1 signaling pathway.

Keywords

Main Subjects

References

1. Morand EF, Fernandez-Ruiz R, Blazer A, Niewold TB. Advances in the management of systemic lupus erythematosus. BMJ 2023;383:e073980.
2. González-García A, Cusácovich I, Ruiz-Irastorza G. Treatment of systemic lupus erythematosus: new therapeutic options. Rev Clin Esp (Barc) 2023;223:629-639.
3. Yu C, Li P, Dang X, Zhang X, Mao Y, Chen X. Lupus nephritis: New progress in diagnosis and treatment. J Autoimmun 2022;132:102871.
4. Alforaih N, Whittall-Garcia L, Touma Z. A Review of Lupus Nephritis. J Appl Lab Med 2022;7:1450-1467.
5. Gasparotto M, Gatto M, Binda V, Doria A, Moroni G. Lupus nephritis: Clinical presentations and outcomes in the 21st century. Rheumatology (Oxford) 2020;59:v39-v51.
6. Zhou DD, Luo M, Huang SY, Saimaiti A, Shang A, Gan RY, et al. Effects and mechanisms of resveratrol on aging and age-related diseases. Oxid Med Cell Longev 2021;2021:9932218.
7. Zhang LX, Li CX, Kakar MU, Khan MS, Wu PF, Amir RM, et al. Resveratrol (RV): A pharmacological review and call for further research. Biomed Pharmacother 2021;143:112164. 
8. Tian J, Huang T, Chen J, Wang J, Chang S, Xu H, et al. SIRT1 slows the progression of lupus nephritis by regulating the NLRP3 inflammasome through ROS/TRPM2/Ca2+ channel. Clin Exp Med 2023;23:3465-3478. 
9. Zheng X, Sun K, Liu Y, Yin X, Zhu H, Yu F, et al. Resveratrol-loaded macrophage exosomes alleviate multiple sclerosis through targeting microglia. J Control Release 2023;353:675-684. 
10. Fantacuzzi M, Amoroso R, Carradori S, De Filippis B. Resveratrol-based compounds and neurodegeneration: Recent insight in multitarget therapy. Eur J Med Chem 2022;233:114242.
11. Spaleniak W, Cuendet M. Resveratrol as a circadian clock modulator: Mechanisms of action and therapeutic applications. Mol Biol Rep 2023;50:6159-6170. 
12. Osmanlıoğlu HÖ, Nazıroğlu M. Resveratrol modulates diabetes-induced neuropathic pain, apoptosis, and oxidative neurotoxicity in mice through TRPV4 channel inhibition. Mol Neurobiol 2024;61:7269-7286. 
13. Alduraibi FK, Tsokos GC. Lupus nephritis biomarkers: A critical review. Int J Mol Sci 2024;25:805-826.
14. Desai SB, Ahdoot R, Malik F, Obert M, Hanna R. New guidelines and therapeutic updates for the management of lupus nephritis. Curr Opin Nephrol Hypertens 2024;33:344-353.
15. Ren H, Shao Y, Wu C, Ma X, Lv C, Wang Q. Metformin alleviates oxidative stress and enhances autophagy in diabetic kidney disease via AMPK/SIRT1-FoxO1 pathway. Mol Cell Endocrinol 2020;500:110628.
16. Chang A, Clark MR, Ko K. Cellular aspects of the pathogenesis of lupus nephritis. Curr Opin Rheumatol 2021;33:197-204.
17. Kwant LE, Vegting Y, Tsang-A-Sjoe MWP, Kwakernaak AJ, Vogt L, Voskuyl AE, et al. Macrophages in lupus nephritis: Exploring a potential new therapeutic avenue. Autoimmun Rev 2022;21:103211.
18. Shen S, Wei J, Kang W, Wang T. Elucidating shared biomarkers and pathways in kidney stones and diabetes: Insights into novel therapeutic targets and the role of resveratrol. J Transl Med 2023;21:491-517. 
19. Tain YL, Chang-Chien GP, Lin SF, Hou CY, Hsu CN. Protective effect of resveratrol on kidney disease and hypertension against microplastics exposure in male juvenile rats. Antioxidants (Basel) 2024;13:1457-1473.
20. Wang XH, Zuo ZF, Meng L, Yang Q, Lv P, Zhao LP, et al. Neuroprotective effect of salidroside on hippocampal neurons in diabetic mice via PI3K/Akt/GSK-3β signaling pathway. Psychopharmacology (Berl) 2023;240:1865-1876.
21. Shao B, Nong Y, Lin Y, Meng Y, Zhou Y, Huang M, et al. Study on the influence and mechanism of resveratrol on cognitive impairment in chronic kidney disease rats through regulating gut microbiota and the TLR4/NFκB pathway. J Inflamm Res 2025;18:6049-6060. 
22. Liu H, Duan C, Yang X, Liu J, Deng Y, Tiselius HG, et al. Metformin suppresses calcium oxalate crystal-induced kidney injury by promoting Sirt1 and M2 macrophage-mediated anti-inflammatory activation. Signal Transduct Target Ther 2023;8:38-41.
23. Sun HJ, Xiong SP, Cao X, Cao L, Zhu MY, Wu ZY, et al. Polysulfide-mediated sulfhydration of SIRT1 prevents diabetic nephropathy by suppressing phosphorylation and acetylation of p65 NF-κB and STAT3. Redox Biol 2021;38:101813.
24. Liu X, Chen A, Liang Q, Yang X, Dong Q, Fu M, et al. Spermidine inhibits vascular calcification in chronic kidney disease through modulation of SIRT1 signaling pathway. Aging Cell 2021;20:e13377.
25. Claude-Taupin A, Isnard P, Bagattin A, Kuperwasser N, Roccio F, Ruscica B, et al. The AMPK-Sirtuin 1-YAP axis is regulated by fluid flow intensity and controls autophagy flux in kidney epithelial cells. Nat Commun 2023;14:8056-8075.
26. Jin Q, Liu T, Ma F, Fu T, Yang L, Mao H, et al. Roles of Sirt1 and its modulators in diabetic microangiopathy: A review. Int J Biol Macromol 2024;264:130761.
27. Han X, Wang J, Li R, Huang M, Yue G, Guan L, et al. Placental mesenchymal stem cells alleviate podocyte injury in diabetic kidney disease by modulating mitophagy via the SIRT1-PGC-1alpha-TFAM pathway. Int J Mol Sci 2023;24:4696-4714.
Iranian Journal of Basic Medical Sciences
Volume 29, Issue 1
January 2026
Pages 138-144

Files

Share

How to cite

Statistics