Salvianolic acid B attenuates tubulointerstitial fibrosis by inhibiting EZH2 to regulate the PTEN/Akt pathway. (31st December 2023)

• Record Type: Journal Article
• Authors: Lin, Pinglan; Qiu, Furong; Wu, Ming; Xu, Lin; Huang, Di; Wang, Chen; Yang, Xuejun; Ye, Chaoyang
• Is Part Of: Pharmaceutical biology. Volume 61:Number 1(2023)
• Page Start: 23
• Page End: 29
• Publication Date: 2023-12-31
• Subjects: Renal fibrosis -- chronic kidney diseases -- ureteral unilateral obstruction -- Aristolochic acid nephropathy -- transforming growth factor-β; Pharmacognosy -- Periodicals; Materia medica, Vegetable -- Periodicals; 615.321
• DOI: 10.1080/13880209.2022.2148169
• Languages: English
• ISSNs: 1388-0209

Abstract

Abstract: Context: Salvianolic acid B (SAB) can alleviate renal fibrosis and improve the renal function. Objective: To investigate the effect of SAB on renal tubulointerstitial fibrosis and explore its underlying mechanisms. Materials and methods: Male C57 mice were subjected to unilateral ureteric obstruction (UUO) and aristolochic acid nephropathy (AAN) for renal fibrosis indication. Vehicle or SAB (10 mg/kg/d, i.p.) were given consecutively for 2 weeks in UUO mice while 4 weeks in AAN mice. The serum creatinine (Scr) and blood urine nitrogen (BUN) were measured. Masson's trichrome staining and the fibrotic markers (FN and α-SMA) were used to evaluate renal fibrosis. NRK-49F cells exposed to 2.5 ng/mL TGF-β were treated with SAB in the presence or absence of 20 μM 3-DZNep, an inhibitor of EZH2. The protein expression of EZH2, H3k27me3 and PTEN/Akt signaling pathway in renal tissue and NRK-49F cells were measured by Western blots. Results: SAB significantly improved the levels of Scr by 24.3% and BUN by 35.7% in AAN mice. SAB reduced renal interstitial collagen deposition by 34.7% in UUO mice and 72.8% in AAN mice. Both in vivo and in vitro studies demonstrated that SAB suppressed the expression of FN and α-SMA, increased PTEN and decreased the phosphorylation of Akt, which were correlated with the down-regulation of EZH2 and H3k27me3. The inhibition of EZH2 attenuated the anti-fibrotic effects of SAB in NRK-49Fs. Conclusion: SAB might have therapeutic potential on renal fibrosis of CKD through inhibiting EZH2, which encourages further clinical trials.