Salvianolic acid B attenuates renal interstitial fibrosis by regulating the HPSE/SDC1 axis

Abstract

Salvianolic acid B (Sal B) is one of the main water-soluble components of Salvia miltiorrhiza Bge. numerous reports have demonstrated that it could exert significant renal-protective effects, but the underlying mechanism remains unclear. The present study demonstrated that Sal B could alleviate renal injury by regulating the heparanase/syndecan-1 (HPSe/Sdc1) axis. In vivo, the serum creatinine, blood urea nitrogen, transforming growth factor-β1 (TGF-β1) and fibroblast growth factor-2 (FGF-2) levels, and the histopathological changes of mice kidneys were examined. Sal B could notably reduce the renal injury caused by left ureteral ligation. In vitro, Sal B downregulated the expression levels of HPSe/FGF-2/TGF-β1/α-smooth muscle actin and upregulated the expression levels of Sdc1/e-cadherin in angiotensin ii-stimulated HK-2 cells in a dose-dependent manner. in summary, to the best of the authors' knowledge, the present study provided evidence for the first time that Sal B could exert renal-protective effects via the inhibition of the HPSe/Sdc1 axis, and these results suggest that the administration of Sal B may be a novel therapeutic strategy in treating renal interstitial fibrosis.

Identification and Quantification of Matrisome Proteins of Mouse Kidneys

“…It is important to note that this study was performed on healthy kidney tissues and it is known that GAGs deposition in ECM is increased during the diseases, e.g. fibrosis 64,65 . Hence, the improvement of analysis by GAG digesting enzymes is still unclear, our study is limited with using only PNGaseF to remove glycans.…”

Salvia miltiorrhiza in thorax and abdomainal organ fibrosis: A review of its pharmacology

“…Salvianolic acid B could notably reduce the renal injury and fibrosis in murine UUO model in vivo. The mechanism was confirmed to be related with the downregulation of HPSE/FGF-2/TGF-β1/α-SMA expression and upregulation of SDC1/E-cadherin levels in vitro (Hu et al, 2020). Tanshinone IIA was demonstrated to have excellent anti-fibrotic properties in streptozotocininduced and 5/6 nephrectomy models, respectively (Ahn et al, 2010;Xu et al, 2020).…”

New Insights Into the Effects of Individual Chinese Herbal Medicines on Chronic Kidney Disease

“…Tanshinone IIA also reduced endoplasmic reticulum stress via attenuated PERK signaling activities ( Xu, et al, 2020a ). In UUO rats, Salvianolic acid B attenuates renal interstitial fibrosis by regulating the heparanase/syndecan-1 axis ( Hu, et al, 2020 ), Salvianolic acid A and C reduced the secretion of renal inflammatory cytokines CCL5 and CXCL10 to protect renal function, improve tubular function and renal pathology ( Li, et al, 2015 ). In adenine and potassium oxonate-induced uric acid nephropathy mice or renal ischemia-reperfusion injury rats, Tanshinone IIA suppressed oxidative stress-activated MAPK pathways ( Zhang, et al, 2020c ), and salvianolic Acid B modulates caspase-1-mediated pyroptosis via blocking Nrf2 Pathway ( Pang, et al, 2020 ), suppressing oxidative stress and inflammation through activation of PI3K/Akt signaling pathway ( Ma, et al, 2017b ).…”