Protective effect of salidroside on streptozotocin-induced diabetic nephropathy by inhibiting oxidative stress and inflammation in rats via the Akt/GSK-3β signalling pathway

Abstract

Context Salidroside (SAL), one of the major glycosides isolated from the roots of Rhodiola rosea L. (Crassulaceae), has anti-inflammatory, antioxidant, and antidiabetic properties. Objective Our study assessed whether SAL exerts a protective effect on streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats via the Akt/GSK-3β signalling pathway. Materials and methods Adult male Wistar rats were divided into three groups ( n = 8): normal control, DN + vehicle, and DN + SAL. SAL (50 mg/kg/day, oral) was administered for 8 weeks. Biochemical and histopathologic examinations were performed to evaluate the therapeutic effects of SAL on oxidative stress, inflammation, renal function, and apoptosis. Results SAL induced rats demonstrated ameliorated levels of FBG (20.53 ± 0.72 mmol/L vs. 26.02 ± 1.44 mmol/L), urine albumin excretion (27.00 ± 1.46 mmol/L vs. 41.00 ± 1.59 mmol/L), blood urea nitrogen (14.42 ± 0.70 mmol/L vs. 17.77 ± 0.72 mmol/L), and serum creatinine (112.80 ± 6.98 mmol/L vs. 159.00 ± 3.81 mmol/L) compared to normal control rats, along with the alleviation of renal pathologic changes by improving the irregular shape of glomeruli tissues. Biochemical analysis showed that SAL-treated animals displayed suppressed levels of serum inflammatory cytokines and kidney oxidative stress markers and attenuated apoptotic characteristics. Moreover, it increased the phosphorylation levels of Akt and GSK-3β in kidneys. Discussion and conclusion The present study validated the involvement of the Akt/GSK-3β signalling pathway in renal improvement. These findings can form the basis to investigate the protective effect of SAL in DN in clinical trials.

Salidroside alleviates cholestasis-induced liver fibrosis by inhibiting hepatic stellate cells via activation of the PI3K/AKT/GSK-3β signaling pathway and regulating intestinal flora distribution

“…In addition previous studies have found that SAL inhibits L-glu-induced activation of JNK and MAKP, thereby inhibiting cytotoxicity and protecting brain tissue from toxic substances ( Lee et al, 2013 ). In addition, SAL protects against diabetic kidney injury by activating the AKT/GSK-3β signaling pathway ( Pei et al, 2022 ). SAL also attenuates myocardial ischaemia/reperfusion injury by inhibiting endoplasmic reticulum stress and mitochondrial fragmentation via AMPK signaling pathway ( Tian et al, 2022 ).…”

Pharmacological functions of salidroside in renal diseases: facts and perspectives

“…GSK-3β is involved in the regulation of apoptosis, promotes glucose metabolism and regulates cell cycle by influencing glucose levels in blood. Pei et al reported that Salidroside (50 mg/kg/day, oral) was given to STZ-induced DN rats for 8 weeks, which could significantly counteracted the glucose-raising effect of STZ and reduce the levels of blood creatinine, urea nitrogen and urinary protein in DN rats ( Pei et al, 2022 ). At the same time, the pathological changes of kidney can be alleviated by improving the abnormal glomerular tissue, swelling and mesangial matrix dilation.…”