Ginsenoside-Rg1 inhibits endoplasmic reticulum stress-induced apoptosis after unilateral ureteral obstruction in rats

Abstract

(2015) Ginsenoside-Rg1 inhibits endoplasmic reticulum stress-induced apoptosis after unilateral ureteral obstruction in rats, Renal Failure, 37:5,[890][891][892][893][894][895] DOI: 10.3109 Aim: Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are implicated in many fibrotic diseases, including renal fibrosis. Whether Ginsenoside-Rg1 (G-Rg1) could attenuate renal fibrosis via suppression of ER stress and UPR has not been reported. The aim of this study was to explore the effect of G-Rg1 on ER stress and UPR-induced apoptosis in kidneys with unilateral ureteral obstruction (UUO) rat model. Methods: Twenty-four male SpragueDawley rats were randomly divided into control group, model group and G-Rg1 treatment group. G-Rg1 was administered to rats by intraperitoneal injection. Renal interstitial fibrosis in the model group was developed by UUO in rats. Renal function was estimated by the levels of serum creatinine (Scr) and blood urea nitrogen (BUN). Renal pathological damage was evaluated by hematoxylin and eosin (HE) and Masson's trichrome staining. The ER stress was assessed with glucose-regulated protein (GRP) 78 expression, and the proapoptotic response was detected with CCAAT/enhancer-binding protein homologous protein (CHOP) and caspase-12 expressions by Western Blot. The number of apoptotic cells was determined by Terminaldeoxynucleotidyl Transferase Mediated Nick End Labeling (TUNEL) analysis. Results: UUO for 14 days aggravated renal function, renal damage and renal interstitial fibrosis, activated ER stress response (induction of GRP78 protein), enhanced the proapoptotic response (increase in CHOP and caspase-12 proteins) and increased the number of apoptotic cells (shown by the TUNEL assay). Treatment with G-Rg1 significantly ameliorates the renal pathological lesions and decreases expressions of ER stress-associated proteins and the level of apoptotic cells in kidneys. Conclusion: G-Rg1 suppresses renal cell apoptotic and fibrotic process partly through inhibition of ERS-and UPR-related apoptotic pathway in the kidneys after UUO.

Notoginsenoside R1 Protects against Neonatal Cerebral Hypoxic-Ischemic Injury through Estrogen Receptor–Dependent Activation of Endoplasmic Reticulum Stress Pathways

“…NGR1 can regulate Akt/Nrf2 pathways or tumor necrosis factor-a via estrogen receptor under the pathologic circumstance Zhong et al, 2015). Li et al (2015) and found that NGR1 could protect from renal injury via inhibition of ER stress. Results of some studies have shown that NGR1 provided neuroprotection in an adult rat model of cerebral ischemia/reperfusion via regulation of Akt/Nrf2 pathways or LC3 and Beclin 1 (Lu et al, 2011;Meng et al, 2104).…”

Ginsenoside-Rg1 Protects against Renal Fibrosis by Regulating the Klotho/TGF-β1/Smad Signaling Pathway in Rats with Obstructive Nephropathy

“…43) We have also observed that G-Rg1 reduced cell apoptosis and TIF in kidney fibrosis. 18,19) G-Rg1 and Klotho are both involved in TIF, and we proposed that the inhibitory effect of G-Rg1 may be related to the Klotho effect. We found that G-Rg1 administration alleviated UUO-associated fibrosis, which was accompanied by alterations in the expression of the TGF-β1/Smad pathway and EMT-related proteins, including upregulation of Smad7, and downregulation of TGF-β1 and p-Smad3.…”

“…The UUO rat model was established as previously described. 11) G-Rg1 (68317; Sigma-Aldrich, St. Louis, MO, U.S.A.) was administered to the rats by intraperitoneal injection at a dose of 50 mg/kg per day based on our previous results 18,19) (in our preliminary experiments, 25 mg/kg failed to yield enough beneficial effects and 100 mg/kg failed to yield extra beneficial effects). Klotho knockdown was mediated by short hairpin RNA interference (shRNA).…”

“…16,17) G-Rg1 is widely used for long for treatment of metabolism disorders, cancers, and cardiovascular and hepatic diseases in oriental countries, especially in China. We have recently reported that G-Rg1 ameliorated cell apoptosis in renal tubular cells, and suppressed TIF through ER stress in cyclosporine A treated rats 18) and in unilateral ureteral obstruction (UUO) rats. 19) The pharmacological activities of G-Rg1 overlap the functions of Klotho, based on the antifibrotic property, indicating that the effects of G-Rg1 on TIF may be associated with Klotho in the kidney.…”

“…We have recently reported that G-Rg1 ameliorated cell apoptosis in renal tubular cells, and suppressed TIF through ER stress in cyclosporine A treated rats 18) and in unilateral ureteral obstruction (UUO) rats. 19) The pharmacological activities of G-Rg1 overlap the functions of Klotho, based on the antifibrotic property, indicating that the effects of G-Rg1 on TIF may be associated with Klotho in the kidney. Continuing our previous study, we established a rat renal fibrosis model by UUO, to investigate the hypothesis that G-Rg1 treatment at-tenuates renal fibrosis by regulating the Klotho/TGF-β1/Smad signaling pathway and the related EMT process.…”