6-gingerol attenuates renal interstitial fibrosis by downregulating PI3K/Akt/mTOR signaling pathway in unilateral ureteral obstruction rats

Renal interstitial fibrosis is the predominant cause of end-stage renal disease. Oxidative stress and an increased PI3K/Akt/mTOR pathway play a key role in the development of renal interstitial fibrosis caused by ureteral obstruction. 6-gingerol (6-G) is known to have a natural antioxidant effect; however, the effect of 6-G on progressive renal fibrosis due to ureteral obstruction has not been fully elucidated. The aim of the study is to evaluate the antifibrotic effect of 6-G and characterize the underlying mechanism of its action on unilateral ureteral obstruction (UUO) rats. Male Sprague-Dawley rats underwent UUO via double ligation of the left ureter for a duration of 14 days. Sham rats underwent identical treatment, with the exception of the absence of double ligation. The levels of phosphorylated PI3K/Akt/mTOR in the kidney were assessed by semiquantitative immunoblotting, while the gene expressions of TGF-β1 and α-SMA were evaluated through qRT-PCR. Oxidative stress parameters were evaluated with an ELISA kit and spectrophotometer, while histopathological assessment was conducted through Masson's trichrome, hematoxylin and eosin (HE), and immunohistochemical analysis of collagen type III. In comparison to UUO rats, renal fibrosis and collagen type III deposition were diminished, and the phosphorylation of PI3K/Akt/mTOR was reduced in rats treated with 6-G. 6-G also reduced the expression of TGF-β1 and α-SMA genes in obstructed kidneys. In comparison to UUO rats, rats administered with 6-G exhibited elevated activities of glutathione peroxidase and decreased levels of malondialdehyde. The findings suggest that 6-G is a potential therapeutic agent for renal interstitial fibrosis, with its antifibrotic actions perhaps facilitated by the enhanced activity of the PI3K/Akt/mTOR pathways and decreased oxidative stress in UUO rats.