Fermented Strawberry (Fragaria x Ananassa Duch.) Mitigates Renal Fibrosis in a Unilateral Ureteral Obstruction Model by Reducing Inflammation, Oxidative Stress, and Regulating Smad Signaling.

Renal fibrosis is a common outcome in many progressive renal diseases. Unilateral ureteral obstruction (UUO) is known to induce oxidative stress and inflammation in the kidneys, leading to the development of renal fibrosis. Fermented strawberry (Fragaria x ananassa Duch.) possesses antioxidant properties; however, its effect on renal fibrosis remains unclear. This study aimed to evaluate the impact of fermented strawberry dry powder (FSP) on renal fibrosis by assessing proinflammatory cytokines, oxidative stress markers, and underlying mechanisms. Male Sprague-Dawley rats were subjected to UUO surgery to induce tubulointerstitial fibrosis and obstructive nephropathy. Ten days postsurgery, the rats were randomly divided into four groups (n = 6), including a sham-operated control group. FSP was administered orally at doses of 0.05 or 0.5 g kg^-1 body weight daily for 21 days. FSP treatment significantly improved renal function, reduced tubular dilation, and decreased interstitial volume in UUO rats. FSP decreased levels of tumor necrosis factor-α and interleukin-6, while enhancing the activities of antioxidant enzymes such as superoxide dismutase and catalase. Treatment with 0.05 and 0.5 g kg^-1 FSP resulted in a reduction of collagen deposition in the kidneys by 49% and 69%, respectively, compared with UUO group. FSP increased E-cadherin expression and decreased α-smooth muscle actin level in the kidneys of UUO rats. Furthermore, FSP reduced transforming growth factor-β and Smad2/3 levels while upregulating Smad7 expression. These findings suggest that FSP mitigates renal tubulointerstitial fibrosis, likely through modulation of Smad signaling and attenuation of oxidative stress and inflammation.