Oxidative Stress and TGF-β1/Smads Signaling Are Involved in Rosa roxburghii Fruit Extract Alleviating Renal Fibrosis

Abstract

Fibrosis is involved in the pathogenesis of kidney diseases. We previously discovered that Rosa roxburghii fruit (Cili) possesses antifibrosis property in chronic renal disease, but the mechanisms are unknown. We hypothesized that Cili might prevent fibrosis development through mediating TGF-β/Smads signaling, which is known to be involved in renal fibrosis. This study aimed to confirm the effects of freeze-dried Cili powder in a rat model of unilateral ureteral obstruction (UUO) and examine TGF-β/Smads signaling. Rats were randomized to (n=12/group): sham operation, UUO, UUO with losartan, UUO with moderate Cili dose (3 g/kg/d), and UUO with high Cili dose (6 g/kg/d). The rats were sacrificed after 14 days of treatment. Collagen deposition was tested using Masson’s staining. TGF-β/Smads signaling was examined by qRT-PCR, western blot, and immunohistochemistry. Rats in the UUO group showed excessive deposition of collagen in kidney interstitium, accompanied with high levels of renal 8-hydroxy-2′-deoxyguanosine, renal malondialdehyde, blood urea nitrogen (BUN), serum creatinine (Scr), and proteinuria (all P<0.05). Cili powder efficiently alleviated the pathological changes and oxidative stress in the kidneys of UUO rats, and decreased BUN, Scr and proteinuria (all P<0.05). Cili powder also inhibited the upregulation of TGFB1, TGFBR1, TGFBR2, SMAD2, and SMAD3 and reversed the downregulation of SMAD7 in obstructed kidneys (mRNA and protein) (all P<0.05). In summary, the results suggest that Cili freeze-dried powder effectively prevents renal fibrosis and impairment in UUO rats, which is associated with the inhibition of oxidative stress and TGF-β1/Smads signaling.

Component analysis and anti-pulmonary fibrosis effects of Rosa sterilis juice

“…Mechanically, RSJ inhibited TGF-β1-induced Smad2/3 phosphorylation, and prevented EMT and fibroblast differentiation to reduce extracellular matrix and collagen deposition, thereby alleviating bleomycin-induced pulmonary fibrosis. The previous study also showed that Rosa roxburghii Tratt mitigated renal fibrosis by inhibiting the TGF-β1/Smads signaling pathway, 13 suggesting a potential protective role of RS or Rosa roxburghii Tratt in fibrosis.…”

“…11,12 Its alpha-glucosidase inhibitory activity has been well described, 10 indicating that Rosa roxburghii Tratt has high nutritive value. In preclinical studies, Rosa roxburghii Tratt freeze-dried powder ameliorated renal fibrosis by regulating the TGF-β1/Smad signaling pathway, 13 suggesting that Rosa roxburghii Tratt has potential health benefits for pulmonary fibrosis. Rose sterilis (RS) is a new variety of Rosa roxburghii Tratt, and its production has already reached 100 000 tons per year.…”

Recent advances in polysaccharides from Rose roxburghii Tratt fruits: isolation, structural characterization, and bioactivities

“…4 In addition, a growing number of scientific studies have demonstrated that RRF presents antioxidant, hypoglycemic, hypolipidemic, radioprotection, immunoregulation, anticancer, aging retarding, and antifibrosis activities. [5][6][7][8][9][10][11] Natural polysaccharides, being a large class of macromolecular compounds, have attracted extensive attention because of their low toxicity and excellent biological activities. Several natural active polysaccharides have been used in functional foods and medicine.…”

“…4 In addition, a growing number of scientific studies have demonstrated that RRF presents antioxidant, hypoglycemic, hypolipidemic, radioprotection, immunoregulation, anticancer, aging retarding, and anti-fibrosis activities. 5–11…”

<p>Renoprotective Effect of Formononetin by Suppressing Smad3 Expression in Db/Db Mice</p>

“…Smad3 protein can directly bind to the promoter region of collagen to up-regulate the expression of collagen and promote the process of renal fibrosis. 14,15 Oxidative stress injury is the basis of EMT, 16 smad3 protein reduces fibrosis and ECM deposition by inhibiting oxidative stress. 17,18 Thus, renal fibrosis is the most important feature of renal pathology of DN, which was related with smad3-mediated fibrosis and oxidative stress.…”