Corni Fructus Alleviates UUO-Induced Renal Fibrosis via TGF-β/Smad Signaling

Abstract

Renal fibrosis is a type of chronic kidney disease (CKD) induced by infiltration of inflammatory cells, myofibroblast accumulation, and ECM production in the kidney. From a long time ago, Corni Fructus (CF) is known to supplement the liver and kidney with its tepid properties. In this study, we investigated the renal protective mechanism of CF, which is known to supplement the kidney, in rat model of unilateral ureteral obstruction (UUO). After inducing UUO through surgery, the group was separated ( n = 8 ) and the drug was administered for 2 weeks; normal rats (normal), water-treated UUO rats (control), CF 100 mg/kg-treated UUO rats (CF100), and CF 200 mg/kg-treated UUO rats (CF200). As a result of histopathological examination of kidney tissue with H&E, MT, and PAS staining, it was confirmed that the infiltration of inflammatory cells and the erosion of collagen were relatively decreased in the kidneys treated with CF. Also, CF significantly reduced the levels of MDA and BUN in serum. As a result of confirming the expression of the factors through western blotting, CF treatment significantly reduced the expression of NADPH oxidase and significantly regulated the AMPK/LKB1/NF-κB pathway associated with inflammation. In addition, it downregulated the expression of major fibrotic signaling factors, such as α-SMA, collagen I, MMP-2, and TIMP-1, and significantly regulated the TGF-β1/Smad pathway, which is known as a major regulator of renal fibrosis. Taken together, these findings indicate that CF can alleviate renal fibrosis by regulating the TGF-β1/Smad pathway through inhibition of oxidative stress in UUO.

Cornelian Cherry (Cornus mas L.) Iridoid and Anthocyanin-Rich Extract Reduces Various Oxidation, Inflammation, and Adhesion Markers in a Cholesterol-Rich Diet Rabbit Model

“…7-O-galloyl-D-sedoheptulose reduced the renal protein expression of NOX-4 and one of the subunits of NADPH oxidase-p22(phox) [ 56 ], while the administration of loganin led to a significant decrease in the expression of both NOX-4 and p22(phox) in the liver of diabetic db/db mice [ 57 ]. Comparable results were obtained among others by Lee et al [ 58 ], Chen et al [ 59 ], and Fang et al [ 60 ].…”

Research progress on the mechanism of renal interstitial fibrosis in obstructive nephropathy

“…The Recombinant Purinergic Receptor P2Y(P2Y12) inhibitor clopidogrel attenuates renal fibrosis by inhibiting the transition of macrophages to myofibroblasts via the TGF-β/Smad3 signaling pathway [ 64 ]. Capsaicin attenuates renal fibrosis by inhibiting TGF-β1-Smad2/3 signaling pathway, delaying myofibroblast activation and protecting renal tubular epithelial cell phenotype changes [ 65 ], Corni Fructus alleviates renal fibrosis by inhibiting oxidative stress in UUO and modulating the TGF-β1/Smad pathway [ 66 ]. Similarly, Nootkatone can also exert anti-fibrotic effects in a mouse model of unilateral ureteral obstruction by regulating the Tgf-β/Smad signaling pathway [ 67 ].…”

Linagliptin Mitigates TGF-β1 Mediated Epithelial–Mesenchymal Transition in Tacrolimus-Induced Renal Interstitial Fibrosis <i>via</i> Smad/ERK/P38 and HIF-1α/LOXL2 Signaling Pathways

“…1) The TGF-β1 exerts its effects on target genes, mainly through downstream phosphorylation of Smad 2/3 proteins, and their role in the transcriptional regulation of ECM genes such as collagen type 1 (COL1A1), fibronectin, and tissue inhibitor of metalloproteinase 1 (TIMP1), which ultimately result in the development and progression of fibrosis. 5,8) In addition, TGF-β1 can signal through Smad-independent signaling cascades. 9) Several studies confirmed that the mitogen-activated protein kinase (MAPK) signaling pathways are directly activated by TGF-β1.…”