Chlorogenic acid-rich Morus alba leaf alleviated renal fibrosis through the regulation of transforming growth factor-beta 1 (TGF-β1) and fibroblast growth factor-2 (FGF-2), and extracellular matrix deposition

Background: Chronic kidney disease (CKD) progression is linked to renal fibrosis, influenced by profibrotic factors like transforming growth factor-beta 1 (TGF-β1) and fibroblast growth factor-2 (FGF-2). Despite advancements in synthetic drugs like enalapril, evidence for plant-derived candidates that slow kidney fibrosis remains limited, underscoring the need for rigorous preclinical evaluation. Objective: This study evaluates the antifibrotic efficacy of Morus alba Linn. leaf extract (MLE) and its primary compound, chlorogenic acid (CGA), in a mouse model of renal fibrosis induced by unilateral ureteral obstruction (UUO). Materials and methods: Twenty-five male Balb/c mice were assigned to five groups: sham operation (SO), UUO control, UUO with enalapril treatment, UUO with MLE, and UUO with CGA. Treatments were administered orally for 14 days, followed by assessments of fibrosis through histological analysis, immunohistochemistry, gene expression profiling, and molecular docking. Results: Results indicated significant reductions in basement membrane thickening (from 31.19% in UUO to 21.87% with MLE), collagen deposition (from 6.85% to 2.7%), and decreased expression of key fibrotic markers such as TGF-β1 (from 26.21% to 11.91% with MLE and 5.92% with CGA), FGF-2, Collagen-1, Smad3, alpha-smooth muscle actin (α-SMA), and β-catenin. Molecular docking analysis suggested that CGA formed plausible interactions with transforming growth factor beta receptor 1 (TGFβR1) (-9.5 kcal/mol) and fibroblast growth factor receptor 2 (FGFR2) (-8.3 kcal/mol), indicating its potential antifibrotic properties. Conclusion: These findings suggest that MLE and CGA effectively alleviate renal fibrosis by modulating crucial profibrotic signaling pathways, presenting them as promising natural therapeutic alternatives for CKD-associated fibrosis.

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