Iranian journal of basic medical sciences · 2024
Suppression of TGF-β/Smad3 signaling pathway by Capparis spinosa and quercetin in a rat model of nonalcoholic steatohepatitis.
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Afarin Reza, Hatami Mahdi, Monjezi Sajad, Bineshfar Fatemeh, Ahangarpour Akram
Аннотация
OBJECTIVES: Liver diseases, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), pose significant global public health challenges. This study investigates the therapeutic effects of quercetin (QC), Capparis spinosa (CS), a QC and CS combination, and Saroglitazar (SARO) on NASH in a Wistar rat model.
MATERIALS AND METHODS: NASH was induced by a 42-day high-fat diet regimen in male Wistar rats. Post-induction, rats were divided into five groups receiving SARO, QC, CS, and CS+QC combination. We monitored changes in liver and body weights and evaluated the expression of genes associated with fatty acid biosynthesis (e.g., ACC and FAS), β-oxidation (e.g., CPT1, PPAR α), inflammation (e.g., TNF-α and IL-6), and fibrosis (e.g., TGF-β and COL1A), as well as protein expression levels of p-Smad2/3 and p-Smad3.
RESULTS: Treatment with QC+CS significantly decreased liver weight, body mass gain, and liver triglyceride (TG) compared to other treatments. The QC and CS combined therapy also resulted in a greater normalization of hepatic enzymatic activities, including decreases in ALT and AST levels, coupled with improvements in lipid profile indicated by decreased LDL-C and increased HDL-C concentrations, as compared to SARO and QC alone. Furthermore, this combined treatment significantly down-regulated the expression of TGF-β, TNF-α, IL-6 genes, and Smad2/3 and Smad3 protein levels.
CONCLUSION: Our study demonstrates that an interactive effect between QC and CS can effectively reduce liver fibrosis and steatosis by inhibiting the TGF-β/Smad3 signaling pathway in a diet-induced model of nonalcoholic steatohepatitis and fibrosis in rats.
MATERIALS AND METHODS: NASH was induced by a 42-day high-fat diet regimen in male Wistar rats. Post-induction, rats were divided into five groups receiving SARO, QC, CS, and CS+QC combination. We monitored changes in liver and body weights and evaluated the expression of genes associated with fatty acid biosynthesis (e.g., ACC and FAS), β-oxidation (e.g., CPT1, PPAR α), inflammation (e.g., TNF-α and IL-6), and fibrosis (e.g., TGF-β and COL1A), as well as protein expression levels of p-Smad2/3 and p-Smad3.
RESULTS: Treatment with QC+CS significantly decreased liver weight, body mass gain, and liver triglyceride (TG) compared to other treatments. The QC and CS combined therapy also resulted in a greater normalization of hepatic enzymatic activities, including decreases in ALT and AST levels, coupled with improvements in lipid profile indicated by decreased LDL-C and increased HDL-C concentrations, as compared to SARO and QC alone. Furthermore, this combined treatment significantly down-regulated the expression of TGF-β, TNF-α, IL-6 genes, and Smad2/3 and Smad3 protein levels.
CONCLUSION: Our study demonstrates that an interactive effect between QC and CS can effectively reduce liver fibrosis and steatosis by inhibiting the TGF-β/Smad3 signaling pathway in a diet-induced model of nonalcoholic steatohepatitis and fibrosis in rats.