Hepatoprotective effect of piceatannol against carbon tetrachloride-induced liver fibrosis in mice

• Published in: Food & function Vol. 12; no. 22; pp. 11229 - 1124
• Main Authors: Hung, Wei-Lun, Hsiao, Yi-Ting, Chiou, Yi-Shiou, Nagabhushanam, Kalyanam, Ho, Chi-Tang, Pan, Min-Hsiung
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 15.11.2021
• Subjects: Animal models; Animals; Antioxidants; Antioxidants - pharmacology; Biocompatibility; Body Weight - drug effects; Carbon tetrachloride; Carbon Tetrachloride - adverse effects; Catalase; Collagen; Collagen (type I); Fibrosis; Glutathione; Growth factors; Inflammation; Liver; Liver Cirrhosis - chemically induced; Liver Cirrhosis - metabolism; Male; Matrix metalloproteinase; Matrix metalloproteinases; Metabolites; Mice; Muscles; Neuroprotection; Oral administration; Piceatannol; Resveratrol; Resveratrol - pharmacology; Signal transduction; Smad protein; Smooth muscle; Stilbenes - pharmacology; Tissue inhibitor of metalloproteinase 1; Toxic diseases; Toxins; Transforming growth factor-b; Vitis; Wines
• ISSN: 2042-6496; 2042-650X
• DOI: 10.1039/d1fo02545g

Piceatannol (3,5,3′,4′- trans -tetrahydroxystilbene) is a natural analog and a metabolite of resveratrol present in grapes and red wine. Previous studies have reported that piceatannol exerts a broad spectrum of health benefits including antioxidant, anti-inflammatory, chemopreventive, and neuroprotective effects. However, little is known about the hepatoprotective effect of piceatannol against toxin-induced liver fibrosis. Therefore, the objective of this study is to evaluate the protective effect of piceatannol in a mouse model of CCl 4 -induced hepatic fibrosis. Oral administration of piceatannol significantly improved the hepatic functions of CCl 4 -treated mice in both therapeutic and preventive models. Additionally, the immunohistochemical staining results revealed that collagen deposition in CCl 4 -injected mice was significantly reduced by treatment with piceatannol. Moreover, piceatannol remarkably suppressed the expressions of collagen I, α-smooth muscle protein (α-SMA), and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) induced by CCl 4 . The anti-fibrotic mechanism of piceatannol was associated with the regulation of the transforming growth factor-β (TGF-β)/Smad signaling pathway. Finally, piceatannol also profoundly alleviated CCl 4 -induced hepatic oxidative damage by elevating the level of glutathione and catalase activity. Altogether, our current findings suggest that piceatannol may serve as a bioactive agent that inhibits or alleviates toxic-induced fibroproliferative diseases, especially in the prevention of liver fibrosis. Supplementation of piceatannol significantly alleviated CCl 4 -induced hepatic fibrosis in mice.