Hung W.-LHsiao Y.-TChiou Y.-SNagabhushanam KHo C.-TMIN-HSIUNG PAN2022-04-252022-04-25202120426496https://www.scopus.com/inward/record.uri?eid=2-s2.0-85119719483&doi=10.1039%2fd1fo02545g&partnerID=40&md5=b20e64ea227ec82df7be0d5d03211896https://scholars.lib.ntu.edu.tw/handle/123456789/606144Piceatannol (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 CCl4-induced hepatic fibrosis. Oral administration of piceatannol significantly improved the hepatic functions of CCl4-treated mice in both therapeutic and preventive models. Additionally, the immunohistochemical staining results revealed that collagen deposition in CCl4-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 CCl4. 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 CCl4-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. ? The Royal Society of Chemistry.MammalsMetabolitesAnti-inflammatory effectsBroad spectrumChemopreventive effectsGrape wineHealth benefitsHepatoprotective effectsLiver fibrosisNatural analogPiceatannolRed wineCollagen3,3',4,5'-tetrahydroxystilbeneantioxidantcarbon tetrachlorideresveratrolstilbene derivativeanimalbody weightdrug effectliver cirrhosismalemetabolismmouseVitisAnimalsAntioxidantsBody WeightCarbon TetrachlorideLiver CirrhosisMaleMiceResveratrolStilbenes[SDGs]SDG3journal article10.1039/d1fo02545g346768432-s2.0-85119719483