Polydatin protects against acute cholestatic liver injury in mice via the inhibition of oxidative stress and endoplasmic reticulum stress

Cholestatic liver injury is a chronic disease caused by the retention of toxic hydrophobic bile salts in the liver, but lack of efficient therapy. Here, we identified that polydatin (PD), a natural precursor of resveratrol (RES), has potent detoxification effects on cholestatic liver injury. PD inhibited hepatocellular apoptosis and attenuated serum alanine aminotransferase (ALT), aspartate transaminase (AST), total bile acid (TBA), alkaline phosphatase (ALP) and total bilirubin (TBIL) levels in the cholestatic mice induced by alpha-naphthylisothiocyanate (ANIT) and bile duct ligation (BDL). Mechanistically, PD reduced malondialdehyde (MDA) levels and increased superoxide dismutase (SOD) activity, suppressed endoplasmic reticulum (ER) stress, CCAAT/enhancer-binding protein homologous protein (CHOP), phosphorylated eukaryotic initiation factor 2 alpha (p-elf2 alpha) and apoptosis in the liver of the mice, suggesting that PD may alleviate cholestatic liver injury via the inhibition of oxidative stress, ER stress and apoptosis. Our data indicate that PD may be a phytoalexin for cholestatic liver diseases.