Scutellarin prevents acute alcohol-induced liver injury via inhibiting oxidative stress by regulating the Nrf2/HO-1 pathway and inhibiting inflammation by regulating the AKT, p38 MAPK/NF-κB pathways. / ç¯ç›èŠ±ä¹™ç´ é€šè¿‡è°ƒèŠ‚Nrf2/HO-1通路抑制氧化应激以及通过调节AKT、p38 MAPK/NF-κBé€šè·¯æŠ‘åˆ¶ç‚Žç—‡ååº”é¢„é˜²æ€¥æ€§é ’ç²¾æ€§è‚æŸä¼¤.

ABSTRACT

Alcoholic liver disease (ALD) is the most frequent liver disease worldwide, resulting in severe harm to personal health and posing a serious burden to public health. Based on the reported antioxidant and anti-inflammatory capacities of scutellarin (SCU), this study investigated its protective role in male BALB/c mice with acute alcoholic liver injury after oral administration (10, 25, and 50 mg/kg). The results indicated that SCU could lessen serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and improve the histopathological changes in acute alcoholic liver; it reduced alcohol-induced malondialdehyde (MDA) content and increased glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) activity. Furthermore, SCU decreased tumor necrosis factor-|α (TNF-|α), interleukin-6 (IL-6), and IL-|1ß messenger RNA (mRNA) expression levels, weakened inducible nitric oxide synthase (iNOS) activity, and inhibited nucleotide-binding oligomerization domain (NOD)|-like receptor protein 3 (NLRP3) inflammasome activation. Mechanistically, SCU suppressed cytochrome P450 family 2 subfamily E member 1 (CYP2E1) upregulation triggered by alcohol, increased the expression of oxidative stress-related nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) pathways, and suppressed the inflammation-related degradation of inhibitor of nuclear factor-|κB (NF-|κB)|-|α (IκBα) as well as activation of NF|-|κB by mediating the protein kinase B (AKT) and p38 mitogen-activated protein kinase (MAPK) pathways. These findings demonstrate that SCU protects against acute alcoholic liver injury via inhibiting oxidative stress by regulating the Nrf2/HO-1 pathway and suppressing inflammation by regulating the AKT, p38 MAPK/NF-κB pathways.