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
- Author:
ZHANG XIAO
1
;
DONG ZHICHENG
;
FAN HUI
;
YANG QIANKUN
;
YU GUILI
;
PAN ENZHUANG
;
HE NANA
;
LI XUEQING
;
ZHAO PANPAN
;
FU MIAN
;
DONG JINGQUAN
Author Information
- Keywords: Scutellarin; Oxidative stress; Alcoholic liver disease; Inflammation
- From: Journal of Zhejiang University. Science. B 2023;24(7):617-631
- CountryChina
- Language:Chinese
- 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-1β 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.
