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Chem Biol Interact. 2018 Apr 1;285:14-20. doi: 10.1016/j.cbi.2018.02.025. Epub 2018 Feb 21.

Oroxylin A prevents alcohol-induced hepatic steatosis through inhibition of hypoxia inducible factor 1alpha.

Author information

1
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
2
Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China; State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
3
Department of Pathology, School of Medicine, Saint Louis University, MO, USA.
4
Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, 210023, China.
5
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China; State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
6
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China; State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: nytws@163.com.

Abstract

Accumulating data reveal that oroxylin A has beneficial effects against chronic liver disease. The previously studies showed oroxylin A, a flavonoid extracted from Scutellariae radix, improved acute liver injury and accelerated liver regeneration in vivo. However, it's unclear that the effect of oroxylin A on alcoholic liver disease. The present study was aimed at elucidating the effect of oroxylin A on alcohol-induced hepatic steatosis and the underlying mechanisms. Human hepatocyte LO2 were cultured and stimulated with ethanol for inducing LO2 damage. We examined the effects of oroxylin A on the accumulation of lipid droplets in ethanol-treated LO2. The results showed that oroxylin A reduced the accumulation of lipid droplets associated with regulating the lipid metabolism genes. Moreover, oroxylin A significantly suppressed the nuclear translocation of HIF-1α in ethanol-treated LO2. Furthermore, activation of HIF-1α significantly attenuated the effect of oroxylin A on lipid droplets accumulation and genes related to lipid metabolism in vitro and in vivo. Altogether, we demonstrated a HIF-1α-associated mechanism underlying oroxylin A inhibition of lipid deposition in ethanol-stimulated LO2. Oroxylin A modulation of HIF-1α level may represent a therapeutic remedy for ALD.

KEYWORDS:

ALD; HIF-1α; Hepatic steatosis; Oroxylin A

PMID:
29476730
DOI:
10.1016/j.cbi.2018.02.025
[Indexed for MEDLINE]

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