Journal
CHEMICO-BIOLOGICAL INTERACTIONS
Volume 285, Issue -, Pages 14-20Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2018.02.025
Keywords
Oroxylin A; ALD; Hepatic steatosis; HIF-1 alpha
Funding
- National Natural Science Foundation of China [31571455, 31401210, 31600653, 81600483, 81270514]
- Open Project Program of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica [JKLPSE 201502]
- Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
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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-1 alpha in ethanol-treated LO2. Furthermore, activation of HIF-1 alpha 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-1 alpha-associated mechanism underlying oroxylin A inhibition of lipid deposition in ethanol-stimulated LO2. Oroxylin A modulation of HIF-1 alpha level may represent a therapeutic remedy for ALD.
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