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.
Chem Biol Interact. 2018 Apr 1;285:14-20. doi: 10.1016/j.cbi.2018.02.025. Epub 2018 Feb 21.
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 LO were cultured and stimulated with ethanol for inducing LO damage. We examined the effects of oroxylin A on the accumulation of lipid droplets in ethanol-treated LO. 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 LO. 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 LO. Oroxylin A modulation of HIF-1α level may represent a therapeutic remedy for ALD.
越来越多的数据表明，白杨素 A 对慢性肝病有有益的影响。先前的研究表明，白杨素 A 是从黄芩中提取的一种黄酮类化合物，它可以改善体内的急性肝损伤和加速肝脏再生。然而，目前还不清楚白杨素 A 对酒精性肝病的作用。本研究旨在阐明白杨素 A 对酒精性肝脂肪变性的作用及其潜在机制。原代人肝细胞 LO 用乙醇刺激培养以诱导 LO 损伤。我们研究了白杨素 A 对乙醇处理的 LO 中脂滴积累的影响。结果表明，白杨素 A 减少了与调节脂代谢基因相关的脂滴积累。此外，白杨素 A 显著抑制了乙醇处理的 LO 中 HIF-1α 的核易位。此外，在体外和体内，HIF-1α 的激活显著减弱了白杨素 A 对脂滴积累和与脂代谢相关基因的作用。总之，我们证明了 HIF-1α 相关机制是白杨素 A 抑制乙醇刺激的 LO 中脂质沉积的基础。白杨素 A 对 HIF-1α 水平的调节可能代表了治疗酒精性肝病的一种治疗方法。
