Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China.
Food Funct. 2021 Jan 7;12(1):362-372. doi: 10.1039/d0fo02653k. Epub 2020 Dec 16.
Excessive alcohol drinking and a high-fat diet (HFD) promote steatohepatitis in the comorbidity of NAFLD and AFLD. Taxifolin (TAX) is a rich dihydroxyflavone compound found in onions, milk thistle and Douglas fir. We aimed to explore the intervention mechanism of TAX on chronic steatohepatitis induced by HFD feeding plus acute ethanol binge. We established an in vivo model by HFD feeding plus a single dose of ethanol binge, and established an in vitro model by oleic acid or palmitic acid on HepG2 cells to induce lipid accumulation. TAX regulated lipid synthesis by inhibiting the expression of SREBP1 and upregulating the PPARγ level. In addition, TAX inhibited the expression of P2X7R, IL-1β, and caspase-1. Moreover, TAX reduced the expression of caspase-1 activation; thereby inhibiting the recruitment of macrophages and neutrophils. TAX also improved the inflammatory response caused by caspase-1 activation in steatotic hepatocytes. TAX exhibited an inhibitory effect on lipid accumulation and caspase-1-related pyroptosis. Collectively, TAX has therapeutic potential as an intervention of steatohepatitis induced by alcohol combined with HFD and for preventing non-alcoholic fatty liver degeneration targeting caspase-1-dependent pyroptosis.
过量饮酒和高脂肪饮食（HFD）可促进非酒精性脂肪性肝病（NAFLD）和酒精性脂肪性肝病（AFLD）合并症中的脂肪性肝炎。根皮苷（TAX）是一种在洋葱、奶蓟和花旗松中富含的二羟基黄酮化合物。我们旨在探索 TAX 对 HFD 喂养加急性乙醇 binge 诱导的慢性脂肪性肝炎的干预机制。我们通过 HFD 喂养加单次乙醇 binge 建立了体内模型，并通过油酸或棕榈酸在 HepG2 细胞上建立了体外模型来诱导脂质积累。TAX 通过抑制 SREBP1 的表达和上调 PPARγ 水平来调节脂质合成。此外，TAX 抑制了 P2X7R、IL-1β 和 caspase-1 的表达。此外，TAX 降低了 caspase-1 激活的表达；从而抑制巨噬细胞和中性粒细胞的募集。TAX 还改善了 casapse-1 激活引起的脂肪性肝细胞的炎症反应。TAX 对脂质积累和 caspase-1 相关细胞焦亡具有抑制作用。总之，TAX 具有作为酒精联合 HFD 诱导的脂肪性肝炎的干预治疗的潜力，并具有针对 caspase-1 依赖性细胞焦亡的非酒精性脂肪性肝病退行性变的预防潜力。
