Department of Geriatrics, The First Affiliated Hospital of China Medical University, Liaoning Province, China.
Food Funct. 2018 Aug 15;9(8):4184-4193. doi: 10.1039/c8fo00650d.
Alcoholic hepatitis (AH) is characterized by inflammation and necrosis of liver tissue caused by excessive alcohol consumption and it even causes organ failure sometimes, in which oxidative stress plays an important role. Quercetin is a bioactive flavonoid in the class of polyphenols with a free-radical scavenging ability and anti-inflammatory activity. Recently it has aroused great interest because of its potential benefits in the prevention and intervention of cancer, cardiovascular abnormalities, neurodegenerative diseases, metabolic disorders and liver fibrosis. However, its role in alcoholic liver injury is still unclear and needs to be elucidated. Through database analysis and serum measurements, we found that there was a decline in the level of heme oxygenase-1 (HO-1) in patients with acute alcoholic hepatitis compared to healthy controls. Quercetin could elevate the expression of nuclear factor E2-related factor 2(Nrf2)/HO-1 and ameliorate ethanol-induced acute liver injury in rats. Moreover, this protective effect of quercetin could be diminished when combined with the HO-1 inhibitor ZnppIX which demonstrated a critical role of HO-1 in quercetin's hepatoprotection. The underlying mechanism of quercetin's benefit on the liver may be explained by its anti-oxidant properties and inhibitory effect on the ROS/NF-κB/NLRP3 inflammasome/IL-1β and IL-18 pathway by inducing HO-1. Meanwhile, quercetin also upregulated the anti-inflammatory factor IL-10, while it was found uncorrelated with HO-1 expression. In conclusion, quercetin can preserve the function of the liver in acute alcoholic injury by upregulating the expression of IL-10 and HO-1 and thus inhibiting NLRP3 inflammasome activation and inflammatory factor secretion. In other words, quercetin looks promising as an alternative treatment and HO-1 may be a potential target in the crosstalk of inflammation and oxidative stress in alcoholic liver damage.
酒精性肝炎（AH）的特征是由过量饮酒引起的肝组织炎症和坏死，有时甚至会导致器官衰竭，其中氧化应激起着重要作用。槲皮素是多酚类黄酮中的一种生物活性类黄酮，具有自由基清除能力和抗炎活性。由于其在预防和干预癌症、心血管异常、神经退行性疾病、代谢紊乱和肝纤维化方面的潜在益处，最近它引起了极大的兴趣。然而，其在酒精性肝损伤中的作用尚不清楚，需要进一步阐明。通过数据库分析和血清测量，我们发现与健康对照组相比，急性酒精性肝炎患者的血红素加氧酶-1（HO-1）水平下降。槲皮素可上调核因子 E2 相关因子 2（Nrf2）/HO-1 的表达，并改善乙醇诱导的大鼠急性肝损伤。此外，当与 HO-1 抑制剂 ZnppIX 联合使用时，槲皮素的这种保护作用会减弱，这表明 HO-1 在槲皮素的肝保护作用中起着关键作用。槲皮素对肝脏有益的潜在机制可能与其抗氧化特性以及通过诱导 HO-1 抑制 ROS/NF-κB/NLRP3 炎性体/IL-1β 和 IL-18 途径有关。同时，槲皮素还上调抗炎因子 IL-10，而与 HO-1 表达无关。总之，槲皮素通过上调 IL-10 和 HO-1 的表达，抑制 NLRP3 炎性小体的激活和炎症因子的分泌，从而保护急性酒精性肝损伤中的肝脏功能。换句话说，槲皮素有望成为一种替代治疗方法，HO-1 可能是酒精性肝损伤中炎症和氧化应激相互作用的潜在靶点。
