Ameliorating Effect Of Quercetin On Ethanol-Induced Liver Injury Via Targeting RISC Machinery

Abstract

Background : Over the past few decades, increased alcohol consumption has had deleterious effects on human health. Alcoholic fatty liver disease (AFLD) is becoming a major global challenge, as the currently approved drugs for AFLDs are subject to several side effects. This has broadened the scope of the use of natural compounds as therapeutics. Recent advances in nutraceuticals as therapeutics have shed light on fl avonoids such as Quercetin. It is a natural antioxidant of multiple dietary origins and has been extensively studied for its bene fi cial role as an anti-in fl ammatory and anti-cancer agent. Objective : Based on this framework, in the proposed study, we investigated the therapeutic role of Quercetin in Ethanol-induced liver damage using the Swiss Albino mice model and the hepatic cell line HepG2. Methodology : WST-1 assay was performed to access the effect of Quercetin on cell proliferation. The impact of Ethanol on the body and liver weights of mice was measured, and liver injury was determined by H & E staining and TMS. The mRNA expression levels of in fl ammatory genes (TNF-a , IL-6, and IL-1 b ) and SND1, a signi fi cant unit of the RNA-induced silencing complex (RISC), were analyzed. The liver enzyme levels were also measured. Results : Our experimental results showed that HepG2 cells treated with ethanol had a lower proliferation rate, which was later mitigated by treatment with quercetin. In the mice model, a considerable reduction in body weight was detected after ethanol treatment. Conversely, there was a signi fi cant elevation in liver weight and enzyme activity. All of these effects were ameliorated by Quercetin treatment. Immunohistochemistry data revealed an improvement in the in fl ammation and fi brosis characteristics in liver tissues of the Quercetin-treated group. Decreased expression of in-fl ammatory markers and SND1 levels were also observed in the Quercetin-treated group. Conclusion : Based on our results it may be concluded that Quercetin demonstrated hepatoprotective activity in both ethanol-treated HepG2 cell line and ethanol-induced liver injury in mice model. Here, we elucidated a novel and possible therapeutic role of Quercetin in Alcohol-Related Liver Disease (ARLD) by targeting the RISC machinery.