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

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 flavonoids such as Quercetin. It is a natural antioxidant of multiple dietary origins and has been extensively studied for its beneficial role as an anti-inflammatory 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 inflammatory genes (TNF-α, IL-6, and IL-1β) and SND1, a significant 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 significant elevation in liver weight and enzyme activity. All of these effects were ameliorated by Quercetin treatment. Immunohistochemistry data revealed an improvement in the inflammation and fibrosis characteristics in liver tissues of the Quercetin-treated group. Decreased expression of inflammatory 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

Elevated serum Homocysteine levels a possible non-invasive diagnostic biomarker in patients with Non-alcoholic fatty liver disease

Lack of independent biomarkers is very much evident in NAFLD. Early detection of NAFLD is difficult due to the absence of specific diagnostic and prognostic markers and clinical symptoms. We retrospectively collected the information of patients hospitalised with NAFLD diagnosis and metabolic syndrome during 2019-2020 using the tertiary care hospital inpatient sample database and evaluated the changes in their serum homocysteine levels. We found that 59.063% of NAFLD in the male population and 41.667% of NAFLD in the female population had increased serum homocysteine. This shows that elevated serum homocysteine can act as a potential biomarker for NAFLD

Quercetin activates vitamin D receptor and ameliorates breast cancer induced hepatic inflammation and fibrosis

AimsTo explore the hepatoprotective role of quercetin and its novel molecular mechanism of action on breast cancer associated hepatic inflammation and fibrosis via Vitamin D receptor (VDR).Main methodsWe used Ehrlich Ascites Carcinoma (mouse mammary carcinoma) model for our in-vivo experiments and human breast cancer cell lines for in-vitro assays. We inoculated 1.5 × 106 Ehrlich ascites carcinoma cells into female Swiss albino mice. Quercetin (50 mg/kg) was administered intraperitoneally for 15 days. Liver enzymes activity was determined using a spectrophotometric assay. The hallmarks of inflammation and fibrosis were determined using Immunohistochemistry. The effect of quercetin on tumor formation was elucidated using human breast cancer cell lines and chick chorioallantoic membrane assay. Docking study was performed to explore the binding mode of quercetin with VDR.Key findingsIn EAC tumor-bearing mice, cell numbers, tumor volume, body weight and liver weight were dramatically increased, while they significantly decreased in mice treated with quercetin. Additionally, the peritoneal neo-angiogenesis was also significantly suppressed in the quercetin-treated mice, compared to the control. In addition, quercetin treated EAC tumor bearing mice had lower levels of liver enzymes, decreased hepatic inflammation and fibrosis compared with EAC tumor bearing mice. Docking study confirmed VDR-quercetin interaction. Furthermore, in-vitro assays and chick chorioallantoic membrane assay revealed the Vitamin D mimicking effect of quercetin.SignificanceDietary flavonoid, quercetin could act as a promising therapeutic drug to suppress the breast cancer induced tumor angiogenesis, hepatic inflammation, and fibrosis possibly via activation of VDR

Image_1_Quercetin activates vitamin D receptor and ameliorates breast cancer induced hepatic inflammation and fibrosis.TIF

AimsTo explore the hepatoprotective role of quercetin and its novel molecular mechanism of action on breast cancer associated hepatic inflammation and fibrosis via Vitamin D receptor (VDR).Main methodsWe used Ehrlich Ascites Carcinoma (mouse mammary carcinoma) model for our in-vivo experiments and human breast cancer cell lines for in-vitro assays. We inoculated 1.5 × 106 Ehrlich ascites carcinoma cells into female Swiss albino mice. Quercetin (50 mg/kg) was administered intraperitoneally for 15 days. Liver enzymes activity was determined using a spectrophotometric assay. The hallmarks of inflammation and fibrosis were determined using Immunohistochemistry. The effect of quercetin on tumor formation was elucidated using human breast cancer cell lines and chick chorioallantoic membrane assay. Docking study was performed to explore the binding mode of quercetin with VDR.Key findingsIn EAC tumor-bearing mice, cell numbers, tumor volume, body weight and liver weight were dramatically increased, while they significantly decreased in mice treated with quercetin. Additionally, the peritoneal neo-angiogenesis was also significantly suppressed in the quercetin-treated mice, compared to the control. In addition, quercetin treated EAC tumor bearing mice had lower levels of liver enzymes, decreased hepatic inflammation and fibrosis compared with EAC tumor bearing mice. Docking study confirmed VDR-quercetin interaction. Furthermore, in-vitro assays and chick chorioallantoic membrane assay revealed the Vitamin D mimicking effect of quercetin.SignificanceDietary flavonoid, quercetin could act as a promising therapeutic drug to suppress the breast cancer induced tumor angiogenesis, hepatic inflammation, and fibrosis possibly via activation of VDR.</p

Image_2_Quercetin activates vitamin D receptor and ameliorates breast cancer induced hepatic inflammation and fibrosis.TIF

AimsTo explore the hepatoprotective role of quercetin and its novel molecular mechanism of action on breast cancer associated hepatic inflammation and fibrosis via Vitamin D receptor (VDR).Main methodsWe used Ehrlich Ascites Carcinoma (mouse mammary carcinoma) model for our in-vivo experiments and human breast cancer cell lines for in-vitro assays. We inoculated 1.5 × 106 Ehrlich ascites carcinoma cells into female Swiss albino mice. Quercetin (50 mg/kg) was administered intraperitoneally for 15 days. Liver enzymes activity was determined using a spectrophotometric assay. The hallmarks of inflammation and fibrosis were determined using Immunohistochemistry. The effect of quercetin on tumor formation was elucidated using human breast cancer cell lines and chick chorioallantoic membrane assay. Docking study was performed to explore the binding mode of quercetin with VDR.Key findingsIn EAC tumor-bearing mice, cell numbers, tumor volume, body weight and liver weight were dramatically increased, while they significantly decreased in mice treated with quercetin. Additionally, the peritoneal neo-angiogenesis was also significantly suppressed in the quercetin-treated mice, compared to the control. In addition, quercetin treated EAC tumor bearing mice had lower levels of liver enzymes, decreased hepatic inflammation and fibrosis compared with EAC tumor bearing mice. Docking study confirmed VDR-quercetin interaction. Furthermore, in-vitro assays and chick chorioallantoic membrane assay revealed the Vitamin D mimicking effect of quercetin.SignificanceDietary flavonoid, quercetin could act as a promising therapeutic drug to suppress the breast cancer induced tumor angiogenesis, hepatic inflammation, and fibrosis possibly via activation of VDR.</p