AUTHOR=Faheem Safaa A. , Saeed Noha M. , El-Naga Reem N. , Ayoub Iriny M. , Azab Samar S. 

TITLE=Hepatoprotective Effect of Cranberry Nutraceutical Extract in Non-alcoholic Fatty Liver Model in Rats: Impact on Insulin Resistance and Nrf-2 Expression

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.00218

DOI=10.3389/fphar.2020.00218

ISSN=1663-9812

ABSTRACT=Background: Non-alcoholic fatty liver disease (NAFLD) is a pathological accumulation of triglycerides (TGs) in the hepatocyte in the absence of alcohol intake. Untreated NAFLD is expected to progress into liver fibrosis. Cranberry is rich in polyphenols with antioxidant and anti-inflammatory activities. Hypothesis: The present study was performed to evaluate our hypothesis of the possible anti-fibrotic effect of cranberry nutraceutical in high fat cholesterol diet induced (HFCD)-NAFLD in rats with focusing on improving insulin sensitivity and modulating the expression of nuclear factor erythroid-2-related factor-2 (Nrf2) (a transcription factor responsible for regulating cellular redox balance). Method: Male albino wistar rats (12 weeks) received HFCD and/or cranberry (50 and 100 mg/kg/day, three times/week) orally for eight consecutive weeks. Results: In comparison to HFCD group, cranberry treated groups (50 and 100 mg/kg) showed marked hepatoprotection, where it significantly decreased liver enzymes (alanine transaminases by 49% and 64 % and aspartate transaminases by 45% and 64%; respectively), TGs and ameliorated the histopathological alterations (such as inflammatory cells infiltration and ballooning degeneration) induced by HFCD. Also, cranberry alleviated oxidative stress (malondialdehyde, glutathione, catalase and superoxide dismutase) and inflammation (tumor necrosis factor- alpha, interleukine-6 and nuclear factor kappa-b) and significantly reduced HOMA-IR and TyG index. On the other hand, cranberry treated groups (50 and 100 mg/kg) showed marked increase in the expression of adiponectin by 8 and 13 folds, insulin receptor substrate-2 by 21% and 79% and Nrf2 by 13% and 61%; respectively. Notably, cranberry significantly reduced the fibrotic markers, TGF–β and α-SMA expression and collagen deposition. Conclusion: The present study showed that cranberry significantly attenuated NAFLD, in a dose dependent manner, which could be partially recognized to its antioxidant, anti-inflammatory activities and its ability to improve insulin sensitivity. Notably, our study proves for the first time that the anti-fibrotic activity of cranberry is promising.