Naringenin attenuates hepatitis B virus X protein-induced hepatic steatosis

Hung-Jen Lin,Chia-Chou Yeh,I-Hsin Lin,Ko-Li Ku

doi:10.1186/s12906-017-2019-2

Abstract

BackgroundNaringenin (Nar), a common dietary flavonoid abundantly present in fruits, vegetables, and Chinese herbs, is believed to possess strong anti-inflammatory properties and to modulate hepatic apolipoprotein and lipid synthesis. However, there are no reports describing Nar’s effects on the hepatitis B virus protein X (HBx) -induced hepatic steatosis, and the detailed molecular mechanisms of the compound’s effects are still unclear.MethodsNar was administered by oral gavage to HBx-transgenic mice from 4 to 6 weeks of age. Mice were sacrificed after 14 days of once-daily naringenin administration. Liver tissues and sera were collected for histopathology and biochemical analysis.ResultsNar counteracted hepatic lipid accumulation and liver dysfunction in HBx-transgenic mice. In addition, Nar significantly decreased expression of adipogenic and lipogenic genes in mice, suggesting that the compound may have therapeutic effects in the early stages of HBx-mediated hepatic steatosis. These results indicated that naringenin inhibits HBx-induced expression of hepatic adipogenic and lipogenic genes through suppression of HBx-induced gene expression, including decreases in the transcriptional activity of SREBP1c, LXRα, and PPARγ in HBx-trangenic mice and HBx-transfected HepG2 cells.ConclusionsResults from this study suggested that Nar may serve as a therapeutic agent for preventing HBx-infected hepatic steatosis in humans.

Highlights

Naringenin (Nar), a common dietary flavonoid abundantly present in fruits, vegetables, and Chinese herbs, is believed to possess strong anti-inflammatory properties and to modulate hepatic apolipoprotein and lipid synthesis
Naringenin promotes recovery from fatty liver in hepatitis B virus protein X (HBx)-transgenic mice To investigate the effects of Nar (30 mg/kg/d, which corresponds to a daily dose that would be feasible in human) on HBx-induced hepatic lipid accumulation, we assessed the hepatic lipid content of liver tissues from HBxtransgenic mice
Our results showed that Nar treatment attenuated fatty liver pathology in the HBx-transgenic mice, indicating that this compound has therapeutic effects during the early stages of liver pathogenesis in this model

Summary

Introduction

Naringenin (Nar), a common dietary flavonoid abundantly present in fruits, vegetables, and Chinese herbs, is believed to possess strong anti-inflammatory properties and to modulate hepatic apolipoprotein and lipid synthesis. The hepatitis B virus (HBV) is strongly associated with hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC) [1,2,3,4]. Several studies have shown that Nar possesses a variety of pharmacological effects, Lin et al BMC Complementary and Alternative Medicine (2017) 17:505 such as antioxidant activity [18], anti-inflammatory activities [19], anti-tumour-invasion activity [20], and regulation of apolipoprotein and lipid synthesis [21]. There are no reports (to our knowledge) on the mechanism of Nar’s effects on HBx-induced hepatic steatosis. In the present study, we investigated the potential therapeutic effects of Nar on HBV-associated liver damage and fatty liver accumulation in HBx-transgenic mice

Methods

Results

Discussion

Conclusion