Naringin attenuates fructose-induced NAFLD progression in rats through reducing endogenous triglyceride synthesis and activating the Nrf2/HO-1 pathway

Abstract

Background: Excessive fructose consumption causes hepatic lipid accumulation via increased triglyceride (TG) synthesis, leading to the development and progression of non-alcoholic fatty liver disease (NALFD). Naringin, a flavanone glycoside found in citrus fruit, has antioxidant and hypolipidemic properties. Therefore, the aim of this study was to investigate the effect of naringin on fructose-induced NAFLD in rats and the possible underlying mechanism.Methods: Male Sprague Dawley rats were given 10% (w/v) fructose in drinking water for 12 weeks. Naringin (100 mg/kg/day) was administered orally to rats for the last 4 weeks of fructose overload. After 12 weeks of treatment, the hepatic lipid content was determined. In addition, the expression of proteins involved in de novo lipogenesis (DNL) and TG synthesis as well as antioxidant and inflammatory mediators in the liver were examined by western blot analysis.Results: Treatment of fructose-fed rats with naringin significantly decreased the hepatic TG and cholesterol content as well as serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. Naringin treatment also decreased the hepatic expression of carbohydrate response element binding protein (ChREBP), sterol regulatory element-binding protein-1c (SREBP-1c) and nuclear SREBP-1c (nSREBP-1c) as well as enzymes involved in DNL (acetyl CoA carboxylase [ACC] and fatty acid synthase [FAS]) and an enzyme involved in TG synthesis (glycerol-3-phosphate acyltransferase 1 [GPAT-1] and diacylglycerol acyltransferase2 [DGAT2]) in fructose-fed rats. In addition, naringin induced a significant decrease in the hepatic expression of nuclear factor kappa B (NF-κB) and tumor necrosis factor α (TNF-α). Furthermore, naringin administration restored the expression of the antioxidant mediators nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 (HO-1) in the liver of fructose-fed rats.Conclusion: These results demonstrate that oral administration of naringin protects against fructose-induced hepatic steatosis by decreasing DNL and TG synthesis. In addition, naringin could prevent NAFLD progression via targeting the Nrf2/HO-1 and the NF-κB/TNF-α pathways.

Naringin from sweet orange peel improves testicular function in high fat diet-induced diabetic rats by modulating xanthine oxidase/uric acid signaling and maintaining redox balance

“…This study demonstrated that naringin from orange peel extract might ameliorate T2DM-induced testicular dysfunction via its antioxidant and anti-inflammatory activities, and XO/UA could be a target for the gonado-protective strategy of naringin. These findings agree with the study of Pengnet et al [ 42 ], Adebiyi et al [ 43 ], and Pengnet et al [ 44 ], which reported that naringin (a major constituent of orange peel) suppressed oxido-inflammatory response by maintaining redox balance. In addition to a redox balance restoration, naringin restored the testicular histoarhitecture and function by preventing seminiferous tubular distortion, spermatogenic cell degeneration, and loss of Leydig cells within the interstitial spaces.…”

Regulatory mechanism and therapeutic potentials of naringin against inflammatory disorders

“…Therefore, hepatoprotective and anti-inflammatory effects of naringin in NAFLD lie in inhibiting NF-κB and MAPK signaling. In line with this, naringin has been shown to reverse the upregulation of NF-κB and TNF-α expression in rat liver in fructose-induced rat NAFLD animal models and target activation of antioxidant mediator Nrf2/HO-1 pathways to block fructose-induced NAFLD progression in rats [ 147 ]. As NAFLD progresses, it may become a common chronic liver disease, and liver fibrosis develops.…”

Effects of Full-Spectrum Cannabis Oil with a Cannabidiol:Tetrahydrocannabinol 2:1 Ratio on the Mechanisms Involved in Hepatic Steatosis and Oxidative Stress in Rats Fed a Sucrose-Rich Diet

“…We recently demonstrated in long-term SRD-fed rats that liver injury and oxidative stress are accompanied by decreased NrF2 expression and increased NF-κB p65 protein expression in the liver [12]. In this line, Pengnet et al [63] showed that NF-κB expression was increased and NrF2 expression was decreased in the liver of fructose-fed rats during 12 weeks. Hernandez-Rodas et al [64] demonstrated significantly decreased hepatic NrF2 DNA binding and increased hepatic NF-κB DNA binding in male C57BL/6J mice fed with a high-fat diet for 12 weeks.…”