Natural Antioxidants for Non-alcoholic Fatty Liver Disease

Molecular Targets and Clinical Perspectives

Federico Salomone; Justyna Godos; Shira Zelber-Sagi


Liver International. 2016;36(1):5-20. 

In This Article

Flavanones: Naringenin, Hesperitin

Citrus peels are a source of the flavanones naringenin, which has been extensively studied for its beneficial metabolic and vascular effects in different animal models. Huong DT studied the effects of dietary supplementation of naringenin in ICR mice fed a standard chow and reported that this flavonoid promotes hepatic activity of several enzymes involved in fatty acid β-oxidation and increase gene expression of CYP4A1 which mediates ω-oxidation.[53] Consistently, Mulvihill EE elegantly showed that dietary naringenin improves dyslipidaemia and reduces liver steatosis in LDL−/− mice fed a western diet by enhancing hepatic fatty acid oxidation through a PGC-1α/PPAR-α mediated transcription program.[54] Recently, naringenin was also demonstrated to reduce hepatic levels of inflammatory cytokines by inhibiting NFkB pathway in rats fed a high cholesterol diet.[55] These data together with naringenin inhibitory effect on in vitro HSC activation[56] provide a rationale for the potential of naringenin not only in fatty liver but also in fibrogenic NASH.

Another citrus flavanone, hesperidin has been shown to exert beneficial effects on lipid metabolism in both in vitro and in vivo models. On the basis of the results of in vivo studies, it can be conclude that hesperidin may be used in NAFLD prevention and treatment. Several studies investigated the protective role of hesperidin on liver and reported promising results: improvement of hypercholesterolaemia and fatty liver by changes in lipid metabolism-related proteins expression[57] and inhibition of fatty acid oxidation.[58] Interestingly, recently, it has been shown that hesperidin may inhibit lipid synthesis.[59] Jeon et al. indicated that hesperidin may interfere with lipid accumulation and a production of reactive oxygen species and reactive nitrogen species in mouse adipocyte-like cells and macrophages.[60] In accordance, two studies on rats reported protective effect of hesperidin against dimethylnitrosamine[61] and carbon tetrachloride induced liver fibrosis[62] by diminishing hepatic inflammation, oxidative stress and liver injury. Furthermore, Lin et al. showed that hersperidin deriviate inhibits PDGF-BB induced hepatic stellate cell activation and proliferation via Wnt/β-catenin pathway.[63]