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

Flavones/Isoflavones: Luteolin, Baicalein, Genistein, Daidzein

Luteolin is a flavone that is present in thyme and in other vegetables including onion, broccoli and cauliflowers. It has been shown that luteolin reduces palmitate-induced lipid accumulation in HepG2 by activating AMPK signalling and thus promotes β-oxidation and inhibiting lipogenesis.[45] Baicalein is another flavone occurring in the root of Scutellaria Baicalensis which has been demonstrated to reduce liver steatosis in HFD fed mice by activating AMPK phosphorylation and down-regulating the activity of lipogenic enzymes.[46] Isoflavones, such as genistein and daidzein, are abundant in soybeans. Isoflavones are a subclass of flavonoids abundant in soybeans, which, apart from an oestrogen-simil activity, exert beneficial metabolic effects on liver glucose and lipid homeostasis. Several experiments have showed the therapeutic potential of genistein in in vitro and in vivo models of NAFLD. Kim S et al. demonstrated that genistein stimulates the activity of PPAR-α and its downstream targets in hepG2, thus promoting FFA oxidation.[47] Consistently, genistein inhibits the activation of SREBP-1 and its targets, thus suppressing de novo lipogenesis in hepG2.[48] Yalniz M studied the effects of subcutaneous genistein in rats fed HFD and reported that genistein reduces liver steatosis and inflammation and decreases serum TNF-α and TGF-β.[49] Similarly, dietary supplementation of genistein not only prevents liver steatosis but also adipose tissue dysfunction in mice fed HFD.[50] Daidzein displayed an insulin sensitizing and antisteatotic effect in mice fed HFD; these effects were mediated by down-regulation of hepatic liver X receptor beta, CHREBP and its downstream targets.[51] Crespillo et al. obtained similar results in rats fed HFD and in addition found that this isoflavone promotes thermogenesis in brown adipose tissue by inducing UCP-1 expression.[52]