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


Anthocyanins (ACN) are flavonoids that are responsible for blue, purple and red colour of fruits and vegetables such as blueberries, strawberries, cherries, plums, grapes, red oranges and red onions.[35] Many in vitro studies report that ACN reduce hepatocyte oxidative stress by promoting antioxidant response.[36] Recently, ACN have been studied for their role in the modulation of lipid homeostasis in different tissues, including the liver. In vitro studies reported that food extracts or synthetic anthocyanins, i.e. cyanidin-3-O-β-glucoside, may reduce lipid accumulation in HepG2 treated with fatty acids either by inhibiting lipogenesis[37] or by promoting lipolysis.[38] Furthermore, in vitro studies show that food extracts or cyanidin-3-O-β-glucoside reduce steatosis by activating AMPK pathway.[39] Similarly, in vivo studies assessed the effects of cyanidin-3-O-β-glucoside or of anthocyanin-rich extracts. Although these studies were conducted in different animal models of NAFLD with different experimental designs, they are concordant in indicating that ACN reduces systemic insulin resistance and hepatic lipid accumulation. ACN stimulates liver PPAR-α activity as demonstrated for tart cherry in the Dahl salt-sensitive rat,[40] for blueberry in Zucker rats,[41] and for mulberry in hamsters fed HFD.[42] In addition with the induction of PPAR-α, we demonstrated that the juice of an anthocyanin-rich orange reduces liver steatosis by suppressing the expression of liver X receptor-α, and its target gene fatty acid synthase.[43] So far, only the study by Suda et al. examined the effect of ACN in NAFLD; by the end of 8-week treatment period with 200 mg of acylated ACN obtained from purple sweet potato administrated twice daily, the authors observed a reduction of liver enzymes in particular GGT.[44] Of course, due to the poor design of the study, well-designed controlled trials are needed to establish if natural or synthetic ACN can exert beneficial effects in patients with NAFLD.