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

Flavanols (Flavan-3-ols): Green and Black Tea Polyphenols

Green tea, extracted from the leaves of Camellia sinensis, is the second most consumed beverage worldwide after coffee. Its content in antioxidants, such as polyphenols, has been considered a possible explanation for the demonstrated beneficial effects on human metabolism.[23] Tea major polyphenols are represented by flavanols, in particular catechins, which have been shown to exert several beneficial effects on health. Epigallocatechin-3-gallate (EGCG) is the most abundant catechin found in green tea accounting for 50–75% of the catechins.[24] EGCG has been extensively studied for its metabolic properties. Klaus et al. showed that chronic dietary EGCG promotes gene expression of UCP-2 in the liver of mice fed HFD,[25] indicating a stimulating activity of EGCG on thermogenesis, an effect which has been confirmed also for acute administration.[26] Bose et al. showed reduced insulin resistance and liver steatosis in mice fed a western diet plus EGCG,[27] whereas Kuzu et al. demonstrated that EGCG intake improves steatosis and inflammation in rats fed a high fat diet by reducing lipid peroxidation and CYP2E1 expression and restoring GSH levels.[28] The ability of EGCG to inhibit hepatic stellate cells activation has been demonstrated in several in vitro studies including human HSC.[29] Recently, Xiao et al. showed that intraperitoneal EGCG is able to reduce liver fibrosis in a rodent model of NASH by suppressing oxidative stress and inhibiting NFkB, Akt and TGF/SMAD signaling.[30] Although results from clinical trials for obesity appear contradictory,[31] there is a significant molecular rationale for studies in patients with NASH. Another mechanism through which liver steatosis could be limited by tea flavonoids has been suggested to be an inhibition of LDL oxidation by enhancing endothelium-bound extracellular superoxide dismutase (EC-SOD) activity, a major antioxidative enzyme in the vasculature.[32]

Theaflavins are another group of flavanols contained in black tea, including theaflavin-1, theaflavin-3-gallate and theaflavin-3,3'-digallate. Theaflavins have been demonstrated to be more effective than green tea catechins in reducing lipid accumulation by inducing beta-oxidation through AMPK activation in HepG2 cells and in the livers of HFD-fed mice.[33] In addition, dietary theaflavin-1 reduces hepatic steatosis and inflammation in mice fed methionine-choline-deficient diet through reduced ROS and inflammatory cytokines production.[34]