Molecular Bases Underlying the Hepatoprotective Effects of Coffee

Abstract

Coffee is the most consumed beverage worldwide. Epidemiological studies with prospective cohorts showed that coffee intake is associated with reduced cardiovascular and all-cause mortality independently of caffeine content. Cohort and case-control studies reported an inverse association between coffee consumption and the degree of liver fibrosis as well as the development of liver cancer. Furthermore, the beneficial effects of coffee have been recently confirmed by large meta-analyses. In the last two decades, various in vitro and in vivo studies evaluated the molecular determinants for the hepatoprotective effects of coffee. In the present article, we aimed to critically review experimental evidence regarding the active components and the molecular bases underlying the beneficial role of coffee against chronic liver diseases. Almost all studies highlighted the beneficial effects of this beverage against liver fibrosis with the most solid results indicating a pivot role for both caffeine and chlorogenic acids. In particular, in experimental models of fibrosis, caffeine was shown to inhibit hepatic stellate cell activation by blocking adenosine receptors, and emerging evidence indicated that caffeine may also favorably impact angiogenesis and hepatic hemodynamics. On the other side, chlorogenic acids, potent phenolic antioxidants, suppress liver fibrogenesis and carcinogenesis by reducing oxidative stress and counteract steatogenesis through the modulation of glucose and lipid homeostasis in the liver. Overall, these molecular insights may have translational significance and suggest that coffee components need clinical evaluation.

Keywords: caffeine; chlorogenic acid; liver cancer; liver fibrosis; liver steatosis.

Figure 1

Chemical structure and cellular targets of coffee hepatoprotective components. (A) Caffeine is an alkaloid belonging to the methylxanthines family; (B) Chlorogenic acids belong to conjugated hydroxycinnamates, a family of non-flavonoid phenols formed by a single phenolic ring linked to three carbons. The main CGAs are 5-O-caffeoylquinic acid (5-CQA) and its isomers 3-O-caffeoylquinic acid (3-CQA) and 4-O-caffeoylquinic acid (4-CQA).

Figure 2

The bioactive components of coffee, caffeine and chlorogenic acids, inhibit de novo lipogenesis, promotes lipid oxidation and induces autophagy, thus reducing hepatocyte steatosis. Furthermore, chlorogenic acids reduce oxidative stress by activating the Nrf2 response whereas caffeine blocks the adenosine receptor A2. Overall, modulation of these pathways suppresses the production of inflammatory cytokines and the activation of hepatic stellate cells leading to reduced fibrogenesis and carcinogenesis.