Table 2.

Proposed Mechanisms of Main Beneficial Effects of Coffee on the Liver.

Effect on liver	Site of action	Chemical involved	Mechanisms
Antifibrotic	Hepatic Stellate Cell (HSC)	Caffeine	Inhibit focal adhesion kinase (FAK) and actin synthesis
Increase HSC apoptosis and intracellular F-actin and cAMP expression
Inhibit procollagen type 1C and alpha-SMA expression
Hepatocyte	Caffeine	Decrease transforming growth factor beta (TGF-B)
Stimulate ARE-regulated signaling
Cancer prevention	Hepatocyte	Cafestol and Kehweol	Inhibit phase I activating enzyme expression and activity
Induce phase II detoxifying enzymes (i.e. glutathione S-transferase)
Stimulate antioxidant responsive element (ARE)-regulated signaling
Induction of gamma-glutamyl cysteine synthetase (GCS)
Antioxidant effect	Hepatocytes	Hydrophilic (caffeine and polyphenols, such as chlorogenic acids); hydrophobic (cafestol, kahweol, and trigenolline), including MRP	Preventing inflammatory reaction downregulation of immune and inflammatory markers, such as interferon-gamma (IFN-γ), chemokine coded by CX3CL1 or fractalkine, chemokine ligand4 or CCL4 also called macrophage inhibitory protein (MIP-1b), fibroblast growth factor-2 (FGF-2), and tumor necrosis factor receptors (sTNFRII)

Modified from Saab et al.⁷⁷