Caffeine attenuates liver fibrosis via defective adhesion of hepatic stellate cells in cirrhotic model

Background and Aim Several epidemiological studies have shown that coffee intake attenuates the progression of liver fibrosis; however, the mechanism is unclear. Aims We investigated the direct effects of caffeine on hepatic stellate cells ( HSC s) and assessed whether caffeine attenuated intrahepatic fibrosis in rat model of liver cirrhosis. Methods Human hepatic stellate cell line, an immortalized human HSC s line, was used in in vitro assay system. Cell migration and proliferation were assessed in presence of various caffeine concentrations (0, 1, 5, and 10 mmol), and levels of procollagen type I c and α‐smooth muscle actin (α‐SMA) were measured by W estern blot. Severity of liver inflammation and fibrosis were compared between thioacetamide‐treated rats with and without caffeine supplementation. Results Caffeine increased HSC s apoptosis and intracellular F ‐actin and cyclic adenosine monophosphate expression. Caffeine also inhibited procollagen type I c and α‐ SMA expression in a dose‐ and time‐dependent manner. In rat model, caffeine decreased periportal inflammation, levels of inflammatory cells (1.4 ± 0.52 vs 2.6 ± 0.46, P  < 0.05), and fibrosis (2.1 ± 0.35 vs 2.9 ± 0.84, P  < 0.05). Transforming growth factor‐β and α‐ SMA expressions were also reduced by caffeine. Conclusion Caffeine attenuates the progression of liver fibrosis by inhibiting HSC s adhesion and activation.