Astaxanthin, a xanthophyll carotenoid, inhibited and reversed the activation of mouse primary hepatic stellate cells via the modulation of histone deacetylases (39.1)

Activation of hepatic stellate cells (HSC) is a major event in the development of liver fibrosis. Previously, we have shown that astaxanthin (ASTX), a xanthophyll carotenoid, has a potent anti‐fibrogenic effect in LX‐2 cells, a human HSC cell line. In this study, we investigated if ASTX prevents the activation of quiescent HSC and also facilitates the deactivation of activated, myofibroblast‐like HSC using mouse primary HSC. Incubation of ASTX with quiescent HSC inhibited their activation as evidenced by decreased loss of intracellular lipid droplets, and repressed expression of HSC activation markers, such as α smooth muscle actin (αSMA), at mRNA and protein levels. Moreover, in activated HSC, the addition of ASTX for 2 or 4 d resulted in reappearance of lipid droplets and decreased αSMA expression, suggesting that ASTX reversed HSC activation. As histone deacetylases (HDAC) have a potential role in HSC activation, we screened the effect of ASTX on the expression of all 11 classical HDAC isoforms. Notably, HDAC9 expression was significantly elevated during HSC activation, which was markedly attenuated by ASTX. Taken together, ASTX not only prevented the activation of quiescent HSC but also reversed morphological changes and repressed αSMA expression in activated HSC, possibly via the modulation of HDAC9 expression. Therefore, ASTX may be used for the prevention of liver fibrosis. Grant Funding Source : USDA AFRI 2012‐67018‐19290