title: Astaxanthin prevents and reverses the activation of mouse primary hepatic stellate cells.
abstract: Activation of hepatic stellate cells (HSCs) is a critical step that leads to the development of liver fibrosis. We showed that astaxanthin (ASTX), a xanthophyll carotenoid, displays antifibrogenic effects in LX-2 cells, a human HSC cell line. In this study, we further determined the effect of ASTX on HSC activation and inactivation using primary HSCs from C57BL/6J mice. Quiescent and activated HSCs were incubated with ASTX (25μM) at different stages of activation. ASTX prevented the activation of quiescent HSCs, as evidenced by the presence of intracellular lipid droplets and reduction of α-smooth muscle actin, an HSC activation marker. Also, ASTX reverted activated HSCs to a quiescent phenotype with the reappearance of lipid droplets with a concomitant increase in lecithin retinol acyltransferase mRNA. Cellular accumulation of reactive oxygen species was significantly reduced by ASTX, which was attributable to a decrease in NADPH oxidase 2 expression. The antifibrogenic effect of ASTX was independent of nuclear erythroid 2-related factor 2 as it was observed in HSCs from wild-type and Nrf2(-/-) mice. In conclusion, ASTX inhibits HSC activation and reverts activated HSCs to a quiescent state. Further investigation is warranted to determine if ASTX effectively prevents the development of liver fibrosis.
authors.affiliation: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Minkyung
authors.initials: M
authors.lastname: Bae
authors.affiliation: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Bohkyung
authors.initials: B
authors.lastname: Kim
authors.affiliation: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Young-Ki
authors.initials: YK
authors.lastname: Park
authors.affiliation: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Sung I
authors.initials: SI
authors.lastname: Koo
authors.affiliation: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA; Institute of Systems Genomics, University of Connecticut, Storrs, CT 06269, USA. Electronic address: ji-young.lee@uconn.edu.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Lee
mesh_terms: D000818:Animals; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D024341:Xanthophylls / Q000494:pharmacology
chemical_list: D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species; D024341:Xanthophylls; C005948:astaxanthine
keywords: Astaxanthin; Carotenoids; Hepatic stellate cells; Liver fibrosis; NASH; Reversal of hepatic stellate cell activation