Abstract:We have studied the inhibitory effect of aloe emodin on hepatic stellate cells activation and proliferation, as these cells play a key role in the pathogenesis of hepatic fibrosis. Rat hepatic stellate cells were activated by contact with plastic dishes, resulting in their transformation into myofibroblast-like cells. Primary hepatic stellate cells were exposed to aloe emodin (1-10 mg/ml). Possible cytotoxic effects were measured on stellate cells and hepatocytes using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of aloe emodin on production of type I collagen and smooth muscle cell a-actin were examined at the same concentration, by quantitative immunoprecipitation. Antiproliferative effects were examined by bromodeoxyuridine incorporation. Aloe emodin at 10 mg/ml restored the morphological changes characteristic of activated primary stellate cells, reduced DNA synthesis to 95% of control hepatic stellate cells at 10 mg/ml without affecting cell viability, and inhibited type I collagen production and smooth muscle aactin expression by 86.77% and 99%, respectively, which suggest that aloe emodin is a potent inhibitor of stellate cell transformation.During chronic liver damage, hepatic stellate cells undergo a transform by ''activation,'' which is the transition of quiescent cells into proliferative, fibrogenic, and contractile myofibroblasts expressing collagen and smooth muscle cell aactin, leading ultimately to liver fibrosis (Friedman et al. 1985;Knittel et al. 1992;Friedman 2000). Therefore, agents that inhibit hepatic stellate cells activation might be candidates for the therapeutic prevention of chronic liver injury and/or liver fibrosis (Friedman 1993).Stellate cells cultured in a medium supplemented with serum undergo spontaneous activation. This in vitro model is useful for understanding the molecular mechanisms underlying the activation and/or inactivation of stellate cells in the injured liver. In this context, interferons (Rockey et al. 1990; Mallat et al. 1995), prostaglandin E2 (Beno et al. 1994, retinoids (Sato et al. 1995), adenosine 3ø,5ø-cyclic monophosphate (cAMP) and methylxanthines (Kawada et al. 1996), pentoxyphylline (Windmeier & Gressner 1996) Aloe emodin (1,8-dihydroxy-3-hydroxymethyl-9,10-anthracenedione) is a hydroxyanthraquinone present in Aloe vera leaves. It has been reported to have antioxidative activity (Yen et al. 2000), to reduce the acute liver injury induced by carbon tetrachloride (Arosio et al. 2000), and to possess hepatoprotective activity (Malterud et al. 1993).Author for correspondence: Dong Hwan Sohn, Department of Pharmacy, Wonkwang University, Iksan, Jeonbuk 570-749, South Korea (fax π82 63 854 6038, e-mail dhsohn/wonkwang.ac.kr).For several years we have been screening candidate hepatoprotectants and antifibrotics from natural products, which have been used in traditional medicine for treating liver disease. As stated above, aloe emodin has hepatoprotective activity, but direct evidence to support its effect on...
