Peretinoin is an oral acyclic retinoid with a vitamin A-like structure that targets retinoid nuclear receptors such as retinoid X receptor (RXR) and retinoic acid receptor (RAR)[3]. Peretinoin inhibits HCV RNA amplification and virus release by altering lipid metabolism with a EC50 of 9 μM. Peretinoin treatment of Huh-7 cells reduced mRNA levels, protein expression and enzymatic activity of SPHK1[4]. Peretinoin prevents the progression of NASH (non-alcoholic steatohepatitis) and the development of HCC (hepatocellular carcinoma) through activating the autophagy pathway by increased Atg16L1 expression, which is an essential regulator of autophagy and anti-inflammatory proteins[5]. Peretinoin inhibited the signaling pathways of fibrogenesis, angiogenesis, and Wnt/β-catenin in Pdgf-c transgenic mice. In vitro, peretinoin repressed the expression of PDGF (platelet-derived growth factor) receptors α/β in primary mouse hepatic stellate cells (HSC), hepatoma cells, fibroblasts, and endothelial cells. Peretinoin also inhibited PDGF-C-activated transformation of HSCs into myofibroblasts[6].
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