physalin-b and Liver-Cirrhosis

Liver fibrosis is one of the leading causes of morbidity and mortality worldwide but lacks any acceptable therapy. The transcription factor glioma-associated oncogene homologue 1 (GLI1) is a potentially important therapeutic target in liver fibrosis. This study investigates the anti-fibrotic activities and potential mechanisms of the phytochemical, physalin B.. Two mouse models (CCl. In vivo, physalin B administration attenuated hepatic histopathological injury and collagen accumulation and decreased expression of fibrogenic genes. Physalin B dose-dependently suppressed fibrotic marker expression in LX-2 cells and mouse pHSCs. Mechanistic studies showed that physalin B inhibited GLI activity by non-canonical Hedgehog signalling. Physalin B blocked formation of lamina-associated polypeptide 2α (LAP2α)/histone deacetylase 1 (HDAC1) complexes, thus inhibiting HDAC1-mediated GLI1 deacetylation. Physalin B up-regulated acetylation of GLI1, down-regulated expression of GLI1 and subsequently inhibited HSC activation.. Physalin B exerted potent antifibrotic effects in vitro and in vivo by disrupting LAP2α/HDAC1 complexes, increasing GLI1 acetylation and inactivating GLI1. This indicates that the phytochemical physalin B may be a potential therapeutic candidate for the treatment of liver fibrosis.

Topics: Animals; Carbon Tetrachloride; Hedgehog Proteins; Hepatic Stellate Cells; Histone Deacetylase 1; Liver; Liver Cirrhosis; Mice; Secosteroids; Transcription Factors; Zinc Finger Protein GLI1

Topics: DNA-Binding Proteins; Glioma; Hepatic Stellate Cells; Histone Deacetylase 1; Humans; Liver; Liver Cirrhosis; Membrane Proteins; Oncogenes; Secosteroids