In vitro and in vivo antifibrotic effects of rosmarinic acid on experimental liver fibrosis

Abstract 

This study was carried out to investigate whether rosmarinic acid (RA) has antifibrotic effect on experimental liver fibrosis in vitro and in vivo and its possible mechanism. Culture of hepatic stellate cells (HSCs) determine proliferation and expression of transforming growth factor-β1 (TGF-β1), connective transforming growth factor (CTGF) and α-smooth muscle actin (α-SMA). In carbon tetrachloride (CCL₄)-induced rat liver fibrosis model, determined biochemical indicator, liver fibrosis grade and histopathological changes, immunohistochemical detected liver TGF-β1 and CTGF expression. The results indicated that RA could inhibit HSCs proliferation, inhibit TGF-β1, CTGF and α-SMA expression in cultured HSCs. It has marked evident in reducing fibrosis grade, ameliorating biochemical indicator and histopathological morphology, reducing liver TGF-β1 and CTGF expression in CCL₄-induced liver fibrosis. These findings suggest that RA has potentially conferring antifibrogenic effects.

Abbrevations: RA, rosmarinic acid, TGF-β1, transforming growth factor-β1, CTGF, connective transforming growth factor, HSCs, hepatic stellate cells, α-SMA, α-smooth muscle actin, CCL₄, carbon tetrachloride, DMEM, Dulbecco's modified Eagle's medium, FBS, fetal bovine serum, HA, hyaluronic acid, LN, laminin, PCIII, collagen types III, ALB, serum albumin, GLB, globulin, ALT, alanine aminotransferase, AST, glutamate-pyruvate transaminase, HYP, hydroxyproline, Sil, silymarin

Keywords: Liver fibrosis, Rosmarinic acid, Transforming growth factor-β1, Connective transforming growth factor, In vitro, In vivo