Amygdalin inhibits TGF beta 1-induced activation of hepatic stellate cells (HSCs) in vitro and CCl4-induced hepatic fibrosis in rats in vivo

The activation of hepatic stellate cells (HSCs) has been considered one of the major events in hepatic fibrosis. Amygdalin has been used to treat cancers and alleviate pain; however, its role and mechanism in HSC activation and hepatic fibrosis remain unclear. In the present study, transforming growth factor-beta 1 (TGF-beta 1) stimulated the activation of HSCs, as indicated by significantly increased alpha-smooth muscle actin (alpha-SMA), desmin, collagen I, and tissue inhibitor of metalloproteinase-1 (TIMP-1) protein levels. Amygdalin treatment dramatically suppressed TGF-beta 1-induced HSC proliferation and activation. Moreover, amygdalin treatment also reduced the TGF-beta 1-induced secretion of cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), platelet-derived growth factor (PDGF), and chemokine (C-C motif) ligand 2 (CCL2), as well as the phosphorylation of Smad2, Smad3, and p65. In the CCl4-stimulated liver fibrosis rat model, amygdalin treatment improved liver fibrosis and liver damage by reducing focal necrosis, collagen fiber accumulation, and the protein levels of alpha-SMA, desmin, collagen I, and TIMP-1 in hepatic tissue samples and reducing serum alanine transaminase (ALT) and aspartate transaminase (AST) levels. In conclusion, we demonstrated the suppressive effects of amygdalin in TGF-beta 1-induced HSC activation through modulating proliferation, fibrogenesis, and inflammation signaling in vitro and the antifibrotic effects of amygdalin in CCl4-stimulated hepatic fibrosis in rats in vivo.

Automated summary

Amygdalin effectively suppressed the activation of hepatic stellate cells induced by TGF-beta 1 by modulating proliferation, fibrogenesis, and inflammation signaling pathways in vitro, leading to improvement in liver fibrosis and damage in a CCl4-stimulated rat model in vivo.