Amygdalin inhibits TGFβ1-induced activation of hepatic stellate cells (HSCs) in vitro and CCl 4 -induced hepatic fibrosis in rats in vivo

• Published in: International immunopharmacology 2021-01, Vol.90, p.107151
• Main Authors: Wang, Ruoyu, Zhang, Dong, Tang, Dan, Sun, Kewei, Peng, Jianping, Zhu, Wenfang, Yin, Sihan, Wu, Yunan
• Format: Article
• Language: English
• Subjects: Amygdalin - pharmacology; Animals; Anti-Inflammatory Agents - pharmacology; Carbon Tetrachloride; Cell Line; Cell Proliferation - drug effects; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - pathology; Chemical and Drug Induced Liver Injury - prevention & control; Cytokines - genetics; Cytokines - metabolism; Gene Expression Regulation; Humans; Inflammation Mediators - metabolism; Kupffer Cells - drug effects; Kupffer Cells - metabolism; Kupffer Cells - pathology; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver Cirrhosis, Experimental - chemically induced; Liver Cirrhosis, Experimental - metabolism; Liver Cirrhosis, Experimental - pathology; Liver Cirrhosis, Experimental - prevention & control; Rats; Rats, Sprague-Dawley; Signal Transduction; Transforming Growth Factor beta1 - pharmacology
• ISSN: 1878-1705

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-β1) stimulated the activation of HSCs, as indicated by significantly increased alpha-smooth muscle actin (α-SMA), desmin, collagen I, and tissue inhibitor of metalloproteinase-1 (TIMP-1) protein levels. Amygdalin treatment dramatically suppressed TGF-β1-induced HSC proliferation and activation. Moreover, amygdalin treatment also reduced the TGF-β1-induced secretion of cytokines, including tumor necrosis factor-alpha (TNF-α), 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 CCl -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 α-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-β1-induced HSC activation through modulating proliferation, fibrogenesis, and inflammation signaling in vitro and the antifibrotic effects of amygdalin in CCl -stimulated hepatic fibrosis in rats in vivo.