Amygdalin Ameliorates Liver Fibrosis through Inhibiting Activation of TGF-β/Smad Signaling

• Published in: Chinese journal of integrative medicine 2023-04, Vol.29 (4), p.316-324
• Main Authors: Xiao, Zhun, Ji, Qiang, Fu, Ya-dong, Gao, Si-qi, Hu, Yong-hong, Liu, Wei, Chen, Gao-feng, Mu, Yong-ping, Chen, Jia-mei, Liu, Ping
• Format: Article
• Language: English
• Subjects: Amygdalin - pharmacology; Amygdalin - therapeutic use; Animals; Carbon Tetrachloride; Collagen Type I - metabolism; Endothelial Cells - metabolism; Hepatic Stellate Cells; Liver; Liver Cirrhosis - drug therapy; Liver Cirrhosis - metabolism; Male; Medicine; Medicine & Public Health; Mice; Olive Oil - metabolism; Olive Oil - pharmacology; Olive Oil - therapeutic use; Original Article; Rats; Rats, Wistar; Signal Transduction; Smad Proteins - metabolism; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta1 - metabolism
• ISSN: 1672-0415; 1993-0402
• DOI: 10.1007/s11655-021-3304-y

Objective To observe the effect of amygdalin on liver fibrosis in a liver fibrosis mouse model, and the underlying mechanisms were partly dissected in vivo and in vitro . Methods Thirty-two male mice were randomly divided into 4 groups, including control, model, low- and high-dose amygdalin-treated groups, 8 mice in each group. Except the control group, mice in the other groups were injected intraperitoneally with 10% carbon tetrachloride (CCl 4 )-olive oil solution 3 times a week for 6 weeks to induce liver fibrosis. At the first 3 weeks, amygdalin (1.35 and 2.7 mg/kg body weight) were administered by gavage once a day. Mice in the control group received equal quantities of subcutaneous olive oil and intragastric water from the fourth week. At the end of 6 weeks, liver tissue samples were harvested to detect the content of hydroxyproline (Hyp). Hematoxylin and eosin and Sirius red staining were used to observe the inflammation and fibrosis of liver tissue. The expressions of collagen I (Col-I), alpha-smooth muscle actin (α-SMA), CD31 and transforming growth factor β (TGF-β)/Smad signaling pathway were observed by immunohistochemistry, quantitative real-time polymerase chain reaction and Western blot, respectively. The activation models of hepatic stellate cells, JS-1 and LX-2 cells induced by TGF-β1 were used in vitro with or without different concentrations of amygdalin (0.1, 1, 10 µmol/L). LSECs. The effect of different concentrations of amygdalin on the expressions of liver sinusoidal endothelial cells (LSECs) dedifferentiation markers CD31 and CD44 were observed. Results High-dose of amygdalin significantly reduced the Hyp content and percentage of collagen positive area, and decreased the mRNA and protein expressions of Col-I, α-SMA, CD31 and p-Smad2/3 in liver tissues of mice compared to the model group ( P