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

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

doi:10.1007/s11655-021-3304-y

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

Original Article | Updated：2023-04-05

- Amygdalin Ameliorates Liver Fibrosis through Inhibiting Activation of TGF-β/Smad Signaling
- Amygdalin Ameliorates Liver Fibrosis through Inhibiting Activation of TGF-β/Smad Signaling
- 中国结合医学杂志（英文版） 2023年29卷第4期页码：316-324
- Affiliations：
  
  1.Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai (201203), China
  2.E-Institute of Shanghai Municipal Education Commission Shanghai University of Traditional Chinese Medicine, Shanghai (201203), China
  3.Shanghai Key Laboratory of Traditional Chinese Medicine, Shanghai (201203), China
- Author bio：
  
  Dr. CHEN Jia-mei, E-mail: cjm0102@126.com
- Funds：
  
  National Natural Science Foundation of China(81530101;81973613;81603681);Shanghai Rising-Star Program(19QA1408900)
- DOI：10.1007/s11655-021-3304-y
  中图分类号：
- 纸质出版日期：2023-04，
  
  网络出版日期：2021-11-24，
  
  录用日期：2021-01-22
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Amygdalin Ameliorates Liver Fibrosis through Inhibiting Activation of TGF-β/Smad Signaling[J]. 中国结合医学杂志（英文版）, 2023,29(4):316-324.

XIAO Zhun, JI Qiang, FU Ya-dong, et al. Amygdalin Ameliorates Liver Fibrosis through Inhibiting Activation of TGF-β/Smad Signaling[J]. Chinese Journal of Integrative Medicine, 2023,29(4):316-324.
Amygdalin Ameliorates Liver Fibrosis through Inhibiting Activation of TGF-β/Smad Signaling[J]. 中国结合医学杂志（英文版）, 2023,29(4):316-324. DOI： 10.1007/s11655-021-3304-y.

XIAO Zhun, JI Qiang, FU Ya-dong, et al. Amygdalin Ameliorates Liver Fibrosis through Inhibiting Activation of TGF-β/Smad Signaling[J]. Chinese Journal of Integrative Medicine, 2023,29(4):316-324. DOI： 10.1007/s11655-021-3304-y.

摘要

Abstract

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

)–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 detected 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

10 μmol/L). 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-Ι

α-SMA

CD31 and p-Smad2/3 in liver tissues of mice compared to the model group (

0.01). Amygdalin down-regulated the expressions of Col-Ⅰ and α-SMA in JS-1 and LX-2 cells

and TGFβR1

TGFβR2 and p-Smad2/3 in LX-2 cells compared to the model group (

0.05 or

0.01). Moreover

1 and 10 μmol/L amygdalin inhibited the mRNA and protein expressions of CD31 in LSECs and increased CD44 expression compared to the model group (

0.05 or

0.01).

Conclusions:

Amygdalin can dramatically alleviate liver fibrosis induced by CCl

in mice and inhibit TGF-β/Smad signaling pathway

consequently suppressing HSCs activation and LSECs dedifferentiation to improve angiogenesis.

关键词

Keywords

amygdalinliver fibrosishepatic stellate cellsliver sinusoidal endothelial cellsTGF-β/Smad signaling pathway

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