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

Your Location：

Home >

Browse articles >

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
- Chinese Journal of Integrative Medicine Vol. 29, Issue 4, Pages: 316-324(2023)
- 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：
- DOI：10.1007/s11655-021-3304-y
  CLC：
- Published：2023-04，
  
  Published Online：24 November 2021，
  
  Accepted：22 January 2021
Scan for full text
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 29(4):316-324(2023)
DOI：

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 29(4):316-324(2023) 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

references

Zhang CY, Yuan WG, He P, Lei JH, Wang CX. Liver fibrosis and hepatic stellate cells: etiology, pathological hallmarks and therapeutic targets. World J Gastroenterol 2016;22:10512-10522.

Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol 2008;214:199-210.

Coulon S, Heindryckx F, Geerts A, van Steenkiste C, Colle I, van Vlierberghe H. Angiogenesis in chronic liver disease and its complications. Liver Int 2011;31:146-162.

Zhou WC, Zhang QB, Qiao L. Pathogenesis of liver cirrhosis. World J Gastroenterol 2014;20:7312-7324.

March S, Hui EE, Underhill GH, Khetani S, Bhatia SN. Microenvironmental regulation of the sinusoidal endothelial cell phenotype in vitro. Hepatology 2009;50:920-928.

Liu XJ, Hu H, Yin JQ. Therapeutic strategies against TGF-beta signaling pathway in hepatic fibrosis. Liver Int 2006;26:8-22.

Xu FY, Liu CW, Zhou DD, Zhang L. TGF-beta/SMAD pathway and its regulation in hepatic fibrosis. J Histochem Cytochem 2016;64:157-167.

Schuppan D, Kim YO. Evolving therapies for liver fibrosis. J Clin Invest 2013;123:1887-1901.

Chinese Pharmacopoeia Commission. Pharmacopoeia of the People's Republic of China. Volume Ⅰ. 2015 ed. Beijing: People's Medical Publishing House; 2015:436.

Xu XH, Li T, Wang YT, Lu JJ. Research progress in Persicae Semen. Chin Tradit Herb Drugs (Chin) 2015;46:2649-2655.

Luo H, Li L, Tang J, Zhang F, Zhao F, Sun D, et al. Amygdalin inhibits HSC-T6 cell proliferation and fibrosis through the regulation of TGF-β/CTGF. Mol Cell Toxicol 2016;12:265-271.

Zhao F, Luo HH, Zhang FX. Effect of amygdalin on proliferation of hepatic stellate cell HSC-T6 and Bax gene expression. J New Chin Med (Chin) 2012;44:111-113.

Zhang DQ, Zhang LJ, Chen GF, Xu Y, Yang HL, Xiao Z, et al. Hepatoprotective effect of Xiayuxue Decoction ethyl acetate fraction against carbon tetrachloride-induced liver fibrosis in mice via inducing apoptosis and suppressing activation of hepatic stellate cells. Pharm Biol 2020;58:1229-1243.

Luo HH, Zhao F, Zhang FX, Liu N. Influence of amygdalin on PDG, IGF and PDGFR expression in HSC-T6 cells. Exp Ther Med 2018;15:3693-3698.

Wrighton KH, Lin X, Feng XH. Phospho-control of TGF-beta superfamily signaling. Cell Res 2009;19:8-20.

Lichtman MK, Otero-Vinas M, Falanga V. Transforming growth factor beta (TGF-beta) isoforms in wound healing and fibrosis. Wound Repair Regen 2016;24:215-222.

Hernandez-Gea V, Friedman SL. Pathogenesis of liver fibrosis. Annu Rev Pathol 2011;6:425-456.

Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 2003;425:577-584.

Verrecchia F, Mauviel A. Transforming growth factor-beta and fibrosis. World J Gastroenterol 2007;13:3056-3062.

Kamato D, Burch ML, Piva TJ, Rezaei HB, Rostam MA, Xu S, et al. Transforming growth factor-beta signalling: role and consequences of Smad linker region phosphorylation. Cell Signal 2013;25:2017-2024.

Xie GH, Wang XD, Wang L, Wang L, Atkinson RD, Kanel GC, et al. Role of differentiation of liver sinusoidal endothelial cells in progression and regression of hepatic fibrosis in rats. Gastroenterology 2012;142:918-927.

Sakata K, Eda S, Lee ES, Hara M, Imoto M, Kojima S. Neovessel formation promotes liver fibrosis via providing latent transforming growth factor-beta. Biochem Biophys Res Commun 2014;443:950-956.

DeLeve LD, Wang XD, Hu LP, McCuskey MK, McCuskey RS. Rat liver sinusoidal endothelial cell phenotype is maintained by paracrine and autocrine regulation. Am J Physiol Gastrointest Liver Physiol 2004;287:G757-G763.

Di Pascoli M, Divi M, Rodriguez-Vilarrupla A, Rosado E, Gracia-Sancho J, Vilaseca M, et al. Resveratrol improves intrahepatic endothelial dysfunction and reduces hepatic fibrosis and portal pressure in cirrhotic rats. J Hepatol 2013;58:904-910.

More>

Views

Downloads

CSCD

Alert me when the article has been cited

Submit

Tools

Publicity Resources

Active Components Formulation Developed from Fuzheng Huayu Recipe for Anti-Liver Fibrosis

Ethyl Acetate Fraction of Dicliptera chinensis (L.) Juss.Ameliorates Liver Fibrosis by Inducing Autophagy via PI3K/AKT/mTOR/p70S6K Signaling Pathways

Efficacy of Biejiajian Pill on Intestinal Microbiota in Patients with Hepatitis B Cirrhosis/Liver Fibrosis:A Randomized Double-Blind Controlled Trial

Treatment of HBV Cirrhosis with Fuzheng Huayu Tablet(扶正化瘀片) and Entecavir: Design of a Randomized, Double-Blind, Parallel and Multicenter Clinical Trial

Research Progress in Astragalus membranaceus and Its Active Components on Immune Responses in Liver Fibrosis

Related Author

No data

Related Institution

Shanghai Key Laboratory of Traditional Chinese Clinical Medicine

Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

Department of Traditional Chinese Medicine, Affiliated Hospital of Jining Medical University

School of Traditional Chinese Medicine, Southern Medical University

College of Integrated Traditional Chinese and Western Medicine, Jining Medical University

Address：1 Caochang, xiyuan, Beijing, People's Republic of China Postal code：100091
Tel：010-62886827, 62877592 Fax：010-62874291
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备05067934号-1 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰