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Quantitative Proteomic Study Reveals Amygdalin Alleviates Liver Fibrosis Through Inhibiting mTOR/ PDCD4/JNK Pathway in Hepatic Stellate Cells

文献类型：期刊论文

作者Huang, Hui6,7; Ru, Su-Jie5; Chen, Jia-Mei3,4; Liu, Wei3,4; Fang, Shan-Hua6; Liu, Qian6; Meng, Qian6; Liu, Ping2,4; Zhou, Hu1,5,6,7
刊名DRUG DESIGN DEVELOPMENT AND THERAPY
出版日期2025
卷号19页码:3735-3749
关键词amygdalin PDCD4 HSC activation proteomics
ISSN号1177-8881
DOI10.2147/DDDT.S500439
英文摘要Purpose: Hepatic fibrosis is a major cause of morbidity and mortality for which there is currently limited therapy. Amygdalin, a cyanogenic glucoside derived from Semen Persicae, exerts significant anti-fibrotic effects in the liver. However, the molecular mechanism by which amygdalin inhibits the progression of liver fibrosis remains unclear. This study aimed to elucidate the potential mechanism of action of amygdalin against liver fibrosis. Methods: Quantitative proteomic profiling of the mouse liver tissues from control, carbon tetrachloride (CCl4)-induced fibrosis, and amygdalin-treated groups was performed to explore the key effector proteins of amygdalin. Histology and immunohistochemistry as well as serum biochemical analysis were performed to evaluate amygdalin efficacy in mice. The key gene programmed cell death protein 4 (PDCD4) was overexpressed or knocked down in human hepatic stellate cells (HSCs). The mRNA and protein levels of related molecules were detected by RT-qPCR and Western blotting, respectively. Results: Amygdalin could effectively ameliorated CCl4-induced liver fibrosis in mice. Bioinformatics analysis revealed that PDCD4 was downregulated in CCl4-induced liver fibrosis, but amygdalin treatment reversed these changes. An in vitro study showed that PDCD4 inhibited the activation of human hepatic stellate cell line LX-2 cells by regulating the JNK/c-Jun pathway and amygdalin inhibited the activation of LX-2 cells in a PDCD4-dependent manner. We further found that amygdalin inhibited the phosphorylation of PDCD4 at Ser67 by inhibiting the mTOR/S6K1 pathway to enhance PDCD4 expression. Conclusion: Our data demonstrated a potential pharmaceutical mechanism by which amygdalin alleviates liver fibrosis by inhibiting the mTOR/PDCD4/JNK pathway in HSCs, suggesting that PDCD4 is a potential target for the treatment of liver fibrosis.
WOS关键词C-JUN ; EXPRESSION ; PHOSPHORYLATION ; PROLIFERATION ; ACTIVATION ; APOPTOSIS
资助项目National Key Research and Development Program[2020YFA0509000] ; National Treasury ; Shanghai Leading Talent Program of Eastern Talent Plan[LJ2023123]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001485052000001
出版者DOVE MEDICAL PRESS LTD
源URL[http://119.78.100.183/handle/2S10ELR8/317860]  
专题新药研究国家重点实验室
通讯作者Liu, Ping; Zhou, Hu
作者单位1.Univ Chinese Acad Sci, Beijing, Peoples R China
2.Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai, Peoples R China
3.Shanghai Key Lab Tradit Chinese Clin Med, Shanghai, Peoples R China
4.Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Inst Liver Dis, Key Lab Liver & Kidney Dis Minist Educ, Shanghai, Peoples R China
5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Jiangsu, Peoples R China
6.Chinese Acad Sci, Dept Analyt Chem, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai, Peoples R China
7.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou, Peoples R China
推荐引用方式
GB/T 7714		 Huang, Hui,Ru, Su-Jie,Chen, Jia-Mei,et al. Quantitative Proteomic Study Reveals Amygdalin Alleviates Liver Fibrosis Through Inhibiting mTOR/ PDCD4/JNK Pathway in Hepatic Stellate Cells[J]. DRUG DESIGN DEVELOPMENT AND THERAPY,2025,19:3735-3749.
APA Huang, Hui.,Ru, Su-Jie.,Chen, Jia-Mei.,Liu, Wei.,Fang, Shan-Hua.,...&Zhou, Hu.(2025).Quantitative Proteomic Study Reveals Amygdalin Alleviates Liver Fibrosis Through Inhibiting mTOR/ PDCD4/JNK Pathway in Hepatic Stellate Cells.DRUG DESIGN DEVELOPMENT AND THERAPY,19,3735-3749.
MLA Huang, Hui,et al."Quantitative Proteomic Study Reveals Amygdalin Alleviates Liver Fibrosis Through Inhibiting mTOR/ PDCD4/JNK Pathway in Hepatic Stellate Cells".DRUG DESIGN DEVELOPMENT AND THERAPY 19(2025):3735-3749.

入库方式： OAI收割

来源：上海药物研究所

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