共 58 条
The Glabridin from Huangqin Decoction Prevents the Development of Ulcerative Colitis into Colitis-Associated Colorectal Cancer by Modulating MMP1/MMP3 Activity
被引:3
作者:

Li, Roude
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Guangdong Med Univ, Dongguan Affiliated Hosp 1, Dongguan 523000, Peoples R China
Guangdong Med Univ, Sch Clin Med 2, Dongguan 523000, Peoples R China Guangdong Med Univ, Dongguan Affiliated Hosp 1, Dongguan 523000, Peoples R China

Chi, Honggang
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Guangdong Med Univ, Dongguan Affiliated Hosp 1, Dongguan 523000, Peoples R China
Guangdong Med Univ, Sch Clin Med 2, Dongguan 523000, Peoples R China Guangdong Med Univ, Dongguan Affiliated Hosp 1, Dongguan 523000, Peoples R China

Liao, Xiaoxia
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Guangdong Med Univ, Dongguan Affiliated Hosp 1, Dongguan 523000, Peoples R China
Guangdong Med Univ, Sch Clin Med 2, Dongguan 523000, Peoples R China Guangdong Med Univ, Dongguan Affiliated Hosp 1, Dongguan 523000, Peoples R China

Cen, Shuimei
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Guangdong Med Univ, Dongguan Affiliated Hosp 1, Dongguan 523000, Peoples R China
Guangdong Med Univ, Sch Clin Med 2, Dongguan 523000, Peoples R China Guangdong Med Univ, Dongguan Affiliated Hosp 1, Dongguan 523000, Peoples R China

Zou, Ying
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Guangdong Med Univ, Dongguan Affiliated Hosp 1, Dongguan 523000, Peoples R China
Guangdong Med Univ, Sch Clin Med 2, Dongguan 523000, Peoples R China
Dongguan Liaobu Hosp, Dept Tradit Chinese Med, Dongguan, Peoples R China Guangdong Med Univ, Dongguan Affiliated Hosp 1, Dongguan 523000, Peoples R China
机构:
[1] Guangdong Med Univ, Dongguan Affiliated Hosp 1, Dongguan 523000, Peoples R China
[2] Guangdong Med Univ, Sch Clin Med 2, Dongguan 523000, Peoples R China
[3] Dongguan Liaobu Hosp, Dept Tradit Chinese Med, Dongguan, Peoples R China
关键词:
Ulcerative colitis;
Colitis -associated colorectal cancer;
Huangqin decoction;
Glabridin;
Matrix metalloproteinase;
Network pharmacology;
MATRIX-METALLOPROTEINASE INHIBITOR;
CARCINOMA-CELLS;
PHASE-I;
EXPRESSION;
MICE;
INFLAMMATION;
LICORICE;
AND-26;
RISK;
D O I:
10.1016/j.intimp.2024.112262
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
Background and Aim: Huangqin decoction (HQD) is a Chinese medicine used to treat colitis and colorectal cancer (CRC). However, the specific compounds and mechanisms of HQD remain unclear despite its good curative clinical results. Through bioinformatics, network pharmacology, and experiments, this study aims to explore the progressive mechanisms of colitis -associated colorectal cancer (CAC) from ulcerative colitis (UC) while examining the protective effects of HQD and its compounds against this. Methods: Bioinformatics was utilized to identify the hub genes between UC and CRC, and their clinical predictive significance, function, and expression were validated. Employing network pharmacology in combination with hub genes, key targets of HQD for preventing the development of UC into CAC were identified. Molecular docking and molecular dynamics (MD) were utilized to procure compounds that effectively bind to these targets and their transcription factors (TFs). Finally, the expression and mechanism of key targets were demonstrated in mice with UC or CAC. Results: (1) Joint analysis of UC and CRC gene sets resulted in 14 hub genes, mainly related to extracellular matrix receptor binding, biological processes in the extracellular matrix, focal adhesion and neutrophil migration; (2) Network pharmacology results show HQD has 133 core targets for treating UC and CRC, acting on extracellular matrix, inflammatory bowel disease, chemical carcinogen receptor activation and other pathways; (3) The intersection of hub genes and core targets yielded two key targets, MMP1 and MMP3; (4) STAT3 is a shared TF of MMP1 and MMP3. (5) Molecular docking and MD verified that the dockings between Glabridin and STAT3/MMP1/MMP3 are stable and reliable; (6) In murine vivo experiments verified that Glabridin reduces inflammation, extracellular matrix degradation, and the occurrence of epithelial-mesenchymal transition to prevent UC transforming into CAC by inhibiting the phosphorylation of STAT3 and regulating the activity of MMP1/3.
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Acad Sinica, Inst Informat Sci, Taipei 115, Taiwan
Natl Hlth Res Inst, Inst Populat Hlth Sci, Div Biostat & Bioinformat, Zhunan 350, Taiwan
Natl Taiwan Univ, Inst Fisheries Sci, Coll Life Sci, Taipei 105, Taiwan Nanhua Univ, Dept Comp Sci & Informat Engn, Dalin Township 62249, Chiayi County, Taiwan
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Swiss Target Prediction: updated data and new features for efficient prediction of protein targets of small molecules
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Daina, Antoine
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Michielin, Olivier
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Zoete, Vincent
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NUCLEIC ACIDS RESEARCH,
2019, 47 (W1)
:W357-W364

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Michielin, Olivier
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Univ Lausanne, Quartier UNIL Sorge, SIB Swiss Inst Bioinformat, Mol Modeling Grp, Batiment Amphipole, CH-1015 Lausanne, Switzerland
Univ Lausanne Hosp, Ludwig Canc Res Lausanne Branch, Dept Oncol, CH-1011 Lausanne, Switzerland Univ Lausanne, Quartier UNIL Sorge, SIB Swiss Inst Bioinformat, Mol Modeling Grp, Batiment Amphipole, CH-1015 Lausanne, Switzerland

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[10]
The risk of colorectal cancer in ulcerative colitis: a meta-analysis
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Eaden, JA
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Abrams, KR
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Mayberry, JF
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GUT,
2001, 48 (04)
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Eaden, JA
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机构: Leicester Gen Hosp, Gastrointestinal Res Unit, Leicester LE5 4PW, Leics, England

Abrams, KR
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机构: Leicester Gen Hosp, Gastrointestinal Res Unit, Leicester LE5 4PW, Leics, England

Mayberry, JF
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机构: Leicester Gen Hosp, Gastrointestinal Res Unit, Leicester LE5 4PW, Leics, England