2. Academic Validation
  3. The Glabridin from Huangqin Decoction Prevents the Development of Ulcerative Colitis into Colitis-Associated Colorectal Cancer by Modulating MMP1/MMP3 Activity

The Glabridin from Huangqin Decoction Prevents the Development of Ulcerative Colitis into Colitis-Associated Colorectal Cancer by Modulating MMP1/MMP3 Activity

  • Int Immunopharmacol. 2024 Jun 30:135:112262. doi: 10.1016/j.intimp.2024.112262.
Roude Li 1,  Honggang Chi 2,  Xiaoxia Liao 3,  Shuimei Cen 4,  Ying Zou 5
Affiliations

Affiliations

  • 1 The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan 523000, China; The second school of clinical medicine, Guangdong Medical University, Dongguan 523000, China. Electronic address: g_lirid@163.com.
  • 2 The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan 523000, China; The second school of clinical medicine, Guangdong Medical University, Dongguan 523000, China. Electronic address: chihonggang@sina.com.
  • 3 The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan 523000, China; The second school of clinical medicine, Guangdong Medical University, Dongguan 523000, China. Electronic address: liewhiuha@163.com.
  • 4 The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan 523000, China; The second school of clinical medicine, Guangdong Medical University, Dongguan 523000, China. Electronic address: 931015763@qq.com.
  • 5 The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan 523000, China; The second school of clinical medicine, Guangdong Medical University, Dongguan 523000, China; Department of Traditional Chinese Medicine, Dongguan Liaobu Hospital, Dongguan 523000, China. Electronic address: zouying@gdmu.edu.cn.
PMID: 38805906 DOI: 10.1016/j.intimp.2024.112262
Abstract

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.

Keywords

Colitis-associated colorectal cancer; Glabridin; Huangqin decoction; Matrix metalloproteinase; Network pharmacology; Ulcerative colitis.

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