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Journal of Traditional Chinese Medicine >

2024 , Vol. 44 >Issue 1: 35 - 43

DOI: https://doi.org/10.19852/j.cnki.jtcm.2024.01.004

Original articles

Identifying Qingkailing (清开灵) ingredients-dependent mesenchymal-epithelial transition factor-axiation “π” structuring module with angiogenesis and neurogenesis effects

  • Kunming CHENG ,
  • Jianan YUAN ,
  • Jun LIU ,
  • Shengpeng ZHANG ,
  • Qixiang XU ,
  • Yong XIE ,
  • Jingfeng ZHAO ,
  • Xiaoxu ZHANG ,
  • Xudong TANG ,
  • Yongqiu ZHENG ,
  • Zhong WANG
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  • 1 Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicines in Southern Anhui, Teaching and Research Section of Traditional Chinese Medicine, School of Pharmacy, Wannan Medical College, Wuhu 241000, China
    2 Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China
    3 Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Department of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China
    4 Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China

Received date: 2023-02-19

  Accepted date: 2023-05-22

  Online published: 2023-12-28

Supported by

National Major Scientific and Technological Special Project for “Significant New Drugs Development”: Clinical Value Prescription Discovery and Evaluation Technology Based on Modular Pharmacology(2017ZX09301059);Joint Innovation Project of China Academy of Chinese Medical Sciences: Study on the Mechanism of Action of Neuronal Regenerative Function Module Activated by Qingkailing Components(ZZ11-026);University Collaborative Innovation Project of Anhui: Creation of a Combined Animal Model of Coronary Heart Disease Based on the Theory of Xin'an Medicine(GXXT-2020-024);University Natural Science Research Project of Anhui Province :Molecular Mechanism of the Anti-hepatic Fibrosis Effect of Wickerwork Amide Based on the Regulation of Intercellular Communication by PTRF(2023AH051752)

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Abstract

OBJECTIVE: To explore the functional role of the drug-dependent mesenchymal-epithelial transition (Met)-axiation "π" structural module of neurogenesis after processing by three components of Qingkailing injection in neurogenesis and angiogenesis in cerebral ischemia.

METHODS: We used a Glutathione S-transferase (GST)-pull down assay, isothermal titration calorimetry assay, and other related methods to identify the relationships among Met, inositol polyphosphate phosphatase like 1 (Inppl1), and death associated protein kinase 3 (Dapk3) in this allosteric module. The biological effects of the modules of neurons generation composed of Met, Inppl1, and Dapk3 were measured through Western blot, apoptosis analysis, and double immunofluorescence labeling.

RESULTS: The GST-pull down assay revealed that proline-serine-threonine rich domain of Met binds to the Src homology domain of Inppl1 to form a protein-protein complex; Dapk3 with a C-terminal domain interacts weakly with the protein kinase C domain of Met in the intracellular region. Thus, we obtained a “π” structuring module considered a neural regeneration module. The biological effects of angiogenesis and neurogenesis modules composed of Met, Inppl1, and Dapk3 were also verified.

CONCLUSION: The study suggested that understanding the functional modules that contribute to pharmaceutics might provide novel signatures that can be used as endpoints to define disease processes under stroke or cerebral ischemia conditions.

Key words： brain ischemia; stroke; neurogenesis; angiogenesis; modular pharmacology; Met-axiation allosteric module

Cite this article

Kunming CHENG , Jianan YUAN , Jun LIU , Shengpeng ZHANG , Qixiang XU , Yong XIE , Jingfeng ZHAO , Xiaoxu ZHANG , Xudong TANG , Yongqiu ZHENG , Zhong WANG . Identifying Qingkailing (清开灵) ingredients-dependent mesenchymal-epithelial transition factor-axiation “π” structuring module with angiogenesis and neurogenesis effects[J]. Journal of Traditional Chinese Medicine, 2024 , 44(1) : 35 -43 . DOI: 10.19852/j.cnki.jtcm.2024.01.004

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