Magnolol, a natural aldehyde dehydrogenase-2 agonist, inhibits the proliferation and collagen synthesis of cardiac fibroblasts
| Autor: | Hong-Mei Chen, Hui-Jie Fan, Ying-Chun Zhou, Gui-qiong Huang, Bin Liu, Wen-Tong Zhang, Jun Li, Xiao-Min Sun, Ling-Peng Xie, Zhang-Bin Tan, Xuan-Ye Gu, Yu-Ting Wu, Ling Chen |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Agonist
medicine.drug_class Clinical Biochemistry Pharmaceutical Science Aldehyde dehydrogenase Endogeny 01 natural sciences Biochemistry Lignans chemistry.chemical_compound Structure-Activity Relationship Western blot Fibrosis Drug Discovery medicine Humans Myocytes Cardiac Molecular Biology ALDH2 Cell Proliferation biology medicine.diagnostic_test Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Aldehyde Dehydrogenase Mitochondrial Organic Chemistry Biphenyl Compounds Fibroblasts medicine.disease Magnolol 0104 chemical sciences Cell biology 010404 medicinal & biomolecular chemistry Magnolia biology.protein Molecular Medicine Myocardial fibrosis Collagen |
| Zdroj: | Bioorganicmedicinal chemistry letters. 43 |
| ISSN: | 1464-3405 |
| Popis: | Inhibiting myocardial fibrosis can help prevent cardiovascular diseases, including heart failure. Magnolol (Mag), a natural component of Magnoliae officinalis, has been reported to inhibit fibrosis. However, the mechanism of Mag activity and its effects on myocardial fibrosis remain unclear. Here, we investigated the involvement of ALDH2, an endogenous protective agent against myocardial fibrosis, in the Mag-mediated inhibition of cardiac fibroblast proliferation and collagen synthesis. We found that Mag significantly inhibited cardiac fibroblast proliferation and collagen synthesis, based on the results of MTT, EdU and western blot assays. Moreover, molecular docking, molecular dynamics simulation and surface plasmon resonance (SPR) assays showed that Mag could bind directly and stably to ALDH2. Further analysis of the mechanism of these effects indicated that treatment with Mag dose-dependently enhanced ALDH2 activity without altering protein expression. Mag could enhance the activity of recombinant human ALDH2 proteins with a half-maximal effective concentration of 5.79 × 10−5 M. In addition, ALDH2 activation via Alda-1 inhibited cardiac fibroblast proliferation and collagen synthesis, while ALDH2 inhibition via daidzin partially blocked the suppressive effects of Mag. In summary, Mag may act as a natural ALDH2 agonist and inhibit cardiac fibroblast proliferation and collagen synthesis. |
| Databáze: | OpenAIRE |
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