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Abstract Title:

Magnolol, a natural aldehyde dehydrogenase-2 agonist, inhibits the proliferation and collagen synthesis of cardiac fibroblasts.

Abstract Source:

Bioorg Med Chem Lett. 2021 Apr 16 ;43:128045. Epub 2021 Apr 16. PMID: 33865968

Abstract Author(s):

Ling Chen, Yu-Ting Wu, Xuan-Ye Gu, Ling-Peng Xie, Hui-Jie Fan, Zhang-Bin Tan, Wen-Tong Zhang, Hong-Mei Chen, Jun Li, Gui-Qiong Huang, Bin Liu, Ying-Chun Zhou, Xiao-Min Sun

Article Affiliation:

Ling Chen

Abstract:

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 × 10M. 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.

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Sayer Ji
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