Journal
FRONTIERS IN PHARMACOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2021.533028
Keywords
astragali radix; estrogen receptor; synergism; isoflavones; neuroprotection
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Funding
- Areas of Excellence Scheme [2016/17]
- Research Grants Council, Hong Kong SAR [AoE/P-705/16]
- General Research Fund (GRF) [17118,717, 17102,915]
- National State Key Lab Fund of China [2014/02]
- Hainan Provincial Key Research and Development Program [ZDYF2019196]
- National Natural Science Fund of China [81,960,227]
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In this study, it was found that isoflavones from Astragali Radix can synergistically alleviate cerebral ischemia-reperfusion injury by activating the ER-PI3K-Akt signaling pathway, demonstrating their neuroprotective effects against neural death induced by ischemia-reperfusion.
Isoflavones are major neuroprotective components of a medicinal herb Astragali Radix, against cerebral ischemia-reperfusion injury but the mechanisms of neuroprotection remain unclear. Calycosin and formononetin are two major AR isoflavones while daidzein is the metabolite of formononetin after absorption. Herein, we aim to investigate the synergistic neuroprotective effects of those isoflavones of Astragali Radix against cerebral ischemia-reperfusion injury. Calycosin, formononetin and daidzein were organized with different combinations whose effects observed in both in vitro and in vivo experimental models. In the in vitro study, primary cultured neurons were subjected to oxygen-glucose deprivation plus reoxygenation (OGD/RO) or l-glutamate treatment. In the in vivo study, rats were subjected to middle cerebral artery occlusion to induce cerebral ischemia and reperfusion. All three isoflavones pre-treatment alone decreased brain infarct volume and improved neurological deficits in rats, and dose-dependently attenuated neural death induced by l-glutamate treatment and OGD/RO in cultured neurons. Interestingly, the combined formulas of those isoflavones revealed synergistically activated estrogen receptor (estrogen receptors)-PI3K-Akt signaling pathway. Using ER antagonist and phosphatidylinositol 3-kinase (PI3K) inhibitor blocked the neuroprotective effects of those isoflavones. In conclusion, isoflavones could synergistically alleviate cerebral ischemia-reperfusion injury via activating ER-PI3K-Akt pathway.
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