Astragali Radix Isoflavones Synergistically Alleviate Cerebral Ischemia and Reperfusion Injury Via Activating Estrogen Receptor-PI3K-Akt Signaling Pathway
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 abso...
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doaj-f4659be7042844ef8e747709ecc2c4b92021-02-22T05:40:08ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-02-011210.3389/fphar.2021.533028533028Astragali Radix Isoflavones Synergistically Alleviate Cerebral Ischemia and Reperfusion Injury Via Activating Estrogen Receptor-PI3K-Akt Signaling PathwayYong Gu0Yong Gu1Xi Chen2Xi Chen3Shuping Fu4Wenlan Liu5Qi Wang6Ke-Jian Liu7Jiangang Shen8Jiangang Shen9Clinical Research Center, Hainan Provincial Hospital of Chinese Medicine, Haikou, ChinaSchool of Chinese Medicine, University of Hong Kong, Hong Kong, ChinaDepartment of Core Facility, The People's Hospital of Bao‐an Shenzhen, Shenzhen, ChinaSchool of Chinese Medicine, University of Hong Kong, Hong Kong, ChinaSchool of Chinese Medicine, University of Hong Kong, Hong Kong, ChinaDepartment of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, United StatesInstitute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, United StatesSchool of Chinese Medicine, University of Hong Kong, Hong Kong, ChinaThe University of Hong Kong-Shenzhen, Institute of Research and Innovation (HKU-SIRI), Shenzhen, ChinaIsoflavones 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.https://www.frontiersin.org/articles/10.3389/fphar.2021.533028/fullastragali radixestrogen receptorsynergismisoflavonesneuroprotection |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yong Gu Yong Gu Xi Chen Xi Chen Shuping Fu Wenlan Liu Qi Wang Ke-Jian Liu Jiangang Shen Jiangang Shen |
spellingShingle |
Yong Gu Yong Gu Xi Chen Xi Chen Shuping Fu Wenlan Liu Qi Wang Ke-Jian Liu Jiangang Shen Jiangang Shen Astragali Radix Isoflavones Synergistically Alleviate Cerebral Ischemia and Reperfusion Injury Via Activating Estrogen Receptor-PI3K-Akt Signaling Pathway Frontiers in Pharmacology astragali radix estrogen receptor synergism isoflavones neuroprotection |
author_facet |
Yong Gu Yong Gu Xi Chen Xi Chen Shuping Fu Wenlan Liu Qi Wang Ke-Jian Liu Jiangang Shen Jiangang Shen |
author_sort |
Yong Gu |
title |
Astragali Radix Isoflavones Synergistically Alleviate Cerebral Ischemia and Reperfusion Injury Via Activating Estrogen Receptor-PI3K-Akt Signaling Pathway |
title_short |
Astragali Radix Isoflavones Synergistically Alleviate Cerebral Ischemia and Reperfusion Injury Via Activating Estrogen Receptor-PI3K-Akt Signaling Pathway |
title_full |
Astragali Radix Isoflavones Synergistically Alleviate Cerebral Ischemia and Reperfusion Injury Via Activating Estrogen Receptor-PI3K-Akt Signaling Pathway |
title_fullStr |
Astragali Radix Isoflavones Synergistically Alleviate Cerebral Ischemia and Reperfusion Injury Via Activating Estrogen Receptor-PI3K-Akt Signaling Pathway |
title_full_unstemmed |
Astragali Radix Isoflavones Synergistically Alleviate Cerebral Ischemia and Reperfusion Injury Via Activating Estrogen Receptor-PI3K-Akt Signaling Pathway |
title_sort |
astragali radix isoflavones synergistically alleviate cerebral ischemia and reperfusion injury via activating estrogen receptor-pi3k-akt signaling pathway |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2021-02-01 |
description |
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. |
topic |
astragali radix estrogen receptor synergism isoflavones neuroprotection |
url |
https://www.frontiersin.org/articles/10.3389/fphar.2021.533028/full |
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