Loan Thanh Thi Nguyen, Xoan Thi Le, Ha Thi Nguyen, Tai Van Nguyen, Hang Nguyet Thi Pham, Anh Van Thi Pham, Kinzo Matsumoto
{"title":"堪非醇-3-O-(2″-O-谷氨酰-β-d-吡喃葡萄糖苷)：一种来自 Diospryros kaki 的新型神经保护剂，可预防脑缺血引起的脑损伤","authors":"Loan Thanh Thi Nguyen, Xoan Thi Le, Ha Thi Nguyen, Tai Van Nguyen, Hang Nguyet Thi Pham, Anh Van Thi Pham, Kinzo Matsumoto","doi":"10.1007/s11418-023-01765-z","DOIUrl":null,"url":null,"abstract":"<div><p>Our previous study demonstrated neuroprotective and therapeutic effects of a standardized flavonoid extract from leaves of <i>Diospyros kaki</i> L.f. (DK) on middle cerebral artery occlusion-and-reperfusion (MCAO/R)-induced brain injury and its underlying mechanisms. This study aimed to clarify flavonoid components responsible for the effects of DK using in vitro and in vivo transient brain ischemic models. Organotypic hippocampal slice cultures (OHSCs) subjected to oxygen- and glucose-deprivation (OGD) were performed to evaluate in vitro neuroprotective activity of DK extract and nine isolated flavonoid components. MCAO/R mice were employed to elucidate in vivo neuroprotective effects of the flavonoid component that exhibited the most potent neuroprotective effect in OHSCs. DK extract and seven flavonoids [quercetin, isoquercetin, hyperoside, quercetin-3-O-(2″-O-galloyl-β-<span>d</span>-galactopyranoside), kaempferol, astragalin, and kaempferol-3-O-(2″-O-galloyl-β-<span>d</span>-glucopyranoside) compound <b>(9)</b>] attenuated OGD-induced neuronal cell damage and compound <b>(9)</b> possessed the most potent neuroprotective activity in OHSCs. The MCAO/R mice showed cerebral infarction, massive weight loss, characteristic neurological symptoms, and deterioration of neuronal cells in the brain. Compound <b>(9)</b> and a reference drugs, edaravone, significantly attenuated these physical and neurological impairments. Compound <b>(9)</b> mitigated the blood–brain barrier dysfunction and the change of glutathione and malondialdehyde content in the MCAO mouse brain. Edaravone suppressed the oxidative stress but did not significantly affect the blood–brain barrier permeability. The present results indicated that compound <b>(9)</b> is a flavonoid constituent of DK with a potent neuroprotective activity against transient ischemia-induced brain damage and this action, at least in part, via preservation of blood–brain barrier integrity and suppression of oxidative stress caused by ischemic insult.</p><h3>Graphical abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"78 2","pages":"312 - 327"},"PeriodicalIF":2.5000,"publicationDate":"2023-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Kaempferol-3-O-(2″-O-galloyl-β-d-glucopyranoside): a novel neuroprotective agent from Diospryros kaki against cerebral ischemia—induced brain injury\",\"authors\":\"Loan Thanh Thi Nguyen, Xoan Thi Le, Ha Thi Nguyen, Tai Van Nguyen, Hang Nguyet Thi Pham, Anh Van Thi Pham, Kinzo Matsumoto\",\"doi\":\"10.1007/s11418-023-01765-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Our previous study demonstrated neuroprotective and therapeutic effects of a standardized flavonoid extract from leaves of <i>Diospyros kaki</i> L.f. (DK) on middle cerebral artery occlusion-and-reperfusion (MCAO/R)-induced brain injury and its underlying mechanisms. This study aimed to clarify flavonoid components responsible for the effects of DK using in vitro and in vivo transient brain ischemic models. Organotypic hippocampal slice cultures (OHSCs) subjected to oxygen- and glucose-deprivation (OGD) were performed to evaluate in vitro neuroprotective activity of DK extract and nine isolated flavonoid components. MCAO/R mice were employed to elucidate in vivo neuroprotective effects of the flavonoid component that exhibited the most potent neuroprotective effect in OHSCs. 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Kaempferol-3-O-(2″-O-galloyl-β-d-glucopyranoside): a novel neuroprotective agent from Diospryros kaki against cerebral ischemia—induced brain injury
Our previous study demonstrated neuroprotective and therapeutic effects of a standardized flavonoid extract from leaves of Diospyros kaki L.f. (DK) on middle cerebral artery occlusion-and-reperfusion (MCAO/R)-induced brain injury and its underlying mechanisms. This study aimed to clarify flavonoid components responsible for the effects of DK using in vitro and in vivo transient brain ischemic models. Organotypic hippocampal slice cultures (OHSCs) subjected to oxygen- and glucose-deprivation (OGD) were performed to evaluate in vitro neuroprotective activity of DK extract and nine isolated flavonoid components. MCAO/R mice were employed to elucidate in vivo neuroprotective effects of the flavonoid component that exhibited the most potent neuroprotective effect in OHSCs. DK extract and seven flavonoids [quercetin, isoquercetin, hyperoside, quercetin-3-O-(2″-O-galloyl-β-d-galactopyranoside), kaempferol, astragalin, and kaempferol-3-O-(2″-O-galloyl-β-d-glucopyranoside) compound (9)] attenuated OGD-induced neuronal cell damage and compound (9) possessed the most potent neuroprotective activity in OHSCs. The MCAO/R mice showed cerebral infarction, massive weight loss, characteristic neurological symptoms, and deterioration of neuronal cells in the brain. Compound (9) and a reference drugs, edaravone, significantly attenuated these physical and neurological impairments. Compound (9) mitigated the blood–brain barrier dysfunction and the change of glutathione and malondialdehyde content in the MCAO mouse brain. Edaravone suppressed the oxidative stress but did not significantly affect the blood–brain barrier permeability. The present results indicated that compound (9) is a flavonoid constituent of DK with a potent neuroprotective activity against transient ischemia-induced brain damage and this action, at least in part, via preservation of blood–brain barrier integrity and suppression of oxidative stress caused by ischemic insult.
期刊介绍：
The Journal of Natural Medicines is an international journal publishing original research in naturally occurring medicines and their related foods and cosmetics. It covers:
-chemistry of natural products
-biochemistry of medicinal plants
-pharmacology of natural products and herbs, including Kampo formulas and traditional herbs
-botanical anatomy
-cultivation of medicinal plants.
The journal accepts Original Papers, Notes, Rapid Communications and Natural Resource Letters. Reviews and Mini-Reviews are generally invited.
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