Kaempferol-3-O-(2″-O-galloyl-β-D-glucopyranoside): a novel neuroprotective agent from Diospryros kaki against cerebral ischemia-induced brain injury.

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  • Additional Information
    • Source:
      Publisher: Springer Country of Publication: Japan NLM ID: 101518405 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1861-0293 (Electronic) Linking ISSN: 13403443 NLM ISO Abbreviation: J Nat Med Subsets: MEDLINE
    • Publication Information:
      Original Publication: Tokyo : Springer
    • Subject Terms:
    • Abstract:
      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.
      (© 2023. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)
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    • Grant Information:
      01/2022/HD-DTCS-DLSH National Institute of Medicinal Materials
    • Contributed Indexing:
      Keywords: Diospyros kaki; Blood–brain barrier integrity; Cerebral ischemia; Kaempferol-3-O-(2″-O-galloyl-β-d-glucopyranoside); Neuroprotective effect; Oxidative stress
    • Accession Number:
      0 (Neuroprotective Agents)
      9IKM0I5T1E (Quercetin)
      S798V6YJRP (Edaravone)
      0 (Kaempferols)
      0 (Flavonoids)
      S88TT14065 (Oxygen)
    • Publication Date:
      Date Created: 20231224 Date Completed: 20240229 Latest Revision: 20240229
    • Publication Date:
      20240229
    • Accession Number:
      10.1007/s11418-023-01765-z
    • Accession Number:
      38143256