PMID- 38143256 OWN - NLM STAT- MEDLINE DCOM- 20240229 LR - 20240229 IS - 1861-0293 (Electronic) IS - 1340-3443 (Linking) VI - 78 IP - 2 DP - 2024 Mar TI - Kaempferol-3-O-(2''-O-galloyl-beta-D-glucopyranoside): a novel neuroprotective agent from Diospryros kaki against cerebral ischemia-induced brain injury. PG - 312-327 LID - 10.1007/s11418-023-01765-z [doi] AB - 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-beta-D-galactopyranoside), kaempferol, astragalin, and kaempferol-3-O-(2''-O-galloyl-beta-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. CI - (c) 2023. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy. FAU - Nguyen, Loan Thanh Thi AU - Nguyen LTT AD - Department of Pharmacology and Biochemistry, National Institute of Medicinal Materials, Hanoi, Vietnam. AD - Department of Pharmacology, Hanoi Medical University, Hanoi, Vietnam. FAU - Le, Xoan Thi AU - Le XT AUID- ORCID: 0000-0002-4471-3155 AD - Department of Pharmacology and Biochemistry, National Institute of Medicinal Materials, Hanoi, Vietnam. xoanle@nimm.org.vn. FAU - Nguyen, Ha Thi AU - Nguyen HT AD - Department of Extraction Technology, Vietnam National Institute of Medicinal Materials, Hanoi, Vietnam. FAU - Nguyen, Tai Van AU - Nguyen TV AD - Department of Phytochemistry, National Institute of Medicinal Materials, Hanoi, Vietnam. FAU - Pham, Hang Nguyet Thi AU - Pham HNT AD - Department of Pharmacology and Biochemistry, National Institute of Medicinal Materials, Hanoi, Vietnam. FAU - Van Thi Pham, Anh AU - Van Thi Pham A AD - Department of Pharmacology, Hanoi Medical University, Hanoi, Vietnam. FAU - Matsumoto, Kinzo AU - Matsumoto K AD - Graduate School of Pharmaceutical Sciences, Daiichi University of Pharmacy, Fukuoka, Japan. LA - eng GR - 01/2022/HD-DTCS-DLSH/National Institute of Medicinal Materials/ PT - Journal Article DEP - 20231224 PL - Japan TA - J Nat Med JT - Journal of natural medicines JID - 101518405 RN - 0 (Neuroprotective Agents) RN - 9IKM0I5T1E (Quercetin) RN - S798V6YJRP (Edaravone) RN - 0 (Kaempferols) RN - 0 (Flavonoids) RN - S88TT14065 (Oxygen) SB - IM MH - Mice MH - Animals MH - *Neuroprotective Agents/pharmacology/therapeutic use MH - Quercetin/pharmacology/therapeutic use MH - Edaravone/therapeutic use MH - *Diospyros MH - Kaempferols/pharmacology/therapeutic use MH - *Brain Ischemia/drug therapy MH - Cerebral Infarction/drug therapy MH - Flavonoids/pharmacology MH - *Reperfusion Injury/drug therapy MH - Oxygen MH - *Brain Injuries/drug therapy OTO - NOTNLM OT - Diospyros kaki OT - Blood-brain barrier integrity OT - Cerebral ischemia OT - Kaempferol-3-O-(2''-O-galloyl-beta-d-glucopyranoside) OT - Neuroprotective effect OT - Oxidative stress EDAT- 2023/12/25 00:42 MHDA- 2024/02/29 06:43 CRDT- 2023/12/24 23:13 PHST- 2023/08/22 00:00 [received] PHST- 2023/11/16 00:00 [accepted] PHST- 2024/02/29 06:43 [medline] PHST- 2023/12/25 00:42 [pubmed] PHST- 2023/12/24 23:13 [entrez] AID - 10.1007/s11418-023-01765-z [pii] AID - 10.1007/s11418-023-01765-z [doi] PST - ppublish SO - J Nat Med. 2024 Mar;78(2):312-327. doi: 10.1007/s11418-023-01765-z. Epub 2023 Dec 24.