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YY-1224,a terpene trilactone-strengthened Ginkgo biloba,attenuates neurodegenerative changes induced by β-amyloid (1-42) or double transgenic overexpression of APP and PS1 via inhibition of cyclooxygenase-2
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نویسنده
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li z.-y. ,chung y.h. ,shin e.-j. ,dang d.-k. ,jeong j.h. ,ko s.k. ,nah s.-y. ,baik t.g. ,jhoo j.h. ,ong w.-y. ,nabeshima t. ,kim h.-c.
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منبع
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journal of neuroinflammation - 2017 - دوره : 14 - شماره : 1
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چکیده
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Background: ginkgo biloba has been reported to possess free radical-scavenging antioxidant activity and anti-inflammatory properties. in our pilot study,yy-1224,a terpene trilactone-strengthened extract of g. biloba,showed anti-inflammatory,neurotrophic,and antioxidant effects. results: we investigated the pharmacological potential of yy-1224 in β-amyloid (aβ) (1-42)-induced memory impairment using cyclooxygenase-2 (cox-2) knockout (-/-) and appswe/ps1de9 transgenic (app/ps1 tg) mice. repeated treatment with yy-1224 significantly attenuated aβ (1-42)-induced memory impairment in cox-2 (+/+) mice,but not in cox-2 (-/-) mice. yy-1224 significantly attenuated aβ (1-42)-induced upregulation of platelet-activating factor (paf) receptor gene expression,reactive oxygen species,and pro-inflammatory factors. in addition,yy-1224 significantly inhibited aβ (1-42)-induced downregulation of paf-acetylhydrolase-1 (paf-ah-1) and peroxisome proliferator-activated receptor γ (pparγ) gene expression. these changes were more pronounced in cox-2 (+/+) mice than in cox-2 (-/-) mice. yy-1224 significantly attenuated learning impairment,aβ deposition,and pro-inflammatory microglial activation in app/ps1 tg mice,whereas it significantly enhanced paf-ah and pparγ expression. a preferential cox-2 inhibitor,meloxicam,did not affect the pharmacological activity by yy-1224,suggesting that the cox-2 gene is a critical mediator of the neuroprotective effects of yy-1224. the protective activity of yy-1224 appeared to be more efficacious than a standard g. biloba extract (gb) against aβ insult. conclusions: our results suggest that the protective effects of yy-1224 against aβ toxicity may be associated with its paf antagonistic- and pparγ agonistic-potential as well as inhibition of the aβ-mediated pro-inflammatory switch of microglia phenotypes through suppression of cox-2 expression. © 2017 the author(s).
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کلیدواژه
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APPswe/PS1dE9 transgenic mice; Cyclooxygenase-2 knockout mice; Microglia; Peroxisome proliferators-activated receptor γ; Platelet-activating factor; Terpene trilactone-strengthened G. biloba
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آدرس
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kangwon national university,neuropsychopharmacology and toxicology program,college of pharmacy,chunchon,24341, South Korea, chung-ang university,department of anatomy,college of medicine,seoul,06974, South Korea, kangwon national university,neuropsychopharmacology and toxicology program,college of pharmacy,chunchon,24341, South Korea, kangwon national university,neuropsychopharmacology and toxicology program,college of pharmacy,chunchon,24341, South Korea, chung-ang university,department of pharmacology,college of medicine,seoul,06974, South Korea, semyung university,department of oriental medical food and nutrition,jecheon,27136, South Korea, konkuk university,ginsentology research laboratory and department of physiology,college of veterinary medicine and bio/molecular informatics center,seoul,05029, South Korea, r and d center,yuyu pharma,seoul,04598, South Korea, kangwon national university,department of psychiatry,medical school,chunchon,24341, South Korea, national university of singapore,department of anatomy,singapore,119260, Singapore, meijo university,nabeshima laboratory,graduate school of pharmaceutical sciences,nagoya,468-8503, Japan, kangwon national university,neuropsychopharmacology and toxicology program,college of pharmacy,chunchon,24341, South Korea
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Authors
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