YY-1224, a terpene trilactone-strengthened Ginkgo biloba, attenuatesneurodegenerative changes induced by beta-amyloid (1-42) or doubletransgenic overexpression of APP and PS1 via inhibition ofcyclooxygenase-2

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/487075.do
DOI
10.1186/s12974-017-0866-x
Title
YY-1224, a terpene trilactone-strengthened Ginkgo biloba, attenuatesneurodegenerative changes induced by beta-amyloid (1-42) or doubletransgenic overexpression of APP and PS1 via inhibition ofcyclooxygenase-2
Description
This study is supported by a grant (No. S111415L020100) of the "ForestryTechnology Projects" (provided by the Korea Forest Service), and in partsupported by Basic Science Research Program through the NationalResearch Foundation of Korea (NRF) funded by the Ministry of Science,ICT & Future Planning (#NRF-2013R1A1A2060894 and#NRF-2016R1A1A1A05005201), Republic of Korea. DK Dang was supported bythe BK21 PLUS program, NRF, Republic of Korea.
abstract
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 beta-amyloid (A beta) (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 A beta (1-42)-induced memory impairment in COX-2 (+/+) mice, but not in COX-2 (-/-) mice. YY-1224 significantly attenuated A beta (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 A beta (1-42)-induced downregulation of PAF-acetylhydrolase-1 (PAF-AH-1) and peroxisome proliferator-activated receptor gamma (PPAR gamma) gene expression. These changes were more pronounced in COX-2 (+/+) mice than in COX-2 (-/-) mice. YY-1224 significantly attenuated learning impairment, A beta deposition, and pro-inflammatory microglial activation in APP/PS1 Tg mice, whereas it significantly enhanced PAF-AH and PPAR gamma 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 A beta insult.
Conclusions: Our results suggest that the protective effects of YY-1224 against A beta toxicity may be associated with its PAF antagonistic-and PPAR gamma agonistic-potential as well as inhibition of the A beta-mediated pro-inflammatory switch of microglia phenotypes through suppression of COX-2 expression.
provenance
Made available in Cube on 2018-09-28T16:24:35Z (GMT). No. of bitstreams: 0
language
English
author
Li, Zheng-Yi
Chung, Yoon Hee
Shin, Eun-Joo
Dang, Duy-Khanh
Jeong, Ji Hoon
Ko, Sung Kwon
Nah, Seung-Yeol
Baik, Tae Gon
Jhoo, Jin Hyeong
Ong, Wei-Yi
Nabeshima, Toshitaka
Kim, Hyoung-Chun
accessioned
2018-09-28T16:24:35Z
available
2018-09-28T16:24:35Z
issued
2017
citation
JOURNAL OF NEUROINFLAMMATION(14)
issn
1742-2094
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/487075.do
Funder
산림청
Funding Program
임업기술연구개발
Project ID
1405002934
Jurisdiction
Rep.of Korea
Project Name
Evaluation on the distinguished pharmacological actions of mountain-cultivated ginseng
rights
openAccess
subject
Terpene trilactone-strengthened G. biloba
Platelet-activating factor
Peroxisome proliferators-activated receptor gamma
Microglia
APPswe/PS1dE9 transgenic mice
Cyclooxygenase-2 knockout mice
type
article


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