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
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-04-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-017-0866-x |
| _version_ | 1828292935174586368 |
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| author | Zheng-Yi Li Yoon Hee Chung Eun-Joo Shin Duy-Khanh Dang Ji Hoon Jeong Sung Kwon Ko Seung-Yeol Nah Tae Gon Baik Jin Hyeong Jhoo Wei-Yi Ong Toshitaka Nabeshima Hyoung-Chun Kim |
| author_facet | Zheng-Yi Li Yoon Hee Chung Eun-Joo Shin Duy-Khanh Dang Ji Hoon Jeong Sung Kwon Ko Seung-Yeol Nah Tae Gon Baik Jin Hyeong Jhoo Wei-Yi Ong Toshitaka Nabeshima Hyoung-Chun Kim |
| author_sort | Zheng-Yi Li |
| collection | DOAJ |
| description | 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 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. |
| first_indexed | 2024-04-13T11:16:37Z |
| format | Article |
| id | doaj.art-6867afb289db48a4b826cd2bd941df8e |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-04-13T11:16:37Z |
| publishDate | 2017-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-6867afb289db48a4b826cd2bd941df8e2022-12-22T02:48:57ZengBMCJournal of Neuroinflammation1742-20942017-04-0114112210.1186/s12974-017-0866-xYY-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-2Zheng-Yi Li0Yoon Hee Chung1Eun-Joo Shin2Duy-Khanh Dang3Ji Hoon Jeong4Sung Kwon Ko5Seung-Yeol Nah6Tae Gon Baik7Jin Hyeong Jhoo8Wei-Yi Ong9Toshitaka Nabeshima10Hyoung-Chun Kim11Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National UniversityDepartment of Anatomy, College of Medicine, Chung-Ang UniversityNeuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National UniversityNeuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National UniversityDepartment of Pharmacology, College of Medicine, Chung-Ang UniversityDepartment of Oriental Medical Food and Nutrition, Semyung UniversityGinsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk UniversityR&D Center, Yuyu PharmaDepartment of Psychiatry, Medical School, Kangwon National UniversityDepartment of Anatomy, National University of SingaporeNabeshima Laboratory, Graduate School of Pharmaceutical Sciences, Meijo UniversityNeuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National UniversityAbstract 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.http://link.springer.com/article/10.1186/s12974-017-0866-xTerpene trilactone-strengthened G. bilobaPlatelet-activating factorPeroxisome proliferators-activated receptor γMicrogliaAPPswe/PS1dE9 transgenic miceCyclooxygenase-2 knockout mice |
| spellingShingle | Zheng-Yi Li Yoon Hee Chung Eun-Joo Shin Duy-Khanh Dang Ji Hoon Jeong Sung Kwon Ko Seung-Yeol Nah Tae Gon Baik Jin Hyeong Jhoo Wei-Yi Ong Toshitaka Nabeshima Hyoung-Chun Kim 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 Journal of Neuroinflammation Terpene trilactone-strengthened G. biloba Platelet-activating factor Peroxisome proliferators-activated receptor γ Microglia APPswe/PS1dE9 transgenic mice Cyclooxygenase-2 knockout mice |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Terpene trilactone-strengthened G. biloba Platelet-activating factor Peroxisome proliferators-activated receptor γ Microglia APPswe/PS1dE9 transgenic mice Cyclooxygenase-2 knockout mice |
| url | http://link.springer.com/article/10.1186/s12974-017-0866-x |
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