GAPT regulates cholinergic dysfunction and oxidative stress in the brains of learning and memory impairment mice induced by scopolamine
Abstract Background Cholinergic dysfunction and oxidative stress are the crucial mechanisms of Alzheimer's disease (AD). GAPT, also called GEPT (a combination of several active components extracted from the Chinese herbs ginseng, epimedium, polygala and tuber curcumae) or Jinsiwei, is a patente...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-05-01
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| Series: | Brain and Behavior |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/brb3.1602 |
| _version_ | 1818841081929793536 |
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| author | Zhenhong Liu Gaofeng Qin Lulu Mana Yunfang Dong Shuaiyang Huang Yahan Wang Yiqiong Wu Jing Shi Jinzhou Tian Pengwen Wang |
| author_facet | Zhenhong Liu Gaofeng Qin Lulu Mana Yunfang Dong Shuaiyang Huang Yahan Wang Yiqiong Wu Jing Shi Jinzhou Tian Pengwen Wang |
| author_sort | Zhenhong Liu |
| collection | DOAJ |
| description | Abstract Background Cholinergic dysfunction and oxidative stress are the crucial mechanisms of Alzheimer's disease (AD). GAPT, also called GEPT (a combination of several active components extracted from the Chinese herbs ginseng, epimedium, polygala and tuber curcumae) or Jinsiwei, is a patented Chinese herbal compound, has been clinically widely used to improve learning and memory impairment, but whether it can play a neuroprotective role by protecting cholinergic neurons and reducing oxidative stress injury remains unclear. Methods Male ICR mice were intraperitoneally injected with scopolamine (3 mg/kg) to establish a learning and memory disordered model. An LC‐MS method was established to study the chemical compounds and in vivo metabolites of GAPT. After scopolamine injection, a step‐down passive‐avoidance test (SDPA) and a Y maze test were used to estimate learning ability and cognitive function. In addition, ELISA detected the enzymatic activities of acetylcholinesterase (AChE), acetylcholine (ACh), choline acetyltransferase (ChAT), malondialdehyde (MDA), glutathione peroxidase (GPX), and total superoxide dismutase (T‐SOD). The protein expressions of AChE, ChAT, SOD1, and GPX1 were observed by western blot, and the distribution of ChAT, SOD1, and GPX1 was observed by immunohistochemical staining. Results After one‐half or 1 month of intragastric administration, GAPT can ameliorate scopolamine‐induced behavioral changes in learning and memory impaired mice. It can also decrease the activity of MDA and protein expression level of AChE, increase the activity of Ach, and increase activity and protein expression level of ChAT, SOD, and GPX in scopolamine‐treated mice. After one and a half month of intragastric administration of GAPT, echinacoside, salvianolic acid A, ginsenoside Rb1, ginsenoside Rg2, pachymic acid, and beta asarone could be absorbed into mice blood and pass through BBB. Conclusions GAPT can improve the learning and memory ability of scopolamine‐induced mice, and its mechanism may be related to protecting cholinergic neurons and reducing oxidative stress injury. |
| first_indexed | 2024-12-19T04:20:25Z |
| format | Article |
| id | doaj.art-e5439355151146b1912cd5de8cddeeb7 |
| institution | Directory Open Access Journal |
| issn | 2162-3279 |
| language | English |
| last_indexed | 2024-12-19T04:20:25Z |
| publishDate | 2020-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Brain and Behavior |
| spelling | doaj.art-e5439355151146b1912cd5de8cddeeb72022-12-21T20:36:10ZengWileyBrain and Behavior2162-32792020-05-01105n/an/a10.1002/brb3.1602GAPT regulates cholinergic dysfunction and oxidative stress in the brains of learning and memory impairment mice induced by scopolamineZhenhong Liu0Gaofeng Qin1Lulu Mana2Yunfang Dong3Shuaiyang Huang4Yahan Wang5Yiqiong Wu6Jing Shi7Jinzhou Tian8Pengwen Wang9Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing Dongzhimen Hospital Beijing University of Chinese Medicine (BUCM) Beijing ChinaKey Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing Dongzhimen Hospital Beijing University of Chinese Medicine (BUCM) Beijing ChinaKey Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing Dongzhimen Hospital Beijing University of Chinese Medicine (BUCM) Beijing ChinaKey Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing Dongzhimen Hospital Beijing University of Chinese Medicine (BUCM) Beijing ChinaKey Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing Dongzhimen Hospital Beijing University of Chinese Medicine (BUCM) Beijing ChinaKey Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing Dongzhimen Hospital Beijing University of Chinese Medicine (BUCM) Beijing ChinaKey Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing Dongzhimen Hospital Beijing University of Chinese Medicine (BUCM) Beijing ChinaKey Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing Dongzhimen Hospital Beijing University of Chinese Medicine (BUCM) Beijing ChinaKey Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing Dongzhimen Hospital Beijing University of Chinese Medicine (BUCM) Beijing ChinaKey Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing Dongzhimen Hospital Beijing University of Chinese Medicine (BUCM) Beijing ChinaAbstract Background Cholinergic dysfunction and oxidative stress are the crucial mechanisms of Alzheimer's disease (AD). GAPT, also called GEPT (a combination of several active components extracted from the Chinese herbs ginseng, epimedium, polygala and tuber curcumae) or Jinsiwei, is a patented Chinese herbal compound, has been clinically widely used to improve learning and memory impairment, but whether it can play a neuroprotective role by protecting cholinergic neurons and reducing oxidative stress injury remains unclear. Methods Male ICR mice were intraperitoneally injected with scopolamine (3 mg/kg) to establish a learning and memory disordered model. An LC‐MS method was established to study the chemical compounds and in vivo metabolites of GAPT. After scopolamine injection, a step‐down passive‐avoidance test (SDPA) and a Y maze test were used to estimate learning ability and cognitive function. In addition, ELISA detected the enzymatic activities of acetylcholinesterase (AChE), acetylcholine (ACh), choline acetyltransferase (ChAT), malondialdehyde (MDA), glutathione peroxidase (GPX), and total superoxide dismutase (T‐SOD). The protein expressions of AChE, ChAT, SOD1, and GPX1 were observed by western blot, and the distribution of ChAT, SOD1, and GPX1 was observed by immunohistochemical staining. Results After one‐half or 1 month of intragastric administration, GAPT can ameliorate scopolamine‐induced behavioral changes in learning and memory impaired mice. It can also decrease the activity of MDA and protein expression level of AChE, increase the activity of Ach, and increase activity and protein expression level of ChAT, SOD, and GPX in scopolamine‐treated mice. After one and a half month of intragastric administration of GAPT, echinacoside, salvianolic acid A, ginsenoside Rb1, ginsenoside Rg2, pachymic acid, and beta asarone could be absorbed into mice blood and pass through BBB. Conclusions GAPT can improve the learning and memory ability of scopolamine‐induced mice, and its mechanism may be related to protecting cholinergic neurons and reducing oxidative stress injury.https://doi.org/10.1002/brb3.1602Alzheimer's diseasebehaviorcholinergic systemGAPTmemory impairmentoxidative stress |
| spellingShingle | Zhenhong Liu Gaofeng Qin Lulu Mana Yunfang Dong Shuaiyang Huang Yahan Wang Yiqiong Wu Jing Shi Jinzhou Tian Pengwen Wang GAPT regulates cholinergic dysfunction and oxidative stress in the brains of learning and memory impairment mice induced by scopolamine Brain and Behavior Alzheimer's disease behavior cholinergic system GAPT memory impairment oxidative stress |
| title | GAPT regulates cholinergic dysfunction and oxidative stress in the brains of learning and memory impairment mice induced by scopolamine |
| title_full | GAPT regulates cholinergic dysfunction and oxidative stress in the brains of learning and memory impairment mice induced by scopolamine |
| title_fullStr | GAPT regulates cholinergic dysfunction and oxidative stress in the brains of learning and memory impairment mice induced by scopolamine |
| title_full_unstemmed | GAPT regulates cholinergic dysfunction and oxidative stress in the brains of learning and memory impairment mice induced by scopolamine |
| title_short | GAPT regulates cholinergic dysfunction and oxidative stress in the brains of learning and memory impairment mice induced by scopolamine |
| title_sort | gapt regulates cholinergic dysfunction and oxidative stress in the brains of learning and memory impairment mice induced by scopolamine |
| topic | Alzheimer's disease behavior cholinergic system GAPT memory impairment oxidative stress |
| url | https://doi.org/10.1002/brb3.1602 |
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