PMID- 30911351 OWN - NLM STAT- MEDLINE DCOM- 20190415 LR - 20200225 IS - 1942-0994 (Electronic) IS - 1942-0900 (Print) IS - 1942-0994 (Linking) VI - 2019 DP - 2019 TI - Studies of the Anti-amnesic Effects and Mechanisms of Single and Combined Use of Donepezil and Ginkgo Ketoester Tablet on Scopolamine-Induced Memory Impairment in Mice. PG - 8636835 LID - 10.1155/2019/8636835 [doi] LID - 8636835 AB - Ginkgo ketoester tablets (GT) and donepezil were a clinically used combination for the treatment of Alzheimer's disease (AD). The aim of the study was undertaken to investigate the antiamnesic effects of the two drugs alone and in combination through in vivo models of the Morris water maze along with in vitro antioxidants, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The potential mechanisms were speculated by the activities of acetylcholine (ACh), AChE, superoxide dismutase (SOD), and malondialdehyde (MDA) and the protein expression of brain-derived neurotrophic factor (BDNF) and tyrosine protein kinase B (TrkB). The combination group showed a concentration-dependent inhibition of cholinesterase and antioxidation. As far as its mechanism was concerned, the combination of two drugs exerted excellent effects on oxidative stress, cholinergic pathway damage, and inactivation of the BDNF-TrkB signaling pathway. Additionally, to elucidate the binding mechanism of GT active ingredients into the structure of AChE, the results of molecular docking studies indicated that hydrogen and/or hydrophobic bonds might play an important role in their binding process. Thus, the combination of drugs could treat AD perfectly and further verify the scientific rationality of clinical medication. FAU - Zhang, Jing AU - Zhang J AD - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China. FAU - Wang, Jun AU - Wang J AD - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China. FAU - Zhou, Gui-Sheng AU - Zhou GS AUID- ORCID: 0000-0002-1295-1917 AD - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China. FAU - Tan, Ya-Jie AU - Tan YJ AD - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China. FAU - Tao, Hui-Juan AU - Tao HJ AD - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China. FAU - Chen, Jia-Qian AU - Chen JQ AD - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China. FAU - Pu, Zong-Jin AU - Pu ZJ AD - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China. FAU - Ma, Jia-Yan AU - Ma JY AD - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China. FAU - She, Wen AU - She W AD - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China. FAU - Kang, An AU - Kang A AD - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China. FAU - Zhu, Yue AU - Zhu Y AD - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China. FAU - Liu, Pei AU - Liu P AD - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China. FAU - Zhu, Zhen-Hua AU - Zhu ZH AD - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China. FAU - Shi, Xu-Qin AU - Shi XQ AD - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China. FAU - Tang, Yu-Ping AU - Tang YP AUID- ORCID: 0000-0003-0377-0791 AD - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China. AD - Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China. FAU - Duan, Jin-Ao AU - Duan JA AD - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China. LA - eng PT - Journal Article DEP - 20190218 PL - United States TA - Oxid Med Cell Longev JT - Oxidative medicine and cellular longevity JID - 101479826 RN - 0 (Benzothiazoles) RN - 0 (Biphenyl Compounds) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cholinesterase Inhibitors) RN - 0 (Ginkgolides) RN - 0 (Ligands) RN - 0 (Picrates) RN - 0 (Plant Extracts) RN - 0 (Sulfonic Acids) RN - 0 (Tablets) RN - 19FUJ2C58T (Ginkgo biloba extract) RN - 28752-68-3 (2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid) RN - 4Y8F71G49Q (Malondialdehyde) RN - 8SSC91326P (Donepezil) RN - DFD3H4VGDH (1,1-diphenyl-2-picrylhydrazyl) RN - DL48G20X8X (Scopolamine) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 3.1.1.7 (Acetylcholinesterase) RN - N9YNS0M02X (Acetylcholine) SB - IM MH - Acetylcholine/metabolism MH - Acetylcholinesterase MH - Amnesia/*drug therapy/pathology MH - Animals MH - Benzothiazoles/chemistry MH - Biphenyl Compounds/chemistry MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cholinesterase Inhibitors/pharmacology MH - Cognition Disorders/drug therapy MH - Donepezil/pharmacology/*therapeutic use MH - Drug Therapy, Combination MH - Ginkgo biloba/*chemistry MH - Ginkgolides/chemistry MH - Ligands MH - Malondialdehyde/metabolism MH - Memory Disorders/*chemically induced/*drug therapy MH - Mice, Inbred ICR MH - Molecular Docking Simulation MH - Picrates/chemistry MH - Plant Extracts/pharmacology/*therapeutic use MH - Receptor, trkB/metabolism MH - Scopolamine MH - Sulfonic Acids/chemistry MH - Superoxide Dismutase/metabolism MH - Tablets PMC - PMC6398023 EDAT- 2019/03/27 06:00 MHDA- 2019/04/16 06:00 PMCR- 2019/02/18 CRDT- 2019/03/27 06:00 PHST- 2018/09/10 00:00 [received] PHST- 2018/11/05 00:00 [revised] PHST- 2018/11/22 00:00 [accepted] PHST- 2019/03/27 06:00 [entrez] PHST- 2019/03/27 06:00 [pubmed] PHST- 2019/04/16 06:00 [medline] PHST- 2019/02/18 00:00 [pmc-release] AID - 10.1155/2019/8636835 [doi] PST - epublish SO - Oxid Med Cell Longev. 2019 Feb 18;2019:8636835. doi: 10.1155/2019/8636835. eCollection 2019.