title: Neuroprotective effects of polygalacic acid on scopolamine-induced memory deficits in mice.
abstract: BACKGROUND
  Polygala tenuifolia Willd is a Traditional Chinese Medicine used for the treatment of learning and memory deficits. Triterpenoid saponins, the main bioactive compounds of Polygala tenuifolia Willd, are easily hydrolyzed to polygalacic acid (PA).
  
  
  OBJECTIVE
  The present study was undertaken to investigate the neuroprotective effects of PA on scopolamine-induced cognitive dysfunction and to elucidate its underlying mechanisms of action.
  
  
  METHODS
  PA (3, 6, and 12 mg/kg) was administered orally to mice for fourteen days, and scopolamine (1 mg/kg) was injected intraperitoneally for fourteen days to induce memory impairment. Memory-related behaviors were evaluated using the Morris water maze. Cholinergic and neuroinflammatory activities were measured in brain tissue. Superoxide dismutase activities, malondialdehyde and reduced glutathione contents were also measured in the brains.
  
  
  RESULTS
  Treatment with scopolamine significantly increased the escape latency time, decreased the number of crossings, and shortened the time spent in the target quadrant, while PA reversed these scopolamine-induced effects. PA significantly improved cholinergic system reactivity, as indicated by decreased acetylcholinesterase (AChE) activity, increased choline acetyltransferase (ChAT) activity, and elevated levels of acetylcholine (ACh) in the hippocampus and frontal cortex. PA also significantly ameliorated neuroinflammation and oxidative stress in mice.
  
  
  CONCLUSIONS
  These results suggest that PA might exert a significant neuroprotective effect on cognitive impairment, driven in part by the modulation of cholinergic activity and neuroinflammation.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: crguocpu@126.com.
authors.forename: Changrun
authors.initials: C
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Jinyang
authors.initials: J
authors.lastname: Shen
authors.affiliation: Jiangsu Kanion Pharmaceutical Co. Ltd., Lianyungang 222001, PR China.
authors.forename: Zhaoqing
authors.initials: Z
authors.lastname: Meng
authors.affiliation: Jiangsu Key Laboratory of Research and Development in Marine Bio-resource Pharmaceutics, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: lifeicpu@163.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects*; D007378:Interleukins / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D031801:Polygala / Q000737:chemistry; D011897:Random Allocation; D012503:Saponins / Q000494:pharmacology*; D012601:Scopolamine / Q000009:adverse effects; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D007378:Interleukins; D018696:Neuroprotective Agents; D012503:Saponins; C067722:polygalacic acid; D008315:Malondialdehyde; D009828:Oleanolic Acid; D012601:Scopolamine; D013482:Superoxide Dismutase; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D005978:Glutathione
keywords: Acetylcholine; Memory deficits; Neuroinflammation; Oxidative stress; Polygalacic acid; Scopolamine