title: Polygalasaponin XXXII, a triterpenoid saponin from Polygalae Radix, attenuates scopolamine-induced cognitive impairments in mice.
abstract: OBJECTIVE
  Recent studies show that the extract of a Chinese herb Polygalae Radix exerts cognition-enhancing actions in rats and humans. The aim of this study was to characterize the pharmacological profiles of active compounds extracted from Polygalae Radix.
  
  
  METHODS
  Two fractions P3 and P6 and two compounds PTM-15 and polygalasaponin XXXII (PGS32) were prepared. Neuroprotective effects were evaluated in primary cortical neurons exposed to high concentration glutamate, serum deficiency or H2O2. Anti-dementia actions were assessed in scopolamine-induced amnesia in mice using step-through avoidance tests and channel water maze tests. After conducting the channel water maze tests, TrkB phosphorylation in mouse hippocampus was detected using Western blotting. Long-term potentiation (LTP) was induced in the dentate gyrus in adult rats; PGS32 (5 μL 400 μmol/L) was injected into the lateral cerebral ventricle 20 min after high frequency stimulation (HFS).
  
  
  RESULTS
  Compared to the fraction P6, the fraction P3 showed more prominent neuroprotective effects in vitro and cognition-enhancing effects in scopolamine-induced amnesia in mice. One active compound PGS32 in the fraction P3 exerted potent cognition-enhancing action: oral administration of PGS32 (0.125 mg·kg(-1)·d(-1)) for 19 days abolished scopolamine-induced memory impairment in mice. Furthermore, PGS32 (0.5 and 2 mg·kg(-1)·d(-1)) significantly stimulated the phosphorylation of TrkB in the hippocampus. Intracerebroventricular injection of PGS32 significantly enhanced HFS-induced LTP in the dentate gyrus of rats.
  
  
  CONCLUSIONS
  PGS32 attenuates scopolamine-induced cognitive impairments in mice, suggesting that it has a potential for the treatment of cognitive dysfunction and dementia.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Pharmacy, Beijing Hospital, Beijing 100730, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xue
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.|Hu-nan University of Chinese Medicine, Changsha 410208, China.
authors.forename: Shi-Feng
authors.initials: SF
authors.lastname: Chu
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Zhen-Zhen
authors.initials: ZZ
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Chuang-Jun
authors.initials: CJ
authors.lastname: Li
authors.affiliation: Hu-nan University of Chinese Medicine, Changsha 410208, China.
authors.forename: Yi-Na
authors.initials: YN
authors.lastname: Jiang
authors.affiliation: Hu-nan University of Chinese Medicine, Changsha 410208, China.
authors.forename: Lin-Ming
authors.initials: LM
authors.lastname: Luo
authors.affiliation: Hu-nan University of Chinese Medicine, Changsha 410208, China.
authors.forename: Piao
authors.initials: P
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, College of Pharmacy, The Inner Mongolian Medical University, Jinshan Development Zone, Hohhot 010110, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Dong-Ming
authors.initials: DM
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.|Hu-nan University of Chinese Medicine, Changsha 410208, China.
authors.forename: Nai-Hong
authors.initials: NH
authors.lastname: Chen
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects; D060825:Cognitive Dysfunction / Q000139:chemically induced* / Q000188:drug therapy*; D018891:Dentate Gyrus / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D031801:Polygala / Q000737:chemistry*; D061251:Primary Cell Culture; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D012601:Scopolamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D012503:Saponins; D014315:Triterpenes; C544870:polygalasaponin XXXII; D018698:Glutamic Acid; D006861:Hydrogen Peroxide; D012601:Scopolamine; D011505:Protein-Tyrosine Kinases