Polygalasaponin XXXII from Polygala tenuifolia root improves hippocampal-dependent learning and memory.
OBJECTIVE
The aim of this study was to investigate the cognition-enhancing activity and underlying mechanisms of a triterpenoid saponin (polygalasaponin XXXII, PGS32) isolated from the roots of Polygala tenuifolia Willd.


METHODS
The Morris water maze was used to evaluate the spatial learning and memory of mice. To detect the basic properties of synaptic transmission and long-term potentiation (LTP) in the dentate gyrus of rats, electrophysiological recordings were made of evoked potentials. Western blotting analysis and immunofluorescence assays were used to determine the phosphorylation of extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), synapsin I and the expression of brain derived neurotrophic factor (BDNF).


RESULTS
When administered at 0.125, 0.5, or 2 mg/kg, PGS32 could significantly prevent scopolamine-induced cognitive impairments in mice. Intracerebroventricular (icv) administration of PGS32 greatly enhanced basic synaptic transmission in the dentate gyrus of rats and induced LTP. In primary hippocampal neurons, as well as in the hippocampus of maze-trained mice, PGS32 activated the mitogen-activated protein (MAP) kinase cascade by promoting phosphorylation of ERK, CREB and synapsin I. The expression of BDNF was also greatly enhanced in the hippocampus.


CONCLUSIONS
Our findings suggest that PGS32 can improve hippocampus-dependent learning and memory, possibly through improvement of synaptic transmission, activation of the MAP kinase cascade and enhancement of the level of BDNF. Therefore, PGS32 shows promise as a potential cognition-enhancing therapeutic drug.
Xue
Wei
W
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Hu
Jin-feng
JF
Yuan
Yu-he
YH
Sun
Jian-dong
JD
Li
Bo-yu
BY
Zhang
Dong-ming
DM
Li
Chuang-jun
CJ
Chen
Nai-hong
NH
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D018891:Dentate Gyrus / Q000187:drug effects; D005071:Evoked Potentials / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018697:Nootropic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D031801:Polygala / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D016704:Synapsins / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*
D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D018697:Nootropic Agents; D012503:Saponins; D016704:Synapsins; D014315:Triterpenes; C544870:polygalasaponin XXXII; D048049:Extracellular Signal-Regulated MAP Kinases
Neuron. 2005 Sep 15;47(6):873-84
16157281
Nat Rev Drug Discov. 2003 Apr;2(4):267-77
12669026
Nature. 1993 Jan 7;361(6407):31-9
8421494
Biol Pharm Bull. 2004 Jul;27(7):1081-5
15256744
Acta Pharmacol Sin. 2006 Jan;27(1):1-26
16364207
Learn Mem. 1999 Sep-Oct;6(5):478-90
10541468
J Physiol. 1973 Jul;232(2):357-74
4727085
J Physiol. 1973 Jul;232(2):331-56
4727084
Neuron. 1996 Jan;16(1):5-8
8562090
Chem Pharm Bull (Tokyo). 1996 Apr;44(4):810-5
8681413
Pharmacogenomics J. 2006 Jan-Feb;6(1):8-15
16314887
J Neurosci Res. 2002 Nov 1;70(3):484-92
12391609
Endocr Rev. 2001 Apr;22(2):153-83
11294822
Biol Pharm Bull. 2005 Oct;28(10):1886-91
16204940
Planta Med. 2008 Feb;74(2):133-41
18256974
Acta Pharmacol Sin. 2001 Dec;22(12):1099-102
11749807
Evid Based Complement Alternat Med. 2006 Mar;3(1):79-85
16550227
Exp Brain Res. 1992;88(1):78-90
1541364
Brain Res Rev. 2008 Nov;59(1):201-20
18708092
J Neurosci. 1999 May 1;19(9):3535-44
10212313
Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3679-83
8622996
J Neurochem. 2001 Jan;76(1):1-10
11145972
Neuron. 2006 Jun 1;50(5):765-79
16731514
Nature. 2001 Mar 1;410(6824):37-40
11242034
Cell. 2004 Feb 6;116(3):467-79
15016380
Zhongguo Yao Li Xue Bao. 1999 Feb;20(2):112-6
10437155
Biol Pharm Bull. 2007 Sep;30(9):1727-31
17827729
Neuron. 1998 Apr;20(4):709-26
9581763
Ageing Res Rev. 2004 Nov;3(4):407-30
15541709
Annu Rev Neurosci. 2000;23:649-711
10845078
Behav Brain Res. 1995 Jan 23;66(1-2):37-40
7755896
Eur Neuropsychopharmacol. 2005 May;15(3):331-46
15820423
Learn Mem. 2002 Sep-Oct;9(5):224-37
12359832
Biol Pharm Bull. 2006 Sep;29(9):1892-6
16946504
J Neurosci. 1993 Sep;13(9):3818-26
8366347