Polygalasaponin XXXII, a triterpenoid saponin from Polygalae Radix, attenuates scopolamine-induced cognitive impairments in mice

  • Acta Pharmacol Sin. 2016 Aug;37(8):1045-53. doi: 10.1038/aps.2016.17.
Heng Zhou  1 ,  Wei Xue  2 ,  Shi-Feng Chu  1  3 ,  Zhen-Zhen Wang  1 ,  Chuang-Jun Li  1 ,  Yi-Na Jiang  3 ,  Lin-Ming Luo  3 ,  Piao Luo  3 ,  Gang Li  4 ,  Dong-Ming Zhang  1 ,  Nai-Hong Chen  1  3
Affiliations
  • 1. 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.
  • 2. Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Pharmacy, Beijing Hospital, Beijing 100730, China.
  • 3. Hu-nan University of Chinese Medicine, Changsha 410208, China.
  • 4. Department of Pharmacology, College of Pharmacy, The Inner Mongolian Medical University, Jinshan Development Zone, Hohhot 010110, China.
PMID: 27180981 DOI: 10.1038/aps.2016.17
Abstract

Aim: 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.

Conclusion: PGS32 attenuates scopolamine-induced cognitive impairments in mice, suggesting that it has a potential for the treatment of cognitive dysfunction and dementia.

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