Cognitive Improving and Cerebral Protective Effects of Acylated Oligosaccharides in Polygala tenuifolia

Abstract

Senile dementia of the Alzheimer type and multi-infarct dementia are considered to be major problems of contemporary societies. In traditional Chinese medicine, Polygalae Radix (Japanese name: Onji), the root of Polygala tenuifolia WILLDENOW (Polygalaceae), is prescribed for amnesia, neurasthenia, palpitation, noctural emission and insomnia. 1) According to the Chinese Materia Medica, the root is guessed to have a special effect upon the will and mental powers, improving understanding and strengthening the memory.There have been numerous studies regarding the reputed memory-enhancing potential of the roots of P. tenuifolia. DX-9368, which is composed of four herbs (Panax ginseng, P. tenuifolia, Acorus gramineus and Poria cocos), ameliorated the ethanol-and scopolamine-induced memory impairment in mice.2) It is reported by Yabe et al. that the water extract of this plant up-regulates choline acetyltransferase (ChAT) activity and increases NGF secretion in vitro.3) Recently, Egashira et al. reported that the water extract improved the scopolamine-induced impairment of passive avoidance response and enhanced oxotremorine-induced tremors in mice.4) There are few reports, however, on the active constituents involved in the reputed memory-enhancing potential of the roots of P. tenuifolia, and we therefore studied these cognitive improving constituents. In this paper, we report that tenuifoliside B (1) 5) showed a cerebral protective effect on potassium cyanide (KCN)-induced anoxia and an ameliorative effect on the scopolamine-induced impairment of passive avoidance response in rats.It is well known that a decrease in oxygen supply to the brain (hypoxia) depresses cerebral function in experimental animals and humans 6,7) and that memory and learning are impaired by hypoxia in animals and humans. 8,9) The KCN anoxia model is widely used in preclinical evaluations of drugs for the treatment of cerebrovascular disorders. 6,10,11) Therefore, we used this model in addition to the scopolamine-induced impairment of passive avoidance performance as screening method. MATERIALS AND METHODSExtraction and Fractionation of P. tenuifolia As shown in Fig 1, the dried roots (9.4 kg) of P. tenuifolia from Shanxi Province in China (purchased from Yamamoto Yakuhin Kogyo Co., Ltd., Tokyo) were pulverized and extracted twice with boiling MeOH (50 l) for 2 h. The concentrated MeOH extract (PM) (2.21 kg) was dissolved in H 2 O and successively extracted with ether and n-BuOH. These layers were concentrated to give an ethereal soluble fraction (PE, xanthone-containing fraction) (398 g), an n-BuOH soluble fraction (902 g), and a water soluble fraction (PW) (609 g), respectively. The n-BuOH soluble fraction was chromatographed on silica gel [Kieselgel 60, 230-400 mesh (Merck)] (5 kg) with EtOAc-MeOH (4 : 1) and then with MeOH. Concentration of elutions with EtOAc-MeOH (4 : 1) and MeOH afforded the acylated oligosaccharide-containing fraction (PA) (468 g) and saponin-containing fraction (PS) Research Division, Tsumura & Co.; 3586 Yoshiwara Ami-...

Cognitive-enhancing effects of hydrolysate of polygalasaponin in SAMP8 mice

“…Recent pharmacological studies have shown that P. tenuifolia could improve memory impairment caused by scopolamine, stress, glutamate, and Aβ, and promote neuronal proliferation in normal brains (Chung et al, 2002;Lin et al, 2012;Li et al, 2014). Polygalasaponins, such as polygalasaponin B, F, G, and XXXII, are the main components responsible for the action of P. tenuifolia and have been shown to improve cognitive impairment in AD effectively (Ikeya et al, 2004;Xu et al, 2009;Wu et al, 2014). However, reports have shown that polygalasaponins could be toxic to animals, leading to nose bleeding, gastrointestinal tract abnormality, and even death (Xue et al, 2009;Lin et al, 2012), which seriously limits their application and development.…”

Antidepressant effects of the extract YZ-50 fromPolygala tenuifoliain chronic mild stress treated rats and its possible mechanisms

“…(Polygalaceae), and has been used in traditional medicine as an expectorant, tonic, tranquilizer and antipsychotic agent (Chung et al, 1992;Huang, 1993). The dried root of this plant Pharmaceutical Biology, 2010; 48(7): 794-800 contains polygalitol, tenuigenin, polygalasaponin, oligosaccharides (Yukinobu et al, 2004) and xanthone derivatives. Recently our laboratory demonstrated antidepressant actions of the active extracted fraction YZ-50 in animal behavior despair models of mice; however, the mechanisms of its action are still unresolved.…”

Polygalasaponin XXXII from Polygala tenuifolia root improves hippocampal-dependent learning and memory

“…Therefore, extensive searches are being carried out for novel, naturally occurring active compounds that can be used to treat multiple-factor dementia. Numerous medicinal plant species are now being screened for advanced therapeutic drugs that possess both high efficacy and low side effects [1][2][3][4][5] . One such plant, Polygala tenuifolia Willd, is the species of interest in this study.…”

“…More recently, there has been renewed interest in the cognition-enhancing potential of P tenuifolia root extracts. Several studies have shown that P tenuifolia extracts have cognition improving effects in vivo, in addition to protective effects on neurotoxicity that is induced in vitro by factors such as glutamate, beta-amyloid, and the C-terminal fragment of amyloid precursor protein (CT) [2,[4][5][6] . However, the biologically active components from these extracts still require identification, and their in vivo functions and mechanisms must be understood before P tenuifolia root extracts can be developed into therapeutic drugs.…”