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-...