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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-...

Kaempferia parviflora Wall. Ex Baker (KP) has been used as a folk medicine in Laos and Thailand to lower blood glucose levels, improve blood flow, and increase vitality. This study investigated the preventive effects of KP on obesity and its downstream symptoms (various metabolic disorders) using Tsumura, Suzuki, Obese Diabetes (TSOD) mice, a multifactorial genetic disease animal model in which metabolic diseases develop spontaneously, similar to metabolic syndrome in humans, and Tsumura, Suzuki, Non-Obesity (TSNO) mice as the corresponding control mice. When feed that was mixed with KP (1 or 3%) was given ad libitum to TSOD and TSNO mice for 8 weeks, body weight increase, visceral fat accumulation, lipid metabolism abnormalities, hyperinsulinemia, glucose intolerance, insulin resistance, hypertension, and peripheral neuropathy were suppressed in TSOD mice, but no marked differences were observed in TSNO mice. Because KP had preventive effects on metabolic diseases, including antiobesity effects, only in obese animals, we propose that KP will be extremely valuable as a medicine or component of food in alternative health care.

The antihepatotoxic effects of twenty-three lignans, twentytwo from the fruits of Schizandra chinensis and one from the fruits of Kadsura japonica, were investigated utilizing carbon tetrachloride (Cd4)-and galactosamine (Ga1N)-induced cytotoxicity in primary cultured rat hepatocytes as model systems. Prominent protective actions were found with wuweizisu C and schisantherin D in CC14-treated cultures, and deoxygomisin A, gomisin N, wuweizisu C, gomisin C and schisantherin D were effective in preventing GaIN-induced cell damage. Structure-activity relationship suggests that the methylenedioxy group of the dibenzocyclooctane skeleton may play an important role in antihepatotoxic activity.

Gomisin A, isolated from the fruits of Schisandra chinensis, is one of the dibenzocyclooctadiene lignans. Application of 12-O-tetradecanoylphorbol-13-acetate (TPA, 1 μg/ear), a tumor-promoting agent, to the ears of mice induces inflammation. Among seven dibenzocyclooctadiene lignans assayed, gomisin A, gomisin J, and wuweizisu C inhibited the inflammatory activity induced by TPA in mice. The ED₅₀ of these compounds for TPA-induced inflammation was 1.4–4.4 μmol. Gomisin A, with an ED₅₀ of 1.4 μmol, showed the strongest inhibitory effect. Furthermore, at 5 μmol/mouse, it markedly suppressed the promotion effect of TPA (2.5 μg/mouse) on skin tumor formation in mice following initiation with 7,12-dimethylbenz[a]anthracene (50 μg/ mouse). It is assumed that the inhibition of tumor promotion by gomisin A is due to its anti-inflammatory activity.

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Accumulating data indicate the existence of natural antisense transcripts (asRNAs), frequently transcribed from eukaryotic genes and do not encode proteins in many cases. However, their importance has been overlooked due to their heterogeneity, low expression level, and unknown function. Genes induced in responses to various stimuli are transcriptionally regulated by the activation of a gene promoter and post-transcriptionally regulated by controlling mRNA stability and translatability. A low-copy-number asRNA may post-transcriptionally regulate gene expression with cis-controlling elements on the mRNA. The asRNA itself may act as regulatory RNA in concert with trans-acting factors, including various RNA-binding proteins that bind to cis-controlling elements, microRNAs, and drugs. A novel mechanism that regulates mRNA stability includes the interaction of asRNA with mRNA by hybridization to loops in secondary structures. Furthermore, recent studies have shown that the functional network of mRNAs, asRNAs, and microRNAs finely tunes the levels of mRNA expression. The post-transcriptional mechanisms via these RNA-RNA interactions may play pivotal roles to regulate inducible gene expression and present the possibility of the involvement of asRNAs in various diseases.