Senile dementia of Alzheimer type and multi-infarct dementia are considered to be major problems of contemporary societies. Recently, Kami-kihi-to, Ninjin-yoei-to and Kamiuntan-to, which are traditional Japanese herbal medicines (Kampo medicines) have been reported to improve memory disturbance and the related behaviors.1-4) Because these Kampo Medicines contain Polygalae Radix (Onji in Japanese), the root of Polygala tenuifolia WILLDENOW as a common herb, it is suggested that the constituent herb may possess the activity to improve memory disturbance. Polygalae Radix itself has been utilized empirically in Chinese medicine, works to relieve amnesia, neurasthenia, palpitations, nocturnal emission, and insomnia. 5) Recently, evidence of the memoryenhancing effects of Polygalae Radix has been accumulated by several in vivo and in vitro studies; it was reported that a water extract of Polygalae Radix improved scopolamine-induced memory impairment in mice, 6) and that DX-9368 belong to the group of Polygalae Radix agents ameliorated ethanol-and scopolamine-induced memory impairment in mice.7) Yabe et al. 8) reported that the water extract up-regulated choline acetyltransferase (ChAT) activity and increased nerve growth factor (NGF) secretion in vitro. However, the pharmacological effects of the ingredients in Polygalae Radix have been little investigated. In these background, more recently, we demonstrated that tenuifoliside B [6Ј-(phydroxybenzoyl)-3-sinapoylsucrose] and 3,6Ј-disinapoylsucrose among the components isolated from Polygalae Radix inhibited potassium cyanide (KCN)-induced hypoxia and scopolamine-induced memory impairment.9) From these results, we suggested that the two ingredients were instrumental in the cerebral protective and cognition-improving effects of Polygalae Radix. More interestingly, both ingredients have a common sinapoyl moiety in their chemical structures. These suggest that sinapic acid might be not only a main active structure in the pharmacological effects of tenuifoliside B and 3,6Ј-disinapoylsucrose but also a candidate for cerebral protective and cognition-improving medicine.In the present study, in order to ascertain the hypothesis, we examined whether sinapic acid possesses cerebral protective and cognition-improving effects in various animal models of hypoxia and amnesia. MATERIALS AND METHODS Drug and ReagentsSodium sinapate (Fig. 1), which is the water-soluble form of sinapic acid, was used in the following experiments. Sodium sinapate (4.92 g) was obtained by lyophilizing a solution of sinapic acid (4.48 g) purchased from Wako Pure Chemical Industries Ltd. (Osaka, Japan) in 200 ml of 0.1 M sodium hydroxide. Ethylhomocholine iodide (EHC), an internal standard for determination of acetylcholine (ACh), was synthesized from 3-dimethylamino-1-propanol and iodoethane purchased from Sigma-Aldrich Fine Chemicals Japan Co., Ltd. (Tokyo, Japan). Other reagents used for analysis were the highest purity commercially available.Animals Male ICR mice (7 weeks old) to evaluate KCN-induced c...

Neurotrophins play an important role in the control of the hair growth cycle. Therefore, neurotrophin receptor antagonists have therapeutic potential for the treatment of hair growth disorders. In this study, we investigated the inhibitory effect of Panax ginseng, a medicinal plant commonly used to treat alopecia, on the binding of neurotrophins to their receptors. In addition, we isolated and characterized the bioactive compounds of P. ginseng extracts. P. ginseng hexane extracts strongly inhibited brain-derived neurotrophic factor (BDNF)-TrkB and β-nerve growth factor (β-NGF)-p75 neurotrophin receptor (p75NTR) binding. Furthermore, we identified the following 6 polyacetylene compounds as the bioactive components in P. ginseng hexane extract: panaxynol (1), panaxydol (2), panaxydol chlorohydrin (3), 1,8-heptadecadiene-4,6-diyne-3,10-diol (4), panaxytriol (5), and dihydropanaxacol (6). In particular, compounds 4, 5, and 6 significantly inhibited BDNF-TrkB binding in a dose-dependent manner. To identify the structural component mediating the inhibitory effect, we investigated the effects of the hydroxyl moiety in these compounds. We found that the inhibitory effect of panaxytriol (5) was strong, whereas the inhibitory effect of Ac-panaxytriol (7) was relatively weak. Our findings suggest that P. ginseng-derived polyacetylenes with a hydroxyl moiety might provide therapeutic benefits to patients with hair growth disorders such as alopecia by inhibiting the binding of neurotrophins to their receptors. Although saponins have been proposed to be the primary mediators of the effects of P. ginseng on hair growth, this study revealed that polyacetylene compounds exert similar effects.