The therapeutic agents for dementia are limited due to the complex system underlying the mechanisms. Taking a preventive point of view, we focused on the inhibition of β-secretase and acetylcholinesterase (AChE). In addition, plant resources including herbs and spices have been widely consumed, and further, may be consumed for a long period over a lifetime. Considering this background, we screened β-secretase and AChE inhibitors from curry spices. Amongst them, curry leaf, black pepper, and turmeric extracts were effective to inhibit β-secretase. Furthermore, black pepper and turmeric extracts were also effective to inhibit AChE. Having these results in hand, we focused on the investigation of β-secretase inhibitors since the inhibitor of this enzyme has not previously been well investigated. As a result, α- and β-caryophyllene, β-caryophyllene oxide (from curry leaf), piperine (from black pepper), curcumin, demethoxycurcumin, and bisdemethoxycurcumin (from turmeric) were successfully identified as low molecular inhibitors. This is the first report to determine α- and β-caryophyllene, β-caryophyllene oxide, and piperine as β-secretase inhibitors. These compounds may pass through the blood brain barrier since their molecular weights are relatively low.

The growing number of Alzheimer's disease (AD) patients prompted us to seek effective natural resources for the prevention of AD. We focused on the inhibition of β-secretase, which is known to catalyze the production of senile plaque. Sixteen spices used in Asian countries were selected for the screening. Among the extracts tested, hexane extracts obtained from turmeric, cardamom, long pepper, cinnamon, Sichuan pepper, betel, white turmeric and aromatic ginger showed potent inhibitory activities. Their active principles were identified as sesquiterpenoids, monoterpenoids, fatty acid derivatives and phenylpropanoids using GC-MS analyses. The chemical structures and IC 50 values of the compounds are disclosed. The results suggest that long-term consumption of aromatic compounds from spices could be effective in the prevention of AD.

Kaempferia parviflora (KP), a Zingiberaceae plant, is used as a folk medicine in Thailand for the treatment of various symptoms, including general pains, colic gastrointestinal disorders, and male impotence. In this study, the inhibitory activities of KP against xanthine oxidase (XOD) were investigated. The extract of KP rhizomes showed more potent inhibitory activity (38% at 500 m mg/ml) than those of the other Zingiberaceae plants tested. Ten methoxyflavones were isolated from the KP extract as the major chemical components and their chemical structures were elucidated by X-ray crystallography. The structurally confirmed methoxyflavones were subjected to the XOD inhibitory test. Among them, 3,5,7,4,5-pentamethoxyflavone and 3,4,5,7-tetramethoxyflavone showed inhibitory activities (IC 50 of 0.9 and Ͼ4 mM, respectively) and their modes of inhibition are clarified as competitive/non-competitive mixed type. To the best of our knowledge, this is the first report to present the inhibitory activities of KP, 3,5,7,4,5-pentamethoxyflavone and 3,4,5,7-tetramethoxyflavone against XOD.

The purpose of this paper is to establish injectivity theorems for higher direct image sheaves of canonical bundles twisted by pseudo-effective line bundles and multiplier ideal sheaves. As applications, we generalize Kollár's torsion freeness and Grauert-Riemenschneider's vanishing theorem. Moreover, we obtain a relative vanishing theorem of Kawamata-Viehweg-Nadel type and an extension theorem for holomorphic sections from fibers of morphisms to the ambient space. Our approach is based on transcendental methods and works for Kähler morphisms and singular hermitian metrics with non-algebraic singularities.

In this note, we prove that for a strictly nef divisor L on a K-trivial fourfold X, L is ample if and only if κ(L) ≥ 0, that is, L is Q-effective. In the case ν(L) = 2, we show that L is Q-effective, thus ample. In the case ν(L) = 2, we show that for any metric h on O X (L) with semipositive curvature current, we must have dim V m = 2 for m ≫ 0, where V m is the closed subscheme defined by the multiplier ideal I(h ⊗m ).