Identification of Two Phenanthrene Derivatives from Australasian Allied Species in Genus Dendrobium.

Genus Dendrobium (Orchidaceae) contains numerous species. Phylogenetic analyses based on morphological characteristics and DNA sequences indicated that this genus is divided into two major groups: Asian and Australasian clades. On the other hand, little is known about the phytochemical differences and similarities among the species in each clade. In this study, we selected 18 Dendrobium species (11 from the Asian clade and 7 from the Australasian clade) and constructed HPLC profiles, arrays composed of relative intensity of the chromatographic peaks. Next, orthogonal partial least square discriminant analysis (OPLS-DA) was applied to the profile matrix to classify Dendrobium species into the Asian and Australasian clades in order to identify the peaks that significantly contribute to the class separation. In the end, two phenanthrenes, 4,9-dimethoxyphenanthrene-2,5-diol 1 and 1,5-dimethoxyphenanthrene-2,7-diol 2, which contributed to the class separation, were isolated from the HPLC peaks. The existence of 2 was limited to the genetically related Australasian species.

Virtual screening system for finding structurally diverse hits by active learning.

Two virtual screening strategies, "query by bagging" (QBag) and "query by bagging with descriptor-sampling" (QBagDS), based on active learning were devised. The QBag strategy generates multiple structure-activity relationship rules by bagging and selects compounds to improve the rules. To find many structurally diverse hits, the QBagDS strategy generates rules by bagging with descriptor sampling. They can also use prior knowledge about hits to improve the efficiency at the beginning of screening. We performed simulation experiments and clustering analysis for several G-protein coupled receptors and showed that the QBag and QBagDS strategies outperform the conventional similarity-based strategy and that using both descriptor sampling and prior knowledge are effective for finding many hits. We applied the bagging with descriptor sampling strategy to novel hit finding, and 4 of the 10 selected compounds showed high inhibition.

Roxithromycin promotes lymphocyte apoptosis in Dermatophagoides-sensitive asthma patients.

A new macrolide, roxithromycin, may be an effective treatment for asthma. Lymphocyte apoptosis is impaired in patients with asthma, while spontaneous apoptosis increases during remission, and such changes may be involved in the onset and remission of mite-sensitive asthma. Lymphocyte apoptosis was evaluated by incubating cells from patients with asthma in the presence of roxithromycin. Low concentrations of roxithromycin (1-500 ng/ml) augmented the early, but not late, phase of apoptosis in Dermatophagoides farinae-stimulated peripheral blood mononuclear (PBM) cells, while high concentrations of roxithromycin (1 microg/ml; 6 microg/ml is the maximum serum level) augmented both the early and late phases of apoptosis. In both unstimulated and phytohemagglutinin-stimulated cells, roxithromycin did not significantly affect the induction of apoptosis. In cells from normal subjects, roxithromycin did not affect the induction of apoptosis. Other antibiotics, including cefazolin and ampicillin, did not cause significant induction of apoptosis. Fas ligand, but not Fas receptor, expression on D. farinae-stimulated cells was up-regulated after stimulation with 1 microg/ml roxithromycin, while Bcl-2 expression on both unstimulated and D. farinae-stimulated cells showed a decrease after the same treatment. Roxithromycin can induce apoptosis of D. farinae-activated lymphocytes in patients with D. farinae-sensitive asthma. Induction of the Fas/Fas ligand system and reduced Bcl-2 expression were involved in the promotion of apoptosis by roxithromycin treatment.