Hisae Oku

Participation of nitric oxide in mouse anaphylactic hypotension

Mouse hen egg-white lysozyme-specific anaphylaxis was estimated by monitoring changes in blood pressure by using a tail-cuff method. Stimulation of histamine H1 receptors of the vascular endothelium was suggested to be critical for mouse anaphylactic hypotension, because pretreatment with diphenhydramine but not with cimetidine completely inhibited the hypotension. Nitric oxide (NO) was indicated to play an important role in mouse anaphylaxis, because NG-nitro-L-arginine methyl ester, a NO synthase inhibitor, significantly blocked the hypotension while a large amount of L-arginine, a precursor of NO synthesis, restored the hypotension.

Antipruritic effect of flavonol and 1,4‐naphthoquinone derivatives from Impatiens balsamina L.

To investigate the effect of antipruritic agents, we developed an animal model to allow quantitative estimation of itching. Dextran T40 and compound 48/80, agents which cause histamine release, significantly induced scratching behaviour in mice. A 35% ethanol extract (IB) of white petals of Impatiens balsamina L. significantly inhibited the scratching behaviour in this model. Kaempferol, quercetin and 1,4‐naphthoquinone derivatives in IB were demonstrated to show antipruritic effects.

Garcinone B reduces prostaglandin E2 release and NF-κB-mediated transcription in C6 rat glioma cells

In the course of our survey of natural compounds inhibiting prostaglandin E2 release and/or lipopolysaccharide (LPS)-induced transcriptional stimulation via NF-kappaB, a central regulator of inflammatory genes, from natural resources, we found garcinone B, a xanthone from callus tissue culture of Hypericum patulum, as a compound with such pharmacological activities, that is a derivative of gamma-mangostin which potently inhibits COX-1 and COX-2 activities to reduce PGE2 release from C6 rat glioma cells, and inhibits IKK activity to prevent NF-kappaB-dependent COX-2 gene transcription. Garcinone B, to a lesser extent, reduced A23187-induced increase in prostaglandin E2 release than gamma-mangostin and its structurally related compound, patulone, in C6 cells. This compound also prevented LPS-induced stimulation of NF-kappaB-dependent transcription. These results suggest that garcinone B becomes a unique pharmacological tool to investigate intracellular signaling pathways involved in inflammation.

Testosterone 5α‐reductase inhibitor bisnaphthoquinone derivative fromImpatiens balsamina

The 35% EtOH extract of aerial parts of Impatiens balsamina L. has been investigated for activity against testosterone 5α‐reductase. Activity‐guided fractionation led to the identification of the bisnaphthquione derivative named impatienol (1), 3‐hydroxy‐2‐{[3‐hydroxy‐1,4‐dioxo (2‐naphthyl)] ethyl} naphthalene‐1,4‐dione, which exhibited significant testosterone 5α‐reductase inhibitory activity. This 5α‐reductase inhibitory compound has been previously synthesized, but this is the first report of its isolation from a natural source. Copyright

Screening method for PAF antagonist substances: on the phenolic compounds from Impatients balsamina L.

A blood pressure monitoring system was developed for studying antagonist effects against platelet activating factor (PAF), a chemical mediator of anaphylactic hypotension. Using this system, we were able to determine the inhibitory effects of a 35% ethanol extract (IB) from the petals of Impatiens balsamina L. against PAF‐induced hypotension and the active principal compounds from IB. One mechanism of the antianaphylactic effects of IB was characterized as PAF‐antagonist effects. Copyright

Uptake of AMP, ADP, and ATP in Escherichia coli W

The uptake activity ratio for AMP, ADP, and ATP in mutant (T-1) cells of Escherichia coli W, deficient in de novo purine biosynthesis at a point between IMP and 5-aminoimidazole-4-carboxiamide-1-β-D-ribofuranoside (AICAR), was 1:0.43:0.19. This ratio was approximately equal to the 5′-nucleotidase activity ratio in E. coli W cells. The order of inhibitory effect on [2-3H]ADP uptake by T-1 cells was adenine > adenosine > AMP > ATP. About 2-fold more radioactive purine bases than purine nucleosides were detected in the cytoplasm after 5 min in an experiment with [8-14C]AMP and T-1 cells. Uptake of [2-3H]adenosine in T-1 cells was inhibited by inosine, but not in mutant (Ad-3) cells of E. coli W, which lacked adenosine deaminase and adenylosuccinate lyase. These experiments suggest that AMP, ADP, and ATP are converted mainly to adenine and hypoxanthine via adenosine and inosine before uptake into the cytoplasm by E. coli W cells.

Development of Environmental Control Method for Rapid Production of High Quality Hedyotis diffusa

Abstract The purpose of this research is to develop environmental control methods to realize rapid and high quality production of Hedyotis diffusa. Hedyotis diffusa has been used as herbal medicine and iridoid is a main medicinal property. In order to inspect the effect of light intensity on the concentration of iridoid in Hedyotis diffusa, the 2 experimental treatments were prepared by using a growth chamber; one was high intensity treatment (photon flux density of 170 μmol·s-1·m-2) and the other was low intensity treatment (70 μmol·s-1·m-2). Hydroponic culture was performed for 6 weeks in the growth chamber. The iridoid concentration was measured by a HPLC. As the results of non-parametric significance test for mean difference between high and low intensity treatment, significant differences were shown in the relative value of iridoid concentration. It was found that the high intensity condition could improve the quality and quantity of Hedyotis diffusa.

Hypericum patulum: In Vitro Culture and Production of Xanthones and Other Secondary Metabolites

Plants of the genus Hypericum (Guttiferae) have been used as traditional medicines in various parts of the world, i.e. South Africa (Madeira, Rocha et al. 1995a), Russia (Taylor et al. 1996a). Europe (Dingermann 1995; Ernst 1995; Cott 1995; Anonymous 1996), Nepal (Taylor et al. 1996b), China (Wu et al. 1996), and Japan (Minami et al. 1996). Recently, there have been reports of the following actions in this species: antifungal (Rocha et al. 1994), antibiotic (Rocha et al. 1995b), antiviral (Diwu 1995), antidepressive (Hansgen et al. 1994; Payk 1994; Ernst 1995; Kerb et al. 1996), antiinflammatory (Recio et al. 1995), anticancer (Diwu 1995) and monoamine oxidase inhibitor (Bladt and Wagner 1994; Thiede and Walper 1994). What has been noted is the significant variation in the secondary metabolites (hypericine, flavonoids, procyanidins and tannins) in Hypericum species depending on the plant origin.

DEVELOPMENT OF AN IN VIVO BIOASSAY METHOD FOR PRIMARY PREVENTIVE SUBSTANCES OF THE METABOLIC SYNDROME – EFFECT OF KINGINKA-CHA

1 We discovered a phenomenon in which the blood flow of vein microcirculation markedly decreased in the pathology of metabolic syndrome using a model of SHR/NDmcr‐cp/cp (SHR/cp) rats. We tried to develop an in vivo assay method to search for substances for primary prevention of the metabolic syndrome using this blood flow decrease as a guide. 2 Using the assay method, we examined various teas that were expected to prevent the metabolic syndrome when consumed daily. We also found that Kinginka‐cha (the buds of Lonicera japonica) utilized as a folk tea for the improvement of blood flow could be used to prevent metabolic syndrome. HPLC analysis showed that Kinginka‐cha contained few catechins, which are known to be the major active components in black and green teas, thus suggesting the presence of other active compounds. Chlorogenic acid, luteolin, luteolin 7‐glucoside, loganin, sweroside and secoxyloganin were isolated from Kinginka‐cha.

Allergy-preventive effects of linarinic acid and its tetrahydropyrrolo[2,1-b]quinazoline derivatives isolated from Linaria vulgaris

Linarinic acid, (−)-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxylic acid (4a), was isolated from the ethanol extract of Linaria vulgaris Mill. In our previous study, a series of tetrahydropyrrolo[2,1-b]quinazoline derivatives 4b, 4c, 5a, 5b, 6a and 6b that were structurally related to 4a and evaluated as neuroprotective agents were synthesized. The aim of the present study was to investigate the novel features of these compounds. We examined their allergy-preventive effects using an in vivo assay system we developed previously, that monitors a decrease in blood flow in the tail vein of mice subjected to sensitization with hen egg-white lysozyme. We observed that 4a and its three derivatives, amide (6a), ester (5a), bromine (4b), and alcohol substituent (6b), showed significant allergy-preventive activities. The study confirmed the allergy-preventive activity of tetrahydropyrrolo[2,1-b]quinazoline derivatives by comprehensively monitoring the specific blood flow decrease occurring in the induction phase of allergy. This finding may aid in the development of new agents for the treatment of allergic diseases such as atopic dermatitis, allergic asthma, and hay fever.