Biomedical subjects

E Okuyama

Publications and source records attributed to E Okuyama.

At least 19 recordsLinked to original sources

PubMed2001

Immunomodulatory constituents from an Ascomycete, Eupenicillium crustaceum, and revised absolute structure of macrophorin D.

Fractionation guided by immunomodulatory activity of the EtOAc extract of the Ascomycete Eupenicillium crustaceum has afforded two new naturally occurring products, 4'-oxomacrophorin D (1) and 4'-oxomacrophorin A (2), as the immunosuppressive components of this fungus [1: 3-hydroxy-3-methylglutaryl (HMG) conjugate of 2]. The structures including the absolute configurations of 1 and 2 have been determined on the basis of chemical correlation of 1 with macrophorin D (3). The absolute configuration of the HMG moiety in 3 has been revised from 3R to 3S.

Adjuvants, Immunologic↗

PubMed2001

New multiflorane-type triterpenoid acids from Sandoricum indicum.

Three new 12beta-hydroxymultiflorane triterpenoid acids, sandorinic acids A-C (1-3), were isolated from the stem bark of Sandoricum indicum together with five known triterpenes (4-8). The structures of 1-3 were elucidated by spectral data interpretation. Compounds 1-8 were evaluated for their inhibiting activity against several tumor cell lines and for their effects on lymphocyte proliferation.

Animals↗

PubMed2001

Analgesic components of saposhnikovia root (Saposhnikovia divaricata).

By activity-oriented separation using the writhing method in mice, the analgesic components of Saposhnikovia root (Saposhnikovia divaricata Schischkin; Umbelliferae) were identified to be chromones, coumarins, polyacetylenes and 1-acylglycerols. Two new components, divaricatol and (3'S)-hydroxydeltoin, were also isolated. The most potent analgesia was observed in chromones such as divaricatol, ledebouriellol and hamaudol, which inhibited writhing inhibition at an oral dose of 1 mg/kg in mice. Acylglycerols also showed inhibition significantly at a dose of 5 mg/kg. In some pharmacological tests using sec-O-glucosylhamaudol, the compound showed analgesia by the tail pressure and the Randall & Selitto methods, and its writhing inhibition was not reversed by naloxone.

Analgesics, Non-Narcotic↗

PubMed2000

Immunomodulatory constituents from an ascomycete, Emericella aurantio-brunnea.

Fractionation monitored by the immunomodulatory activity of the AcOEt extract of an Ascomycete, Emericella aurantio-brunnea, afforded two known fungal sesterterpenes, variecolin (1) and variecolactone (2), two new variecolin congeners named variecoacetals A (3) and B (4), and a new sesquiterpenetriol diester named emeremophiline (5), as the immunosuppressive constituents of this fungus. The absolute configuration of 1, which was previously not determined, was determined to be (2S,3S,6R,10S,11R,14S,15R,16S) from the NMR spectral data of the (6R,7R)-dimethyl-1,3,5-trioxacycloheptyl derivative of 1 (7). The absolute configurations of the other variecolin congeners, 2-4, and variecolol (6) are also proposed from biosynthetic considerations.

Adjuvants, Immunologic↗

PubMed2000

Analgesic principle from Abutilon indicum.

Bioactivity guided isolation of Abutilon indicum yielded eugenol [4-allyl-2-methoxyphenol], which was found to possess significant analgesic activity. At doses of 10, 30, and 50 mg/kg body weight, eugenol exhibited 21.30 (p < 0.05), 42.25 (p < 0.01) and 92.96% (p < 0.001) inhibition of acetic acid induced writhing in mice. At a dose of 50 mg/kg body weight, eugenol showed 33.40% (p < 0.05) prolongation of tail flicking time determined by the radiant heat method.

Acetates↗

PubMed1999

Interaction of anisatin with rat brain gamma-aminobutyric acidA receptors: allosteric modulation by competitive antagonists.

Anisatin, a toxic sesquiterpene isolated from the Japanese star anise (Illicium anisatum L.), competitively inhibited the specific binding of [3H]4'-ethynyl-4-n-propylbicycloorthobenzoate ([3H]EBOB), a non-competitive antagonist of gamma-aminobutyric acid (GABA)A receptors, to rat brain membranes with an IC50 value of 0.43 microM. R 5135, a competitive GABA antagonist, decreased the potency of anisatin in inhibiting [3H]EBOB binding in a negatively cooperative manner. Two other competitive antagonists, SR 95531 (gabazine) and (-)-bicuculline methiodide, had similar effects. On the other hand, R 5135 exerted little influence on the potencies of the other non-competitive antagonists tested: EBOB, picrotoxinin, isopropylbicyclophosphate, and dieldrin. Thus, anisatin was clearly different from the other non-competitive antagonists in responding to the action of competitive antagonists on (GABA)A receptors. These findings suggest that the binding region of anisatin might overlap with that of the other non-competitive antagonists, but that anisatin must interact with other specific region(s).

Affinity Labels↗

PubMed1999

Casein kinase II inhibitors isolated from two Brazilian plants Hymenaea parvifolia and Wulffia baccata.

Two dihydroflavonol rhamnosides (1 and 2) isolated from the bark of Hymenaea parvifolia and two pentacyclic triterpenoids (3 and 6) obtained from the leaves of Wulffia baccata have been found to exhibit inhibitory effects of casein kinase II (CK-II) dose-dependently, suggesting that at higher doses more than 10 microM, these four compounds may act as potent CK-II suppressors of the CK-II-mediated activation of 60S acidic ribosomal P proteins in vitro.

Brazil↗

PubMed1999

The molecular structure of 2alpha-hydroxyneoanisatin and structure-activity relationships among convulsant sesquiterpenes of the seco-prezizaane and picrotoxane types.

The molecular structure of 2alpha-hydroxyneoanisatin, a positional isomer of the potent neurotoxin anisatin, was determined by X-ray crystallographic analysis. This compound and four further seco-prezizaane type sesquiterpene lactones previously isolated from Illicium floridanum, which represent different structural types with respect to the mode of cyclisation, did not induce anisatin/picrotoxinin-like convulsions in mice. Based on these results and literature data for other seco-prezizaanes, structural requirements for convulsant activity are discussed. Comparison of the three dimensional molecular shape and electrostatic properties of active and inactive seco-prezizaane type lactones with compounds of the picrotoxane type resulted in the identification of a common pharmacophore structure for these different skeletal classes of convulsant natural products.

Animals↗

PubMed1999

Anisatin modulation of the gamma-aminobutyric acid receptor-channel in rat dorsal root ganglion neurons.

1. Anisatin, a toxic, insecticidally active component of Sikimi plant, is known to act on the GABA system. In order to elucidate the mechanism of anisatin interaction with the GABA system, whole-cell and single-channel patch clamp experiments were performed with rat dorsal root ganglion neurons in primary culture. 2. Repeated co-applications of GABA and anisatin suppressed GABA-induced whole-cell currents with an EC50 of 1.10 microM. No recovery of currents was observed after washout with anisatin-free solution. 3. However, pre-application of anisatin through the bath had no effect on GABA-induced currents. The decay phase of currents was accelerated by anisatin. These results indicate that anisatin suppression of GABA-induced currents requires opening of the channels and is use-dependent. 4. Anisatin suppression of GABA-induced currents was not voltage dependent. 5. Picrotoxinin attenuated anisatin suppression of GABA-induced currents. [3H]-EBOB binding to rat brain membranes was competitively inhibited by anisatin. These data indicated that anisatin bound to the picrotoxinin site. 6. At the single-channel level, anisatin did not alter the open time but prolonged the closed time. The burst duration was reduced and channel openings per burst were decreased indicating that anisatin decreased the probability of openings.

Affinity Labels↗

PubMed1999

Adenosine, the anxiolytic-like principle of the Arillus of Euphoria longana.

According to traditional usage, the extract of Longan Arillus was tested for its anxiolytic-like effect by application of the Vogel-type anti-conflict method in mice. The extract indicated significant activity at a dose of 2 g/kg, s.c., and results of the bioassay-oriented isolation revealed adenosine to be the active principle. Adenosine produced the anti-conflict effect significantly at a dose of 30 mg/kg, s.c. Adenine, uridine, and 5-methyluridine did not exhibit the effect, although these compounds were isolated from the extract. Some other related compounds such as AMP and c-AMP showed no effect, except for inosine. Adenosine also contributed to the analgesic effect which was observed in the extract by the writhing method.

Adenosine↗

PubMed1999

Estimation of chemical structure of notopterol metabolites.

Notopterol, 5[(2E)-5-hydroxy-3,7-dimethyl-2,6-octadienyloxy]psoralen showed an inhibitory effect on aminopyrine N-demethylase activity in liver microsomes. In addition, notopterol has been found to be metabolized by cytochrome P450, and two kinds of metabolites were formed from notopterol. Furthermore, specific cytochrome P450 3A4 inhibitors which were isolated from grapefruit juice had the same furocoumarin structure as notopterol. Two metabolites of notopterol were separated by HPLC, and the chemical structures of the hydroxylated metabolites were estimated by 1H-NMR spectra and liquid chromatography-mass spectrometry.

Animals↗

PubMed1999

Immunomodulatory constituents from an ascomycete, Microascus tardifaciens.

Fractionation guided by the immunosuppressive activity of the defatted AcOEt extract of an Ascomycete, Microascus tardifaciens, afforded eight constituents, questin (emodin 8-O-methylether) (1), rubrocristin (2), 5,7-dihydroxy-4-methylphthalide (3), cladosporin (asperentin) (4), cladosporin 8-O-methylether (5), tradioxopiperazine A [cyclo-L-alanyl-5-isopentenyl-2-(1',1'-dimethylallyl)-L-tryptophan] (6), tradioxopiperazine B [cyclo-L-alanyl-7-isopentenyl-2-(1',1'-dimethylallyl)-L-tryptophan] (7), and asperflavin (8), among which 6 and 7 were new compounds. Compounds 1 and 2 showed considerably high immunosuppressive activity, 6 was moderate and, 3, 4, 5, 7 and 8 showed low activity.

Anthracenes↗

PubMed1999

Monoamine oxidase inhibitory naphthoquinone and/or naphthalene dimers from Lemuni Hitam (Diospyros sp.), a Malaysian herbal medicine.

From the extract of a Malaysian herbal medicine, Lemuni Hitam (Diospyros sp.), which exhibited monoamine oxidase (MAO) inhibition, three new naphthoquinone and/or naphthalene dimers (lemuninols A-C, 1-3) were isolated together with 4,6-dihydroxy-5-methoxy-2-methyl-naphthalene (8) and six known monomers (4-7, 9 and 10). The structures were determined by spectroscopic methods including 2D-NMR techniques. Among them, lemuninol A showed 45% inhibition of MAO (mouse liver) at 5.0 x 10(-6) g/ml, and lemuninols B and C and a naphthoquinone (9) indicated weak activity. Some related quinones were also tested for their MAO inhibitory activities.

Animals↗

PubMed1999

Immunomodulatory constituents from three ascomycetes, Gelasinospora heterospora, G. multiforis, and G. longispora.

Three new 2-pyrones (2H-pyran-2-ones) called multiforisins G (3), H (1), and I (4), and a known hexaketide sordarial (2) have been isolated from an Ascomycete Gelasinospora heterospora. Among them, 1, 2, and 3 have been proved to be the immunosuppressive components of the fungus. Compounds 1, 3, and 4 have also been isolated from G. multiforis together with multiforisin A (5), which was formerly isolated from this fungus as its main immunosuppressive feature, and 1-5 have also been isolated from G. longispora. The absolute stereostructure of 2, which was not previously certain, has finally been determined to be (3'R,4'S). It has been found that the multiforisins 1, 3, and 5 in which one of the two substituents at positions 3 and 5 is a hydroxymethyl group and the other is a formyl or an acetoxymethyl group, show high immunosuppressive activity; the immunosuppressive activity of 3 does not seem to be due to inhibition of interleukin 2 (IL-2) production.

Adjuvants, Immunologic↗

PubMed1998

Structural basis for the electron transfer across the chromaffin vesicle membranes catalyzed by cytochrome b561: analyses of cDNA nucleotide sequences and visible absorption spectra.

We isolated cDNA clones for cytochromes b561 from sheep and porcine adrenal medullae using the RT-PCR technique. Comparison of the deduced amino acid sequences of various species showed that there are two fully-conserved regions in this cytochrome. In addition, one methionyl and six histidyl residues (potential heme ligands) are fully-conserved. Based on a plausible structural model in which a polypeptide spans the vesicle membranes six times and holds two heme B molecules, the first conserved sequence (69ALLVYRVFR77) is located on the extravesicular side of an alpha-helical segment and the second one (120SLHSW124) is located in an intravesicular loop connecting two alpha-helical segments, respectively. Consideration of the relative locations of the fully-conserved sequences, and the methionyl and histidyl residues in the model led to a proposal that the first and second conserved sequences are likely to form the binding sites for extravesicular ascorbic acid and intravesicular semidehydroascorbic acid, respectively. A mild alkaline-treatment of purified bovine cytochrome b561 in oxidized state led to a specific loss of an electron-accepting ability from ascorbic acid for a half of the heme center, suggesting a distinct role for each of the two hemes.

Adrenal Medulla↗

PubMed1998

Pharmacologically active components of viticis fructus (Vitex rotundifolia). II. The components having analgesic effects.

The extract of Viticis Fructus appeared to have an analgesic effect, and was subjected to activity-guided separation using acetic acid-induced writhing in mice. The active fraction gave new compounds, vitexfolin A (1A), B and C, 10-O-vanilloylaucubin (3), dihydrodehydrodiconiferylalcohol-beta-D- (2'-O-p-hydroxybenzoyl)glucoside (4), and vanilloyl-beta-D-(2'O-p-hydroxybenzoyl)glucoside, together with agnuside (2) and erythro- and threoguaiacylglycerols. Compounds 1A and 2-4 showed significant writhing inhibition following oral administration at doses of 15, 50, 25, and 50 mg/kg, respectively. The effect on pressure pain threshold was tested using compounds 1A and 2 at a dose of 50 mg/kg, and only the former produced the analgesia. The analgesic effect of some related iridoid glucosides is also discussed.

Administration, Oral↗

PubMed1997

Existence of two heme B centers in cytochrome b561 from bovine adrenal chromaffin vesicles as revealed by a new purification procedure and EPR spectroscopy.

We have established a new purification procedure of cytochrome b561 from bovine adrenomedullary chromaffin vesicles. The heme content analysis of the purified sample indicated the presence of 1.7 molecules of heme B/cytochrome b561 molecule. EPR spectroscopy of the purified enzyme in oxidized state showed that there were three types of low spin heme species. Two of them showed usual EPR signals at gz = 3.14 and gz = 2.84 arising from the same heme and were interconvertible depending on pH. The other species showed a highly anisotropic low spin signal at gz = 3.70, with a lower redox potential than the others, and a temperature-sensitive character. These properties are very similar to low potential cytochrome b (bL or b566) of the mitochondrial complex III, indicating that the gz = 3.70 species is derived from a heme component different from the one that shows the usual low spin EPR signals. Based on our new structural model, these two heme B prosthetic groups are likely to be located on both sides of the membranes in close contact with the ascorbic acid- and semidehydroascorbic acid-binding sites, respectively, to facilitate the electron transfer across the membranes. This molecular architecture may provide a structural basis for the transmembrane electron transfer catalyzed by this hemoprotein.

Adrenal Medulla↗

PubMed1997

Molecular analysis of the intergenic region of the duplicated Amy genes of Drosophila melanogaster and Drosophila teissieri.

The intergenic regions between the duplicated amylase coding regions (Amy) of D. melanogaster and D. teissieri were sequenced. Their lengths in D. melanogaster and D. teissieri were 4,536 bp and 4,621 bp, respectively. Since homology between the upstream regions of the two duplicated genes was found up to 450 bp from the initiation codon of the Amy genes, the ancestral Amy coding region duplicated together with at least 450 bp of the 5'-flanking region as one unit. Comparison of the regions between the two species revealed that the level of divergence was very heterogeneous. Although the mean level of the nucleotide difference in this region was 0.107, no nucleotide substitution was found in four subregions whose sizes were more than 100 bp. Since the probability of these four subregions being completely conserved between D. melanogaster and D. teissieri was very low, these subregions were considered to have relatively important roles in evolution. Large insertions and deletions were not observed in this region but small ones were observed all over the region except for an about 1-kb subregion. This 1-kb region corresponded to an open reading frame encoding a protein which had some sequence identity with the proteins of the serine protease inhibitor superfamily (serpin). Since we could find a transcript of this gene and the synonymous substitution rate was higher than the replacement substitution rate, we suggest that this gene encodes an active serpin in Drosophila.

Amino Acid Sequence↗