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Biomedical subjects

Bong-Sik Yun

Publications and source records attributed to Bong-Sik Yun.

At least 19 recordsLinked to original sources

Free radical scavengers from the medicinal mushroom Inonotus xeranticus and their proposed biogenesis.

New free radical scavengers, inoscavin D (1) and methylinoscavin D (2), were isolated from the methanolic extract of the fruiting bodies of Inonotus xeranticus (Hymenochaetaceae), along with the known compounds phelligridin D (3), 3,4-dihydroxybenzaldehyde (4), and 3,4-dihydroxybenzoic acid (5). Their structures were established by various spectroscopic analyses. Compounds 1 and 3 were proposed to be biosynthesized from the oxidative coupling of the precursor hispidin with 3,4-dihydroxybenzaldehyde and 3,4-dihydroxybenzoic acid, respectively. These compounds exhibited significant scavenging activity against the ABTS radical cation, and compounds 2 and 4 displayed moderate superoxide radical scavenging activity.

Agaricales↗

Isolation of chebulic acid from Terminalia chebula Retz. and its antioxidant effect in isolated rat hepatocytes.

A hepatoprotective compound was isolated from the ethanolic extract of the fruits of Terminalia chebula Retz. by consecutive solvent partitioning, followed by silica gel and Sephadex LH-20 column chromatographies. The purified compound was identified as a mixture of chebulic acid and its minor isomer, neochebulic acid, with a ratio of 2:1 by spectroscopic analysis including 1D and 2D NMR and MS spectroscopy. To our knowledge, this is the first report on the protection of rat hepatocytes against oxidative toxicity by chebulic acid obtained from T. chebula Retz. This compound exhibited in vitro a free radical-scavenging activity and ferric-reducing antioxidant activity. Also, the specific ESR spectrum for the (*)OOH radical signals consisting of three-line ESR spectra was within the field of 0.27 mT, whereas 2.5 and 0.25 mg/ml of chebulic acid significantly reduced the signal intensity of the ESR spectra to 0.06 mT and 0.11 mT, respectively. Using isolated rat hepatocyte experiment, we demonstrated that the treatment of hepatocytes with chebulic acid significantly reduced the tert-butyl hydroperoxide (t-BHP)-induced cell cytotoxicity, intracellular reactive oxygen species level, and the ratio of GSSH, oxidized form of glutathione (GSH) to the over total GSH (GSH + GSSG) (4.42%) as compared to that with t-BHP alone (8.33%).

Animals↗

Ca(2+)-inositol phosphate chelation mediates the substrate specificity of beta-propeller phytase.

Inositol phosphates are recognized as having diverse and critical roles in biological systems. In this report, kinetic studies and TLC analysis indicate that beta-propeller phytase is a special class of inositol phosphatase that preferentially recognizes a bidentate (P-Ca(2+)-P) formed between Ca(2+) and two adjacent phosphate groups of its natural substrate phytate (InsP(6)). The specific recognition of a bidentate chelation enables the enzyme to sequentially hydrolyze one of the phosphate groups in a bidentate of Ca(2+)-InsP(6) to yield a myo-inositol trisphosphate (InsP(3)) and three phosphates as the final products. A comparative analysis of (1)H- and (13)C NMR spectroscopy with the aid of 2D NMR confirms that the chemical structure of the final product is myo-Ins(2,4,6)P(3). The catalytic properties of the enzyme suggest a potential model for how the enzyme specifically recognizes its substrate Ca(2+)-InsP(6) and produces myo-Ins(2,4,6)P(3) from Ca(2+)-InsP(6). These findings potentially provide evidence for a selective Ca(2+)-InsPs chelation between Ca(2+) and two adjacent phosphate groups of inositol phosphates.

6-Phytase↗

Isoliquiritigenin selectively inhibits H(2) histamine receptor signaling.

Isoliquiritigenin, one of the major constituents of Glycyrrhiza uralensis (licorice), is a natural pigment with a simple chalcone structure 4,2',4'-trihydroxychalcone. In this study, isoliquiritigenin showed selective H(2) histamine receptor (H(2)R) antagonistic effect and remarkably reduced several H(2)R-mediated physiological responses. Preincubation of U937 and HL60 hematopoietic cells with isoliquiritigenin significantly inhibited H(2)R agonist-induced cAMP response in a concentration-dependent manner without affecting the viability of cells. Isoliquiritigenin also blocked the binding affinity of [(3)H]tiotidine to membrane receptors in HL-60 cells. Isoliquiritigenin did not affect the elevation of cAMP levels induced by cholera toxin, forskolin, or isoproterenol, indicating that the action site of isoliquiritigenin is not G(s) protein, effector enzyme, adenylyl cyclase, or beta(2)-adrenoceptor. Isoliquiritigenin affected neither H(1)R-nor H(3)R-mediated signaling. In molecular docking studies, isoliquiritigenin exhibited more favorable interactions with H(2)R than histamine. Isoliquiritigenin prominently inhibited H(2)R selective agonist dimaprit-induced cAMP generation in MKN-45 gastric cancer cell. Moreover, isoliquiritigenin reduced gastric acid secretion and protected gastric mucosal lesion formation in pylorus-ligated rat model. Taken together, the results demonstrate that isoliquiritigenin is an effective H(2)R antagonist and provides the basis for designing novel H(2)R antagonist.

Adenylyl Cyclases↗

Two novel furan derivatives from Phellinus linteus with anti-complement activity.

Two novel stereoisomers of furan derivatives, phellinusfurans A (1) and B (2), were isolated from the fruiting body of Phellinus linteus. Their structures were elucidated by spectroscopic analysis. Compounds 1 and 2 exhibited significant anti-complement activity with IC50 values of 33.6 and 33.7 microM, respectively, in inhibiting the hemolytic activity of human serum against erythrocytes.

Basidiomycota↗

Hispidin analogs from the mushroom Inonotus xeranticus and their free radical scavenging activity.

Three new free radical scavengers were isolated from the methanolic extract of the fruiting bodies of Inonotus xeranticus (Hymenochaetaceae), along with the known compound davallialactone. Their structures were established as hispidin analogs by extensive NMR spectral data. Compounds 3 and 4 displayed significant scavenging activity against the superoxide radical anion, ABTS radical cation, and DPPH radical, while 1 and 2 exhibited potent antioxidative activity only against ABTS radical cation.

Agaricales↗

Hispidin derivatives from the mushroom Inonotus xeranticus and their antioxidant activity.

In an effort to identify antioxidants from edible and medicinal mushrooms, three new hispidin derivatives, methylinoscavin A (2), inoscavin B (4), and methylinoscavin B (5), together with the known compounds inoscavin A and phelligridin F, were isolated from the methanolic extract of the fruiting bodies of Inonotus xeranticus. Their structures were determined on the basis of spectroscopic analyses.

Agaricales↗

Deoxyverrucosidin, a novel GRP78/BiP down-regulator, produced by Penicillium sp.

Glucose-regulated protein 78 (GRP78) resides in endoplasmic reticulum (ER) and plays a role in protecting tumor cells against the toxic effects of anticancer agents. During the search for down-regulators of GRP78 using a reporter gene (luciferase) assay system, we isolated a novel compound designated as deoxyverrucosidin (1), a congener of verrucosidin (2), from Penicillium sp. and identified it as a down-regulator of the grp78 gene. The structure of 1 was determined by mainly ESI-mass and two-dimensional NMR spectra. 1 dose-dependently inhibited the expression of GRP78 promoter with an IC50 of 30 nM.

Cell Line↗

Antifungal activity of beta-asarone from rhizomes of Acorus gramineus.

An antifungal substance was isolated from the extract of Acorus gramineus using various chromatographic procedures. The antibiotic was identified as beta-asarone, cis-2,4,5-trimethoxy-1-propenylbenzene, on the basis of the high-resolution EI-mass, NMR, and UV spectral data. Beta-asarone completely inhibited mycelial growth of some plant pathogenic fungi, Cladosporium cucumerinum,Colletotrichum orbiculare, Magnaporthe grisea, and Pythium ultimum, in a range of 0.5-30 microg/mL. The growth of Bacillus subtilis, Erwinia carotovora subsp. carotovora, Ralstonia solanacearum, and Xanthomonas campestris pv. vesicatoria was slightly suppressed by beta-asarone. As the concentration of beta-asarone increased, M. grisea infection was drastically inhibited on rice leaves. Treatment with 500 microg/mL of beta-asarone also greatly suppressed lesion formation of Co. orbiculare on cucumber leaves. This is the first study to demonstrate in vitro and in vivo antifungal activity of beta-asarone against plant fungal pathogens M. grisea and C. orbiculare.

Acorus↗

Complestatin prevents apoptotic cell death: inhibition of a mitochondrial caspase pathway through AKT/PKB activation.

Complestatin, a bicyclo hexapeptide from Streptomyces, was isolated as a possible regulator of neuronal cell death. In this study, we report an anti-apoptotic activity of complestatin and its underlying molecular mechanism. Complestatin blocked TRAIL (TNF-related apoptosis-inducing ligand)-induced apoptosis and activation of caspase-3 and -8 at micromolar concentration levels without inhibiting the catalytic activities of these caspases. Complestatin potently induced a rapid and sustained AKT/PKB activation and Bad phosphorylation, resulting in inhibition of mitochondrial cytochrome c release. These anti-apoptotic activities of complestatin were significantly abrogated in cells expressing dominant negative AKT/PKB. Taken together, our results suggest that complestatin prevents apoptotic cell death via AKT/PKB-dependent inhibition of the mitochondrial apoptosis signal pathway. The novel property of complestatin may be valuable for developing new pharmaceutical means that will control unwanted cell death.

Apoptosis↗

p-Terphenyl curtisians protect cultured neuronal cells against glutamate neurotoxicity via iron chelation.

The hyperactivity of ionotropic glutamate receptors has been implicated in the development of the neuronal cell death seen in many neurodegenerative processes including ischemic stroke, traumatic brain injury, and epilepsy. Thus neuronal protection against glutamate-induced neurotoxicity is considered as an appropriate therapeutic strategy for preventing and treating neurodegenerative diseases. Whilst searching for blockers of glutamate-induced toxicity in mouse cortical cells, we isolated p-terphenyl curtisians A - D from the mushroom Paxillus curtisii. Curtisians protected cortical neurons from glutamate-induced toxicity in a dose-dependent manner. Among the glutamate receptor subtypes, curtisians were found to block NMDA receptor-mediated but not AMPA/kainate-mediated cell death. In addition, we found that curtisians exhibited potent antioxidative activity against iron-mediated oxidative damage which was generated by H2O2 neurotoxocity and lipid peroxidation, but no activity was detected in the superoxide, DPPH and ABTS radical scavenging systems, and in protection of N18-RE-105 cells subjected to glutamate-induced glutathione depletion. This effect was likely due to the iron chelating properties of curtisians. The iron chelation ability of curtisians was then further investigated on DNA single strand breakage (SSB) induced by the addition of iron and H2O2, and curtisians prevented DNA SSB like the iron chelator desferrioxamine. These results suggest that the neuroprotective action of curtisians is dependent on their ability to chelate iron as well as to block the NMDA receptor, and that in this context curtisians may be useful as neuroprotective agents against neurological disorders which result in neuronal cell death.

Animals↗

Neuroprotective activity of p-terphenyl leucomentins from the mushroom Paxillus panuoides.

The neuroprotective mechanism of p-terphenyl leucomentins from the mushroom Paxillus panuoides was studied. Leucomentins showed potent inhibition of lipid peroxidation and H2O2 neurotoxicity, but free from any role as reactive oxygen species (ROS) scavengers. Iron-mediated oxidative damage has been implicated in these processes, as a provider of ROS via iron. Leucomentins can chelate iron when DNA is present with iron and H2O2, and so inhibiting DNA single strand breakage. These results suggest that the neuroprotective action of leucomentins is dependent on their ability to chelate iron.

Agaricales↗

Melanocins A, B and C, new melanin synthesis inhibitors produced by Eupenicillium shearii. I. Taxonomy, fermentation, isolation and biological properties.

New melanin synthesis inhibitors, melanocins A, B and C, were isolated from the fermentation broth and mycelium extract of Eupenicillium shearii F80695. Melanocin A, an isocyanide compound, inhibited mushroom tyrosinase and melanin biosynthesis of B16 melanoma cells with IC50 value of 9.0 nM and MIC value of 0.9 microM, respectively. Melanocin A also inhibited growth of Streptomyces bikiniensis. While, the structurally very related but non-isocyanide compounds melanocins B and C did not show inhibitory activity in these assays. Melanocins A, B and C showed potent antioxidant activity with scavenging activity of DPPH radical and superoxide anion radical.

Agaricales↗

Dictyoquinazols A, B, and C, new neuroprotective compounds from the mushroom Dictyophora indusiata.

In an effort to identify neuroprotective compounds against excitatory neurotoxins from edible and medicinal mushrooms, dictyoquinazols A (1), B (2), and C (3) have been isolated from the methanolic extract of the mushroom Dictyophora indusiata. On the basis of NMR studies, their structures have been assigned as unique quinazoline compounds, which are very rare in nature. 2 and 3 existed as mixtures of rotamers (2a, 2b and 3a, 3b) inseparable by HPLC because of fast interconversion. The E/Z isomers of these compounds were assigned by comparison of (1)H NMR, (13)C NMR, and NOESY spectra and by (3)J(C,H) coupling constants. Dictyoquinazols protected primary cultured mouse cortical neurons from glutamate- and NMDA-induced excitotoxicities in a dose-dependent manner.

Agaricales↗