Induced production of methyl bromodihydroxyphenyl acetates by the marine-derived fungus Aspergillus sp.

The addition of metal bromides (NaBr and CaBr2) during fermentation of a marine isolate of the fungus Aspergillus sp. induced production of two new brominated dihydroxyphenylacetic acid derivatives, methyl 2-(6-bromo-3,4-dihydroxyphenyl)acetate (1) and methyl 2-(2,5-dibromo-3,4-dihydroxyphenyl)acetate (2), and a known compound, 2-(3,4-dihydroxyphenyl)acetic acid (3). The structures of the two new compounds (1, 2) were assigned through the combination of spectroscopic data analyses and comparison with the spectral data of compound 3. Compounds 1-3 exhibited potent radical-scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) with IC50 values (14.2, 12.1, 11.0 µm, respectively) demonstrating greater activity than the positive control (l-ascorbic acid; IC50, 20.0 µm).

Effect of coenzyme Q10 and Ardisia japonica Blume on plasma and liver lipids, platelet aggregation, and erythrocyte Na efflux channels in simvastatin-treated guinea pigs.

Forty guinea pigs were divided into four groups and fed 0.04% cholesterol based control diet, plus 0.05% simvastatin, and statin plus 0.1% CoQ10 or 10% Ardisia Japonica Blume (AJB) leave powder for 4 weeks. Plasma total cholesterol levels decreased significantly in all groups fed the statin-containing diet compared with that in guinea pigs fed the control diet (P < 0.01). Plasma and liver triglycerides decreased significantly in the statin plus CoQ10 group compared with those in the control (both P < 0.05). Maximum platelet aggregation was significantly higher in the statin plus CoQ10 group than that in the other groups (P < 0.05). Na-K ATPase activity increased in the statin group and decreased in the statin plus CoQ10 group (P < 0.01). Na-K co-transport and Na passive transport decreased significantly in the control group compared with those in the other groups (both P < 0.05). Intracellular Na was highest in the statin group and lowest in the statin plus CoQ10 group and was correlated with Na-K ATPase activity. Thiobarbituric acid reactive substance production in platelet-rich plasma and liver tended to decrease in the statin plus CoQ10 group compared with those in the other groups. Plasma glutamic-pyruvic transaminase and glutamic-oxaloacetic transaminase increased significantly in the statin group compared with those in the control (P < 0.05). These result suggest that antioxidant rich AJB did not have positive effects on cardiovascular disease parameters. The statin plus CoQ10 seemed to decrease cholesterol more efficiently than that of statin alone.

Effects of green tea or Sasa quelpaertensis bamboo leaves on plasma and liver lipids, erythrocyte Na efflux, and platelet aggregation in ovariectomized rats.

This study was conducted to investigate the effects of Sasa quelpaertensis bamboo and green tea on plasma and liver lipids, platelet aggregation, and erythrocyte membrane Na channels in ovariectomized (OVX) rats. Thirty female rats were OVX, and ten female rats were sham-operated at the age of 6 weeks. The rats were divided into four groups at the age of 10 weeks and fed the experiment diets: sham-control, OVX-control, OVX-bamboo leaves (10%), or OVX-green tea leaves (10%) for four weeks. Final body weight increased significantly in the OVX groups compared with that in the sham-control, whereas body weight in the OVX-green tea group decreased significantly compared with that in the OVX-control (P < 0.01). High density lipoprotein (HDL)-cholesterol level decreased in all OVX groups compared with that in the sham-control rats (P < 0.05) but without a difference in plasma total cholesterol. Plasma triglycerides in the OVX-green tea group were significantly lower than those in the sham-control or OVX-control group (P < 0.05). Liver triglycerides increased significantly in the OVX-control compared with those in the sham-control (P < 0.01) but decreased significantly in the OVX-green tea group compared with those in the OVX-control or OVX-bamboo group (P < 0.01). Platelet aggregation in both maximum and initial slope tended to be lower in all OVX rats compared with that in the sham-control rats but was not significantly different. Na-K ATPase tended to increase and Na-K cotransport tended to decrease following ovariectomy. Na-K ATPase decreased significantly in the OVX-green tea group compared with that in the OVX-control group (P < 0.01), and Na-K cotransport increased significantly in the OVX-bamboo and OVX-green tea groups compared with that in the OVX-control (P < 0.05). Femoral bone mineral density tended to be lower in OVX rats than that in the sham-control, whereas the green tea and bamboo leaves groups recovered bone density to some extent. The results show that ovariectomy caused an increase in body weight and liver triglycerides, and that green tea was effective for lowering body weight and triglycerides in OVX rats. Ovariectomy induced an increase in Na efflux via Na-K ATPase and a decrease in Na efflux via Na-K cotransport. Furthermore, consumption of green tea and bamboo leaves affected Na efflux channels, controlling electrolyte and body water balance.

New production of 5-bromotoluhydroquinone and 4-O-methyltoluhydroquinone from the marine-derived fungus Dothideomycete sp.

The addition of NaBr to the fermentation medium of a marine isolate of the fungus Dothideomycete sp. resulted in induced production of two toluhydroquinone derivatives, 5- bromotoluhydroquinone (1) and 4-O-methyltoluhydroquinone (2), and two known compounds, toluhydroquinone (3) and gentisyl alcohol (4). The structures of 1 and 2 were assigned through the spectroscopic data analyses. Compounds 1-4 showed a potent antibacterial activity against the methicillinresistant and multidrug-resistant Staphylococcus aureus (MRSA and MDRSA) with MIC (minimum inhibitory concentration) values of 6.2, 12.5, 6.2, and 12.5 microgram/ml, respectively. Compounds 1-4 also exhibited a moderate radical scavenging activity against 1,1-diphenyl-2- picrylhydrazyl (DPPH) with IC(50) values of 11.0, 17.0, 12.0, and 7.0 microM, respectively, which were more active than the positive control, L-ascorbic acid (IC(50), 20.0 µM).

Flavusides A and B, antibacterial cerebrosides from the marine-derived fungus Aspergillus flavus.

Flavusides A (1) and B (2), two new antibacterial cerebroside derivatives, and the previously described phomaligol A (3), kojic acid (4), methyl kojic acid (5), and dimethyl kojic acid (6) have been isolated from the extract of a marine isolate of the fungus Aspergillus flavus. The structure and absolute stereochemistry of two cerebrosides were assigned on the basis of NMR and Tandem FAB-MS/MS experiments. Compounds 1, 2, and 3 exhibited a mild antibacterial activity against Staphylococcus aureus, methicillin-resistant S. aureus, and multidrug-resistant S. aureus. The minimum inhibitory concentration (MIC) values for each strain are as follows: compounds 1 and 2 showed 15.6 µg/ml for S. aureus and 31.2 µg/ml for methicillin-resistant S. aureus and multidrug-resistant S. aureus, and compound 3 exhibited 31.2 µg/ml for S. aureus and methicillin-resistant S. aureus and 62.5 µg/ml for multidrug-resistant S. aureus.

Microbial mannosidation of bioactive chlorogentisyl alcohol by the marine-derived fungus Chrysosporium synchronum.

The biological transformation of the biologically active chlorogentisyl alcohol (1), isolated from the marine-derived fungus Aspergillus sp., was studied. Preparative-scale fermentation of chlorogentisyl alcohol with marine-derived fungus Chrysosporium synchronum resulted in the isolation of a new glycosidic metabolite, 1-O-(α-D-mannopyranosyl)chlorogentisyl alcohol (2). The stereostructure of the new metabolite obtained was assigned on the basis of detailed spectroscopic data analyses, chemical reaction, and chemical synthesis. Compounds 1 and 2 exhibited significant radical-scavenging activity against 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) with IC(50) values of 1.0 and 4.7 µM, respectively. The compounds 1 and 2 were more active than the positive control, L-ascorbic acid (IC(50), 20.0 µM).

Dynamics of tRNAtyr probed with long-lifetime metal-ligand complexes.

The metal-ligand complexes, [Ru(bpy)(2)(dppz)](2+) (bpy = 2,2'-bipyridine, dppz = dipyrido[3,2-a:2',3'-c]phenazine) (RuBD) and [Ru(phen)(2)(dppz)](2+) (phen = 1,10-phenanthroline) (RuPD), display favorable photophysical properties including long lifetime, polarized emission, and very little background fluorescence. To check if RuBD and RuPD reflect the overall rotational mobility of small nucleic acid, we measured the intensity and anisotropy decays of RuBD and RuPD when intercalated into tRNA(tyr) using pBC SK(+) phagemid as a control. We used frequency-domain fluorometry with a blue light-emitting diode (LED) as the modulated light source. We observed shorter lifetimes for tRNA(tyr) than those for the pBC SK(+) phagemid for both probes, however, RuPD showed much larger decrease in the mean lifetime values (64%). The slow rotational correlation time of RuBD (31.3 ns) and the fast rotational correlation time of RuPD (26.0 ns) reflected the overall rotational mobility of tRNA(tyr). In addition, the steady-state anisotropy and time-resolved anisotropy decay data showed a clear difference between tRNA(tyr) and pBC SK(+) phagemid. This suggests the possibility of a homogeneous assay for identifying target nucleic acids and/or nucleic acid binding proteins.

Induced production of halogenated diphenyl ethers from the marine-derived fungus Penicillium chrysogenum.

Manipulation of the fermentation of the marine-derived fungus Penicillium chrysogenum by addition of CaBr(2) resulted in induced production of bromodiphenyl ether analogs. Two new free-radical-scavenging polybrominated diphenyl ethers, 1 and 2, and three known diphenyl ethers, 3,3'-dihydroxy-5,5'-dimethyldiphenyl ether (3), and an inseparable mixture of violacerol-I (4) and violacerol-II (5) were isolated. The structures of the two new polybromodiphenyl ethers 1 and 2 were assigned by combined spectroscopic-data analysis, including deuterium-induced isotope effect. Compounds 1-3, and a mixture of 4 and 5 exhibited radical-scavenging activities against 1,1-diphenyl-2-picrylhydrazyl with IC(50) values of 18, 15, 42, and 6 µM, respectively. With the exception of 3, the compounds were, therefore, more active than the positive control, ascorbic acid (IC(50) 20 µM).

Induced production of bromomethylchlamydosporols A and B from the marine-derived fungus Fusarium tricinctum.

The addition of CaBr(2) to the fermentation of a marine-derived Fusarium tricinctum resulted in production of halogenated chlamydosporol analogues. Two new antimicrobial halogenated pyranopyranones, bromomethylchlamydosporols A (1) and B (2), and two known compounds, chlamydosporol (an inseparable epimeric mixture of 7R:7S = 1:1 from (1)H NMR data) (3) and fusarielin A (4), were isolated from the culture. The structures of 1 and 2 were assigned through a combination of spectroscopic data analyses. Compounds 1-4 exhibited mild antibacterial activity against Staphylococcus aureus, methicillin-resistant S. aureus, and multidrug-resistant S. aureus. The MIC values of each strain were as follows: compounds 1 and 2 showed an MIC of 15.6 µg/mL against S. aureus, methicillin-resistant S. aureus, and multidrug-resistant S. aureus, and compounds 3 and 4 exhibited an MIC of 31.5 µg/mL against S. aureus and methicillin-resistant S. aureus and 62.5 µg/mL against multidrug-resistant S. aureus.

Biotransformation of bioactive (-)-mellein by a marine isolate of bacterium Stappia sp.

The biological transformation of the bioactive dihydroisocoumarin, (-)-mellein, isolated from the marine-derived fungus Cladosporium sp., was studied. The preparative-scale culture of (-)-mellein with a marine isolate of a bacterium Stappia sp. resulted in the isolation of its oxidized metabolite, (3R,4S)-4-hydroxymellein. The stereostructure of the metabolite obtained was assigned on the basis of detailed physicochemical data analyses.

Dynamics of bacteriophage R17 probed with a long-lifetime Ru(II) metal-ligand complex.

The metal-ligand complex, [Ru(2,2'-bipyridine)(2)(4,4'-dicarboxy-2,2'-bipyridine)](2+) (RuBDc), was used as a spectroscopic probe for studying macromolecular dynamics. RuBDc is a very photostable probe that possesses favorable photophysical properties including long lifetime, high quantum yield, large Stokes' shift, and highly polarized emission. To further show the usefulness of this luminophore for probing macromolecular dynamics, we examined the intensity and anisotropy decays of RuBDc when conjugated to R17 bacteriophage using frequency-domain fluorometry with a blue light-emitting diode (LED) as the modulated light source. The intensity decays were best fit by a sum of two exponentials, and we obtained a longer mean lifetime at 4 degrees C ( = 491.8 ns) as compared to that at 25 degrees C ( = 435.1 ns). The anisotropy decay data showed a single rotational correlation time, which is typical for a spherical molecule, and the results showed a longer rotational correlation time at 4 degrees C (2,574.9 ns) than at 25 degrees C (2,070.1 ns). The use of RuBDc enabled us to measure the rotational correlation time up to several microseconds. These results indicate that RuBDc has significant potential for studying hydrodynamics of biological macromolecules.

Microbial transformation of a monoterpene, geraniol, by the marine-derived fungus Hypocrea sp.

Geraniol (1) is the biogenetic precursor of a number of monoterpenes. We tested various marine-derived microorganisms to determine their ability to biotransform 1. Only Hypocrea sp. was capable of transforming 1 into its oxidized derivative, 1,7-dihydroxy-3,7-dimethyl-(E)-oct- 2-ene (2). The structure of the metabolite obtained was assigned on the basis of detailed spectroscopic data analyses.

8'-Hydroxyzearalanone and 2'-hydroxyzearalanol: resorcyclic acid lactone derivatives from the marine-derived fungus Penicillium sp.

Two new 14-membered resorcyclic acid lactone derivatives, 8'-hydroxyzearalanone (1) and 2'-hydroxyzearalanol (2), and four known zearalanone derivatives (3-6) were isolated from the marine-derived fungus Penicillium sp. The structures of compounds 1-6 were elucidated by spectroscopic methods.

Chlorohydroaspyrones A and B, antibacterial aspyrone derivatives from the marine-derived fungus Exophiala sp.

Chlorohydroaspyrones A (1) and B (2), antibacterial aspyrone derivatives, and the previously described aspyrone (3), asperlactone (4), and penicillic acid (5) have been isolated from the broth of a marine isolate of the fungus Exophiala. The structure and absolute stereochemistry of the compounds were determined on the basis of the physicochemical data analysis and chemical reactions. Compounds 1 and 2 exhibited a mild antibacterial activity against Staphylococcus aureus, methicillin-resistant S. aureus, and multidrug-resistant S. aureus. The MIC values of each strain are as follows: compound 1 showed 62.5 microg/mL for S. aureus and 125 microg/mL for methicillin-resistant S. aureus and multidrug-resistant S. aureus, and compound 2, 62.5 microg/mL for S. aureus and methicillin-resistant S. aureus and 125 microg/mL for multidrug-resistant S. aureus.

Dietary flavonoids differentially reduce oxidized LDL-induced apoptosis in human endothelial cells: role of MAPK- and JAK/STAT-signaling.

Endothelial apoptosis is a driving force in atherosclerosis development. Oxidized LDL promotes inflammatory and thrombotic processes and is highly atherogenic, as it stimulates macrophage cholesterol accumulation and foam cell formation. This study investigated multiple mitogen-activated protein kinase (MAPK)-responsive death/survival signaling pathways, through which flavonoids of (-)epigallocatechin gallate (EGCG) and hesperetin exerted antiapoptosis in endothelial cells exposed to oxidized LDL. EGCG and hesperetin substantially diminished the oxidized LDL-induced 2',7'-dichlorofluorecein staining, suggesting that these flavonoids inhibited intracellular accumulation of oxidized LDL-triggered reactive oxygen species and consequent apoptosis. The Western-blot data revealed that oxidized LDL upregulated c-Jun N-terminal kinase (JNK) phosphorylation, which was rapidly reversed by EGCG and hesperetin. They mitigated the consequent activation of the JNK downstream on p53 and c-Jun. Moreover, oxidized LDL increased luciferase activity of p53 in endothelial cells transfected with a p53 promoter construct, the increase of which was strikingly downregulated by EGCG and hesperetin. Surprisingly, hesperetin but not EGCG attenuated phosphorylation of p38MAPK and its downstream c-myc and signal transducers and activators of transcription (STAT)1 evoked by oxidized LDL. This study also attempted to explore a linkage of Janus kinase (JAK)2/STAT3 activation to MAPK signaling in oxidized LDL-induced endothelial apoptosis. Notably, we found that the JAK2 inhibitor substantially blocked the JNK activation. Our findings suggest that EGCG and hesperetin may act as antiatherogenic agents blocking oxidized LDL-induced endothelial apoptosis via differential cellular apoptotic machinery. These data provide evidence that the interplay between p38MAPK and JAK-STAT pathways is involved in dietary flavonoid protection against oxidized LDL through hampering MAPK-dependent pathways involving the activation of JAK2.

Circumdatin I, a new ultraviolet-A protecting benzodiazepine alkaloid from a marine isolate of the fungus Exophiala.

A new ultraviolet-A (UV-A) protecting benzodiazepine alkaloid, circumdatin I (1), along with the previously described circumdatin C (2) and circumdatin G (3), have been isolated from the mycelium of a marine-derived fungus of the genus Exophiala. The structures of the three circumdatins were assigned on the basis of physicochemical evidence. The absolute stereochemistry of 1 was determined by comparison of optical rotation and CD experiments with those of 2 and 3.

Effect of onion and beet on plasma and liver lipids, platelet aggregation, and erythrocyte Na efflux in simvastatin treated hypercholesterolmic rats.

This study was purposed to investigate the effect of onion or beet on plasma and liver lipids, erythrocyte Na efflux channels and platelet aggregation in simvastatin (SIM) treated hypercholesterolemic rats. Forty Sprague Dawley rats were divided into four groups and fed 0.5% cholesterol based diets containing 2 mg/kg BW simvastatin or simvastatin with 5% onion or beet powder. Plasma total cholesterol was significantly increased in SIM group compared with the control (p<0.01), and the elevated plasma total cholesterol of SIM group was significantly decreased in SIM-onion and SIM-beet groups (p<0.05). HDL-cholesterol in SIM-beet group was significantly increased compared with other groups (p<0.05). Platelet aggregation in both the maximum and initial slope was significantly decreased in SIM group compared with SIM-onion group (p<0.05). Na-K ATPase was significantly decreased in SIM group compared with the control, SIM-onion and SIM-beet groups (p<0.05). Na passive leak was significantly increased in all groups treated with SIM compared with the control (p<0.05). The total Na efflux was decreased in SIM group and increased in SIM-onion group and the difference between these two groups was significant (p<0.05). There was no difference in intracellular Na among groups. In present study, simvastatin, a HMG CoA reductase inhibitor at dose of 2mg/kg BW/day rather increased plasma total cholesterol in rats, inferring that the action mechanism of simvastatin on cholesterol metabolism differ between rat and human. Onion and beet play favorable roles in cardiovascular system by restoring the reduced Na efflux through Na-K ATPase and Na-K cotransport in SIM treated rats.

Redoxcitrinin, a biogenetic precursor of citrinin from marine isolate of fungus Penicillium sp.

A chemical analysis of the fermentation of the marine-derived fungus Penicillium sp. led to the isolation of a biogenetic precursor of citrinin, redoxcitrinin (1), together with polyketide mycotoxins, phenol A (2), citrinin H2 (3), 4-hydroxymellein (4), citrinin (5), and phenol A acid (6). The structures of compounds 1-6 were determined on the basis of physicochemical data analyses. Among them, compounds 1-3 exhibited a potent radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) with IC50 values of 27.7, 23.4, and 27.2 microM, respectively.

Dehydroxychlorofusarielin B, an antibacterial polyoxygenated decalin derivative from the marine-derived fungus Aspergillus sp.

Dehydroxychlorofusarielin B (1), a new antibacterial polyoxygenated decalin derivative, and the previously described fusarielins A (2) and B (3) have been isolated from the broth of a marine isolate of the fungus Aspergillus. The structure and absolute stereochemistry of the new compound was determined on the basis of the physicochemical data and X-ray diffraction. Compounds 1-3 exhibited a mild antibacterial activity against Staphylococcus aureus, methicillin-resistant S. aureus, and multidrug-resistant S. aureus. The MIC values for each strain were as follows: compounds 1 and 3, 62.5 microg/mL for all strains; compound 2, 32.5 microg/mL for S. aureus and methicillin-resistant S. aureus and 62.5 microg/mL for multidrug-resistant S. aureus.