[Antifungal activity of essential oils and their constituents against Candida spp. and their effects on activity of amphotericin B].

Candidiasis is a common opportunistic fungal infection that responds well to amphotericin B (AMPH) treatment. However, AMPH often causes adverse effects such as kidney injury and hypokalemia. Because some essential oils have been reported to have antifungal effects, we investigated the antifungal activity of various essential oils and their major constituents against Candida spp. Most essential oils examined in this study showed antifungal activity, and several enhanced the antifungal effect of AMPH. Clove oil in particular, and its major constituent eugenol, had potent effects. These findings suggest that combining certain essential oils or their constituents with AMPH may be useful for suppressing the adverse effects of AMPH treatment.

Interaction of polyphenolic metabolites with human serum albumin: a circular dichroism study.

Binding sites of polyphenolic compounds on human serum albumin (HSA) were investigated using induced Cotton effects on the circular dichroism (CD) spectra. Polyphenolic compounds used in this study are known to be metabolites from tannins and their related polyphenols in food and medicinal plants. The present investigation revealed that the structural differences markedly affected the binding of the compounds to HSA. Protocatechuic acid, together with its methylated compounds vanillic and isovanillic acids, were assigned to be bound to sites I and II of HSA, based on the competitive relationships with site-I-binding phenylbutazone (PB) and site-II-binding diazepam (DP). 4-O-Methylgallic acid, which is the metabolite from gallic acid, was bound to site I on HSA, while gallic acid did not affect the binding of PB and DP at the concentration examined. Neither ellagic acid nor its metabolite urolithin A was competitive with PB and DP on HSA. The addition of digitoxin did not affect the induced CD of the polyphenolic acids examined.

Interaction of polyphenols with proteins: binding of (-)-epigallocatechin gallate to serum albumin, estimated by induced circular dichroism.

The binding of (-)-epigallocatechin gallate (EGCG), a representative natural polyphenol, to human serum albumin (HSA) and bovine serum albumin (BSA) was investigated using induced circular dichroism (CD). The site of the binding EGCG-HSA was analyzed based on the competition with drugs with known binding sites on HSA, such as phenylbutazone (PB) and diazepam (DP). Double-reciprocal plot analyses showed the competitive relations with the site-I- (PB and tolbutamide, TB) and site-II-binding drugs (DP and ibuprofen, IP) indicating the binding of EGCG to sites I and II on HSA, while digitoxin (DG), a site-III-binding drug, did not affect the binding of EGCG. In an analogous way, the competitive relations were observed between EGCG and the site-I- (PB and TB) and site-II-binding (ethacrynic acid, EA) drugs for the binding of EGCG and BSA. The site-III drug DG also showed competitive binding with EGCG to BSA. The binding of EGCG to the albumins indicated its affinity to sites I and II on HSA, while competitive binding for all three sites was observed on BSA.

Stereoselective pharmacokinetics of RS-8359, a selective and reversible MAO-A inhibitor, by species-dependent drug-metabolizing enzymes.

RS-8359, (+/-)-4-(4-cyanoanilino)-5,6-dihydro-7-hydroxy-7H-cyclopenta[d]pyrimidine selectively and reversibly inhibits monoamine oxidase A (MAO-A). After oral administration of rac-RS-8359 to rats, mice, dogs, monkeys, and humans, plasma concentrations of the (R)-enantiomer were greatly higher than were those of the (S)-enantiomer in all species studied. The AUC((R)) to AUC((S)) ratios were 2.6 in rats, 3.8 in mice, 31 in dogs, and 238 in monkeys, and the (S)-enantiomer was almost negligible in human plasma. After intravenous administration of RS-8359 enantiomers to rats, the pharmacokinetic parameters showed that the (S)-enantiomer had a 2.7-fold greater total clearance (CL(t)) and a 70% shorter half-life (t(1/2)) than those for the (R)-enantiomer but had no difference in distribution volume (V(d)). No significant difference in the intestinal absorption rate was observed. The principal metabolites were the 2-keto form, possibly produced by aldehyde oxidase, the cis-diol form, and the 2-keto-cis-diol form produced by cytochrome P450 in rats, the cis-diol form in mice, RS-8359 glucuronide in dogs, and the 2-keto form in monkeys and humans. Thus, the rapid disappearance of the (S)-enantiomer from the plasma was thought to be due to the rapid metabolism of the (S)-enantiomer by different drug-metabolizing enzymes, depending on species.

Anti-oxidative stress system in cyanobacteria. Significance of type II peroxiredoxin and the role of 1-Cys peroxiredoxin in Synechocystis sp. strain PCC 6803.

Two antioxidant proteins, SLL1621 and SLR1198, were captured in the cyanobacteria Synechocystis sp. PCC 6803 using thioredoxin affinity chromatography, which was first applied to the survey of thioredoxin target proteins in chloroplasts (Motohashi, K., Kondoh, A., Stumpp, M. T., and Hisabori, T. (2001) Proc. Natl. Acad. Sci. U. S. A. 98, 11224-11229). They are annotated as AhpC/TSA family protein (SLL1621) and antioxidant protein (SLR1198) in CyanoBase (Nakamura, Y., Kaneko, T., Hirosawa, M., Miyajima, N., and Tabata, S. (1998) Nucleic Acids Res. 26, 63-67). Based on sequence homology analysis SLL1621 and SLR1198 are categorized into type II peroxiredoxin and 1-Cys type peroxiredoxin, respectively. In vitro interaction between SLL1621 and thioredoxin was confirmed using the recombinant proteins expressed in Escherichia coli. Furthermore, we found that SLL1621 shows remarkable glutathione-dependent peroxidase activity. Disruption of the sll1621 gene had a dramatic effect on the viability of the cyanobacterial cells even under weak light conditions (50 micromol.m(-2).s(-1)), suggesting this peroxiredoxin is essential for this cyanobacterium. In contrast, although the peroxidase activity of SLR1198 was scarcely detected, disruption of the gene, slr1198, certainly affected the growth rate of the cells. The results indicate the physiological significance of two different peroxiredoxins as an anti-oxidative stress system in cyanobacteria.