Antidermatophytic Activity of Ethanolic Extract from Croton tiglium.

Dermatophytosis, which is caused mainly by genera of Trichophyton, Epidermophyton, and Microsporum, is a frequent dermatological problem in tropical and subtropical countries. Investigations were carried out in this study to evaluate the antidermatophytic activity of the stems, leaves, and seeds of Croton tiglium, one of the traditional medicine plants indigenous to Asia. Ethanolic extracts of the stems, leaves, and seeds of C. tiglium were prepared by cold soak or heat reflux methods. The antidermatophytic activities of the extracts were evaluated by disc diffusion and microdilution susceptibility assays against Trichophyton mentagrophytes, T. rubrum, and Epidermophyton floccosum. The active components in the extracts were analyzed and identified by GC-MS. All ethanolic extracts of C. tiglium showed some antifungal activities against the three dermatophytes. The ethanolic stem extract had the greatest inhibitory activities against T. mentagrophytes and E. floccosum with MICs at 0.16 mg/mL and had a lower activity against T. rubrum (MIC: 0.31 mg/mL). Oleic acid and hexadecanoic acid were found to be the major constituents in the stem extract that demonstrated strong antidermatophytic activities. The ethanolic extracts of stem or seed of C. tiglium exhibit strong antidermatophytic activities and, thus, could be considered for application on treating skin fungal infections after appropriate processing.

Resveratrol suppresses myofibroblast activity of human buccal mucosal fibroblasts through the epigenetic inhibition of ZEB1 expression.

Oral submucous fibrosis (OSF) is a precancerous condition of the oral mucosa without specific therapeutic drugs. We previously demonstrated that the zinc finger E-box binding homeobox 1 (ZEB1) plays a pathogenic role in the induction of the myofibroblast activity of buccal mucosal fibroblasts (BMFs) and contributes to the pathogenesis of OSF. Resveratrol is a natural polyphenolic flavonoid with anti-fibrosis activity in various tissues and has the capability to inhibit ZEB1 in oral cancer cells. We examined the effect of resveratrol on the myofibroblast activity of human primary fibrotic BMFs (fBMFs) derived from OSF tissues. With the collagen contraction assay, resveratrol displayed anti-myofibroblast activity in three fBMF lines. Resveratrol also inhibited the expression of fibrogenic genes at the mRNA and protein levels in a dose- and time-dependent manner. The downregulation of ZEB1 in fBMFs by resveratrol was mediated by epigenetic mechanisms, such as the upregulated expression of miR-200c and the enhancer of zeste homolog 2 (EZH2), as well as the trimethylated lysine 27 of histone H3 (H3K27me3). Resveratrol also increased the binding of H3K27me3 to the ZEB1 promoter. The knockdown of EZH2 in fBMFs caused the upregulation of ZEB1 and suppressed the inhibitory effect of resveratrol. Furthermore, the reversed expression pattern between EZH2 and ZEB1 was observed in 6/8 OSF tissues with twofold upregulation of ZEB1 expression compared with the adjacent normal mucosa. In conclusion, our data suggest that resveratrol epigenetically inhibits ZEB1 expression to suppress the myofibroblast activity of fBMFs and may serve as a dietary supplement for OSF patients.

Green tea catechins: inhibitors of glycerol-3-phosphate dehydrogenase.

Green tea catechins, especially (-)-epigallocatechin-3-gallate (EGCG), are known to regulate obesity and fat accumulation. We performed a kinetic analysis in a cell-free system to determine the mode of inhibition of glycerol-3-phosphate dehydrogenase (GPDH; EC 1.1.1.8) by EGCG. GPDH catalyzes the beta-nicotinamide adenine dinucleotide (NADH)-dependent reduction of dihydroxyacetone phosphate (DHAP) to yield glycerol-3-phosphate, which serves as one of the major precursors of triacylglycerols. We found that EGCG dose-dependently inhibited GPDH activity at a concentration of approximately 20 muM for 50 % inhibition. The IC (50) values of other green tea catechins, such as (-)-epicatechin, (-)-epicatechin-3-gallate, and (-)-epigallocatechin, were all above 100 microM. This suggests a catechin type-dependent effect. Based on double-reciprocal plots of the kinetic data, EGCG was a noncompetitive inhibitor of the GPDH substrates, NADH and DHAP, with respective inhibition constants (Ki) of 18 and 31 microM. Results of this study possibly support previous studies that EGCG mediates fat content.