Antidermatophyte activity of the essential oil of Hypericum perforatum of north of Iran

Dermatophytes are the main cause of human superficial mycosis that is still a public health problem especially in tropical countries such as Iran. The aim of this study was determining the antifungal effect of Hypercom perforatum essential oil. The minimum inhibitory concentration [MIC] and minimum fungicidal concentration [MFC] for the essential oil of the plant Hypericum perforatum against various dermatophytes were determined. The essential oil of Hypericum perforatum was obtained by hydro distillation of the dried plant. Clinical isolates of dermatophytes [Epidermophyton floccosum, Microsporum canis, Microsporum gypseum, T. mentagrophytes var. interdigital, T. mentagrophytes var. mentagrophytes., T. rubrum and Trichophyton tonsurans] were used for determining antifungal activity of this essential oil by in vitro tube dilution technique. MIC90 and MFC90 values were remarkable. T. mentagrophytes var. interdigital showed a>1 log10 difference in viable count between treatment and control within the first hour, whereas E. floccosum did not. The essential oil of H. perforatum sufficiently inhibited and killed all tested dermatophytes in all different dilutions. The changes in growth curve of the treated dermatophytes were significant compared with the untreated dermatophytes. Terpinen-4-ol is the main component of the essential oil of H. perforatum, and perhaps could play the important role in antidermatophyte activity among the other components. It is suggested trying the in-vivo effects of Hypericum perforatum ointment or its other medicinal forms in the treatment and controlling of dermatophytes infections

Menthol derivative WS-12 selectively activates transient receptor potential melastatin-8 [TRPM8] ion channels

Transient receptor potential melastatin-8 [TRPM8], a cationic ion channel is involved in detection of normal cooling-sensation in mammals. TRPM8 activation by cooling or chemical agonists have been shown to produce profound, mechanistically novel analgesia in chronic pain states such as neuropathic pain in rodents. Known TRPM8 agonists such as menthol and icilin have a relatively low potency and cross-activate nociceptors like TRPA1; thus bearing a limited therapeutic usefulness. For that reason, characterising ligands, which selectively activate TRPM8, presents a clinical need. Using Xenopus laevis oocytes as expression system, we evaluated WS-12, a menthol derivative, for its potential interaction with all six thermo-sensitive TRP ion channels. Oocytes were injected with cRNA of gene of interest and incubated for 3-5 days [at 16°C] before testing for functional characterisation of the recombinant ion channels. Oocytes were superfused with the test and standard substances respectively. Responses were measured by two-electrode voltage clamp technique and the amplitudes of evoked currents were compared with baseline values. WS-12 robustly activated TRPM8 in low micromolar concentrations [EC[50] 12 +/- 5 microM] thereby displaying a higher potency and efficacy compared to menthol [EC[50] 196 +/- 22 microM]. Any of the other described thermo-sensitive TRP ion channels including TRPV1, TRPV2, TRPV3, TRPV4 and TRPA1 were not activated at a concentration [1 mM] optimally effective for TRPM8 responses; a characteristic which is in sharp contrast to menthol as it activates TRPA1 and TRPV3 in addition to TRPM8. Unlike icilin [tilde75% reduction; p<0.001, n=6], WS-12 does not induce tachyphylaxis [4 +/- 2.3% increase in responses; p<0.08, n=6] of TRPM8 mediated currents to repeated exposure of 1 mM doses. In addition, acidosis or variations in extracellular calcium have no influence on potency/efficacy of WS-12 for TRPM8. The selectivity profile of WS-12, its several-fold higher potency and around two-fold increase in efficacy compared to menthol warrants its potential utility for therapy in chronic neuropathic pain states and as a diagnostic probe in prostate cancer