Antidermatophytic and Protease-inhibiting Activities of Zerumbone: A Natural Sesquiterpene from the Rhizome of Zingiber zerumbet (L.) Roscoe ex J.E; Smith.

CONTEXT: Due to increase in the number of patients with impaired immunity, incidence of dermatophytoses has increased considerably. Antidermatophytic agents with anti-inflammatory and protease-inhibiting activities will help in restricting inflammatory response associated with dermatophytoses. AIMS: The present study aims to evaluate antidermatophytic and protease-inhibiting activities of zerumbone. Cytotoxicity was tested using Chang liver cell line as a preliminary step in toxicity study. METHODS AND MATERIALS: Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of zerumbone purified from the rhizome of Zingiber zerumbet were determined against Epidermophyton floccosum var. nigricans, Microsporum canis, Microsporum gypseum, and Trichophyton rubrum. MIC was determined according to Clinical and Laboratory Standards Institute (CLSI) method M38-A2. Protease-inhibiting property was tested using trypsin as the enzyme. In vitro cytotoxic effect was studied using the MTT assay. RESULTS: MIC of zerumbone was 8 mg/L against E. floccosum and M. canis and 16 mg/L for M. gypseum and T. rubrum. MFC of zerumbone was 64 mg/L against E. floccosum and M. canis and 128 mg/L for M. gypseum and T. rubrum. Zerumbone exhibited remarkable protease-inhibiting activity. In the MTT assay, IC(50) values were 150 and 0.31 µg, respectively, for zerumbone and reference drug. STATISTICAL ANALYSIS USED: For protease inhibition, assay and cytotoxicity assay control and tests were done in triplicate and the results are expressed as mean ± SD, where n = 3. CONCLUSIONS: Zerumbone is a novel candidate for use in dermatophytoses therapy because of the combined antifungal, anti-inflammatory (unpublished results), and protease-inhibiting properties. Cytotoxicity of zerumbone was found to be very low compared with the reference drug. KEY MESSAGES: Zerumbone possesses antidermatophytic, anti-inflammatory, and protease-inhibiting activities. Hence, it is a novel candidate for the development of new antidermatophytic drug.Cytotoxicity of zerumbone against Chang liver cell line was found to be very low compared with the reference drug doxorubicin. SUMMARY: Zerumbone isolated from the rhizome of Zingiber zerumbet exhibited antidermatophytic activity against E. floccosum and M. canis (MIC 8 mg/L) and M. gypseum and T. Rubrum (MIC 16 mg/L).Zerumbone exhibited remarkable protease-inhibiting activity.Zerumbone is a novel candidate for the development of new antidermatophytic drug.Cytotoxicity of zerumbone against Chang liver cell line was found to be very low compared with the reference drug doxorubicin. Abbreviations used: CFU: colony forming unit, CLSI: Clinical and Laboratory Standards Institute, COX: cyclooxygenase, DMSO: dimethyl sulphoxide, EDTA: ethylene diamine tetra acetic acid, FT-IR: Fourier transform-infra red spectroscopy, HPLC: high-performance liquid chromatography, LOX: lipoxygenase, IMTECH: Institute of Microbial Technology, LCMS: liquid chromatography mass spectrometry, MTT: 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, MTCC: microbial type culture collection, MFC: minimum fungicidal concentration, MIC: minimum inhibitory concentration, MPO: myeloperoxidase, NMR: nuclear magnetic resonance spectroscopy, PAR: proteinase-activated receptor, PBS: phosphate-buffered saline, TCA: trichloro acetic acid.