Asarones from Acorus calamus in Combination with Azoles and Amphotericin B: A Novel Synergistic Combination to Compete Against Human Pathogenic Candida Species In Vitro

Abstract

The increase in drug resistance to current antifungal drugs brings enormous challenges to the management of Candida infection. Therefore, there is a continuous need for the discovery of new antimicrobial agents that are effective against Candida infections especially from natural source especially from medical plants. The present investigation describes the synergistic anticandidal activity of two asarones (∞ and β) purified from Acorus calamus in combination with three clinically used antifungal drugs (fluconazole, clotrimazole, and amphotericin B). The synergistic anticandidal activities of asarones and drugs were assessed using the checkerboard microdilution and time-kill assays. The results of the present study showed that the combined effects of asarones and drugs principally recorded substantial synergistic activity (fractional inhibitory concentration index (FICI) <0.5). Time-kill study by combination of the minimal inhibitory concentration (MIC) of asarones and drugs (1:1) recorded that the growth of the Candida species was significantly arrested between 0 and 2 h and almost completely attenuated between 2 and 6 h of treatment. These findings have potential implications in adjourning the development of resistance as the anticandidal activity is achieved with lower concentrations of asarones and drugs. The combination of asarones and drugs also significantly inhibit the biofilm formation by Candida species, and this would also help to fight against drug resistance because biofilms formed by Candida species are ubiquitous in nature and are characterized by their recalcitrance toward antimicrobial treatment. The in vitro synergistic activity of asarones and drugs against pathogenic Candida species is reported here for the first time.

Promising Alternative Therapeutics for Oral Candidiasis

“…infections has also been assessed. Kumar et al [91] described a synergistic anti-candidal activity of two asarones (∞ and β) purified from Acorus calamus in combination with fluconazole (Flu), clotrimazole, and amphotericin B (AmB), further reducing their minimal inhibitory concentrations necessary to inhibit the biofilm formation of Candida spp.. Similar results were demonstrated in a study with a combination of AmB and acteoside, from Colebrookea oppositifolia [92].…”

Synergistic action of amphotericin B and rhamnolipid in combination on Candida parapsilosis and Trichosporon cutaneum

“…The planktonic MIC P for amphotericin was found within the usual range of units of mg L -1 (Kumar et al 2015;Samadi et al 2012). The results of testing the compounds alone and in combinations against the planktonic cells are expressed in isobolograms (Fig.…”

“…1), which show the synergistic effect of the simultaneous use of rhamnolipid and amphotericin B for planktonic cells (FICi = 0.5). Several studies suggest a threshold for synergistic effect at FICi B 1.0 (Franzot and Casadevall 1997;Yu et al 1984); in more recent publications, this threshold is set at FICi B 0.5 (Kumar et al 2015).…”

“…to commonly used drugs by combination therapy or with new medications. One option is the use of natural substances such as essential oils (Hyldgaard et al 2012), plant extracts (Kumar et al 2015) or the use of biosurfactants (Monteiro et al 2011;Samadi et al 2012).…”

ANTICANDIDA ACTIVITY OF ETHANOL EXTRACT JERINGAU (Acorus calamus L) RHIZOME AGAINST Candida albicans ISOLATE REMOVABLE FULL DENTURE ACRYLIC

“…Jeringau (Acorus calamus L), very popularly known as "sweet flag," is native to Central Asia, North America, and Eastern Europe. A. calamus L is an herbal plant that its rhizome extract has antifungal activity against C.albicans [7].…”