The synergy of honokiol and fluconazole against clinical isolates of azole-resistant Candida albicans

Abstract

Aims: To evaluate the interaction of fluconazole (FLC) and honokiol (HNK) in vitro and vivo against azole‐resistant (azole‐R) clinical isolates of Candida albicans. Methods and Results: A checkerboard microdilution method was used to study the in vitro interaction of FLC and HNK in 24 azole‐R clinical isolates of C. albicans. In vivo antifungal activity was performed to further analyse the interaction between FLC and HNK. In the in vitro study, synergism was observed in all 24 FLC‐resistant strains tested as determined by fractional inhibitory concentration index (FICI), and in 22 strains by ΔE models. No antagonistic activity was observed in any of the strains tested. These positive interactions were also confirmed by using the time‐killing test for the selected strain C. albicans YL371, which shows strong susceptible to the combination of HNK and FLC. In the in vivo study, the mice with candidiasis were treated successfully by a combination therapy of HNK with FLC, the results showed a decrease of the colony forming unit in infected and treated animals compared to the controls, at the conditions of the treatment used in this study. Conclusions: Synergistic activity of HNK and FLC against clinical isolates of FLC‐resistant C. albicans was observed in vitro and in vivo. Significance and Impact of the Study: This report might provide a potential therapeutic method to overcome the problem of drug‐resistance in C. albicans.

Honokiol inhibits in vitro and in vivo growth of oral squamous cell carcinoma through induction of apoptosis, cell cycle arrest and autophagy

“…). In the current reports, honokiol has been demonstrated to augment and exhibit a synergism with chemotherapeutic agents including rapamycin, gemcitabine, fluconazole and imatinib . Moreover, in animal models, our study and others show no obvious impacts in pathologic changes and genotoxicity after honokiol treatment, suggesting that honokiol is safe in animals and thus could be applicable in clinical practice.…”

Synergistic activity of magnolol with azoles and its possible antifungal mechanism againstCandida albicans

“…Jin et al reported the synergy of honokiol and FLC against isolates of azole-resistant C. albicans. In their report, honokiol MICs were 64-128 lg ml À1 against FLC-resistant C. albicans (Jin et al 2010). These differences might be due to the high degree of FLC resistance and thus manifest as a cross-resistance to honokiol and FLC.…”

“…In their report, honokiol MICs were 64–128 μ g ml −1 against FLC‐resistant C. albicans (Jin et al . ). These differences might be due to the high degree of FLC resistance and thus manifest as a cross‐resistance to honokiol and FLC.…”

Structural Optimization of Berberine as a Synergist to Restore Antifungal Activity of Fluconazole against Drug‐Resistant Candida albicans

“…[3] Unfortunately, however, the effective use of fluconazole has been limited significantly by the development of azole resistance, which has been attributed to the failure of antifungal treatments in the clinic. [4][5][6] One promising approach aimed at overcoming azole resistance has been reported that involves sensitizing C. albicans toward fluconazole with small molecules, including piperazinyl quinolines, [7] amiodarone, [8] tacrolimus, [9] honokiol, [10] and Allicin. [11] The recent screening of a natural product library in our research group revealed berberine (1) as the most active synergist in a series of antifungal agents, including fluconazole, [12] ketoconazole, amphotericin B, and miconazole.…”