Antifungal Activity and Potential Mechanism of 6,7, 4′-O-Triacetylscutellarein Combined With Fluconazole Against Drug-Resistant C. albicans

Abstract

The increased resistance of Candida albicans to conventional antifungal drugs poses a huge challenge to the clinical treatment of this infection. In recent years, combination therapy, a potential treatment method to overcome C. albicans resistance, has gained traction. This study assessed the effect of 6,7,4′-O-triacetylscutellarein (TA) combined with fluconazole (FLC) on C. albicans in vitro and in vivo. TA combined with FLC showed good synergistic antifungal activity against drug-resistant C. albicans in vitro, with a partial inhibitory concentration index (FICI) of 0.0188–0.1800. In addition, the time-kill curve confirmed the synergistic effect of TA and FLC. TA combined with FLC showed a strong synergistic inhibitory effect on the biofilm formation of resistant C. albicans. The combined antifungal efficacy of TA and FLC was evaluated in vivo in a mouse systemic fungal infection model. TA combined with FLC prolonged the survival rate of mice infected with drug-resistant C. albicans and reduced tissue invasion. TA combined with FLC also significantly inhibited the yeast-hypha conversion of C. albicans and significantly reduced the expression of RAS-cAMP-PKA signaling pathway-related genes (RAS1 and EFG1) and hyphal-related genes (HWP1 and ECE1). Furthermore, the mycelium growth on TA combined with the FLC group recovered after adding exogenous db-cAMP. Collectively, these results show that TA combined with FLC inhibits the formation of hyphae and biofilms through the RAS-cAMP-PKA signaling pathway, resulting in reduced infectivity and resistance of C. albicans. Therefore, this study provides a basis for the treatment of drug-resistant C. albicans infections.

Polyphyllin I Effects Candida albicans via Inhibition of Virulence Factors

“…For yeast-to-hyphae transition, yeast cells were induced in Spider liquid medium and SD + 10% FBS liquid medium [ 21 ]. A 1 mL suspension of CA23 cells (1 × 10 5 CFU/mL) treated with FLC (4 μ g/mL) or PPI (4 μ g/mL, 2 μ g/mL, or 1 μ g/mL) alone was incubated in 24-well plates at 37°C.…”

Synergistic Effect of Plant Compounds in Combination with Conventional Antimicrobials against Biofilm of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida spp.

“…Indian medicine uses this plant's rhizome to treat several diseases like epilepsy, mental ailments, chronic diarrhoea, and dysentery and for the following symptoms and conditions: helminthiasis, amenorrhea, dysmenorrhea, nephropathy, calculi, strangury, hoarseness, flatulence, and dyspepsia [137]. αand β-asarones, the primary bioactive substances, showed several bioactive features like antibacterial and antifungal properties [118,[138][139][140][141]. The in vitro synergistic activity of α-asarone and β-asarone purified from Acorus calamus rhizomes and amphotericin B, fluconazole, and clotrimazole against Candida species has been reported by Kumar and colleagues.…”