{Reference Type}: Journal Article
{Title}: N-Butylphthalide Potentiates the Effect of Fluconazole Against Drug-Resistant Candida glabrata and Candida tropicalis. Evidence for Its Mechanism of Action.
{Author}: Liu Y;Ren F;Li S;Li X;Shi D;Zhang Z;
{Journal}: Infect Drug Resist
{Volume}: 17
{Issue}: 0
{Year}: 2024
{Factor}: 4.177
{DOI}: 10.2147/IDR.S459378
{Abstract}: <B>UNASSIGNED: </B>To define the antifungal activity of n-butylphthalide alone or in combination with fluconazole in Candida glabrata and Candida tropicalis.<BR><B>UNASSIGNED: </B>The antifungal activity of n-butylphthalide alone and in combination with fluconazole was investigated by the classical broth microdilution method and the time-killing curve method. The QRT-PCR method was used to determine gene expressions changes of mitochondrial respiratory chain enzymes, drug efflux pumps and drug target enzymes in Candida glabrata and Candida tropicalis after n-butylphthalide treatment.<BR><B>UNASSIGNED: </B>The MIC values of n-butylphthalide against Candida glabrata and Candida tropicalis ranged from 16 to 64 μg·mL-1. The FICI value of the combination of n-butylphthalide and fluconazole against drug-resistant Candida glabrata and Candida tropicalis ranged from 0.5001 to 0.5315 with partial synergism. Time-killing curves showed that 256 μg·mL-1 n-butylphthalide significantly inhibited the growth of drug-resistant colonies of Candida glabrata and Candida tropicalis, and 128 μg·mL-1 n-butylphthalide combined with 1 μg·mL-1 fluconazole had an additive effect. N-butylphthalide could alter the expression of mitochondrial respiratory chain enzymes COX1, COX2, COX3, and CYTB genes in Candida glabrata and Candida tropicalis (P< 0.05) and downregulate the expression of the drug efflux pump genes CDR1 and CDR2 in drug-resistant Candida glabrata to 3.36% and 3.65%, respectively (P<0.001), but did not affect the drug target enzyme ERG11 in drug-resistant Candida tropicalis.<BR><B>UNASSIGNED: </B>N-butylphthalide had antifungal activity against Candida glabrata and Candida tropicalis. N-butylphthalide improved the activity of fluconazole against drug-resistant Candida glabrata by affecting the expression of mitochondrial respiratory chain enzyme genes and reversing the high expression of drug efflux pump genes CDR1 and CDR2.