Study On Synergistic Effect Of Tetrandrine On Econazole Against Trichophyton

ObjectiveTo investigate the synergistic effect of tetrandrine(TET) on econazole(ECZ) against Trichophyton both in vivo and in vitro for the sake of offering experimental basis and new idea for the treatment of superficial fungal infections.MethodsThe most non-cytotoxic dose of tetrandrine in the 15 Trichophyton rubrum was determined by the microdilution test. The minimum inhibitory concentration(MICs) of ECZ alone and combined with the most non-cytotoxic dose of tetrandrine were determined in 15 Trichophpyton rubrum by the Clinical and Laboratory Standards Institute (CLSI) proposed M38-A microdilution method. The paired-sample t-test was adopted to test the statistic difference.Animal model of dermatophytosis in guinea pig was made by inoculating Trichophyton mentagrophytes conidia. The 50 infected animals were separated into 5 groups randomly and tested with the following formulations once per day for successive 7 days started at day 4 after inoculation:1%Econazole with 1%Tetrandrine compound cream (ECZ+TET group), 1%Econazole cream(ECZ group),1%TET cream(TET group) and matrix cream(matrix group), no treatment was given to the blank control group. The alterations in the skin lesions(score of skin lesion), hair root test, colony forming units, culture of skin sections as well as the pathological changes were observed. The score of skin lesion were tested by repeated measures design analysis of variance, the positive rate of hair root test and culture of skin sections were tested by chi-square test, colony forming unit was tested by completely random design analysis of variance. ResultsThe most non-cytotoxin dose of tetrandrine to the Trichophyton rubrum is 40μg/mL. The MICs of ECZ alone against Trichophyton rubrum are 0.25-2μg/mL and decreased to 0.0313-0.0625μg/mL when combined with the most non-cytotoxin dose of tetrandrine with obviously statistical difference (P=0.006).From the 2th day of applying drugs, the tendency of lesion score of ECZ+TET group and ECZ group continued to decline, TET group, matrix group and blank control group continued to raise. There is significantly statistical difference (F=51.042,P=0.000) among these 5 groups. On the 10th of applying drugs, the lesion score of ECZ group decreased to 4.2. More reduction of lesion score was in ECZ+TET group than in ECZ group (mean 2.8VS 4.2) with obviously statistical difference (P=0.009). Comparing with the other 4 groups, the positive rate of fungal cultures in hair root test, skin sections and colony forming units in ECZ+TET group were decreased significantly (P= 0.000,P= 0.000 and P= 0.000). The pathological changes in ECZ+TET group were slighter than other 4 groups.Conclusions1. Tetrandrine can inhance the effect of econazole (ECZ) against Trichophyton rubrum in vitro.2. There is synergistic effect of Tetrandrine to the anti-Trichophyton mentagrophytes of Econazole in animal model of dermatophytosis in guinea pigs.