In Vitro and in Vivo antifungal activities of the eight steroid saponins from Tribulus terrestris L. with potent activity against fluconazole-resistant fungal

Abstract

Antifungal activity of natural products is being studied widely. Saponins are known to be antifungal and antibacterial. We have isolated eight steroid saponins from Tribulus terrestris L., namely TTS-8, TTS-9, TTS-10, TTS-11, TTS-12, TTS-13, TTS-14 and TTS-15. TTS-12 and TTS-15 were identified as tigogenin-3-O-β-D-xylopyranosyl(1→2)-[β-D-xylopyranosyl(1→3) ]-β-D-glucopyranosyl(1→4)-[α-L-rhamnopyranosyl(1→2)] -β-D-galactopyranoside and tigogenin-3-O-β-D-glucopyranosyl(1→2)- [β-D-xylopyranosyl(1→3)]-β-D-glucopyranosyl(1→4) -β-D-galactopyranoside, respectively. The in vitro antifungal activities of the eight saponins against six fluconazole-resistant yeasts, Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, Candida krusei, and Cryptococcus neoformans were studied using microbroth dilution assay. The results showed that TTS-12 and TTS-15 were very effective against several pathogenic candidal species and C. neoformans in vitro. It is noteworthy that TTS-12 and TTS-15 were very active against fluconazole-resistant C. albicans (MIC80=4.4, 9.4 μg/ml), C. neoformans (MIC80=10.7, 18.7 μg/ml) and inherently resistant C. krusei (MIC80=8.8, 18.4 μg/ml). So in vivo activity of TTS-12 in a vaginal infection model with fluconazole-resistant C. albicans was studied in particular. Our studies revealed TTS-12 also showed in vivo activities against fluconazole-resistant yeasts. In conclusion, steroid saponins TTS-12 and TTS-15 from Tribulus terrestris L. have significant in vitro antifungal activity against fluconazole-resistant fungi, especially TTS-12 also showed in vivo activity against fluconazole-resistant C. albicans. © 2005 Pharmaceutical Society of Japan.