title: In vitro and in vivo antifungal activities of the eight steroid saponins from Tribulus terrestris L. with potent activity against fluconazole-resistant fungal pathogens.
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-beta-D-xylopyranosyl(1-->2)-[beta-D-xylopyranosyl(1-->3)]-beta-D-glucopyranosyl(1-->4)-[alpha-L-rhamnopyranosyl(1-->2)]-beta-D-galactopyranoside and tigogenin-3-O-beta-D-glucopyranosyl(1-->2)-[beta-D-xylopyranosyl(1-->3)]-beta-D-glucopyranosyl(1-->4)-beta-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 (MIC(80)=4.4, 9.4 microg/ml), C. neoformans (MIC(80)=10.7, 18.7 microg/ml) and inherently resistant C. krusei (MIC(80)=8.8, 18.4 microg/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.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Second Military Medical University, Shanghai, PR China.
authors.forename: Jun-Dong
authors.initials: JD
authors.lastname: Zhang
authors.forename: Yong-Bing
authors.initials: YB
authors.lastname: Cao
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xu
authors.forename: Hui-Hua
authors.initials: HH
authors.lastname: Sun
authors.forename: Mao-Mao
authors.initials: MM
authors.lastname: An
authors.forename: Lan
authors.initials: L
authors.lastname: Yan
authors.forename: Hai-Sheng
authors.initials: HS
authors.lastname: Chen
authors.forename: Ping-Hui
authors.initials: PH
authors.lastname: Gao
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Xin-Ming
authors.initials: XM
authors.lastname: Jia
authors.forename: Yuan-Ying
authors.initials: YY
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects; D003455:Cryptococcus neoformans / Q000187:drug effects; D004195:Disease Models, Animal; D025141:Drug Resistance, Fungal; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification; D005260:Female; D015725:Fluconazole / Q000494:pharmacology; D005690:Galactose / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013256:Steroids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013997:Time Factors; D032444:Tribulus / Q000737:chemistry; D014623:Vaginal Diseases / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000935:Antifungal Agents; D004365:Drugs, Chinese Herbal; D012503:Saponins; D013256:Steroids; C508219:tigogenin-3-O-beta-D-glucopyranosyl(1-2)-(beta-D-xylopyranosyl(1-3))-beta-D-glucopyranosyl(1-4)-beta-D-galactopyranoside; C508218:tigogenin-3-O-beta-D-xylopyranosyl(1-2)-(beta-D-xylopyranosyl(1-3))-beta-D-glucopyranosyl(1-4)-(alpha-L-rhamnopyranosyl(1-2))-beta-D-galactopyranoside; D015725:Fluconazole; D005690:Galactose