Aline Luiza Duarte de Freitas1, Vanessa Kaplum2, Diego Conrado Pereira Rossi3, Leandro Buffoni Roque da Silva4, Márcia de Souza Carvalho Melhem5, Carlos Pelleschi Taborda6, João Carlos Palazzo de Mello7, Celso Vataru Nakamura8, Kelly Ishida9. 1. Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, SP, Brazil. Electronic address: alineludfreitas@gmail.com. 2. Departamento de Ciências Básicas da Saúde, Universidade Estadual de Maringá, PR, Brazil. Electronic address: vkap18@gmail.com. 3. Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, SP, Brazil. Electronic address: rossi.dcp@gmail.com. 4. Laboratory of Medical Mycology, Tropical Medicine Institute USP-LIM53, University of São Paulo, São Paulo, Brazil. Electronic address: leandro_br87@hotmail.com. 5. Instituto Adolfo Lutz, São Paulo, SP, Brazil. Electronic address: melhemmr@uol.com.br. 6. Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, SP, Brazil; Laboratory of Medical Mycology, Tropical Medicine Institute USP-LIM53, University of São Paulo, São Paulo, Brazil. Electronic address: taborda@usp.br. 7. Departamento de Farmácia, Universidade Estadual de Maringá, PR, Brazil. Electronic address: mello@uem.br. 8. Departamento de Ciências Básicas da Saúde, Universidade Estadual de Maringá, PR, Brazil. Electronic address: cvnakamura@uem.br. 9. Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, SP, Brazil. Electronic address: ishidakelly@usp.br.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: The stem bark of Stryphnodendron adstringens (Mart.) Coville is popularly used as anti-inflammatory, astringent and in the treatment of wounds and vaginal infections. Several pharmacological activities have been scientifically proven by in vitro and in vivo experimental assays for antibacterial, antiviral, antiprotozoan, anti-inflammatory and antioxidant. AIM OF THE STUDY: We investigated whether proanthocyanidin polymeric tannins from the Stryphnodendron adstringens stem bark with antifungal activity against Candida albicans in vitro are also active against planktonic and biofilm cells of Candida non-albicans (CNA, including fluconazole-resistant isolates) and are capable of controlling Candida vaginitis in vivo. MATERIALS AND METHODS: A total of 46 clinical isolates and 5 reference Candida spp. strains were used in this study. The antifungal effects in vitro of tannins (F2 and sub-fraction F2.4) from S. adstringens stem bark were evaluated using a broth microdilution assay (for planktonic yeasts and biofilm dispersion cells) or by XTT assay (for biofilm sessile cells). For in vivo antifungal activity analysis, mice with vaginal infection by C. albicans or C. glabrata were treated with a topical gel containing F2 (alone or combined with oral fluconazole), and the vaginal histopathology and fungal burden (by CFU counts from vaginal homogenates) were analyzed. RESULTS: F2 and F2.4 inhibited the proliferation of planktonic cells of Candida spp., especially that of fluconazole- and/or amphotericin B-resistant isolates. F2 and F2.4 also inhibited the proliferation of Candida biofilm dispersion cells. Moreover, a gel containing F2 efficiently controlled vaginal infection by C. albicans and C. glabrata in mice, with no noticeable toxicity to vaginal tissue. CONCLUSIONS: Our data show that proanthocyanidin polymeric tannins obtained from S. adstringens have antifungal activity in vitro against C. albicans and CNA (including fluconazole-resistant isolates) and presented efficacy in the control of candidiasis in murine model. Therefore, these tannins have potential use in the treatment of vaginal candidiasis, representing interesting alternatives to current antifungals.
ETHNOPHARMACOLOGICAL RELEVANCE: The stem bark of Stryphnodendron adstringens (Mart.) Coville is popularly used as anti-inflammatory, astringent and in the treatment of wounds and vaginal infections. Several pharmacological activities have been scientifically proven by in vitro and in vivo experimental assays for antibacterial, antiviral, antiprotozoan, anti-inflammatory and antioxidant. AIM OF THE STUDY: We investigated whether proanthocyanidin polymeric tannins from the Stryphnodendron adstringens stem bark with antifungal activity against Candida albicans in vitro are also active against planktonic and biofilm cells of Candida non-albicans (CNA, including fluconazole-resistant isolates) and are capable of controlling Candida vaginitis in vivo. MATERIALS AND METHODS: A total of 46 clinical isolates and 5 reference Candida spp. strains were used in this study. The antifungal effects in vitro of tannins (F2 and sub-fraction F2.4) from S. adstringens stem bark were evaluated using a broth microdilution assay (for planktonic yeasts and biofilm dispersion cells) or by XTT assay (for biofilm sessile cells). For in vivo antifungal activity analysis, mice with vaginal infection by C. albicans or C. glabrata were treated with a topical gel containing F2 (alone or combined with oral fluconazole), and the vaginal histopathology and fungal burden (by CFU counts from vaginal homogenates) were analyzed. RESULTS: F2 and F2.4 inhibited the proliferation of planktonic cells of Candida spp., especially that of fluconazole- and/or amphotericin B-resistant isolates. F2 and F2.4 also inhibited the proliferation of Candida biofilm dispersion cells. Moreover, a gel containing F2 efficiently controlled vaginal infection by C. albicans and C. glabrata in mice, with no noticeable toxicity to vaginal tissue. CONCLUSIONS: Our data show that proanthocyanidin polymeric tannins obtained from S. adstringens have antifungal activity in vitro against C. albicans and CNA (including fluconazole-resistant isolates) and presented efficacy in the control of candidiasis in murine model. Therefore, these tannins have potential use in the treatment of vaginal candidiasis, representing interesting alternatives to current antifungals.
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