RESUMO
The use of antifungal agents in clinical settings is limited by the appearance of drug resistance and adverse side effects. There is, therefore, an urgent need to develop new drugs to strengthen the treatment of invasive fungal diseases. The aim of this study is to describe the potential repurposing of ribavirin as an adjunct therapy against Candida spp. Primary screening of a Prestwick Chemical library against Candida albicans ATCC 90028 and fluconazole-resistant Candida albicans strains was performed. Subsequently, we evaluated the responses of 100 Candida sp. strains to ribavirin, an antiviral agent, using the broth microdilution method as recommended by CLSI. We checked the involvement of efflux pump activity in the development of ribavirin resistance. We studied time-kill curves and performed a checkerboard assay for a ribavirin-antifungal combination study. Twenty-one nonstandard antifungal compounds were identified, including ribavirin. Ribavirin had antifungal activity in vitro against 63 Candida strains, including strains of C. albicans, C. parapsilosis, and C. tropicalis, with MICs ranging from 0.37 to 3.02 µg/ml, while MICs for C. krusei, C. glabrata, C. lusitaniae, and some C. albicans strains remained high (≥24.16 µg/ml). No relation was observed between efflux pump activity and ribavirin resistance. Ribavirin exhibited fungistatic activity against multidrug-resistant (MDR) C. albicans and fungicidal activity against a C. parapsilosis strain. In addition, ribavirin acted synergistically with azoles against Candida strains for which ribavirin MICs were <24.4 µg/ml. This study highlights the potential clinical application of ribavirin, alone or in association with other antifungal agents, as an adjunct anti-Candida drug.
Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida parapsilosis/efeitos dos fármacos , Candida tropicalis/efeitos dos fármacos , Reposicionamento de Medicamentos , Farmacorresistência Fúngica/efeitos dos fármacos , Ribavirina/farmacologia , Candida albicans/genética , Candida albicans/crescimento & desenvolvimento , Candida parapsilosis/genética , Candida parapsilosis/crescimento & desenvolvimento , Candida tropicalis/genética , Candida tropicalis/crescimento & desenvolvimento , Candidíase Invasiva/tratamento farmacológico , Candidíase Invasiva/microbiologia , Sinergismo Farmacológico , Fluconazol/farmacologia , Expressão Gênica , Genes MDR , Humanos , Testes de Sensibilidade Microbiana , Medicamentos sob Prescrição/farmacologia , Triazóis/farmacologiaRESUMO
Solidago species are often used in traditional medicine as anti-inflammatory, diuretic, wound-healing and antimicrobial agents. Still, the bioactive compounds and biological activities of some species have not been studied. The present work aimed to investigate the polyphenolic profile and the biological properties of Solidago graminifolia L. Salisb., a poorly explored medicinal plant. The hydroalcoholic extracts from aerial parts were evaluated for total phenolic content (TPC), total flavonoid content (TFC) and the polyphenolic compounds were investigated by HPLC-MS. The antioxidant potential in vitro was determined using DPPH and FRAP assays. Antibacterial and antifungal effects were evaluated by dilution assays and MIC, MBC and MFC were calculated. The results showed that Solidago graminifolia aerial parts contain an important amount of total phenolics (192.69 mg GAE/g) and flavonoids (151.41 mg RE/g), with chlorogenic acid and quercitrin as major constituents. The hydroalcoholic extracts showed promising antioxidant and antimicrobial potential, with potent antibacterial activity against Staphylococcus aureus and important antifungal effect against Candida albicans and C. parapsilosis. The obtained results indicated that the aerial parts of Solidago graminifolia could be used as novel resource of phytochemicals in herbal preparations with antioxidant and antimicrobial activities.
Assuntos
Anti-Infecciosos/isolamento & purificação , Antioxidantes/isolamento & purificação , Ácido Clorogênico/isolamento & purificação , Flavonoides/isolamento & purificação , Fenóis/isolamento & purificação , Quercetina/análogos & derivados , Solidago/química , Anti-Infecciosos/classificação , Anti-Infecciosos/farmacologia , Antioxidantes/classificação , Antioxidantes/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Candida parapsilosis/efeitos dos fármacos , Candida parapsilosis/crescimento & desenvolvimento , Clorofórmio/química , Ácido Clorogênico/farmacologia , Etanol/química , Flavonoides/classificação , Flavonoides/farmacologia , Metanol/química , Testes de Sensibilidade Microbiana , Fenóis/classificação , Fenóis/farmacologia , Picratos/antagonistas & inibidores , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Quercetina/isolamento & purificação , Quercetina/farmacologia , Solventes/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimentoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The dried rhizomes of Paris polyphylla var. yunnanensis are widely used in traditional Chinese medicine (TCM) as hemostatic, antitumor, and antimicrobial agents. More than 70 Chinese patent medicines are based on P. polyphylla var. yunnanensis rhizomes. Steroidal saponins are considered as the main active ingredients of these rhizomes. However, wild populations of P. polyphylla var. yunnanensis are greatly threatened due to the illegal wild harvest and over-utilization of the rhizomes. In contrast, the renewable above-ground parts (leaves and stems) of P. polyphylla var. yunnanensis are usually thrown away as waste material, whether from wild or cultivated material. AIM OF THE STUDY: The aim of this study was to use HPLC analyses of chemical constituents and bioactive assays to assess whether the above-ground parts could be an alternative source of active ingredients to the rhizomes of P. polyphylla var. yunnanensis. MATERIALS AND METHODS: The saponin components of the rhizomes and above-ground parts of P. polyphylla var. yunnanensis were analyzed by HPLC-UV. The total saponins extracted from the rhizomes and above-ground parts of P. polyphylla var. yunnanensis were evaluated for their hemostatic, cytotoxic, and antimicrobial activities by using the rabbit blood in vitro based on turbidimetric method, MTT assay method, and a dilution antimicrobial susceptibility test method, respectively. RESULTS: Four bioactive spirostanol saponins (paris saponins I, II, VI, and VII) were detected in the total saponins from the rhizomes and above-ground parts of P. polyphylla var. yunnanensis, which indicated they should have similar pharmacological properties. The bioactive assays revealed that both the parts of P. polyphylla var. yunnanensis exhibited the same hemostatic, cytotoxic, and antimicrobial effects. CONCLUSION: Our results revealed that based on saponin content in the above-ground parts of P. polyphylla var. yunnanensis and the requirements stipulated in 2015 of Chinese Pharmacopoeia, the above-ground parts (especially its leaves) can be an alternative and more sustainable source of active ingredients compared to the rhizomes.