Activity of antifungal drugs and Brazilian red and green propolis extracted with different methodologies against oral isolates of Candida spp.

Abstract

Background Oral candidiasis is an opportunistic disease caused by fungi of the Candida genus. The occurrence of Candida spp. resistance to the commercial antifungal drugs points to the search for alternative treatments. Propolis has been successfully used in the treatment of infectious diseases for centuries. It has been proposed that an ultrasound pretreatment in the propolis extraction protocol can enhance the concentrations of molecules with antimicrobial activities in the final extract. Thus, this study aimed to compare the antifungal activity against oral Candida spp. isolates of green and red propolis extracts submitted or not to an ultrasound pretreatment before the extraction procedure. Methods Candida spp. were isolated from denture stomatitis lesions and identified by sequencing. Oral Candida spp. isolates and reference strains were submitted to broth microdilution assays using commercial antifungals and Brazilian green and red propolis extracts submitted or not to an ultrasound pretreatment. Minimal Inhibitory Concentrations (MIC) and Minimal Fungicide Concentrations (MFC) were determined and biofilm formation interference was evaluated for resistant isolates. Results C. albicans, Candida tropicalis and Candida dubliniensis were isolated from denture stomatitis lesions. Growth inhibition was observed in all Candida isolates incubated with all green and red propolis extracts. At lower doses, red propolis extracts presented significant antifungal activity. The ultrasound pretreatment did not promote an increase in the antifungal activity of green or red propolis. Three isolates, which were highly resistant to fluconazole and itraconazole, were susceptible to low doses of red propolis extracts. These same three specimens had their biofilm formation inhibted by red propolis ethanolic extract. Conclusions Thus, red propolis can be faced as a promising natural product to be used in the auxiliary antifungal therapy of denture stomatitis.

Antifungal Properties of Chemically Defined Propolis from Various Geographical Regions

“…Therefore, it can be concluded that the synergy of action of all components of propolis extract determines the antifungal activity. However, it should be noted that the extracts of Brazilian propolis showed very wide variability in antifungal activity, e.g., according to Freires et al [54] Brazilian reed propolis showed MIC = 2.0 µg/mL), Siqueira et al [75] revealed for the same type of propolis showed MIC = 32-64 µg/mL, whereas Sokolonski et al [13] stated values of MIC from 0.5 to more than 8 mg/mL (Table 2). This indicates the need to standardize the chemical composition of the different types of propolis collected all over the world.…”

“…Generally, ethanolic extracts of propolis, which come from different regions of Brazil, are investigated most often (199 publications in PubMed between 2011 and 2021) [8,14,17,40,54]. High-quality chemical analysis mainly concerns two types of propolis such as Brazilian red propolis (using gas chromatography coupled to mass spectrometry [54], and liquid chromatography-high-resolution mass spectrometry [53]), and Brazilian green propolis (using liquid chromatography-high-resolution mass spectrometry [53], and highperformance liquid chromatography (HPLC-DAD) [13]. Table 1.…”

“…Antifungal activities of various extracts of propolis have been examined against several yeasts, such as Candida albicans, C. dubliniensis, C. glabrata, C. krusei, C. parapsisolis, C. tropicalis, Saccharomyces cerevisiae [13,[16][17][18]21,50,[54][55][56][57][60][61][62][63][64], as well as against molds, such as Alternaria solani, Alternaria alternata, Aspergillus niger, Aspergillus ochraceus, Botrytis cinerea, Cladosporium spp., Fusarium solani, Fusarium oxysporum, Mucor mucedo, Penicillium digitatum, Penicillium expansum, Penicillium chrysogenum, Rhizopus stolonifera, Rhodotorula mucilaginosa and Trichophyton spp. [9,19,43,64].…”

“…It was shown that the most active were the following ethanolic extracts: Irish propolis (MIC = 0.3 µg/mL) [21] > Czech propolis (MIC = 0.6 µg/mL) [21] > Brazilian reed propolis (MIC = 2.0 µg/mL) [54] > Brazilian poplar propolis (MIC = 4 µg/mL) [54] > German propolis (MIC = 5 µg/mL) [21] > Iranian propolis (MIC 50 = 21 µg/mL) [63] > French poplar propolis (MIC = 31.25 µg/mL) [56] > Portuguese propolis (MIC 50 = 32.0 µg/mL) [64] > Brazilian reed propolis (MIC = 32-64 µg/mL) [75] > Brazilian organic propolis (MIC = 100 µg/mL) [17] > Cameroonian propolis (MIC = 125-500 µg/mL) [18] > Nepalese propolis (MIC = 256 µg/mL) > Brazilian green propolis (MIC = 2-4 mg/mL) [13] > Polish propolis (MIC = 2-32 mg/mL) [43]. Moreover, in five studies [13,17,18,54,75] antifungal activities of extracts of propolis against three or more species of Candida were compared. Many authors demonstrated that C. albicans is more sensitive than other species of Candida (C. dubliniensis, C. glabrata, C. krusei, C. tropicalis, C. parapsilosis) to ethanolic extracts from various propolis.…”

“…Propolis has shown mainly antifungal [8,9,[13][14][15][16][17][18][19][20][21][22], antibacterial [10,19,20,23,24], antiviral [20,[25][26][27][28][29], antiparasitic [5,20,30,31], anti-inflammatory [17,[32][33][34] and neuroprotective activity [35][36][37][38], and also anticancer properties [39][40][41][42].…”