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Ethnopharmacological Relevance: Paracoccidioidomycosis (PCM) is a systemic mycosis with high prevalence in South America and especially in Brazil with severe clinical consequences that need broadened therapeutic options. Propolis is a natural resin from bees used in folk medicine for centuries with the first report in the ancient history of Egypt by Eberly papyrus, in Middle-Ages used to wash the newborn's umbilical cord and World War II as antiseptic or antibiotics. Nowadays it is a natural product worldwide consumed as food and traditionally used for oral and systemic diseases as an anti-inflammatory, antimicrobial, antifungal, and other diseases. Brazilian red propolis (BRP) is a new type of propolis with a distinguished chemical profile and biological activities from propolis (green) with pharmacological properties such as antimicrobial, anti-inflammatory, antioxidant, and others., Aim of Study: Thus, the main purpose of this study was to investigate the direct in vitro and ex vivo effect of BRP on Paracoccidioides brasiliensis., Material and Methods: Antifungal activity of different concentrations of BRP on a virulent P. brasiliensis isolate (Pb18) was evaluated using the microdilution technique. Also, mice splenic cells co-cultured with Pb18 were treated with BRP at different times and concentrations (only Pb18 = negative control). Mice were inoculated with Pb18 and treated with different concentrations of BRP (50-500 mg/mL) in a subcutaneous air pouch. In this later experimental model, macroscopic characteristics of the air pouch were evaluated, and cellular exudate was collected and analyzed for cellular composition, mitochondrial activity, total protein reactive oxygen specimens (ROS), and nitric oxide production, as well as the number of viable fungal cells., Results: The in vitro experiments showed remarkable direct antifungal activity of BRP, mainly with the highest concentration employed (500 mg/mL), reducing the number of viable cells to 10% of the original inoculum after 72 h incubation. The splenocytes co-cultivation assays showed that BRP had no cytotoxic effect on these cells, on the contrary, exerted a stimulatory effect. This stimulation was also observed on the PMNs at the air pouch, as verified by production of ROS and total proteins and mitochondrial activity. This activation resulted in enhanced fungicidal activity, mainly with the 500 mg/mL concentration of BRP. An anti-inflammatory effect was also detected, as verified by the smaller volume of the BRP-treated air pouch as well as by an earlier shift from neutrophils to mononuclear cells present in the infection site., Conclusion: Our results strongly suggest, for the first time in the literature, that Brazilian Red propolis has four protective mechanisms in experimental paracoccidioidomycosis: activating neutrophils, exerting a direct antifungal effect, preventing fungal dissemination, and controlling excessive inflammation process., (Published by Elsevier B.V.)

Ethnopharmacological Relevance: Propolis has been used in folk medicine for thousands of years and, in the past few decades, it has attracted renewed interest. Although propolis has been traditionally used in many communities worldwide against parasitic diseases, its effect against Schistosoma mansoni infection remains unclear., Aim of the Study: To demonstrate the effects of Brazilian red propolis on Schistosoma mansoni ex vivo and in an animal model of schistosomiasis., Materials and Methods: In vitro, we monitored phenotypic and tegumental changes as well as the effects of the crude extract of propolis on pairing and egg production. In a mouse infected with either immature (early infection) or adult (chronic infection) worms, propolis was administered by oral gavage and we studied the influence of this natural product on worm burden and egg production., Results: Propolis 25 μg/mL reduced motility and caused 100% mortality of adult parasites ex vivo. Further analysis revealed a pronounced reduction in oviposition after exposure to propolis at sub-lethal concentrations. In addition, scanning electron microscopy showed morphological alterations in the tegument of schistosomes. In the animal model, propolis markedly reduced worm burden and egg production in both early and chronic S. mansoni infection when compared to untreated control animals., Conclusions: The efficacy of Brazilian red propolis in both in vitro and in vivo studies suggests its potential anthelmintic properties against S. mansoni infection., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Propolis has been used in folk medicine since ancient times and it presented inhibitory effect on neutrophil recruitment previously. However, its effect on macrophage obtained from mice remains unclear., Aim of the Study: To demonstrate BRP effects on LPS activated peritoneal macrophage., Materials and Methods: Peritoneal macrophages, obtained from C57BL6 mice and activated with LPS, were treated with 50-80µg/mL of crude extract of Brazilian red propolis (BRP) during 48h. Cell viability, levels of NO, 20 cytokines and expression of 360 genes were evaluated., Results: BRP 60µg/mL reduced NO production by 65% without affecting the cell viability and decreased production IL1α, IL1β, IL4, IL6, IL12p40, Il12p70, IL13, MCP1 and GM-CSF. Molecular mechanism beyond the anti-inflammatory activity may be due to BRP-effects on decreasing expression of Mmp7, Egfr, Adm, Gata3, Wnt2b, Txn1, Herpud1, Axin2, Car9, Id1, Vegfa, Hes1, Hes5, Icam1, Wnt3a, Pcna, Wnt5a, Tnfsf10, Ccl5, Il1b, Akt1, Mapk1, Noxa1 and Cdkn1b and increasing expression of Cav1, Wnt6, Calm1, Tnf, Rb1, Socs3 and Dab2., Conclusions: Therefore, BRP has anti-inflammatory effects on macrophage activity by reducing NO levels and diminished release and expression of pro-inflammatory cytokine and genes, respectively., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: The pharmacological activity of geopropolis collected by stingless bees (important and threatened pollinators), a product widely used in folk medicine by several communities in Brazil, especially in the Northeast Region, needs to be studied., Objective: The aim of this study was to evaluate the antinociceptive activity of Melipona scutellaris geopropolis (stingless bee) using different models of nociception., Material and Methods: The antinociceptive activity of the ethanolic extract of geopropolis (EEGP) and fractions was evaluated using writhing induced by acetic acid, formalin test, carrageenan-induced hypernociception, and quantification of IL-1β and TNF-α. The chemical composition was assessed by quantification of total flavonoids and phenolic compounds., Results: EEGP and its hexane and aqueous fractions showed antinociceptive activity. Both EEGP and its aqueous fraction presented activity in the mechanical inflammatory hypernociception induced by the carrageenan model, an effect mediated by the inhibition of IL-1β and TNF-α. The chemical composition of EEGP and its hexane and aqueous fractions showed a significant presence of phenolic compounds and absence of flavonoids., Conclusion: Our data indicate that geopropolis is a natural source of bioactive substances with promising antinociceptive activity., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Propolis has been used as a medicinal agent to treat infections and promote wound healing for centuries. The aim of the present study was to test the antimicrobial, antioxidant, and cytotoxic activities of a new type of Brazilian propolis, popularly called red propolis, as well as to analyze its chemical composition. The antimicrobial activity against Staphylococcus aureus ATCC 25923 and Staphylococcus mutans UA159 was evaluated and the chloroform fraction (Chlo-fr) was the most active with lower MIC ranging from 25 to 50 microg/ml. The hexane fraction (H-fr), having the highest concentration of total flavonoids, showed the best sequestrating activity for the free radical DPPH. The ethanolic extract of propolis (EEP) showed cytotoxic activity for the HeLa tumor cells with an IC(50) of 7.45 microg/ml. When the EEP was analyzed by GC-MS, seven new compounds were found, among which four were isoflavones. Our results showed that the red propolis has biologically active compounds that had never been reported in other types of Brazilian propolis.