The Candida genus comprises opportunistic fungi that can become pathogenic when the immune system of the host fails. Candida albicans is the most important and prevalent species. Polyenes, fluoropyrimidines, echinocandins, and azoles are used as commercial antifungal agents to treat candidiasis. However, the presence of intrinsic and developed resistance against azole antifungals has been extensively documented among several Candida species. The advent of original and re-emergence of classical fungal diseases have occurred as a consequence of the development of the antifungal resistance phenomenon. In this way, the development of new satisfactory therapy for fungal diseases persists as a major challenge of present-day medicine. The design of original drugs from traditional medicines provides new promises in the modern clinic. The urgent need includes the development of alternative drugs that are more efficient and tolerant than those traditional already in use. The identification of new substances with potential antifungal effect at low concentrations or in combination is also a possibility. The present review briefly examines the infections caused by Candida species and focuses on the mechanisms of action associated with the traditional agents used to treat those infections, as well as the current understanding of the molecular basis of resistance development in these fungal species. In addition, this review describes some of the promising alternative molecules and/or substances that could be used as anticandidal agents, their mechanisms of action, and their use in combination with traditional drugs.

Using a murine model of susceptibility and resistance to paracoccidioidomycosis, we have previously demonstrated that immunosuppression occurs in susceptible (B10.A), but not in resistant (A/Sn), mouse strains. Accumulating evidence shows that NO is involved in the induction of T cell immunosuppression during infection as well as in the killing of Paracoccidioides brasiliensis. In the present work, we focused on NO and other macrophage products that could be associated with resistance or susceptibility to paracoccidioidomycosis. A striking difference was related to NO and TNF production. Macrophages from B10.A mice produced high and persistent NO levels, while in A/Sn animals, TNF production predominated. In in vitro cultures, P. brasiliensis-infected macrophages from A/Sn mice also produced large amounts of TNF, while B10.A macrophages only produced NO. TNF production by B10.A macrophages appeared to be suppressed by NO, because the addition of aminoguanidine sulfate, an inducible NO synthase (NOS2) inhibitor, resulted in TNF production. These results suggested that enhanced TNF or NO production is associated with resistance and susceptibility, respectively. However, regardless of the mouse strain, NOS2-deficient or aminoguanidine sulfate-treated mice presented extensive tissue lesions with increased fungal load in lungs and liver compared with their controls. We conclude that NOS2-derived NO is essential for resistance to paracoccidioidomycosis, but overproduction is associated with susceptibility.

The immunomodulatory and anti-inflammatory activities of green propolis extracts from Apis mellifera were investigated using acute and chronic inflammation models. Swiss mice were anesthetized and a cotton pellet granuloma was implanted in subcutaneous tissue. Then the mice were divided into six groups and received apyrogenic water or different propolis extracts by oral route (5 mg/kg). According to the treatment the groups were designated as E1A, E1B, E10, E11, and E12. The control group received apyrogenic water. The treatment was performed by six days when the mice were killed. The blood and the bronchoalveolar lavage (BAL) were collected to measure the leukocyte recruitment. In acute pulmonary inflammation, Balb/c mice received lipopolysaccharide (LPS) of Escherichia coli by intranasal route for three days. Concomitantly the mice received by oral route apyrogenic water (control) or E10 and E11 propolis extracts. BAL was performed to assess the inflammatory infiltrate and cytokine quantification. The results showed that the E11 extract has anti-inflammatory property in both models by the inhibition of proinflammatory cytokines and increase of anti-inflammatory cytokines suggesting an immunomodulatory activity.

Geopropolis is a mixture of plant resins, waxes, and soil produced by the stingless bee Melipona fasciculata Smith. This paper describes the antioxidant activity and chemical composition of geopropolis produced by M. fasciculata. The total phenolic content determined with the Folin-Ciocalteu reagent was highest in the ethyl acetate fraction and hydroalcoholic extract. Antioxidant activity was assayed by the in vitro DPPH, ABTS, and FRAP assays. The hydroalcoholic extract and fractions of geopropolis, except for the hexane fraction, exhibited antioxidant activity against DPPH, ABTS, and FRAP. The phenolic compounds were identified by HPLC-DAD-MS on the basis of the evaluation of their UV-vis absorption maxima (λmax) and mass spectral analysis. Eleven compounds belonging to the classes of phenolic acids and hydrolyzable tannins (gallotannins and ellagitannins) were tentatively identified. These compounds are responsible for the antioxidant activity and high phenolic content of geopropolis produced by M. fasciculata.

Propolis is a resinous substance made by bees. It possesses many biological activities, and many studies have reported its potential application in the control of dental caries. However, variability in the chemical composition of propolis is a potential problem in its quality control, especially since propolis has already been incorporated into products for oral use. Therefore, a critical analysis of the available data on propolis is warranted. The present review discusses the in vitro and in vivo studies published in the period between 1978 and 2008 regarding the effects of propolis on Streptococcus mutans growth, bacterial adherence, glucosyltransferase activity, and caries indicators. Several investigations carried out with crude propolis extracts, isolated fractions, and purified compounds showed reductions in Streptococcus mutans counts and interference with their adhesion capacity and glucosyltransferase activity, which are considered major properties in the establishment of the cariogenic process. Data from in vivo studies have demonstrated reductions in Streptococcus mutans counts in saliva, the plaque index, and insoluble polysaccharide formation. These findings indicate that propolis and/or its compounds are promising cariostatic agents. However, the variation in the chemical composition of propolis due to its geographical distribution is a significant drawback to its routine clinical use. Thus, further studies are needed to establish the quality and safety control criteria for propolis in order for it to be used in accordance with its proposed activity.