Propolis is a resinous material collected by bees from bud and exudates of the plants, mixed with bee enzymes, pollen and wax. In this review, the biological properties of propolis and some therapeutic applications are discussed. The same biological activities have been investigated until today, using samples from different geographic regions. Thus, the study of the biological properties of a given sample should always be associated with its chemical composition and botanical source, representing a particular sample of a given geographic area, exploring its biological potential and the role of its constituents. Efforts have been carried out to explain propolis' mechanisms of action in vivo and in vitro, but the majority of propolis' targets and actions are still unclear. The number of formulations containing propolis and patents have increased, although propolis extracts have been used deliberately with different recommendations, not always mentioning the chemical composition, vegetal source and the methods of extraction. Clinical studies will help to obtain criterious recommendations in view of the expected outcomes. Further investigation should explore the effects of common compounds found in the samples from all over the world in an attempt to standardize the research on propolis and to obtain new drugs. Copyright © 2016 John Wiley & Sons, Ltd.

Propolis is one of the most fascinating honey bee (Apis mellifera L.) products. It is a plant derived product that bees\ud produce from resins that they collect from different plant organs and with which they mix beeswax. Propolis is a building\ud material and a protective agent in the bee hive. It also plays an important role in honey bee social immunity, and is\ud widely used by humans as an ingredient of nutraceuticals, over-the-counter preparations and cosmetics. Its chemical\ud composition varies by geographic location, climatic zone and local flora. The understanding of the chemical diversity of\ud propolis is very important in propolis research. In this manuscript, we give an overview of the available methods for\ud studying propolis in different aspects: propolis in the bee colony; chemical composition and plant sources of propolis;\ud biological activity of propolis with respect to bees and humans; and approaches for standardization and quality control\ud for the purposes of industrial application

Propolis has been the subject of several recent studies, with the aim of elucidating its biological and pharmacological properties. Propolis has a well-known antimicrobial activity as well as antioxidant, antitumoral, antiinflammatory, and regenerative properties, but literature about its effects on the immune response is scarce. The goal of this work was to evaluate the propolis effect on macrophage activation by oxygen (H2O2) and nitrogen (NO) metabolite determination. Propolis was produced by africanized honeybees and hydroalcoholic solutions were prepared at different concentrations. Peritoneal macrophages were obtained from male BALB/c mice and culture cells were stimulated in vitro with propolis or interferon-gamma (IFN-gamma). In the in vivo assay, the animals were sacrificed after propolis treatment and cells were stimulated with IFN-gamma. We also investigated the co-stimulant action of propolis associated with IFN-gamma on macrophages. The results show that propolis induces a discreet elevation in H2O2 release and a mild inhibition of NO generation, depending on concentration. Propolis had no co-stimulant activity, diminishing IFN-gamma action on H2O2 and NO production. Data suggest that propolis acts on host non-specific immunity by macrophage activation

Propolis and its constituent caffeic acid suppress LPS-stimulated pro-inflammatory response by blocking NF-κB and MAPK activation in macrophages, Journal of Ethnopharmacology, http://dx.doi.org/ 10. 1016/j.jep.2013.06.004 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractEthnopharmacological relevance: Propolis is a bee product with numerous biological and pharmacological properties, such as immunomodulatory and anti-inflammatory activities.It has been used in folk medicine as a healthy drink and in food to improve health and prevent inflammatory diseases. However, little is known about its mechanism of action.Thus, the goal of this study was to verify the antioxidant activity and to explore the antiinflammatory properties of propolis by addressing its intracellular mechanism of action.Caffeic acid was investigated as a possible compound responsible for propolis action. Materials and Methods:The antioxidant properties of propolis and caffeic acid were evaluated by using the 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH) scavenging method. To analyze the anti-inflammatory activity, Raw 264.7 macrophages were treated with different concentrations of propolis or caffeic acid, and nitric oxide (NO) production, a strong pro-inflammatory mediator, was evaluated by the Griess reaction. The concentrations of propolis and caffeic acid that inhibited NO production were evaluated on intracellular signaling pathways triggered during inflammation, namely p38 mitogenactivated protein kinase (MAPK), c-jun NH 2 -terminal kinase (JNK1/2), the transcription nuclear factor (NF)-NB and extracellular signal-regulated kinase (ERK1/2), through Western blot using specific antibodies. A possible effect of propolis on the cytotoxicity of hepatocytes was also evaluated, since this product can be used in human diets.Results: Caffeic acid showed a higher antioxidant activity than propolis extract. Propolis and caffeic acid inhibited NO production in macrophages, at concentrations without cytotoxicity. Furthermore, both propolis and caffeic acid suppressed LPS-induced signaling pathways, namely p38 MAPK, JNK1/2 and NF-NB. ERK1/2 was not affected by propolis extract and caffeic acid. In addition, propolis and caffeic acid did not induce hepatotoxicity at concentrations with strong anti-inflammatory potential. Conclusions:Propolis exerted an antioxidant and anti-inflammatory action and caffeic acid may be involved in its inhibitory effects on NO production and intracellular signaling cascades, suggesting its use as a natural source of safe anti-inflammatory drugs.

Propolis, A raucaria angustifolia, B accharis dracunculifolia, Eucalyptus citriodora, Botanical Origin Propolis and plant secretions from three species, most frequently mentioned as botanical sources of the bee glue in Brazil (B accharis dracunculifolia, A raucaria angustifolia and E u ca lyptus citriodora) have been investigated using GC-MS. Based on chemical evidence, B. dra cunculifolia was shown to be the main propolis source in Säo Paulo state. The antibacterial and antifungal activities of all four materials were also tested, the most active being propolis and B accharis leaf exudate.

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Recently, propolis has been attracting the attention of researchers due to various biological activities and therapeutic properties. In Brazil, propolis is produced all year long, so there may be some seasonal variations. This work was carried out in order to compare propolis collected during the four seasons by its in vitro antimicrobial activity on yeast pathogens isolated from human infections. Propolis was produced by africanized honeybees in Botucatu, São Paulo State, collected throughout a year and pooled by season. Hydroalcoholic solutions of propolis were prepared with each pool and diluted in agar, using serial concentrations of propolis from each pool. A determination of minimal inhibitory concentration (MIC) was performed. The results show that Candida tropicalis and Candida albicans were susceptible to low concentrations of propolis, the latter showing a higher susceptibility. No differences were seen in relation to seasonal effects in the minimal inhibitory concentration of propolis

Propolis exerted an immunomodulatory action on cell receptors, cytokine production and fungicidal activity of human monocytes without affecting cell viability and depending on concentration. TLR-2 and TLR-4 may be involved in its mechanism of action.