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      Therapeutic Properties of Bioactive Compounds from Different Honeybee Products

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          Abstract

          Honeybees produce honey, royal jelly, propolis, bee venom, bee pollen, and beeswax, which potentially benefit to humans due to the bioactives in them. Clinical standardization of these products is hindered by chemical variability depending on honeybee and botanical sources, but different molecules have been isolated and pharmacologically characterized. Major honey bioactives include phenolics, methylglyoxal, royal jelly proteins (MRJPs), and oligosaccharides. In royal jelly there are antimicrobial jelleins and royalisin peptides, MRJPs, and hydroxy-decenoic acid derivatives, notably 10-hydroxy-2-decenoic acid (10-HDA), with antimicrobial, anti-inflammatory, immunomodulatory, neuromodulatory, metabolic syndrome preventing, and anti-aging activities. Propolis contains caffeic acid phenethyl ester and artepillin C, specific of Brazilian propolis, with antiviral, immunomodulatory, anti-inflammatory and anticancer effects. Bee venom consists of toxic peptides like pain-inducing melittin, SK channel blocking apamin, and allergenic phospholipase A2. Bee pollen is vitaminic, contains antioxidant and anti-inflammatory plant phenolics, as well as antiatherosclerotic, antidiabetic, and hypoglycemic flavonoids, unsaturated fatty acids, and sterols. Beeswax is widely used in cosmetics and makeup. Given the importance of drug discovery from natural sources, this review is aimed at providing an exhaustive screening of the bioactive compounds detected in honeybee products and of their curative or adverse biological effects.

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          Most cited references 211

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          Review of the biological properties and toxicity of bee propolis (propolis).

           G.A. Burdock (1998)
          Propolis is a multifunctional material used by bees in the construction and maintenance of their hives. Use of propolis by humans has a long history, predated only by the discovery of honey. Use of products containing propolis have resulted in extensive dermal contact and it is now increasingly being used a dietary supplement. Unlike many 'natural' remedies, there is a substantive database on the biological activity and toxicity of propolis indicating it may have many antibiotic, antifungal, antiviral and antitumour properties, among other attributes. Although reports of allergic reactions are not uncommon, propolis is relatively non-toxic, with a no-effect level (NOEL) in a 90-mouse study of 1400 mg/kg body weight/day.
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            Royalactin induces queen differentiation in honeybees.

            The honeybee (Apis mellifera) forms two female castes: the queen and the worker. This dimorphism depends not on genetic differences, but on ingestion of royal jelly, although the mechanism through which royal jelly regulates caste differentiation has long remained unknown. Here I show that a 57-kDa protein in royal jelly, previously designated as royalactin, induces the differentiation of honeybee larvae into queens. Royalactin increased body size and ovary development and shortened developmental time in honeybees. Surprisingly, it also showed similar effects in the fruitfly (Drosophila melanogaster). Mechanistic studies revealed that royalactin activated p70 S6 kinase, which was responsible for the increase of body size, increased the activity of mitogen-activated protein kinase, which was involved in the decreased developmental time, and increased the titre of juvenile hormone, an essential hormone for ovary development. Knockdown of epidermal growth factor receptor (Egfr) expression in the fat body of honeybees and fruitflies resulted in a defect of all phenotypes induced by royalactin, showing that Egfr mediates these actions. These findings indicate that a specific factor in royal jelly, royalactin, drives queen development through an Egfr-mediated signalling pathway.
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              Functional properties of honey, propolis, and royal jelly.

              Honey, propolis, and royal jelly, products originating in the beehive, are attractive ingredients for healthy foods. Honey has been used since ancient times as part of traditional medicine. Several aspects of this use indicate that it also has functions such as antibacterial, antioxidant, antitumor, anti-inflamatory, antibrowning, and antiviral. Propolis is a resinous substance produced by honeybees. This substance has been used in folk medicine since ancient times, due to its many biological properties to possess, such as antitumor, antioxidant, antimicrobial, anti-inflammatory, and immunomodulatory effects, among others. Royal jelly has been demonstrated to possess numerous functional properties such as antibacterial activity, anti-inflammatory activity, vasodilative and hypotensive activities, disinfectant action, antioxidant activity, antihypercholesterolemic activity, and antitumor activity. Biological activities of honey, propolis, and royal jelly are mainly attributed to the phenolic compounds such as flavonoids. Flavonoids have been reported to exhibit a wide range of biological activities, including antibacterial, antiviral, anti-inflammatory, antiallergic, and vasodilatory actions. In addition, flavonoids inhibit lipid peroxidation, platelet aggregation, capillary permeability and fragility, and the activity of enzyme systems including cyclo-oxygenase and lipoxygenase.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                28 June 2017
                2017
                : 8
                Affiliations
                1Dipartimento di Scienze della Terra, dell’Ambiente e della Vita, Università degli Studi di Genova Genova, Italy
                2Unità Operativa di Biologia Farmaceutica, Dipartimento di Scienze Fisiche, della Terra e dell’Ambiente, Università degli Studi di Siena Siena, Italy
                3Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau Taipa, Macau
                4Dipartimento di Farmacia, Università degli Studi di Genova Genova, Italy
                Author notes

                Edited by: Monique S. J. Simmonds, Royal Botanic Gardens, Kew, United Kingdom

                Reviewed by: Parimal C. Sen, Bose Institute, India; Letizia Angiolella, Sapienza Università di Roma, Italy

                *Correspondence: Laura Cornara, cornara@ 123456dipteris.unige.it

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2017.00412
                5487425
                Copyright © 2017 Cornara, Biagi, Xiao and Burlando.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 0, Tables: 1, Equations: 0, References: 223, Pages: 21, Words: 0
                Funding
                Funded by: Università degli Studi di Genova 10.13039/501100004702
                Award ID: 100022-2015 FRA
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine

                royal jelly, bee venom, beeswax, honey, propolis, bee pollen

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