Cytotoxic, hepatoprotective and free radical scavenging effects of propolis from Brazil, Peru, the Netherlands and China

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.

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“…Cinnamic acid derivatives from Brazilian propolis showed a potent antioxidant activity as well (Banskota et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Propolis and its constituent caffeic acid suppress LPS-stimulated pro-inflammatory response by blocking NF-κB and MAPK activation in macrophages

Búfalo

Ferreira

Costa

et al. 2013

Journal of Ethnopharmacology

155

102

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“…Some specific effects of the aqueous extract of propolis have been demonstrated, such as the inhibition of platelet aggregation, inhibition of prostaglandin biosynthesis in vitro, prevention of formaldehyde-induced paw edema and arthritis and inhibition of 5-lipoxygenase (5-LOX) activity (Dobrowolski et al, 1991;Khayyal et al, 1993;Massaro et al, 2011). In addition, propolis has shown in vitro free radical scavenging activity and a hepatoprotective effect on TNF-α-induced cell death (Banskota et al, 2000;Alencar et al, 2007). The ethanol extract of propolis has shown dose-dependent anti-inflammatory effects in models of carrageenan-induced paw edema, Freund's adjuvantinduced arthritis and foreign body-induced granuloma, effects on vascular permeability, and analgesic activity (Park et al, 1996).…”

Section: Anti-inflammatory and Immunomodulatory Response To Propolis mentioning

confidence: 99%

Mechanisms of action underlying the anti-inflammatory and immunomodulatory effects of propolis: a brief review

Araújo

Libério

Guerra

et al. 2012

Rev. bras. farmacogn.

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Many biological properties have been attributed to various types of propolis, including anti-inflammatory, antimicrobial, antioxidant, antitumor, wound healing, and immunomodulatory activities. This article reviewed studies published that investigated the anti-inflammatory activity of propolis of different origins and/ or its isolated components, focusing on the mechanisms of action underlying this activity and also addressing some aspects of immunomodulatory effects. The search was performed of the following databases: PubMed, Science Direct, HighWire Press, Scielo, Google Academics, Research Gate and ISI Web of Knowledgement. The anti-inflammatory activity was associated with propolis or compounds such as polyphenols (flavonoids, phenolic acids and their esters), terpenoids, steroids and amino acids. CAPE is the most studied compounds. The main mechanisms underlying the anti-inflammatory activity of propolis included the inhibition of cyclooxygenase and consequent inhibition of prostaglandin biosynthesis, free radical scavenging, inhibition of nitric oxide synthesis, reduction in the concentration of inflammatory cytokines and immunosuppressive activity. Propolis was found to exert an antiinflammatory activity in vivo and in vitro models of acute and chronic inflammation and others studies, indicating its promising potential as anti-inflammatory agent of natural origin and as a source of chemical compounds for the development of new drugs.

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“…Este resultado sugere uma atividade antitumoral, devido a DL 50 ser menor que 1000 µg/mL, dosagem letal máxima para uma substância ser considerada ativa, além de uma correlação estatística entre a DL 50 e a atividade antitumoral (McLaughlin, 1993). Banskota et al (1998) (Banskota et al, 1998;Burdock, 1998;Banskota et al, 2000).…”

Section: Bioensaio Com Artemia Salina Leachunclassified

Variabilidade sazonal dos constituintes da própolis vermelha e bioatividade em Artermia salina

Nunes¹,

Galindo²,

Deus³

et al. 2009

Rev. bras. farmacogn.

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RESUMO:A própolis é uma substância resinosa coletada pelas abelhas de diversas partes das plantas. Sua composição depende da época, vegetação e local de coleta. Apresenta diversas atividades biológicas como antimicrobiana, antioxidante, antitumoral, dentre outras. Foi realizado estudo da variabilidade sazonal, nos meses de fevereiro, junho e outubro de 2006, dos constituintes voláteis da própolis vermelha de Pernambuco através da extração por headspace dinâmico e identificação por cromatografia gasosa acoplada com espectrometria de massas (CG-EM). Foram identificados 34 constituintes voláteis, sendo monoterpenos e monoterpenóides, sesquiterpenos e sesquiterpenóides, fenilpropanóides, aldeídos, cetonas e η-alcanos. Os constituintes majoritários foram o trans-anetol, α-copaeno e o metil cis-isoeugenol. Também foi realizado o perfil fitoquímico por cromatografia em camada delgada (CCD), através da qual os constituintes fenólicos foram identificados como majoritários. Com o extrato bruto metanólico da própolis, realizou-se o ensaio de letalidade em Artemia salina, que demonstrou DL 50 de 18,9 µg/mL, sugerindo uma possível atividade antitumoral. Unitermos: Própolis vermelha, constituintes voláteis, Artemia salina.ABSTRACT: "Seasonal variability of red propolis constituents and brine shrimp bioassay". Propolis is a resinous hive product collected by honeybees from plant sources. The composition of the propolis depends on the season, the vegetation, and the area of collection. It presents a diverse biological activities such as antimicrobial, antioxidant and antitumoral. The seasonal variability of the red propolis constituents from Pernambuco State were accomplished in the months of February, June and October of 2006. The volatile red propolis constituients were captured by the dynamic headspace technique and analyzed by GC-MS. In the analysis of the samples, 34 constituents were identified as the mono and sesquiterpens, phenylpropanoids, aldehydes, cetons and n-alcanes, presenting as majority constituents the trans-anethol, α-copaene and methyl cis-isoeugenol. The phytochemistry profile was performed by thin layer chromatography (TLC). Through this technique the majority constituents were identified as phenols. The Brine shrimp bioassay was used to evaluate of the red propolis methanolic extract, which demonstrated a DL 50 of 18.9 µg/mL and an activity antitumoral was possibly suggested.

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Cytotoxic, hepatoprotective and free radical scavenging effects of propolis from Brazil, Peru, the Netherlands and China

Cited by 210 publications

References 28 publications

Propolis and its constituent caffeic acid suppress LPS-stimulated pro-inflammatory response by blocking NF-κB and MAPK activation in macrophages

Propolis and its constituent caffeic acid suppress LPS-stimulated pro-inflammatory response by blocking NF-κB and MAPK activation in macrophages

Mechanisms of action underlying the anti-inflammatory and immunomodulatory effects of propolis: a brief review

Variabilidade sazonal dos constituintes da própolis vermelha e bioatividade em Artermia salina

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