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

Ethnopharmacological 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 anti-inflammatory 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 mitogen-activated protein kinase (MAPK), c-jun NH2-terminal kinase (JNK1/2), the transcription nuclear factor (NF)-κB 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-κB. 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. © 2013 Elsevier B.V.

MyD88 or TRAM knockdown regulates interleukin (IL)-6, IL-8, and CXCL12 mRNA expression in human gingival and periodontal ligament fibroblasts

Background: In a previous report, it was shown that Toll-like receptor (TLR) 2 knockdown modulates interleukin (IL)-6 and IL-8 but not the chemokine CXCL12, an important mediator with inflammatory and proangiogenic effects, in human gingival fibroblasts (HGF) and human periodontal ligament fibroblasts (HPDLF). This study investigates whether knocking down two important TLR adaptor molecules, such as myeloid differentiation protein 88 (MyD88) and TRIF-related adaptor molecule (TRAM), could affect mRNA expression of IL-6, IL-8, and CXCL12 in HGF and HPDLF. Methods: After small interfering (si) RNA-mediated silencing of MyD88 or TRAM, HGF and HPDLF were stimulated with Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS) or two synthetic ligands of TLR2 (Pam2CSK4 and Pam3CSK4) for 6 hours. IL-6, IL-8, and CXCL12 mRNAs were evaluated by quantitative polymerase chain reaction. Results: Knockdown of MyD88 or TRAM partially impaired the IL-8 mRNA upregulation in both fibroblast subpopulations. Similarly, IL-6 upregulation was partially prevented by siMyD88 or siTRAM in HGF stimulated with Pg LPS, as well as in both fibroblast subtypes challenged with Pam2CSK4. Conversely, constitutive CXCL12 mRNA levels were upregulated by MyD88 or TRAM knockdown in non-stimulated cells. Conclusions: These results suggest that TLR adaptor molecules knockdown, such as MyD88 or TRAM, can decrease IL-6 and IL-8 mRNA and increase CXCL12 mRNA expression in HGF and HPDLF. This can be an important step for better understanding the mechanisms that control the inflammatory cytokine and chemokine expression, which in turn contributes to periodontal pathogenesis.

Imunomarcação de COX-2 e TGF-beta nas lesòes proliferativas da próstata do cão

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Professores de artes: formação continuada e os reflexos na sala de aula das séries iniciais

Pós-graduação em Artes - IA

Arte, vida e formação de professores

Pós-graduação em Artes - IA

Olhares que pensam e sentem: arte e mediação cultural na aula de geometria

Pós-graduação em Artes - IA

Comunicação pública e cidadania: um estudo exploratório na unidade do poupatempo Bauru (SP)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Educação ambiental e escola pública: concepções e práticas pedagógicas nos materiais didáticos institucionais (1988-2005)

Pós-graduação em Educação - IBRC

O jogo e a educação matemática: um estudo sobre as crenças e concepções dos professores de matemática quanto ao espaço do jogo no fazer pedagógico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Adaptação de livros de literatura infantil para alunos com deficiência visual

Pós-graduação em Educação - FFC

Analogias e metáforas no ensino de física: o discurso do professor e o discurso do aluno

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

As inter-relações das tecnologias de informação e de comunicação com alguns conceitos da teoria de Davydov para o ensino de matemática

Pós-graduação em Educação Matemática - IGCE

A organização do trabalho pedagógico no contexto das atividades de leitura e escrita

Pós-graduação em Educação - FFC

Estratégias de mediação em atividade de reconto de histórias com alunos com paralisia cerebral sem oralidade

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Orientação e mobilidade: estudo sobre equilíbrio e estratégias de locomoção utilizadas pelo professor

Pós-graduação em Educação - FFC