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

Abstract

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.

Green propolis modulates gut microbiota, reduces endotoxemia and expression of TLR4 pathway in mice fed a high-fat diet

“…Our results show that propolis lowers the inflammatory response through a diminished expression of the TLR4 pathway. Búfalo et al (2013) did report the antiinflammatory effect of propolis by holding back the unphosphorylated IκBα and down-regulating NF-κB, central to the inflammatory cascade.…”

Antinociceptive and anti-inflammatory effects of Brazilian red propolis extract and formononetin in rodents

“…actions have been demonstrated, like antioxidant (Frozza et al, 2013), anti-nociceptive (Franchin et al, 2012), and anti-inflammatory (Búfalo et al, 2013;Szliszka et al, 2013). These activities are linked to its bioactive compounds and it is noteworthy that propolis from different geographic regions can vary significantly in its chemical composition (López et al, 2014;Piccinelli et al, 2011;Sawaya et al, 2011).…”

Insight into the molecular mechanism of a herbal injection by integrating network pharmacology and in vitro

“…Recent studies demonstrated that Chlorogenic Acid, Isochlorogenic Acid A, Isochlorogenic Acid B and Isochlorogenic Acid C could attenuate the release of PGE 2 and IL-6 in macrophage Shan et al, 2009). Caffeic Acid suppressed LPS-stimulated pro-inflammatory response in RAW264.7 cells (Bufalo et al, 2013;Uwai et al, 2008). However, to date, no scientific study has been done on the combination effects of the compounds in RDN.…”