Anti-inflammatory effects of cinnamon extract and identification of active compounds influencing the TLR2 and TLR4 signaling pathways.

PURPOSE: Inflammatory processes are involved in many diseases. The bark of Cinnamomum verum and its extracts are well known for anti-inflammatory effects, but the underlying active compounds and chemical mechanisms are not yet fully identified. The objective of this study was to elucidate how cinnamon extract, specifically active compounds, and their combinations influence the signaling pathways of inflammation, especially through toll-like receptors TLR2 and TLR4. METHODS: Bioassay-guided fractionation was performed for standard ethanolic cinnamon extract using high performance liquid chromatography followed by compound identification in the determined active fractions by high-resolution mass spectrometry and gas chromatography-mass spectrometry. THP-1 monocytes were pre-incubated with cinnamon extract, cinnamon fractions or its compounds and stimulated with lipopolysaccharides (LPS), followed by determination of interleukin 8 (IL-8) secretion, and phosphorylation of protein kinase B (Akt), nuclear factor (NF)-κB inhibitor alpha (IκBα) and p38. Furthermore, testing was performed in stimulated HEK-TLR2 and HEK-TLR4 reporter cells for direct receptor agonistic effects. RESULTS: Among the identified compounds, trans-cinnamaldehyde and p-cymene significantly reduced the LPS-dependent IL-8 secretion in THP-1 monocytes. Synergistic anti-inflammatory effects were observed for combinations of trans-cinnamaldehyde with p-cymene, cinnamyl alcohol or cinnamic acid. Moreover, cinnamon extract as well as trans-cinnamaldehyde and p-cymene mitigated the phosphorylation of Akt and IκBα. CONCLUSIONS: Trans-cinnamaldehyde and p-cymene contribute to the strong anti-inflammatory effects of cinnamon extract. Furthermore, our experiments indicate that also synergistic effects among compounds that do not exhibit anti-inflammatory effects themselves might be present to positively influence the beneficial effects of cinnamon bark extract.

Fresh water, marine and terrestrial cyanobacteria display distinct allergen characteristics.

During the last decades, global cyanobacteria biomass increased due to climate change as well as industrial usage for production of biofuels and food supplements. Thus, there is a need for thorough characterization of their potential health risks, including allergenicity. We therefore aimed to identify and characterize similarities in allergenic potential of cyanobacteria originating from the major ecological environments. Different cyanobacterial taxa were tested for immunoreactivity with IgE from allergic donors and non-allergic controls using immunoblot and ELISA. Moreover, mediator release from human FcεR1-transfected rat basophilic leukemia (RBL) cells was measured, allowing in situ examination of the allergenic reaction. Phycocyanin content and IgE-binding potential were determined and inhibition assays performed to evaluate similarities in IgE-binding epitopes. Mass spectrometry analysis identified IgE-reactive bands ranging between 10 and 160kDa as phycobiliprotein compounds. Levels of cyanobacterial antigen-specific IgE in plasma of allergic donors and mediator release from sensitized RBL cells were significantly higher compared to non-allergic controls (p<0.01). Inhibition studies indicated cross-reactivity between IgE-binding proteins from fresh water cyanobacteria and phycocyanin standard. We further addressed IgE-binding characteristics of marine water and soil-originated cyanobacteria. Altogether, our data suggest that the intensive use and the strong increase in cyanobacterial abundance due to climate change call for increasing awareness and further monitoring of their potential health hazards.