Cinnamon extract and its active compounds attenuate TLR2-/TLR4-mediated inflammatory processes.
Herbal extracts represent an ample source of natural compounds, with potential to be used in improving human health. There is a growing interest in using natural extracts as possible new treatment strategies for inflammatory diseases. We therefore aimed at identifying herbal extracts that affect inflammatory signaling pathways through toll-like receptors (TLRs), TLR2 and TLR4. Ninety-nine ethanolic extracts were screened in THP-1 monocytes and HeLa-TLR4 transfected reporter cells for their effects on stimulated TLR2 and TLR4 signaling pathways. The 28 identified anti-inflammatory extracts were tested in comparative assays of stimulated HEK-TLR2 and HEK-TLR4 transfected reporter cells to differentiate between direct TLR4 antagonistic effects and interference with downstream signaling cascades. Furthermore, the ten most effective anti-inflammatory extracts were tested on their ability to inhibit nuclear factor-κB (NF-κB) translocation in HeLa-TLR4 transfected reporter cell lines and for their ability to repolarize M1-type macrophages. Ethanolic extracts which showed the highest anti-inflammatory potential, up to a complete inhibition of pro-inflammatory cytokine production were Castanea sativa leaves, Cinchona pubescens bark, Cinnamomum verum bark, Salix alba bark, Rheum palmatum root, Alchemilla vulgaris plant, Humulus lupulus cones, Vaccinium myrtillus berries, Curcuma longa root and Arctostaphylos uva-ursi leaves. Moreover, all tested extracts mitigated not only TLR4, but also TLR2 signaling pathways. Seven of them additionally inhibited translocation of NF-κB into the nucleus. Two of the extracts showed impact on repolarization of pro-inflammatory M1-type to anti-inflammatory M2-type macrophages. Several promising anti-inflammatory herbal extracts were identified in this study, including extracts with previously unknown influence on key TLR signaling pathways and macrophage repolarization, serving as a basis for novel lead compound identification.
During sample preparation and analysis, samples are coming in contact with different labware materials. By four unrelated analytical (phytochemical and pharmaceutical) case-studies and employing different analytical techniques, we demonstrated the potential misinterpretation of analytical results due to the use of contaminants-leaching labware during sample handling. Oleamide, a common polymer lubricant and a bioactive compound, was identified as a main analytical interference, leaching from different labware items into solvents, recognised as chemically compatible with the tested polymer material. Moreover, anti-inflammatory effect of oleamide at 100 μg mL −1 and considerable pro-inflammatory effect of the plastic syringe extractables (containing oleamide) at the same level were shown in a TLR4-based bioassay. Taking these results into account, together with the fact that oleamide can be a compound of natural origin, we would like to notify the professional public regarding the possible erroneous oleamide-related analytical and bioassay results due to the use of oleamide-leaching labware. Researchers are alerted to double check the real source of oleamide (labware or natural extract), which will prevent further reporting of false results. Analysis of procedural blanks with de-novo developed UHPLC-ESI-MS method is, among some other strategies, proposed for detection of oleamide interference and avoidance of misleading results of certain analyses.Due to the convenient use, plastic equipment is omnipresent in analytical and biological laboratories. Plastic additives, which enhance polymer properties, prolong their shelf-life and increase their functionality, are inevitably used during its production 1 . Among the known lubricants and slip additives, fatty acid amides are recognised, including oleamide, erucamide and stearamide 2,3 . Due to the lower number of carbon atoms, oleamide migrates faster from the polymer compared to erucamide and stearamide 2 .Moreover, oleamide is a bioactive signaling molecule found in cerebrospinal fluid of sleep-deprived animals 4,5 . It is reported to affect cannabinergic CB-1 6 , GABA A and serotonergic 5-HT receptors 7,8 and to possess anti-inflammatory activity 9-13 . Various other pharmacological effects of oleamide such as cannabinoid like behaviour 6,14 , inhibition of the enzyme human monoamine oxidase B 8,15 , closure of gap-junctions 16 and activation of TRPV1 vanilloid receptors 16 are also communicated. Despite the already reported studies regarding bioassay interferences 8,15,17 from plastic labware leachables, including oleamide, it has been continuously reported as analyte in natural extracts 5,11,12,[18][19][20][21] . At the same time, it has been rarely double checked to be a possible plastic labware interference 22-25 , perhaps due to its natural origin. For instance, few fatty acid amides (myristamide, palmitamide, linoleamide, elaidamide, stearamide and erucamide), frequently used as lubricating agents in polymer industry 26 , were reported to be the responsible co...
Background Ceylon cinnamon has been shown to possess anti‐inflammatory properties in many diseases including allergic inflammation. Objective The aim of this study was to analyse in more detail the effects of cinnamon extract (CE) and its major compounds p‐cymene and trans‐cinnamaldehyde (CA) on allergen‐specific immune responses in vitro and in vivo. Methods Therefore, monocyte‐derived mature dendritic cells (DC) from grass or birch pollen allergic donors were pulsed with the respective allergen in the presence or absence of CE, p‐cymene, CA or the solvent ethanol and co‐cultured with autologous CD4+ T cells. Furthermore, basophil activation test was performed with or without CE or ethanol treatment. For the in vivo experiments, BALB/c mice were immunized with ovalbumin (OVA) and orally treated with CE or ethanol. Results Addition of CE, p‐cymene or CA, but not ethanol significantly inhibited DC maturation and subsequent allergen‐specific T cell proliferation as well as Th1 and Th2 cytokine production. Sulphidoleukotriene release and CD63 expression by basophils were also significantly diminished after addition of CE. In vivo, treatment of OVA‐sensitized mice with CE led to a significant shift from OVA‐specific IgE towards IgG2a production and to a strong inhibition of OVA‐specific proliferation. Moreover, airway inflammation as well as anaphylaxis after intranasal or systemic allergen challenge was significantly reduced in CE‐treated mice. Furthermore, topical application of CE prevented calcipotriol‐induced atopic dermatitis‐like inflammation in these mice. Conclusions and Clinical Relevance Taken together, our data indicate that the anti‐inflammatory effect of cinnamon might be exploited for treatment of allergic inflammation, which needs to be further investigated.
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