Carnosic acid inhibits mast cell pro‐inflammatory mediator release in allergic inflammation
Bibliographic record
Abstract
Over the past several decades, developed countries have been plagued by the increasing prevalence of allergic disorders. This allergy epidemic has led to an exponential increase in health care‐associated costs, while significantly deteriorating quality of life for those affected. Allergic inflammation is a consequence of an excessive and undesirable immune response towards environmental allergens, mediated by immune sentinels known as mast cells. Mast cells are ubiquitously distributed in vascularized tissues, where they play an essential role in host defence, in addition to pathological contexts of inflammation. Allergen detection by the immune system results in IgE‐mediated mast cell activation, characterized by rapid degranulation during the early phase, and sustained release of newly synthesized pro‐inflammatory mediators in the late phase. Plant derived micronutrients, known as polyphenols, have been explored as therapeutic options in pathological models, due to the modulatory effects they have on pro‐inflammatory mediator release. We have recently established rosemary extract (RE); a mixture abundant in polyphenolic compounds, as a potent inhibitor of mast cell mediated allergic inflammation, through attenuation of essential signalling cascades required for pro‐inflammatory mediator secretion. The objective of this study was to evaluate the therapeutic potential of three major polyphenolic constituents of RE including: carnosic acid (CA), carnosol (CO), and rosmarinic acid (RA), assessing the ability of isolated polyphenols to inhibit pro‐inflammatory mediator release following mast cell activation. Bone marrow‐derived mast cells (BMMCs) were sensitized with IgE and stimulated with allergen, while simultaneously treated with various concentrations of CA, CO, or RA. Mast cell degranulation was measured via the β‐hexosaminidase release assay, while late phase pro‐inflammatory mediator release was quantified by enzyme‐linked immunosorbent assay. Following individual treatment with CA and CO, β‐hexosaminidase release was significantly inhibited dose‐dependently to 14% and 17% of control respectively (p < 0.001), while RA had no effect on β‐hexosaminidase release. ELISA analysis showed that CA significantly inhibited release of TNF (p<0.0001), IL‐6 (p<0.0001), IL‐13 (p<0.0001), CCL1 (p<0.001), and CCL2 (p<0.05), RA inhibited CCL2 (p<0.05), and treatment with CO did not inhibit the release of any cytokine examined. These results suggest that CA is a potent inhibitor of both the early and late phase of allergen‐induced mast cell activation. Further dissection of the mechanism behind CA mediated modulation of essential mast cell signalling and subsequent pro‐inflammatory mediator release will inform on its utility in regulation of mast cell function in numerous mast cell‐dependent inflammatory disorders. Support or Funding Information Supported by the Natural Sciences and Engineering Research Council of Canada (NSERC); Canada Foundation for Innovation (CFI); Government of Ontario; and Brock University.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".