Nov. 1, 2004 BETHESDA, Md. (October 28, 2004) – Homing in on mechanisms for the reported effectiveness of resveratrol, which is found in red wine, researchers at Imperial College London, England, confirmed its broad anti-inflammatory action, and found potential for applications in chronic obstructive pulmonary disease (COPD), asthma, and possibly even arthritis. Clinical preparation and delivery remain issues, though an aerosol version would have obvious benefits.
Indeed, lead researcher Louise Donnelly said "Resveratrol exhibited anti-inflammatory activity in all the systems we examined: laboratory cells lines as well as 'real' human airway epithelial cells," or HAEC. The research paper published by Donnelly et al. in the American Journal of Physiology-Lung Cellular and Molecular Physiology, notes: "Our study is novel as it examines the anti-inflammatory mechanism(s) of resveratrol in cells relevant to human disease and explores all of the proposed mechanisms in a single study."
Most importantly, resveratrol "inhibited anti-inflammatory mediator release from human airway epithelial cells." And contrary to earlier conjecture, the Imperial College researchers showed that "resveratrol did not act as an estrogen or glucocorticosteroid," each of which have patient acceptance issues.
Resveratrol from red wine has long been associated with the so-called "French Paradox," reflecting the low incidence of heart disease among the French despite their relatively high-fat diet. It is a polyphenolic compound found in the skins of such red fruits as grapes and plums, the red skin of peanuts, and even peanut butter. However, Donnelly noted there's "no evidence that COPD, asthma (especially in asthmatic smokers) or related diseases have lower incidence in France or elsewhere in the Mediterranean region."
OTC versions not useful: aerosol version needed
Moreover, Donnelly warned that their research group had "looked at the over-the-counter" versions of resveratrol and found that "it's not very pure and probably wouldn't be worth taking." The major problem is bioavailability. The compound dissolves only in certain solvents, including alcohol, "and is cleared very rapidly in the liver," Donnelly said.
Especially for such respiratory diseases as COPD and asthma, developing an aerosol version for inhalation probably would be a better option," Donnelly said, noting that it would overcome one of the problems with steroids, which is noncompliance.
The current research aimed to confirm and quantify the effect of resveratrol and quercetin, a related plant-derived polyphenolic compound that often mimics its diverse activities, and to further study the molecular mechanisms involved.
While resveratrol "exhibited anti-inflammatory activity in all the systems we examined," the researchers said, "it appeared to be more effective, although less potent, than glucocorticoids. Resveratrol also inhibited inflammatory mediator release from human airway epithelial cells (HAEC), inhibited iNOS and COX-2 (cyclooxygenase) gene transcription, together with IL-8 and GM-CSF expression in HAEC. The inhibition of iNOS (inducible nitric oxide synthase) expression and activity in primary HAEC is significant, because steroids are ineffective in this system," the paper states.
IL-8 (interleukin-8) and GM-CSF (granulocyte-macrophage colony-stimulating factor) are important in the inflammation development, they noted, because IL-8 plays a major role in the recruitment of inflammatory leukocytes, particularly neutrophils, and GM-CSF is a cell survivor factor, thus prolonging the resident time of inflammatory cells. "The differential inhibitory effects of resveratrol on IL-8 and GM-CSF release (shown in this study) further suggest that resveratrol is not simply acting as a general inhibitor of inflammatory mediator release but exhibits some selectivity."
Next steps: further narrow mechanisms of broad anti-inflammatory
Donnelly et al. conclude that resveratrol and quercetin "can act as novel anti-inflammatory agents. Their mechanism of action is not via the estrogen or glucocorticoid receptor; thus these agents might be beneficial in inflammatory diseases where glucocorticosteroids have proved to be ineffective, such as COPD, steroid-resistant asthma, and arthritis. These compounds may provide candidate molecules for the development of novel anti-inflammatory therapies."
The current study "excluded a lot" of potential mechanisms of action, Donnelly said, but we "still don't know what its target receptor is as it binds like a protein, but acts like an estrogen," which it's not. "The good thing is that it does stop inflammation" across a broad range of systems, she added.
Source and funding: The article, "Anti-inflammatory effects of resveratrol in lung epithelial cells: molecular mechanisms," appears in the October issue of American Journal of Physiology-Lung Cellular and Molecular Physiology, published by the American Physiological Society.
In addition to Donnelly, other members of the research team, all from the Department of Thoracic Medicine, National Heart & Lung Institute, Imperial College London, England, are: Robert Newton, Gina E. Kennedy, Peter S. Fenwick, Rachel H.F. Leung, Kazuhiro Ito, Richard E.K. Russell and Peter J. Barnes.
Research was funded by grants from Pharmascience Inc., Pharmacia (part of Pfizer Inc.), the British Lung Foundation and the National Asthma Campaign (UK).
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