Falcarinol (Panaxynol) is a CB1 cannabinoid receptor antagonist and induces pro-allergic effects in skin

• Published in: Planta Medica
• Main Authors: Gertsch, J, Leonti, M, Casu, L, Cottiglia, F, Raduner, S, Altmann, KH
• Format: Conference Proceeding
• Language: English
• Published: 21.07.2009
• ISSN: 0032-0943; 1439-0221
• DOI: 10.1055/s-0029-1234271

In our ongoing search for new cannabinoid receptor (CB) ligands we isolated falcarinol (panaxynol) from the endemic Sardinian plant species Seseli praecox Gramisans. This polyyne is also found in different food plants, such as carrots, parsley, celery, and in the medicinal plant Panax ginseng C.A. Meyer. We show that falcarinol exhibits non-selective binding affinity to human CB receptors ( h CB 1 =3.78±0.23µM; h CB 2 =2.36±0.4µM) whereas its natural derivative falcarindiol does not bind. Since purified falcarinol was highly unstable under all conditions tested we repeatedly isolated this compound for biological characterization. Major breakdown products were identified and one new polyyne was isolated. Based on experiments measuring intracellular calcium and cAMP using CB 1 /CB 2 transfected cell lines and selective antagonists, falcarinol is a weak partial CB 2 agonist but a more significant CB 1 inverse agonist. In CB receptor expressing human HaCaT keratinocytes falcarinol (5–20µM) but not falcarindiol increased the expression of the pro-allergic chemokines CCL2/MCP-1 and IL-8 and blocked the inhibition of TNF-alpha/tolerogen-stimulated CCL2/MCP-1 and IL-8 expression exerted by the endocannabinoid anandamide. Intriguingly, falcarinol strongly aggravated histamine-induced allergic reactions in skin prick tests performed on humans. Given the known contact allergic potential of topical falcarinol and the known anti-allergic effects mediated by anandamide and Δ9-tetrahydrocannabinol (THC) in the skin, falcarinol-associated dermatitis may be directly related to its blockage of the CB 1 receptor and increased IL-8 and CCL2/MCP-1 expression. Overall, falcarinol may facilitate sensitization to other allergens rather than being an allergen itself.