Falcarinol has effects on CaCo-2 cells appear to be biphasic, inducing pro-proliferative and apoptotic characteristics at low and high concentrations of Falcarinol, respectively. Falcarinol-associated dermatitis is due to antagonism of the CB(1) receptor in keratinocytes, leading to increased chemokine expression and aggravation of histamine action.
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Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20C. Generally, these will be useable for up to two weeks. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at least 1 hour.
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Falcarinol is a covalent cannabinoid CB1 receptor antagonist and induces pro-allergic effects in skin.[Pubmed: 20206138
The skin irritant polyyne Falcarinol (panaxynol, carotatoxin) is found in carrots, parsley, celery, and in the medicinal plant Panax ginseng.
METHODS AND RESULTS:
In our ongoing search for new cannabinoid (CB) receptor ligands we have isolated Falcarinol from the endemic Sardinian plant Seseli praecox. We show that Falcarinol exhibits binding affinity to both human CB receptors but selectively alkylates the anandamide binding site in the CB(1) receptor (K(i)=594nM), acting as covalent inverse agonist in CB(1) receptor-transfected CHO cells. Given the inherent instability of purified Falcarinol we repeatedly isolated this compound for biological characterization and one new polyyne was characterized. In human HaCaT keratinocytes Falcarinol increased the expression of the pro-allergic chemokines IL-8 and CCL2/MCP-1 in a CB(1) receptor-dependent manner. Moreover, Falcarinol inhibited the effects of anandamide on TNF-alpha stimulated keratinocytes. In vivo, Falcarinol strongly aggravated histamine-induced oedema reactions in skin prick tests. Both effects were also obtained with the CB(1) receptor inverse agonist rimonabant, thus indicating the potential role of the CB(1) receptor in skin immunopharmacology.
Our data suggest anti-allergic effects of anandamide and that Falcarinol-associated dermatitis is due to antagonism of the CB(1) receptor in keratinocytes, leading to increased chemokine expression and aggravation of histamine action.
J Agric Food Chem. 2007 Feb 7;55(3):618-23.
Biphasic effect of falcarinol on caco-2 cell proliferation, DNA damage, and apoptosis.[Pubmed: 17263451
The polyacetylene Falcarinol, isolated from carrots, has been shown to be protective against chemically induced colon cancer development in rats, but the mechanisms are not fully understood.
METHODS AND RESULTS:
In this study CaCo-2 cells were exposed to Falcarinol (0.5-100 microM) and the effects on proliferation, DNA damage, and apoptosis investigated. Low-dose Falcarinol exposure (0.5-10 microM) decreased expression of the apoptosis indicator caspase-3 concomitantly with decreased basal DNA strand breakage. Cell proliferation was increased (1-10 microM), whereas cellular attachment was unaffected by <10 microM Falcarinol. At concentrations above 20 microM Falcarinol, proliferation of CaCo-2 cells decreased and the number of cells expressing active caspase-3 increased simultaneously with increased cell detachment. Furthermore, DNA single-strand breakage was significantly increased at concentrations above 10 microM Falcarinol.
Thus, the effects of Falcarinol on CaCo-2 cells appear to be biphasic, inducing pro-proliferative and apoptotic characteristics at low and high concentrations of Falcarinol, respectively.