Spilanthol permeates the human skin[3] and the inside lining of the cheeks in the mouth (buccal mucosa),[4] resulting in local as well as systemic pharmacological concentrations. In the skin and in the pancreas, spilanthol has also been shown to exert anti-inflammatory effects.[5] The underlying mechanism involves inhibition of nitric oxide production due to reduced expression of inducible nitric oxide synthase enzyme (iNOS) in macrophages. Transcription factor array experiments revealed that spilanthol inhibits the activation of several transcription factors (NFκB, ATF4, FOXO1, IRF1, ETS1, and AP-1) which may explain the effect of spilanthol on gene expression.[5]
The antihypertensive effect of spilanthol was blocked by CB1 antagonist rimonabant and TRPV1 antagonist capsazepine, suggesting spilanthol mediates some activity by interaction with the cannabinoid receptors and TRPV1 channels.[6]
^Boonen, Jente; Baert, Bram; Roche, Nathalie; Burvenich, Christian; De Spiegeleer, Bart (2010). "Transdermal behaviour of the N-alkylamide spilanthol (affinin) from Spilanthes acmella (Compositae) extracts". Journal of Ethnopharmacology. 127 (1): 77–84. doi:10.1016/j.jep.2009.09.046. PMID19808085.
^Boonen, Jente; Baert, Bram; Burvenich, Christian; Bondeel, Phillip; De Saeger, Sarah; De Spiegeleer, Bart (2010). "LC-MS profiling of N-alkylamides in Spilanthes acmella extract and the transmucosal behaviour of its main bio-active spilanthol". Journal of Pharmaceutical and Biomedical Analysis. 53 (3): 243–249. doi:10.1016/j.jpba.2010.02.010. PMID20227845.