Targeting Cannabinoid Receptors and Fatty Acid Amide Hydrolase: An Innovative Food-Grade Delivery System of Zingiber officinale and Acmella oleracea Extracts as Natural Adjuvant in Pain Management

Abstract

Background: Anti-inflammatory and analgesic properties are displayed by several natural products, in particular Acmella oleracea and Zingiber officinale. Literature data suggests that both botanical extracts can be useful as inflammation/pain modulators, so technological efforts have been made to associate them together in a unique delivery new food-grade formulation, Mitidol, with the purpose of improving their beneficial effects. Objective: The aim of the present work was to assess if Mitidol and its active ingredients are able to modulate the endocannabinoid 2 receptor system, one of the major systems responsible for positive effects of Cannabis treatment. Cannabinoid 2 receptor represents an attractive pharmacological target in obtaining an anti-inflammatory/analgesic effect with low central nervous system side-effects. Methods: The new food-grade Phytosome, together with all the botanical ingredients and active compounds, were tested in a cell-based assay in human recombinant Cannabinoid 2 Receptor cells, in order to evaluate a possible agonist effect on those receptors, and in a Fatty Acid Amide Hydrolase Inhibition Activity assay, to evaluate potential inhibition of that hydrolase, which is responsible for degradation of the endogenous cannabinoid anandamide. Results: Zingiber officinale showed potent activity in Fatty Acid Amide Hydrolase Inhibition Activity assay, being about six fold more effective than the flavonoid Kaempferol. Acmella oleracea proved to be highly active in Fatty Acid Amide Hydrolase inhibition and Cannabinoid 2 activation. Conclusion: Our data suggest a strong rationale for the use of Mitidol as a natural adjuvant in pain management.