Biochemometric Analysis of Fatty Acid Amide Hydrolase Inhibition by Echinacea Root Extracts.

Recent research demonstrates that Echinacea possesses cannabimimetic activity with potential applications beyond common contemporary uses for relief of cold and flu symptoms. In this study, we investigated the inhibitory effect of root extracts of and on fatty acid amide hydrolase, the main enzyme that degrades the endocannabinoid anandamide. The objective was to relate variation in bioactivity between commercial Echinacea genotypes to their phytochemical profiles and to identify determinants of activity using biochemometric analysis. Forty root extracts of each of species were tested for inhibition of fatty acid amide hydrolase and analyzed by HPLC-DAD/MS to identify and quantitate alkylamides and caffeic acid derivatives. Fatty acid amide hydrolase inhibition ranged from 34 - 80% among genotypes and from 33 - 87% among genotypes. Simple linear regression revealed the caffeic acid derivatives caftaric acid and cichoric acid, and the alkylamide dodeca-2,4-diene-8,10-diynioc acid 2-methylbutylamide, as the strongest determinants of inhibition in (r* = 0.53, 0.45, and 0.20, respectively) while in , only CADs were significantly associated with activity, most notably echinacoside (r* = 0.26). Regression analysis using compound groups generated by hierarchical clustering similarly indicated that caffeic acid derivatives contributed more than alkylamides to activity. Testing pure compounds identified as determinants of activity revealed cichoric acid (IC = 45 ± 4 µM) and dodeca-2,4,8,10-tetraenoic acid isobutylamide (IC = 54 ± 2 µM) as the most active. The results suggest that several phytochemicals may contribute to Echinacea's cannabimimetic activity and that ample variation in genotypes exists for selection of high-activity germplasm in breeding programs.