Abstract
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 in vitro inhibitory effect of root extracts of Echinacea purpurea and Echinacea angustifolia 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 E. angustifolia genotypes and from 33 – 87% among E. purpurea genotypes. Simple linear regression
revealed the caffeic acid derivatives caftaric acid and cichoric acid, and the
alkylamide dodeca-2E,4Z-diene-8,10-diynioc acid 2-methylbutylamide, as the strongest determinants of inhibition
in E. purpurea (r* = 0.53, 0.45, and 0.20, respectively) while in E. angustifolia, 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 in vitro activity. Testing pure compounds identified as determinants of activity revealed
cichoric acid (IC50 = 45 ± 4 µM) and dodeca-2E,4E,8Z,10E-tetraenoic acid isobutylamide (IC50 = 54 ± 2 µM) as the most active. The results suggest that several phytochemicals
may contribute to Echinaceaʼs cannabimimetic activity and that ample variation in
genotypes exists for
selection of high-activity germplasm in breeding programs.
Key words
Echinacea
- Asteraceae - coneflowers - alkamides - phenolics - endocannabinoid system
