Biochemometric Analysis of Fatty Acid Amide Hydrolase Inhibition by Echinacea Root Extracts
| Autor: | John T. Arnason, John Baker, Rui Liu, Cory S. Harris, Franklin Johnson, Kelly M. Burkett, Michel Rapinski, Phil Hintz |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Pharmaceutical Science
01 natural sciences Echinacea Amidohydrolases Analytical Chemistry Caftaric acid 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Fatty acid amide hydrolase Drug Discovery Caffeic acid Food science Chromatography High Pressure Liquid 2. Zero hunger Pharmacology biology Plant Extracts Echinacea angustifolia Cichoric acid Organic Chemistry Anandamide biology.organism_classification 0104 chemical sciences 010404 medicinal & biomolecular chemistry Complementary and alternative medicine chemistry Phytochemical 030220 oncology & carcinogenesis Echinacoside Molecular Medicine |
| Zdroj: | Planta Medica. 87:294-304 |
| ISSN: | 1439-0221 0032-0943 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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