Phenolic compounds from nutmeg (Myristica fragrans Houtt.) inhibit the endocannabinoid-modulating enzyme fatty acid amide hydrolase. J Pharm Pharmacol 2019 Dec;71(12):1879-1889
Date
10/09/2019Pubmed ID
31595522Pubmed Central ID
PMC7938946DOI
10.1111/jphp.13174Scopus ID
2-s2.0-85074090803 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
OBJECTIVES: The study aimed to identify nutmeg compounds that indirectly interact with the endocannabinoid system through inhibition of the fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) enzymes.
METHODS: Thirteen compounds were screened for FAAH and MAGL inhibition. Compounds demonstrating significant FAAH inhibition were evaluated to determine the halfmaximal inhibitory concentration (IC50 ). The most potent compound was investigated in the elevated plus maze (EPM) rodent anxiety model.
KEY FINDINGS: Three compounds, licarin A (9), 5'-methoxylicarin A (8) and malabaricone C (6) were most active in inhibiting FAAH with IC50 of 7.02 μm ± 2.02, 4.57 μm ± 0.66 and 38.29 μm ± 6.18, respectively. None of the purified compounds showed significant MAGL inhibition. Because of its relative high potency and selectivity, compound 8 was further evaluated in the EPM animal model of anxiety. The compound showed significant increase in number of open arm entries (P < 0.05) when administered at 120 mg/kg dose. No effect was observed on the locomotor activity.
CONCLUSIONS: Results collected introduce active nutmeg compounds as potential leads for further development. Of the three compounds, 8 possesses highest potency and FAAH selectivity as well as anxiolytic activity. Furthermore, in vivo testing in appropriate behavioural animal paradigms is warranted.
Author List
El-Alfy AT, Abourashed EA, Patel C, Mazhari N, An H, Jeon AAuthor
Ehab A. Abourashed PhD Professor in the School of Pharmacy Administration department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AmidohydrolasesAnimals
Anti-Anxiety Agents
Anxiety
Disease Models, Animal
Endocannabinoids
Enzyme Inhibitors
Inhibitory Concentration 50
Male
Maze Learning
Mice
Monoacylglycerol Lipases
Phenols
