Open AccessPhenolic compounds from nutmeg ( Myristica fragrans Houtt.) inhibit the endocannabinoid‐modulating enzyme fatty acid amide hydrolase
Author(s) -
ElAlfy Abir T.,
Abourashed Ehab A.,
Patel Christina,
Mazhari Nunmoula,
An HeaRe,
Jeon Andrew
Publication year - 2019
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.13174
Subject(s) - fatty acid amide hydrolase , monoacylglycerol lipase , myristica fragrans , endocannabinoid system , chemistry , pharmacology , ic50 , potency , cannabinoid , nutmeg , elevated plus maze , enzyme , biochemistry , medicine , antagonist , cannabinoid receptor , anxiety , traditional medicine , in vitro , food science , psychiatry , receptor
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 ( IC 50 ). 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 IC 50 of 7.02 μ m ± 2.02, 4.57 μ m ± 0.66 and 38.29 μ m ± 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.