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Phenolic compounds from nutmeg (Myristica fragrans Houtt.) inhibit the endocannabinoid‐modulating enzyme fatty acid amide hydrolase
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 de...
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| Published in: | Journal of pharmacy and pharmacology 2019-12, Vol.71 (12), p.1879-1889 |
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| Main Authors: | , , , , , |
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| cited_by | cdi_FETCH-LOGICAL-c4484-98c78c81a11fc1f00b1db8ce4dd24cc9f1f6fef8fb6e2d413d2e34a3025ad5c83 |
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| cites | cdi_FETCH-LOGICAL-c4484-98c78c81a11fc1f00b1db8ce4dd24cc9f1f6fef8fb6e2d413d2e34a3025ad5c83 |
| container_end_page | 1889 |
| container_issue | 12 |
| container_start_page | 1879 |
| container_title | Journal of pharmacy and pharmacology |
| container_volume | 71 |
| creator | El‐Alfy, Abir T. Abourashed, Ehab A. Patel, Christina Mazhari, Nunmoula An, HeaRe Jeon, Andrew |
| description | 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 |
| doi_str_mv | 10.1111/jphp.13174 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7938946</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2312743619</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4484-98c78c81a11fc1f00b1db8ce4dd24cc9f1f6fef8fb6e2d413d2e34a3025ad5c83</originalsourceid><addsrcrecordid>eNp9kU1v1DAQhi1ERZfChR-ALHEBpCz-SuJcKqGqsK2K2AOcLccfG68SO9gOKD1x4c5v5JeQdksFF-Yy0syjZ0Z6AXiG0Rov9WY_duMaU1yzB2BFECNFjUv-EKwQIqSgZU2PweOU9gihuqqqR-CY4rIpS0JW4Me2Mz70TkEVhjFMXidoYxign_JgdvDlhzm6lJ2Sy1juovQJbsKU8_oVdL5zrcswdwYar4OS3svW-eD0r-8_h6CnXmbnd8vyeh4MtDLnGUrlNJSD0wZ2s46hl8k8AUdW9sk8vesn4PO7809nm-Lq4_uLs7dXhWKMs6LhquaKY4mxVdgi1GLdcmWY1oQp1VhsK2sst21liGaYamIokxSRUupScXoCTg_ecWoHo5XxOcpejNENMs4iSCf-3XjXiV34KuqG8oZVi-DFnSCGL5NJWezDFP3ysyAUk5rRCjcL9fpAqRhSisbeX8BI3EQmbiITt5Et8PO_f7pH_2S0APgAfHO9mf-jEpfbzfYg_Q22nadN</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2312743619</pqid></control><display><type>article</type><title>Phenolic compounds from nutmeg (Myristica fragrans Houtt.) inhibit the endocannabinoid‐modulating enzyme fatty acid amide hydrolase</title><source>Oxford Journals Online</source><creator>El‐Alfy, Abir T. ; Abourashed, Ehab A. ; Patel, Christina ; Mazhari, Nunmoula ; An, HeaRe ; Jeon, Andrew</creator><creatorcontrib>El‐Alfy, Abir T. ; Abourashed, Ehab A. ; Patel, Christina ; Mazhari, Nunmoula ; An, HeaRe ; Jeon, Andrew</creatorcontrib><description>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.</description><identifier>ISSN: 0022-3573</identifier><identifier>EISSN: 2042-7158</identifier><identifier>DOI: 10.1111/jphp.13174</identifier><identifier>PMID: 31595522</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject><![CDATA[Amidohydrolases - antagonists & inhibitors ; Animal models ; Animals ; Anti-Anxiety Agents - administration & dosage ; Anti-Anxiety Agents - isolation & purification ; Anti-Anxiety Agents - pharmacology ; Anxiety ; Anxiety - drug therapy ; Anxiety - physiopathology ; Cannabinoids ; Disease Models, Animal ; Endocannabinoid system ; Endocannabinoids - metabolism ; Enzyme Inhibitors - administration & dosage ; Enzyme Inhibitors - isolation & purification ; Enzyme Inhibitors - pharmacology ; Fatty acids ; Fatty-acid amide hydrolase ; Hydrolase ; Inhibitory Concentration 50 ; licarin A ; Lipase ; Locomotor activity ; malabaricone C ; Male ; Maze Learning - drug effects ; Mice ; Monoacylglycerol Lipases - antagonists & inhibitors ; Myristica - chemistry ; Myristica fragrans ; Nutmeg ; Phenolic compounds ; Phenols ; Phenols - administration & dosage ; Phenols - isolation & purification ; Phenols - pharmacology ; Research Paper ; Selectivity]]></subject><ispartof>Journal of pharmacy and pharmacology, 2019-12, Vol.71 (12), p.1879-1889</ispartof><rights>2019 Royal Pharmaceutical Society</rights><rights>2019 Royal Pharmaceutical Society.</rights><rights>Copyright © 2019 Royal Pharmaceutical Society</rights><rights>2019 Royal Pharmaceutical Society 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4484-98c78c81a11fc1f00b1db8ce4dd24cc9f1f6fef8fb6e2d413d2e34a3025ad5c83</citedby><cites>FETCH-LOGICAL-c4484-98c78c81a11fc1f00b1db8ce4dd24cc9f1f6fef8fb6e2d413d2e34a3025ad5c83</cites><orcidid>0000-0003-0588-1233</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31595522$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>El‐Alfy, Abir T.</creatorcontrib><creatorcontrib>Abourashed, Ehab A.</creatorcontrib><creatorcontrib>Patel, Christina</creatorcontrib><creatorcontrib>Mazhari, Nunmoula</creatorcontrib><creatorcontrib>An, HeaRe</creatorcontrib><creatorcontrib>Jeon, Andrew</creatorcontrib><title>Phenolic compounds from nutmeg (Myristica fragrans Houtt.) inhibit the endocannabinoid‐modulating enzyme fatty acid amide hydrolase</title><title>Journal of pharmacy and pharmacology</title><addtitle>J Pharm Pharmacol</addtitle><description>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.</description><subject>Amidohydrolases - antagonists & inhibitors</subject><subject>Animal models</subject><subject>Animals</subject><subject>Anti-Anxiety Agents - administration & dosage</subject><subject>Anti-Anxiety Agents - isolation & purification</subject><subject>Anti-Anxiety Agents - pharmacology</subject><subject>Anxiety</subject><subject>Anxiety - drug therapy</subject><subject>Anxiety - physiopathology</subject><subject>Cannabinoids</subject><subject>Disease Models, Animal</subject><subject>Endocannabinoid system</subject><subject>Endocannabinoids - metabolism</subject><subject>Enzyme Inhibitors - administration & dosage</subject><subject>Enzyme Inhibitors - isolation & purification</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Fatty acids</subject><subject>Fatty-acid amide hydrolase</subject><subject>Hydrolase</subject><subject>Inhibitory Concentration 50</subject><subject>licarin A</subject><subject>Lipase</subject><subject>Locomotor activity</subject><subject>malabaricone C</subject><subject>Male</subject><subject>Maze Learning - drug effects</subject><subject>Mice</subject><subject>Monoacylglycerol Lipases - antagonists & inhibitors</subject><subject>Myristica - chemistry</subject><subject>Myristica fragrans</subject><subject>Nutmeg</subject><subject>Phenolic compounds</subject><subject>Phenols</subject><subject>Phenols - administration & dosage</subject><subject>Phenols - isolation & purification</subject><subject>Phenols - pharmacology</subject><subject>Research Paper</subject><subject>Selectivity</subject><issn>0022-3573</issn><issn>2042-7158</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kU1v1DAQhi1ERZfChR-ALHEBpCz-SuJcKqGqsK2K2AOcLccfG68SO9gOKD1x4c5v5JeQdksFF-Yy0syjZ0Z6AXiG0Rov9WY_duMaU1yzB2BFECNFjUv-EKwQIqSgZU2PweOU9gihuqqqR-CY4rIpS0JW4Me2Mz70TkEVhjFMXidoYxign_JgdvDlhzm6lJ2Sy1juovQJbsKU8_oVdL5zrcswdwYar4OS3svW-eD0r-8_h6CnXmbnd8vyeh4MtDLnGUrlNJSD0wZ2s46hl8k8AUdW9sk8vesn4PO7809nm-Lq4_uLs7dXhWKMs6LhquaKY4mxVdgi1GLdcmWY1oQp1VhsK2sst21liGaYamIokxSRUupScXoCTg_ecWoHo5XxOcpejNENMs4iSCf-3XjXiV34KuqG8oZVi-DFnSCGL5NJWezDFP3ysyAUk5rRCjcL9fpAqRhSisbeX8BI3EQmbiITt5Et8PO_f7pH_2S0APgAfHO9mf-jEpfbzfYg_Q22nadN</recordid><startdate>201912</startdate><enddate>201912</enddate><creator>El‐Alfy, Abir T.</creator><creator>Abourashed, Ehab A.</creator><creator>Patel, Christina</creator><creator>Mazhari, Nunmoula</creator><creator>An, HeaRe</creator><creator>Jeon, Andrew</creator><general>Wiley Subscription Services, Inc</general><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-0588-1233</orcidid></search><sort><creationdate>201912</creationdate><title>Phenolic compounds from nutmeg (Myristica fragrans Houtt.) inhibit the endocannabinoid‐modulating enzyme fatty acid amide hydrolase</title><author>El‐Alfy, Abir T. ; Abourashed, Ehab A. ; Patel, Christina ; Mazhari, Nunmoula ; An, HeaRe ; Jeon, Andrew</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4484-98c78c81a11fc1f00b1db8ce4dd24cc9f1f6fef8fb6e2d413d2e34a3025ad5c83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Amidohydrolases - antagonists & inhibitors</topic><topic>Animal models</topic><topic>Animals</topic><topic>Anti-Anxiety Agents - administration & dosage</topic><topic>Anti-Anxiety Agents - isolation & purification</topic><topic>Anti-Anxiety Agents - pharmacology</topic><topic>Anxiety</topic><topic>Anxiety - drug therapy</topic><topic>Anxiety - physiopathology</topic><topic>Cannabinoids</topic><topic>Disease Models, Animal</topic><topic>Endocannabinoid system</topic><topic>Endocannabinoids - metabolism</topic><topic>Enzyme Inhibitors - administration & dosage</topic><topic>Enzyme Inhibitors - isolation & purification</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Fatty acids</topic><topic>Fatty-acid amide hydrolase</topic><topic>Hydrolase</topic><topic>Inhibitory Concentration 50</topic><topic>licarin A</topic><topic>Lipase</topic><topic>Locomotor activity</topic><topic>malabaricone C</topic><topic>Male</topic><topic>Maze Learning - drug effects</topic><topic>Mice</topic><topic>Monoacylglycerol Lipases - antagonists & inhibitors</topic><topic>Myristica - chemistry</topic><topic>Myristica fragrans</topic><topic>Nutmeg</topic><topic>Phenolic compounds</topic><topic>Phenols</topic><topic>Phenols - administration & dosage</topic><topic>Phenols - isolation & purification</topic><topic>Phenols - pharmacology</topic><topic>Research Paper</topic><topic>Selectivity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>El‐Alfy, Abir T.</creatorcontrib><creatorcontrib>Abourashed, Ehab A.</creatorcontrib><creatorcontrib>Patel, Christina</creatorcontrib><creatorcontrib>Mazhari, Nunmoula</creatorcontrib><creatorcontrib>An, HeaRe</creatorcontrib><creatorcontrib>Jeon, Andrew</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of pharmacy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>El‐Alfy, Abir T.</au><au>Abourashed, Ehab A.</au><au>Patel, Christina</au><au>Mazhari, Nunmoula</au><au>An, HeaRe</au><au>Jeon, Andrew</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phenolic compounds from nutmeg (Myristica fragrans Houtt.) inhibit the endocannabinoid‐modulating enzyme fatty acid amide hydrolase</atitle><jtitle>Journal of pharmacy and pharmacology</jtitle><addtitle>J Pharm Pharmacol</addtitle><date>2019-12</date><risdate>2019</risdate><volume>71</volume><issue>12</issue><spage>1879</spage><epage>1889</epage><pages>1879-1889</pages><issn>0022-3573</issn><eissn>2042-7158</eissn><abstract>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.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>31595522</pmid><doi>10.1111/jphp.13174</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-0588-1233</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Oxford Journals Online |
| subjects | Amidohydrolases - antagonists & inhibitors Animal models Animals Anti-Anxiety Agents - administration & dosage Anti-Anxiety Agents - isolation & purification Anti-Anxiety Agents - pharmacology Anxiety Anxiety - drug therapy Anxiety - physiopathology Cannabinoids Disease Models, Animal Endocannabinoid system Endocannabinoids - metabolism Enzyme Inhibitors - administration & dosage Enzyme Inhibitors - isolation & purification Enzyme Inhibitors - pharmacology Fatty acids Fatty-acid amide hydrolase Hydrolase Inhibitory Concentration 50 licarin A Lipase Locomotor activity malabaricone C Male Maze Learning - drug effects Mice Monoacylglycerol Lipases - antagonists & inhibitors Myristica - chemistry Myristica fragrans Nutmeg Phenolic compounds Phenols Phenols - administration & dosage Phenols - isolation & purification Phenols - pharmacology Research Paper Selectivity |
| title | Phenolic compounds from nutmeg (Myristica fragrans Houtt.) inhibit the endocannabinoid‐modulating enzyme fatty acid amide hydrolase |
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