| Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis. | |
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MedLine Citation:
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PMID: 18556441 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In the present study it was revealed that cannabidiolic acid (CBDA) selectively inhibited cyclooxygenase (COX)-2 activity with an IC(50) value (50% inhibition concentration) around 2 microM, having 9-fold higher selectivity than COX-1 inhibition. In contrast, Delta(9)-tetrahydrocannabinolic acid (Delta(9)-THCA) was a much less potent inhibitor of COX-2 (IC(50) > 100 microM). Nonsteroidal anti-inflammatory drugs containing a carboxyl group in their chemical structures such as salicylic acid are known to inhibit nonselectively both COX-1 and COX-2. CBDA and Delta(9)-THCA have a salicylic acid moiety in their structures. Thus, the structural requirements for the CBDA-mediated COX-2 inhibition were next studied. There is a structural difference between CBDA and Delta(9)-THCA; phenolic hydroxyl groups of CBDA are freed from the ring formation with the terpene moiety, although Delta(9)-THCA has dibenzopyran ring structure. It was assumed that the whole structure of CBDA is important for COX-2 selective inhibition because beta-resorcylic acid itself did not inhibit COX-2 activity. Methylation of the carboxylic acid moiety of CBDA led to disappearance of COX-2 selectivity. Thus, it was suggested that the carboxylic acid moiety in CBDA is a key determinant for the inhibition. Furthermore, the crude extract of cannabis containing mainly CBDA was shown to have a selective inhibitory effect on COX-2. Taken together, these lines of evidence in this study suggest that naturally occurring CBDA in cannabis is a selective inhibitor for COX-2. |
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Authors:
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Shuso Takeda; Koichiro Misawa; Ikuo Yamamoto; Kazuhito Watanabe |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-06-12 |
Journal Detail:
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Title: Drug metabolism and disposition: the biological fate of chemicals Volume: 36 ISSN: 1521-009X ISO Abbreviation: Drug Metab. Dispos. Publication Date: 2008 Sep |
Date Detail:
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Created Date: 2008-08-21 Completed Date: 2008-11-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421550 Medline TA: Drug Metab Dispos Country: United States |
Other Details:
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Languages: eng Pagination: 1917-21 Citation Subset: IM |
Affiliation:
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Organization for Frontier Research in Preventive Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cannabinoids
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chemistry,
pharmacology* Cannabis / chemistry* Cyclooxygenase 2 / drug effects* Cyclooxygenase Inhibitors / chemistry, pharmacology* Dose-Response Relationship, Drug Molecular Structure |
| Chemical | |
Reg. No./Substance:
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0/Cannabinoids; 0/Cyclooxygenase Inhibitors; 1244-58-2/cannabidiolic acid; EC 1.14.99.1/Cyclooxygenase 2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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