Abstract |
OAS-1000 is a semisynthetic derivative of pseudopterosine A, isolated from sea whip (Pseudopterogorgia elizabethae), that has been shown to have topical anti-inflammatory activity. The purpose of this research was to investigate OAS-1000 for potential use as an anti-inflammatory agent for topical oral application, and to begin to investigate a mechanism of action. OAS-1000 was therefore evaluated as an inhibitor of 4 enzymes of the arachidonic acid metabolic pathways ( prostaglandin G/H synthase I (PGHS-1, COX-1), prostaglandin G/H synthase II (PGHS-2, COX-2), arachidonate 5-lipoxygenase (5-LOX), and arachidonate 15-lipoxygenase (15-LOX)). It was found that OAS-1000 inhibits PGHS-1 activity with an IC-50 value of 80.3 microM, but had much less activity versus PGHS-2 enzyme and no activity versus the 15-LOX enzyme. 5-LOX activity showed some inhibition, but only at a high OAS-1000 concentrations. Additionally, OAS-1000 was tested for it's ability inhibit 1 ng/ml IL-1beta stimulated PGE2 production in a cell culture system. Inhibition of 46% was seen at an OAS-1000 concentration of 22.4 microM. Taken together, these experiments suggest that at least some of the topical anti-inflammatory activity of OAS-1000 may be attributed to inhibition of the arachidonic acid metabolites that have been shown to be important in inflammation and tissue destruction.
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Authors | D S Scherl, J Afflitto, A Gaffar |
Journal | Journal of clinical periodontology
(J Clin Periodontol)
Vol. 26
Issue 4
Pg. 246-51
(Apr 1999)
ISSN: 0303-6979 [Print] United States |
PMID | 10223396
(Publication Type: Journal Article)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Cyclooxygenase Inhibitors
- Diterpenes
- Glycosides
- Inflammation Mediators
- Interleukin-1
- Lipoxygenase Inhibitors
- pseudopterosins
- Dinoprostone
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Topics |
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(administration & dosage, pharmacology)
- Cells, Cultured
- Cyclooxygenase Inhibitors
(administration & dosage, pharmacology)
- Dinoprostone
(antagonists & inhibitors)
- Diterpenes
(administration & dosage, pharmacology)
- Dose-Response Relationship, Drug
- Glycosides
(administration & dosage, pharmacology)
- Humans
- Inflammation Mediators
(metabolism)
- Interleukin-1
(pharmacology)
- Lipoxygenase Inhibitors
- Mesoderm
(cytology, drug effects, enzymology)
- Regression Analysis
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