<p>To examine cyclooxygenase-2 (COX-2) inhibitory effects of natural compounds and structurally related compounds, a radiochemical assay for measuring inhibition of COX-2 and COX-1 catalysed prostaglandin biosynthesis was optimised. That process resulted in the development of a reliable assay for finding COX-2 inhibitors in plants, and for investigating plant constituents pertaining to the inhibition of COX-2 and COX-1. </p><p>By means of bioassay-guided isolation of the plant Plantago major L., several inhibitors of COX-2 were found: ursolic, oleanolic, a-linolenic and linoleic acid. Subsequently, structural derivatives of these triterpenoids and fatty acids were investigated. The polyunsaturated and the thioether containing fatty acids were the most potent COX-2 and COX-1 inhibitors, with a-linolenic and all-(Z)-5-thia-8,11,14,17-eicosatetraenoic acid expressing selectivity toward COX-2. </p><p>For rapid evaluation of plant constituents, a COX-2 assay using scintillation proximity assay-technology was used to evaluate 49 ubiquitous plant metabolites of different biosynthetic origin for inhibition of COX-2. Eugenol, cinnamaldehyde, and pyrogallol expressed inhibition. Later, in an attempt to find COX-2 inhibitors in plants, but without prior purification, several approaches to the surface plasmon resonance technique were examined, with the measurement of prostaglandin E2 being most successful.</p><p>In mouse macrophage cells, two fatty acids were analysed for effects on COX-2 and iNOS, mRNA, protein, prostaglandin E2, and nitrite levels. 5-Thia-8,11,14,17-eicosatetraenoic acid decreased COX-2 protein expression.</p><p>This thesis contributes to our growing knowledge of methods for measuring COX-2 inhibition, and also knowledge of COX-2 inhibitory effects of commonly occurring compounds in plants, herbal drugs and functional food. Thus the experimental results can facilitate future searches for new COX-2 inhibitors of natural origin.</p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-1907 |
| Date | January 2002 |
| Creators | Ringbom, Therese |
| Publisher | Uppsala University, Division of Pharmacognosy, Uppsala : Acta Universitatis Upsaliensis |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, text |
| Relation | Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, 0282-7484 ; 269 |
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