Trifunctional inhibition of COX-2 by extracts of Lonicera japonica: Direct inhibition, transcriptional and post-transcriptional down regulation

The anti-inflammatory properties of aqueous extracts from Lonicera japonica (LJ) flower, an anti-inflammatory treatment in traditional Chinese medicine, were tested by radioimmunoassay of cyclooxygenase isoenzyme-generated prostaglandin E2 (PGE2) synthesis as well as by Western and Northern blot analysis of COX-2 protein and mRNA expression, respectively. Boiled LJ aqueous extracts directly inhibited both COX-1 and COX-2 activity, while non-boiled extracts stimulated COX-1. Boiled LJ extracts also inhibited expression of IL-1β-induced COX-2 protein expression and suppressed its mRNA induction by IL-1β in A549 cells. Suppression of COX-2 mRNA induction required a significantly higher dose of aqueous extract than did suppression of protein expression, indicating that compounds in the extract act translationally or post-translationally at lower doses and transcriptionally or post-transcriptionally at higher doses. Direct inhibition of COX isoenzymes as well as down-regulation of COX-2 mRNA and protein may represent the mechanism by which this ancient herbal treatment decreases inflammation.