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-1beta-induced COX-2 protein expression and suppressed its mRNA induction by IL-1beta 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.
Xu
Yibing
Y
Department of Chemistry and Biochemistry, Benson Science Building, Brigham Young University, Provo, UT 84602, USA.
Oliverson
Bryant G
BG
Simmons
Daniel L
DL
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D051545:Cyclooxygenase 1 / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D035264:Flowers; D015870:Gene Expression / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D053583:Interleukin-1beta; D031239:Lonicera / Q000737:chemistry*; D008516:Medicine, Chinese Traditional; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D014158:Transcription, Genetic
D016861:Cyclooxygenase Inhibitors; D053583:Interleukin-1beta; D010936:Plant Extracts; D012333:RNA, Messenger; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone