Cryptotanshinone inhibits cyclooxygenase-2 enzyme activity but not its expression.
Cyclooxygenase-2 (COX-2) is a key enzyme that catalyzes the biosynthesis of prostaglandins from arachidonic acid and plays a critical role in some pathologies including inflammation, neurodegenerative diseases and cancer. Cryptotanshinone is a major constituent of tanshinones, which are extracted from the medicinal herb Salvia miltiorrhiza Bunge, and has well-documented antioxidative and anti-inflammatory effects. This study confirmed the remarkable anti-inflammatory effect of cryptotanshinone in the carrageenan-induced rat paw edema model. Since the action of cryptotanshinone on COX-2 has not been previously described, in the present study, we further examined the effect of cryptotanshinone on cyclooxygenase activity in the exogenous arachidonic acid-stimulated insect sf-9 cells, which highly express human COX-2 or human COX-1, and on cyclooxygenases expression in human U937 promonocytes stimulated by lipopolysaccharide (LPS) plus phorbolmyristate acetate (PMA). Cryptotanshinone reduced prostaglandin E2 synthesis and reactive oxygen species generation catalyzed by COX-2, without influencing COX-1 activity in cloned sf-9 cells. In PMA plus LPS-stimulated U937 cells, cryptotanshinone had negligible effects on the expression of COX-1 and COX-2, at either a mRNA or protein level. These results demonstrate that the anti-inflammatory effect of cryptotanshinone is directed against enzymatic activity of COX-2, not against the transcription or translation of the enzyme.
Jin
Dao-Zhong
DZ
Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai, 201203, China. dzjin@sibs.ac.cn
Yin
Lin-Lin
LL
Ji
Xin-Quan
XQ
Zhu
Xing-Zu
XZ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000494:pharmacology; D015153:Blotting, Western; D002351:Carrageenan; D002460:Cell Line; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D006801:Humans; D015394:Molecular Structure; D010616:Phenanthrenes / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027544:Salvia / Q000737:chemistry; D018411:Spodoptera; D020298:U937 Cells
D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D004365:Drugs, Chinese Herbal; D010616:Phenanthrenes; D017382:Reactive Oxygen Species; D016718:Arachidonic Acid; C037886:cryptotanshinone; D002351:Carrageenan; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone