[Discussion of anti-inflammatory mechanism of cyclooxygenase (COX-2) inhibitor in improving cardiovascular safety].
The new generation cyclooxygenase (COX-2) inhibitor could reduce the gastrointestinal side effect of NSAID drugs, but eventually increase the cardiovascular risk, because its selective inhibition of COX-2 induces the imbalance between PGI2 and TXA2 and the reduction of vasodilatory NO. Under pathological conditions, active oxygen species (O2-*2, etc) were used to induce endo- thelial dysfunction, activate NF-κB to induce expressions of pro-inflammatory cytokines IL-1β and TNF-α, increase ET-1, TXA2 with vasoconstrictor effect, reduce PGI2 and NO with vasodilatory effect, generate further oxidative damage together with NO, and reduce the bioavailability of NO. NO-NSAIDs and NO-Coxibs drugs raised the level of NO by introducing NO-donor (ONO2). NSAIDs drugs enhanced the anti-inflammatory activity of COX-2 and reduced gastrointestinal side effects by inhibiting selectively COX-2. If antioxidant structures with active ingredients of traditional Chinese medicines were introduced to improve the antioxidant activity of NSAIDs, they could scavenge the active oxygen species to protect the normal function of vascular endothelia and enhance the bioavailability of NO, which is conducive to enhance the cardiovascular safety of cyclooxygenase (COX-2) inhibitor.
Jin-Long
JL
Mao
Xiao-Yu
XY
Li
Rong
R
Sun
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D051546:Cyclooxygenase 2 / Q000276:immunology; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D006801:Humans; D016328:NF-kappa B / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000893:Anti-Inflammatory Agents; D054316:Biomarkers, Pharmacological; D052246:Cyclooxygenase 2 Inhibitors; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human