Triflusal

Triflusal is an orally bioavailable, blood-brain barrier-permeable dual Cyclooxygenase-1 (COX-1)/cAMP phosphodiesterase inhibitor. Triflusal inhibits platelet aggregation, NF-κB activation, iNOS activity, and prostaglandin synthesis in ischaemic tissue. Triflusal stimulates neutrophil nitric oxide production, eNOS protein expression, and cNOS activity. Triflusal alleviates cerebral ischemic injury in rats and ameliorates pathological lesions and related gene expression in transgenic Alzheimer’s disease models. Triflusal can be used for the research of thromboembolic/ischemic cardiovascular and cerebrovascular diseases, and Alzheimer’s disease^{[1][2][3][4][5]}. In Vitro:Triflusal (37.5-300 μM; 30 min pre-incubation) does not significantly inhibit endothelial Cox-2 activity or reduce prostacyclin synthesis in Phorbol 12-myristate 13-acetate (HY-18739)-stimulated porcine aortic endothelial cells^[2].
Triflusal irreversibly inhibits COX-1 and reduces TXB₂ production in human platelets while sparing vascular endothelial cell arachidonic acid metabolism, and exhibits greater anti-aggregant potency in human whole blood than in platelet rich plasma^[3].
Triflusal increases NO production by human neutrophils by 150%, inhibits NF-κB activation in human mononuclear cells^[3].
Triflusal (3.3 mM) inhibits thrombin-induced platelet activation by 61% in human platelet-rich plasma^[4].
Triflusal (1 mM) increases basal cAMP levels by 36% in rat^[4].
Triflusal (3 mM) inhibits NF-κB activation in human peripheral blood mononuclear cells^[4].
Triflusal potently inhibits cAMP phosphodiesterase, significantly elevates cGMP levels in human platelets and neutrophils: it is ~2-fold more potent at inhibiting TNFα-induced NFκB activation, ~4-10-fold more potent at inhibiting NFAT-mediated transcription, and effective at attenuating anoxia/reperfusion-related injury, iNOS activity and lipid peroxidation in rat brain slices^[4].
Triflusal inhibits NF-κB activation and downstream expression of proinflammatory mediators in human peripheral blood mononuclear cells and endothelial cells, and strongly suppresses inflammation-induced COX-2 expression in human cells^[5]. In Vivo:Triflusal (40 mg/kg/day; p.o.; daily; 8 days) reduces vascular Cox-2 mRNA and protein expression in normal rabbit aortas while sparing Cox-1 mRNA, with only a 39% reduction in Cox-2 protein levels^[2].
Triflusal (40 mg/kg/day; p.o.; daily; 8 days) reduces secondary platelet deposition on preformed primary thrombi in a rabbit model of severe carotid stenosis by 53-63% ^[2].
Triflusal (10 mg/kg; i.v.; single dose) reduces secondary platelet deposition on preformed primary thrombi in a rabbit model of thrombosis by 48-66%^[2].
Triflusal (chronic administration) provides 60% protection against arachidonic acid-induced cerebral ischaemia in rats^[3].
Triflusal (30 mg/kg) reduces NMDA (HY-17551)-induced excitotoxic brain lesions in rats^[3].
Triflusal inhibits neuronal and glial NF-κB activation, reduces lesion volume by approximately 50%, and dampens the astroglial response in a postnatal rat model of excitotoxic brain injury^[4].
Triflusal reduces inflammatory markers and functional deficits in rat models of isolated cerebral ischaemia or isolated Alzheimer's disease-like pathology, but has reduced efficacy in a model of concurrent cerebral ischaemia and Alzheimer's disease-like pathology^[4].
Triflusal (30 mg/kg; p.o.; daily; 3-5 consecutive months) rescues cognitive deficits, reduces dense-core amyloid plaque load by up to 64%, lowers neuroinflammatory markers, normalizes axonal curvature, and upregulates memory-related gene expression in Tg2576 Alzheimer's disease transgenic mice^[5].