Galantamine potentiates the protective effect of rofecoxib and caffeic acid against intrahippocampal Kainic acid-induced cognitive dysfunction in rat

Role of neuroinflammatory mediators particularly cyclooxygenase (COX), lipoxygenase (LOX), have been well suggested in the pathophysiology of neurodegenerative disorders. Rofecoxib is a selective cyclooxygenase 2 enzymes belongs to non-steroidal anti-inflammatory drug, commonly called as coxibs. Whereas, caffeic acid (3,4-dihydroxycinnamic acid) is one of the natural phenolic compounds and reported to inhibit 5-lipoxygenase (5-LOX) activity as one of mechanisms. Present study has been designed to investigate the effects of rofecoxib, caffeic acid and its potentiation by galantamine against intrahippocampal kainic acid-induced cognitive impairment, oxidative damage and mitochondrial respiratory enzyme alterations in rats. Kainic acid (KA) was administrated in the hippocampus region of rat brain. Various behavioral (locomotor activity and memory performances were assessed by using actophotometer and Morris water maze respectively) followed by oxidative stress, mitochondrial enzyme complex were assessed. Intrahippocampal administration of KA significantly impaired locomotor activity, memory performance, mitochondrial enzyme complexes and caused oxidative stress as compared to sham treatment. Rofecoxib (5 and 10 mg/kg), caffeic acid (5 and 10 mg/kg), Gal (2.5 and 5 mg/kg) treatment for 14 days significantly improved locomotor activity, memory retention and oxidative defense (as evidenced by decrease lipid peroxidation, nitrite, increased superoxide dismutase activity and redox ratio) in hippocampus. Besides, alterations in the levels of mitochondrial enzymes and acetylcholine esterase enzyme were significantly restored by rofecoxib and caffeic acid as compared to control. Further, combination of rofecoxib (5 mg/kg) with caffeic acid (5 mg/kg) and lower dose of gal (2.5 mg/kg) with rofecoxib (5 mg/kg) treatments significantly potentiated their protective effect which was significant as compared to their effect per se. The results of the present study suggest that galantamine potentiates the protective effect of rofecoxib and caffeic acid against kainic acid induced cognitive impairment and associated oxidative damage.

► Kainic acid produced memory deficits, mitochondrial and oxidative damage.
► Galantamine potentiates the protective effect of rofecoxib and caffeic acid
► Rofecoxib/caffeic acid could be used along with galantamine against dementia.