Protective effect of flavonoids against aging- and lipopolysaccharide-induced cognitive impairment in mice.

Flavonoids, naturally occurring polyphenolic compounds, are known to inhibit both lipopolysaccharide (LPS) stimulated tumor necrosis factor alpha and interleukin 6 release which modulate the proinflammatory molecules that have been reported in many progressive neurodegenerative disorders, including Alzheimer's disease (AD), viral and bacterial meningitis, AIDS dementia complex, and stroke. The present experiments were performed to study the possible effects of exogenously administered flavonoids (apigenin-7-glucoside and quercetin) on the cognitive performance in aged and LPS-treated mice (an animal model for AD) using passive avoidance and elevated plus-maze tasks. Aged and LPS-treated mice showed poor retention of memory in step-through passive avoidance and in plus-maze tasks. Chronic administration of the flavonoids apigenin-7-glucoside (5-20 mg/kg i.p.) and quercetin (25-100 mg/kg i.p.) dose dependently reversed the age-induced and LPS-induced retention deficits in both test paradigms. However, flavonoids after chronic administration in young mice did not show any improvement of memory retention in both paradigms. Apigenin-7-glucoside showed more efficacy as compared with quercetin in both models that may be probably due to its greater efficacy to inhibit cyclooxygenase-2 and inducible nitric oxide synthase. Chronic treatment with flavonoids did not alter the locomotor activity in both young and aged mice; however, aged mice showed improvement of performance on Rota-Rod test. The results showed that chronic treatment with flavonoids reverses cognitive deficits in aged and LPS-intoxicated mice which suggests that modulation of cyclooxygenase-2 and inducible nitric synthase by flavonoids may be important in the prevention of memory deficits, one of the symptoms related to AD.