curcumin and 7-nitroindazole

A plant alkaloid obtained from Curcuma longa, curcumin possesses anti-oxidant and anti-inflammatory effects. Nanoformulations have been developed for preclinical studies which demonstrate enhanced therapeutic efficacy. Effect of acute intraperitoneal (i.p.) administration of curcumin C3 complex nanoparticles [1,5, 10, 20, 40, 80mg/kg, (i.p.)] 75min prior to PTZ, on clonic seizure thresholds induced by intravenous infusion of pentylenetetrazole (PTZ) 0.5% was investigated in comparison with curcumin (40 and 80mg/kg, i.p.) in male mice. Moreover, to clarify the probable role of NO in the anticonvulsant property of nanocurcumin, non-effective doses of l-arginine (l-Arg), a NO donor; 7-nitroindazole, 7-NI, a preferential neuronal NO synthase inhibitor; L-NAME, a non-selective NO synthase inhibitor and aminoguanidine (AG), a selective inducible NO synthase inhibitor (iNOS), in combination with nanocurcumin (80mg/kg, i.p.), 15-30min before it were employed.. While curcumin did not show any anticonvulsant effect, nanocurcumin revealed dose-dependent anticonvulsant property at the doses 20, 40 and 80mg/kg, P<0.01, P<0.01 and P<0.001, respectively. l-Arg (30 and 60mg/kg) dose-dependently reversed the anticonvulsant effect of the most effective nanocurcumin dose (80mg/kg), P<0.01 and P<0.001, respectively. On the other hand, L-NAME (3 and 10mg/kg, i.p.) markedly potentiated the sub effective dose of nanocurcumin (10mg/kg), P<0.01 and P<0.001, respectively. Similarly, AG (50 and 100mg/kg, i.p.) profoundly augmented the seizure thresholds of nanocurcumin (10mg/kg), P<0.01 and P<0.001, respectively. In addition, 7-NI (10, 30 and 60mg/kg, i.p.) failed to influence the responses.. These data may support excess of NO production following PTZ infusion probably resulting from iNOS source. Consequently, nanocurcumin probably down regulated NO. To conclude, nanocurcumin showed anticonvulsant effect. Furthermore, this effect was reversed following l-arginine as an external NO precursor. However, both the non-selective NOS inhibitor and selective iNOS inhibitor increased the thresholds. It is evident that nanocurcumin may influence the seizure thresholds at least in part through a decrease in NO.

Topics: Animals; Anticonvulsants; Convulsants; Curcumin; Dose-Response Relationship, Drug; Indazoles; Male; Mice; Nanoparticles; Nitric Oxide; Nitric Oxide Synthase Type I; Pentylenetetrazole; Seizures

A number of neuroprotective effects of curcumin have been demonstrated in recent years. However, whether curcumin exerts any beneficial effects on age-related impaired cognition and memory has not been well characterized; nor was there any detailed data on the molecular pathways activated by curcumin. The present study attempts to investigate the effects of curcumin on memory decline of aged mice with a focus upon the possible contribution of the neuronal nitric oxide synthase (nNOS)/nitric oxide (NO) pathway in the memory amelioration effect of curcumin. The results showed that chronic administration of curcumin (50mg/kg, i.p., 21 days) significantly ameliorated the memory acquisition ability of aged male mice in the novel object recognition and passive avoidance tasks. Immunoblotting revealed that chronic treatment of curcumin increased nNOS expression in the prefrontal cortex, amygdala and hippocampus, as well as the enhancement of nNOS activity and NO concentration. This enhancement was suppressed by pre-treatment with 7-nitroindazole (7-NI), a specific inhibitor of neuronal nitric oxide synthase (nNOS). Furthermore, inhibition of nNOS synthase by 7-NI also prevented the memory improvement effects of curcumin in aged mice. Taken together, the results of the present study suggest that the amelioration of memory deficits by curcumin in aged mice was mediated, at least in part, by activating the nNOS activity in specific brain regions. These findings reveal the therapeutic potential of curcumin as a preventive agent upon the deterioration of cognitive faculties.

Topics: Aging; Animals; Brain; Curcumin; Indazoles; Male; Memory Disorders; Mice; Neuroprotective Agents; Nitric Oxide; Nitric Oxide Synthase Type I