Microemulsion of Trichilia catigua A. Juss. (Meliaceae) improves memory recovery and reduces oxidative stress after cerebral ischemia in rats

Abstract

We reported that a lyophilized ethyl-acetate fraction (EAF-L) of Trichilia catigua (popular ‘Catuaba’) facilitated memory recovery and reduced oxidative stress after cerebral ischemia in rats. However, oral doses as high as 400 mg/kg seem necessary to achieve those effects. Here we used an  EAF microemulsion (EAF-ME) to evaluate whether a dose lower than that used previously can be suitable for memory neuroprotection. Intact rats were trained in the aversive radial maze (LRA) and subjected to transient global cerebral ischemia (TGCI). EAF-ME or EAF-L (100 mg/kg each) was administered at 4 hours of reperfusion and repeated in the next 6 days. Retrograde memory performance was assessed 7-, 14-, and 21-days postischemia. In a second experiment, a single EAF-ME dose was given at 4 h of reperfusion. Oxidative stress of brain tissue was assessed at 24 h of reperfusion. Lastly, after the FAE-ME treatment, the brain was examined for GFAP and Iba-1 immunoreactivity as neuroinflammation markers. The rats' ability to recall the AvRM task learned before ischemia was significantly reduced after ischemia (amnesia). Treatment with EAF-ME (100 mg/kg) mitigated this outcome, whereas the same dose of the EAF-L formulation did not. Furthermore, a single administration of the EAF-ME prevented oxidative stress by restoring SOD and CAT activities and reducing protein carbonylation and lipoperoxidation. Ischemia-induced glial cell immunoreactivity, however, was not precluded by the EAF-ME formulation. The current findings demonstrate that the neuroprotective efficacy of T. catigua can be improved by developing appropriate formulations that may enhance the bioavailability of polyphenolic constituents in the brain.