Ethyl-acetate fraction of Trichilia catigua protects against oxidative stress and neuroinflammation after cerebral ischemia/reperfusion

Ethnopharmacological relevance: Trichilia catigua A. Juss (Meliaceae) preparations have been used in folk medicine to alleviate fatigue, stress, and improve memory. Antinociceptive, antiinflammatory, and in vitro neuroprotective effects have been observed in animals. Cerebral ischemia/reperfusion (I/R) leads to severe neuropsychological deficits that are largely associated with oxidative stress, inflammation and neurodegeneration. We reported previously that an ethyl-acetate fraction (EAF) of T. catigua reduced brain ischemia-induced learning and memory impairments in the absence of histological protection. Aim of the study: Continuing those studies, here we aimed to investigate the antioxidant and antiinflammatory properties of T. catigua in an in vivo model of I/R. Material and methods: Rats were subjected to 15 min of brain ischemia (4-VO model) followed by up to 15 days of reperfusion. Vehicle was given by gavage 30 min before ischemia and at 1 h of reperfusion. In a first experiment, brain ischemia-induced changes in oxidative stress markers, i.e., reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and protein carbonyl groups (PCGs) were measured on days 1, 3, and 5 post-ischemia. Similar time course analysis was done for neuroinflammation markers, i.e., microglia (OX42 immunorreactivity) and astrocytes (GFAP immunorreactivity), in the hippocampus. In a second experiment, the time points at which these markers of oxidative stress and neuroinflammation peaked were used to test the effects of T. catigua (400 mg/kg, p.o.). Results: Oxidative stress markers peaked on day 1 post-ischemia. GSH decreased (-23.2%) while GSSG increased ( + 71.1%), which yielded a significant reduction in the GSH/GSSG ratio (-39.1%). The activity of CAT was largely reduced by ischemia (-54.6% to 65.1%), while the concentration of PCG almost doubled in the brain of ischemic rats ( + 99.10%) in comparison to sham. Treatment with the EAF of T. catigua normalized these changes in oxidative markers to the control levels (GSH: + 27.5%; GSSG: -23.8%; GSH/GSSG: + 44.6%; PCG: -80.3%). In the hippocampus, neuroinflammation markers peaked on day 5 post-ischemia, with microglial and astrocytic responses increasing to 54.8% and 37.1%, respectively. The elevation in glial cells response was completely prevented by EAF. Conclusion: These results demonstrate that T. catigua has both antioxidant and antiinflammatory activities after transient global cerebral ischemia in rats, which may contribute to the previously reported memory protective effect of T. catigua.