RESUMEN
Para-methoxycinnamic acid (PMCA) and Ethyl-p-methoxycinnamate (EPMC) are reported to possess neuroprotective effect in reversing an acute memory deficit. However, there is a dearth of evidence for their therapeutic effect in chronic memory deficit. Thus, there is a scope to study these derivatives against the chronic model of cognitive dysfunction. The present study was aimed to determine the cognitive enhancing activity of PMCA and EPMC in aluminum-induced chronic dementia. Cognitive enhancing property of PMCA and EPMC was assessed using Morris water maze by analyzing spatial memory parameters such as escape latency, D-quadrant latency, and island entries. To find a possible mechanism, the effect of test compounds on altered acetylcholinesterase (AChE) activity and oxidative stress was determined in the hippocampus and frontal cortex of rats. Docking interaction of these derivatives with acetylcholinesterase enzyme and glutamate receptors was also studied. Treatment with PMCA and EPMC showed a significant improvement in spatial memory markers and altered hippocampal AChE activity in rats with cognitive dysfunction. The implication of hippocampal and cortical oxidative stress in memory impairment was confirmed with decreased catalase/increased thiobarbituric acid reactive substances (TBARS) in rats. PMCA and EPMC reversed the oxidative stress in the brain by negatively affecting TBARS levels. Against depleted catalase levels, PMCA was more effective than EPMC in raising the depleted catalase levels. In silico analysis revealed poor affinity of EPMC and PMCA with AChE enzyme and glutamate receptor. To conclude, PMCA and EPMC exerted cognitive enhancing property independent of direct AChE and glutamate receptor inhibition.
Asunto(s)
Aluminio/toxicidad , Cinamatos/farmacología , Trastornos de la Memoria/prevención & control , Fármacos Neuroprotectores/farmacología , Acetilcolinesterasa/metabolismo , Animales , Reacción de Prevención/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Lóbulo Frontal/efectos de los fármacos , Lóbulo Frontal/enzimología , Hipocampo/efectos de los fármacos , Hipocampo/enzimología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/inducido químicamente , Simulación del Acoplamiento Molecular , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Memoria Espacial/efectos de los fármacosRESUMEN
Research has identified a potential inverse correlation between coffee consumption and the risk of depression. The aim of this study was to investigate the effects of caffeinated coffee on lipopolysaccharide-induced depressive-like behaviors and inflammatory biomarkers in an in vivo model of depression in a C57BL/6J mouse model. The behavioral studies showed that caffeinated coffee decreased immobility time in both the tail suspension test (caffeinated coffee 56.60 ± 9.17; p < 0.0001) and the forced swimming test (caffeinated coffee 28.80 ± 5.93; p < 0.0001), suggesting antidepressant-like activity. The effects of caffeinated coffee on the inflammatory biomarkers associated with depression supported the results observed in the behavioral studies. Statistically significant decreases in indoleamine 2,3-dioxygenase activity (p < 0.001) and the neopterin/biopterin ratio (p < 0.001) were observed in animals pretreated with caffeinated coffee 24 h post-lipopolysaccharide exposure in comparison to the lipopolysaccharide control group. In conclusion, this study has provided evidence to suggest that caffeinated coffee has antidepressant-like activities; however, further studies are required to fully investigate these effects.