Abstract
Modern diets containing high quantities of salt and cholesterol have exhibited to cause a considerable effect on our health. Such diets, when consumed in the long term, have also shown to be a precursor to several disorders such as the metabolic disorder and consequently, various other diseases, including cognitive deficits. In the present study, we used a high salt and cholesterol diet (HSCD) to induce cognitive impairment in rats and also investigated the pharmacological action of tannins enriched fractions of Emblica officinalis (EOT) – a fruit that has been traditionally used for the treatment of numerous disorders for centuries. Significant alterations in MDA, GSH, TBARS, GPx, mitochondrial ATP, and mitochondrial membrane potential levels were observed in rats fed HSCD, which indicated presence of oxidative stress. Moreover, classic signs of cognitive impairment and deficits in spatial learning and memory were observed in the neurobehavioral tests. E. officinalis tannins exhibited good affinity to Nrf2 receptors in in silico studies, significantly reversed the changes in the aforementioned biomarkers of oxidative stress which were altered in the model group, as well as improved the performance of rats in Morris water maze task. Our results also reflected that EOT supplementation significantly increased the expression of Nrf2 in the CA1 region of hippocampus and cortex. Additionally, TUNEL assay indicated that EOT supplementation led to reversal of DNA fragmentation and apoptosis caused by HSCD. Immunohistochemical analysis and western blot further revealed a surge in the nuclear location of Nrf2. Through our study, we have demonstrated that cognitive impairment can be caused in rats via HSCD as a result of the oxidative stress induced by the same. Additionally, we have investigated a novel mechanism of action for EOT (which strongly suggests to be via the Nrf2–ARE pathway) and demonstrated that it has the potential to be used in the treatment of cognitive impairment.
Highlights
Dementia is a clinical syndrome characterized by a progressive decline in memory in addition to impairment or difficulties in cognitive functions such as language, executive function, or skilled movements
The more hydrogen as well as hydrophobic binding with the drug emblicanin A as compared to the standard piracetam resulted in higher docking score
The results obtained from the study reflected that rats fed high salt and cholesterol diet (HSCD) had poor performance in the Morris water maze (MWM) task and administration of EOT led to significantly better performance, there was no significant difference between the performance of the EOT groups and the PCT group
Summary
Dementia is a clinical syndrome characterized by a progressive decline in memory in addition to impairment or difficulties in cognitive functions such as language (aphasia), executive function (such as abstract reasoning, planning, attention), or skilled movements (apraxia). It is estimated that about 135 million people would suffer from dementia by the year 2050 and that the global cost of dementia care would increase to one trillion United States dollars by the year 2030 (American Psychiatric Association, 2013; Prince et al, 2014). Numerous risk factors that have shown to increase the susceptibility of a person to suffer from dementia. Among psychological factors – depression, anxiety, sleep disorders and mental distress in mid or late life have shown to influence risk of dementia. As far as lifestyle and cardiovascular risk factors are concerned smoking, hypertension, obesity, hyperlipidemia, and diabetes have shown to play a role in the pathogenesis of dementia (Tzourio, 2007)
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