High-salt- and cholesterol diet-associated cognitive impairment attenuated by tannins-enriched fraction of Emblica officinalis via inhibiting NF-kB pathway

Abstract

Metabolic disorders are closely associated with dietary habits and seem to be related to neuroinflammation and neurodegenerative disease in humans. Emblica officinalis (EOT) fruits not only have good nutritional value but also have excellent therapeutic potential. We used a tannins-enriched fraction of EOT fruit with the expectation of controlling diet-induced neuroinflammation and cognitive impairment in rats. A high-salt and cholesterol diet (HSCD) was used to induce neuroinflammation and cognitive impairment in rats. The diet of the rats was then supplemented with EOT (100 and 200 mg/kg b.w.) for 7 weeks. In order to evaluate the neuroprotective effects of EOT; in silico study, neurobehavioral tests, biochemical analyses, and immunohistochemical studies were performed. In silico study of p50 (NF-κB1) receptors with emblicanin (the main constituent of EOT) suggests that EOT has binds to NF-κB. EOT treatment reversed the HSCD-induced behavioral and memory disturbances in a step-down-type passive avoidance test. EOT treatment also inhibited HSCD-induced NF-κB upstream signaling, including the release of Th1, such as TNF-α, and downstream signaling Th2, such as IL-10, by flow cytometer. In addition, EOT treatment attentuated the HSCD-induced increase in the level of cognitive impairment markers, such as amyloid β. Furthermore, immunohistochemical results demonstrated that EOT modulated neuronal cell death by inhibiting the overexpression of NF-kB in brain. This study confirms that EOT may be a promising therapy in ameliorating the neurotoxicity of HSCD; however further studies are warranted to elucidate the exact mechanism of action of EOT.