Neuroprotective Effect of the Hydro-Ethanolic Extract of Khaya grandifoliola in a Model of Alzheimer’s-Like Pathology Induced in Rats by Lipopolysaccharides

Abstract

Neuroinflammation plays a crucial role in Alzheimer's disease (AD) pathology. AD is a neurodegenerative disorder characterized by progressive memory loss, cognitive decline and loss of autonomy. Present in our living environment, lipopolysaccharides (LPS) are known as potent neurotoxins causing progressive neurodegeneration in the brain. So far, available treatments for the disease only limit its symptoms. Fortunately, Khaya grandifoliola (KG) is used in Cameroonian traditional medicine for the treatment of brain disorders. In this study, we evaluated the neuroprotective effect of KG against LPS-induced neuroinflammation in rats. LPS intoxication was assayed in 25 rats divided into 5 groups of 5 rats each for 6 days at 1 mg/kg and behavioral tests (FST and ECM) were performed on the 4th and 6th days during induction. Thereafter, the rats were treated with reference drug (Baicalin 10 mg/kg) and KG at two doses (75 mg/kg and 225 mg/kg) for 15 days. The FST and ECM tests were performed for 4 days: 3; 7; 10 and 15. On day 22, after 24 hours of fasting, the rats were sacrificed and blood was collected in order to measure ASAT, ALAT, total protein levels, creatinine, markers of oxidative stress (CAT, MDA, GSH, and NO), acetylcholinesterase and pro-inflammatory cytokines (IL1-β and TNF-α). Overall, we observed that LPS-induced anxiety and depression decreased by 30% after the administration of KG-75 and KG-225. Treatment with the plant extract led to an improvement of oxidative stress parameters including catalase, lipid peroxidation, glutathione, nitric oxide and did not cause toxicity. Moreover, acetylcholinesterase activity showed a significant increase in group II (control LPS) and a significant decrease in enzyme activity by 60% (P<0.05) in the drug treated groups. Evaluation of inflammatory cytokines showed a decrease of IL1-β and TNF-α by 75% for IL1-β and 100% for TNF-α respectively in the groups treated with KG in comparison to the LPS-treated group. Altogether, KG-75 and KG-225 extracts effectively protected the rat’s brain from the toxic effects of LPS.