Polyphenols from Conyza dioscoridis (L.) ameliorate Alzheimer's disease- like alterations through multi-targeting activities in two animal models

Recent investigations suggested that anticancer agents may inhibit the progression of Alzheimer's disease (AD) pathology. Conyza dioscoridis (L.) was demonstrated to have anticancer, antioxidant, anti-inflammatory and antidiabetic effects. This study was carried out to investigate the efficacy of polyphenols from Conyza dioscoridis (L.) extract (PCDE) on AD. Impacts of 3 doses of PCDE and donepezil, a reference drug, on the features of Alzheimer's disease in two animal models were investigated. PCDE ameliorated the memory and learning impairment shown in rats following a single dose of scopolamine (scopolamine model) or 17 weeks of high-fat/high-fructose(HF/Hfr) diet coupled with a single dose of streptozotocin, (25 mg/kg) (T2D model). They reduced significantly the high hippocampal cholinesterase activity in the two models of rats. Administration of PCDE for 8 weeks in the T2D model showed a significant reduction in hippocampal GSK-3β, caspase-3 activity and increase in the inhibited glutamate receptor expression (AMPA GluR1 subunit and NMDA receptor subunits NR1, NR2A, NR2B). A significant reduction of HOMA-insulin resistance and serum hypercholesterolemia was observed. The Tau hyperphosphorylation and Aβ 1-42 generation in the hippocampal of T2D rats were significantly decreased by PCDE. Modulation of the oxidative stress markers, (rise in GH and SOD; decrease in MDA levels) and a significant reduction of TNF-α and IL-1β in the hippocampus of T2D rats treated by PCDE extract were important findings in this study. The highest dose tested was 4% of the highest safe dose. Our study suggests that PCDE is multi-targeting agent with multiple beneficial activities in combating features of AD. This study may provide a novel therapeutic strategy for AD treatment that warrants clinical studies.