The incidence of neurodegeneration leading to the conditions such as Alzheimer's and Parkinson's diseases are on the increase, they require the approaches that focus on protection prevention rather than treatment. Plants are rich sources of many compounds which possess medicinal properties. We sought to investigate the neuroprotective effects of Uncaria hirsuta and its compounds on D-galactose-induced stress in BALB/c mice as well as 6-hydroxydopamine (6-OHDA)-induced stress in mouse nerve growth factor (mNGF)-differentiated PC12 cells. Our results demonstrate that the 95% ethanol extract of U. hirsuta reversed the D-galactose-induced learning and memory dysfunctions and decreased the malodialdehyde levels. Furthermore, the isolated compounds, 5β-carboxystrictosidine (1) and chlorogenic acid (2), protected mNGF-differentiated PC12 cells against toxicity induced by 6-OHDA by acting as antiapoptotic agents. The 50% inhibitory concentration (IC50) for intracellular reactive oxygen species (ROS) scavenging was found to be 24.5 (for 1) and 19.7 μM (for 2), and both 1 and 2 reduced intracellular calcium levels with respective IC50 values of 46.9 and 27 μM. Interestingly, both compounds inhibited caspase 3 and 9 activities with respective IC50 values of 25.6 and 24.5 μM for 1 and 19.4 and 16.3 μM for 2. Our results identify U. hirsuta and its active compounds as potential neuroprotective agents and deserve further evaluation for drug development for neuroprotection in the future. © 2019

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