Antioxidant Activity and Neuroprotective Activity of Stilbenoids in Rat Primary Cortex Neurons via the PI3K/Akt Signalling Pathway
2018
Haichao Wen | Zheng Fu | Yangji Wei | Xiaoxu Zhang | Liyan Ma | Liwei Gu | Jingming Li
Antioxidant activity and neuroprotective activity of three stilbenoids, namely, trans-4-hydroxystilbene (THS), trans-3,5,4&prime:-trihydroxy-stilbene (resveratrol, RES), and trans-3&prime:,4&prime:,3,5-tetrahydroxy-stilbene (piceatannol, PIC), against &beta:-amyloid (A&beta:)-induced neurotoxicity in rat primary cortex neurons were evaluated. THS, RES, and PIC significantly scavenged DPPH&bull: and &bull:OH radicals. All three stilbenoids were able to inhibit A&beta: neurotoxicity by decreasing intracellular reactive oxygen species (ROS) via the PI3K/Akt signalling pathway. Specifically, stilbenoids significantly promoted Akt phosphorylation: suppressed Bcl-2/Bax expression: and inhibited caspase-9, caspase-3, and PARP cleavage. Molecular docking between stilbenoids with Akt indicated that stilbenoids could form hydrogen bond interactions with the COOH-terminal region of Akt. Additionally, the neuroprotective activity of stilbenoids correlated with the number and position of hydroxyl groups. The lack of meta-dihydroxyl groups on THS did not affect its neuroprotective activity in comparison with RES, whereas the ortho-dihydroxyl moiety on PIC significantly enhanced neuroprotective activity. These results provide new insights into the correlation between the biological activity and chemical structure of stilbenoids.
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