Medicinal chemistry perspective on polyphenolic neuroprotectants: Cellular efficacy and acetylcholinesterase targeting

Polyphenols that occur in nature have shown strong potential as agents that protect nerve cells. They act on multiple targets at once, mainly because they scavenge harmful oxidants and adjust the activity of crucial enzymes in nerve tissue. The study compared how well five plant based compounds protect brain cells. The compounds were Naringenin, Formononetin, Gallic Acid, Cyanidin besides Delphinidin. Each was tested for its ability to shield human SH-SY5Y nerve cells from damage caused by hydrogen peroxide. The SH-SY5Y cells were pretreated and then exposed to a concentration of 200-/mu M H2O2 after the pretreatment phase of 24 h for test compounds. MTT analysis was carried out for the cellular viability test, and the value of DeltaPsi M and ROS were measured for understanding the mechanistic action. Furthermore, molecular docking analysis was performed for the binding affinities of the ligands for the Acetylcholinesterase-protein (AChE-protein). All tested compounds caused a significant increase in neuronal viability compared with the stress control at 39.8 ± 2.6%. Among these tested compounds, the highest potency was found for delphinidin, which increased viability to 82.6 ± 3.7%, and ROS lowering effect 63.8 ± 3.5%. The second was gallic acid, which was 78.9%, and cyanidin, which was 75.4% .These findings also supported each other well through the molecular interaction study, which indicated that cyanidin has a high binding affinity with a score of −9.652 to AChE10. The greater neuroprotection was always associated with the mitochondrial integrity enhancement. These results make Delphinidin a lead compound in the field of neurotherapy. They confirm and consolidate the interest of using natural polyphenols to effectively and multi-targetedly counteract oxidative damage in the context of neurodegenerative diseases.