Neuroprotective potential of phenolic compounds from Cameroonian propolis: In vitro, molecular docking and molecular dynamics simulation studies

Propolis is a resinous plant-derived bee product with medicinal properties. In this study, three phenolic compounds including icaritin, triacontyl p -coumarate and apigenin-7-O-glucoside were isolated from Cameroonian propolis and characterized using ¹ H and ¹³ C NMR. The potential neuroprotective effects of the compounds against Alzheimer’s disease was performed through acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitions. Icaritin, with an IC ₅₀ value of 73.91±0.34 µg/mL, exhibited the higher AChE inhibitory activity compared with Triacontyl p -coumarate (IC ₅₀ = 81.65±0.90 µg/mL) and Apigenin-7-O-glucoside, with (IC ₅₀ = 91.08±0.76 µg/mL), and moderate activity compared to reference drug Galantamine (IC ₅₀ =5.50±0.25 µg/mL). In the BChE assay, Icaritin (IC ₅₀ = 48.92±0.62 µg/mL) exhibited relatively similar activity as the reference drug galantamine (IC ₅₀ = 42.10 ± 0.15 µg/mL), and higher activity than Triacontyl p -coumarate and Apigenin-7-O-glucoside. Icaritin was the most active compound and exhibited best binding affinity of −7.721 kcal/mol, representing 94% and 81% of the binding strength of Galantamine and Donepezil respectively. 50 ns molecular dynamics simulation indicated that icaritin is a promising lead compound ensuring structural integrity of the receptor proteins and maintaining close contact with the enzyme. The phenolic compounds from Cameroonian propolis are possible candidates for the development of neuroprotective substances.