Fahmy_2025_Chem.Biol.Drug.Des_106_e70175

The antioxidant and enzyme inhibition properties of the isoflavone genistein (1) and the alkaloid 11-alpha-hydroxyerysotrine (2) isolated from the leaves of Erythrina speciosa were assessed. Both compounds exhibited notable in vitro antioxidant activities; 11-alpha-hydroxyerysotrine (2) demonstrated stronger effects than genistein in DPPH, ABTS, CUPRAC, and FRAP assays. On the other hand, genistein (1) demonstrated a higher metal chelating activity than 11-alpha-hydroxyerysotrine (2). Regarding enzyme inhibition, 11-alpha-hydroxyerysotrine (2) inhibited both acetyl- (AchE) and butyryl- (BchE) cholinesterases, though to a lesser extent than the standard drug galanthamine. Both compounds inhibited tyrosinase, yet a good inhibition was observed for 11-alpha-hydroxyerysotrine (2) as compared to genistein (1). Genistein (1) showed a lower alpha-amylase inhibition effect (IC(50): 3.43 mg/mL, p < 0.05) compared to the standard acarbose (IC(50): 0.80 mg/mL). Regarding alpha-glucosidase inhibition, genistein (1) (IC(50): 1.02 mg/mL, p < 0.05) was more active than acarbose (IC(50): 1.78 mg/mL). 11-alpha-Hydroxyerysotrine (2) exhibited lower alpha-amylase (IC(50): 4.09 mg/mL) and alpha-glucosidase (IC(50): 4.48 mg/mL) inhibition effects. The in vitro biological results were further supported by network pharmacology approaches on Alzheimer's disease and in silico studies performed on AChE, BChE, tyrosinase, alpha-amylase, and beta-glucosidase enzymes. The results of our study suggest 11-alpha-hydroxyerysotrine as a potential drug candidate for further investigation in managing oxidative stress-related conditions, Alzheimer's disease, and hyperpigmentation disorders.