Antioxidant and Amylase, Glucosidase, and Tyrosinase Enzymes Inhibitory Potential of Genistein and 11‐α‐Hydroxyerysotrine Supported by In Silico and Network Pharmacology Approaches

The antioxidant and enzyme inhibition properties of the isoflavone genistein (1) and the alkaloid 11-α-hydroxyerysotrine (2) isolated from the leaves of Erythrina speciosa were assessed. Both compounds exhibited notable in vitro antioxidant activities; 11-α-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-α-hydroxyerysotrine (2). Regarding enzyme inhibition, 11-α-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-α-hydroxyerysotrine (2) as compared to genistein (1). Genistein (1) showed a lower α-amylase inhibition effect (IC₅₀: 3.43 mg/mL, p < 0.05) compared to the standard acarbose (IC₅₀: 0.80 mg/mL). Regarding α-glucosidase inhibition, genistein (1) (IC₅₀: 1.02 mg/mL, p < 0.05) was more active than acarbose (IC₅₀: 1.78 mg/mL). 11-α-Hydroxyerysotrine (2) exhibited lower α-amylase (IC₅₀: 4.09 mg/mL) and α-glucosidase (IC₅₀: 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, α-amylase, and β-glucosidase enzymes. The results of our study suggest 11-α-hydroxyerysotrine as a potential drug candidate for further investigation in managing oxidative stress-related conditions, Alzheimer's disease, and hyperpigmentation disorders.