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

Abstract

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.