Antioxidant compounds of leaves and seeds extracts of Parkia Speciosa overcome ferroptosis

• Parkia speciosa seeds and leaves are rich in bioactive compounds with potential health benefits. • Ethanol extracts of P. speciosa leaves (PSL) exhibited higher antioxidant activity than seeds (PSS). • PSL and PSS extracts protected HT22 cells from erastin-induced ferroptotic cell death and activated the ARE pathway, enhancing endogenous antioxidant defense. • Molecular docking identified 7,7′-Dihydroxy-5′‑methoxy-2′,2′-dimethyl-4-oxo-3′,4′-dihydro-2′H,4H-3,6′-bichromen-5-yl hexopyranosiduronic acid as a promising bioactive compound. Parkia speciosa seeds, a widely consumed plant in Southeast Asia, are known for their rich bioactive compounds with potential health benefits. This study investigates the antioxidant properties of ethanol extracts from P. speciosa leaves (PSL) and seeds (PSS) to combat oxidative stress. Antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays, revealing that PSL exhibited higher antioxidant potential than PSS, with values of 14.34 ± 0.02 and 19.39 ± 0.04 μg ascorbic acid equivalent (AAE)/g extract, respectively. The ethanol extracts of PSL and PSS significantly protected HT22 cells from erastin-induced ferroptotic cell death and activated the antioxidant response element (ARE) pathway, enhancing endogenous antioxidant defense mechanisms. Furthermore, in silico molecular docking analysis identified 7,7′-Dihydroxy-5′‑methoxy-2′,2′-dimethyl-4-oxo-3′,4′-dihydro-2′H,4H-3,6′-bichromen-5-yl hexopyranosiduronic acid as a promising bioactive compound with strong binding affinities to oxidative stress-related receptors (5i6x, 6cm4, 2f8a, 8bxn, and 8ivr). These findings suggest that P. speciosa ethanol extract, particularly from its leaves, exhibits strong antioxidant and neuroprotective properties, supporting its potential application as a natural therapeutic agent for oxidative stress-related disorders.