Cholinesterase Inhibitory and Antioxidant Activities of Seed Extracts from Cucurbitaceous Plants and Hydrocotyle asiatica: Potential Natural Therapeutics for Alzheimer’s Disease

Abstract

Neurodegenerative disorders such as Alzheimer’s disease are closely associated with oxidative stress and cholinergic dysfunction. This study evaluated the cholinesterase inhibitory and antioxidant potential of sequential solvent extracts of seeds from Cucurbita maxima, Cucumis melo, Cucumis sativus, and Citrullus lanatus, along with Hydrocotyle asiatica. Butyrylcholinesterase (BChE) inhibition and radical scavenging activity were assessed in vitro at concentrations of 0.2, 0.5, and 1.0 mg·mL⁻¹. The methanolic seed extract of C. lanatus showed the strongest BChE inhibition with an IC₅₀ of 98 µg·mL⁻¹ and 81.19% inhibition at 1 mg·mL⁻¹. The ethyl acetate extract of C. maxima demonstrated 81.7% inhibition at the same concentration, while the chloroform extract of H. asiatica achieved 88.88% inhibition at 1 mg·mL⁻¹. Antioxidant assays revealed that the chloroform seed extract of C. sativus was the most active scavenger with an IC₅₀ of 642 µg·mL⁻¹, followed by the ethyl acetate extract of C. lanatus (IC₅₀ = 708 µg·mL⁻¹). In comparison, the positive controls galantamine and ascorbic acid exhibited IC₅₀ values of 3.6 ± 0.1 µg·mL⁻¹ and 4.2 ± 0.2 µg·mL⁻¹, respectively. These findings suggest that cucurbitaceous seeds and H. asiatica are promising sources of neuroprotective phytochemicals with dual cholinesterase inhibitory and antioxidant activities. Future studies should focus on bioassay-guided isolation and in vivo validation of the active constituents to confirm their therapeutic potential.