Neuroprotective effects of isoflavone-enriched soybean leaves (Glycine Max) on scopolamine-induced memory deficits in C57BL/6 mice via antioxidative mechanisms

Introduction: This study aimed to investigate the neuroprotective and memory-enhancing effects of isoflavone-enriched soybean leaves (IESLs) against scopolamine-induced cognitive impairment. While soybean leaves (SLs) are naturally rich in kaempferol glycosides and soyasaponins, IESLs are characterized by significantly elevated isoflavone levels through metabolite farming. Methods: To assess the efficacy of IESLs, C57BL/6 mice were orally administered IESLs (6.25 and 18.8 mg isoflavones/kg/day) for 5 weeks, with scopolamine (1 mg/kg, i.p.) administered to induce memory impairment. Spatial learning and memory functions were evaluated using the Morris water maze and passive avoidance tests. Results: Scopolamine-induced behavioral deficits were significantly restored by IESLs administration in a dose-dependent manner. Mechanistically, IESLs treatment reduced the intracellular accumulation of reactive oxygen species and enhanced the antioxidant defense system. Furthermore, IESLs significantly upregulated the expression of brain-derived neurotrophic factor (BDNF) and activated the cAMP response element-binding protein (CREB) via phosphorylation. Histological analysis also revealed that IESLs suppressed the activation of astrocytes and microglia, thereby attenuating neuroinflammation. Discussion: These findings suggest that IESLs effectively alleviate cognitive impairment by strengthening antioxidant defenses and activating the CREB-BDNF signaling pathway. Consequently, IESLs may serve as a promising therapeutic or preventive candidate for amnesia and neurodegenerative diseases.