Nanoencapsulation of mulberry ( Morus alba ) polyphenols potentiates neuroprotection against glyphosate‐induced oxidative and inflammatory brain injury in rats

BACKGROUND Polyphenols derived from Morus alba leaves exhibit strong antioxidant and neuroprotective activities, positioning them as promising candidates for mitigating neurotoxicity caused by environmental contaminants such as glyphosate. Nevertheless, their clinical translation is hindered by poor physicochemical stability, low aqueous solubility, and limited bioavailability. This study investigates whether nanoencapsulation can enhance the stability and neuroprotective efficacy of M. alba polyphenols against glyphosate‐induced oxidative brain injury. RESULTS Morus alba leaf extract was nanoencapsulated using maltodextrin‐based freeze‐drying encapsulation. The encapsulated M. alba leaf extract (EMLE) demonstrated superior stability, retaining higher levels of total polyphenols (2136.36 mg GAE/100 g), flavonoids (389.45 mg QE/100 g), and enhanced antioxidant capacity (DPPH: 161.69 mmol Trolox/100 g) compared to free extracts. In vivo evaluation in glyphosate‐treated rats revealed that EMLE significantly reduced oxidative stress biomarkers including malondialdehyde (from 3.86 to 1.68 nmol/mg), protein carbonyls, and hydrogen peroxide levels. EMLE restored antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)), normalized brain calcium and iron homeostasis, and reduced neuronal membrane damage as evidenced by decreased lactate dehydrogenase (LDH) release. CONCLUSION Nanoencapsulation substantially enhances the stability, bioavailability, and neuroprotective efficacy of M. alba polyphenols through multiple synergistic mechanisms including physical shielding, reduced molecular mobility, and controlled release kinetics. These findings support the development of encapsulated M. alba extracts as targeted nutraceutical interventions against environmental neurotoxicants.