Malva parviflora (MP), a readily available wild plant, exhibits inherent antioxidants and hepatoprotective properties. Chitosan nanoparticles (ChNPs) can reduce phytochemicals to the nanoscale, aiding their entry into cell membranes. This study explores the efficacy of MP leaf extract and its chitosan nano-formulation (MP@ChNPs) as a cost-effective supplement to reduce Pb-induced liver toxicity in mice. MP@ChNPs revealed a particle size of 460 nm and a zeta potential of 18.0 mV, indicating good stability and distribution. In vitro tests revealed the superiority of MP@ChNPs in antioxidant activities over MP extract. The Pb-intoxicated mice were orally treated with MP-extract and MP@ChNPs for three weeks. Pb-intoxicated mice exhibited marked hepatic damage, elevated liver enzymes, and oxidative stress (increased malondialdehyde; decreased SOD and catalase), as well as dysregulation of cell death pathways (increased apoptosis and autophagy). MP@ChNPs treatment was more effective in restoring antioxidant enzyme expression, reducing oxidative damage, suppressing apoptosis (upregulating Bcl-2), and modulating autophagy (downregulating Beclin-1) compared to MP extract. Histological analysis confirmed the superior hepatoprotective efficacy of MP@ChNPs, preserving near-normal liver architecture. These findings suggest that a low-dose nano-formulation of MP holds significant promise as an inexpensive strategy to mitigate Pb-induced hepatotoxicity, particularly benefiting resource-limited communities in polluted areas. |