The Beneficial Effect of Ononis natrix Against Pb-Induced Sensorimotor, Neurobehavioral, and Oxidative Stress Impairments in Mice Offspring during Gestation and Lactation

Lead (Pb) is an environmental metal with toxic effects primarily targeting the central nervous system (CNS). Early-life exposure is linked to long-term behavioral and cognitive impairments. This study aims to evaluate the behavioral effects of Pb exposure during gestation and lactation and investigate the neuroprotective effect of the aqueous extract of Ononis natrix (AEON), a medicinal plant recognized for its antioxidant and anti-inflammatory properties, selected for its potential to counteract Pb-induced neurological damage. Pregnant mice were assigned to four groups: control, Pb-exposed (1 g/L in drinking water), and two groups receiving AEON (100 mg/kg and 500 mg/kg) by oral gavage alongside Pb from the first day of gestation until the end of lactation. Reproductive parameters were measured, such as fertility rate, gestation period, and offspring viability. Sensorimotor development was assessed using negative geotaxis, surface righting reflex, cliff avoidance, and suspension test. In adulthood, neurobehavioral functions such as anxiety-related behavior, locomotion, memory, depression-like behavior, and motor performance were assessed. We also measured markers of oxidative stress, notably catalase (CAT) and malondialdehyde (MDA), in the whole brain, hippocampus, and prefrontal cortex. Our results showed that Pb exposure led to a significant reduction in gestation period in pregnant females and considerably disrupted sensorimotor development in the offspring. In adulthood, Pb-exposed mice exhibited pronounced anxiety-like behavior and depressive-like symptoms, along with hyperactivity and impaired motor coordination. These dysfunctions were correlated with increased CAT activity and MDA levels in different brain regions. However, co-administration of AEON improved reproductive parameters, enhanced sensorimotor functions, normalized neurobehavioral performance in adulthood, and restored disrupted oxidative stress markers. These findings provide the first evidence of AEON's efficacy in mitigating developmental Pb-induced neurotoxicity, highlighting its potential as a novel neuroprotective agent and paving the way for future therapeutic strategies.