Neuroprotective efficacy of Curcuma longa extract against lead-induced trace element dysregulation and amyloid-like deposition in the hippocampal CA1 and CA3 regions of wistar rats

Abstract

Lead (Pb) remains a pervasive environmental neurotoxin implicated in cognitive dysfunction and hippocampal injury. Identifying natural compounds capable of mitigating these deficits is critical for developing safe neuroprotective interventions as standard chelation therapies carry adverse systemic side effects. This study evaluated the neuroprotective efficacy of graded doses of an ethanol extract of Curcuma longa (EECl) against lead acetate-induced hippocampal β-amyloid deposition and alterations in neurochemical trace element homeostasis (Ca²⁺ and Zn²⁺) in adult male Wistar rats. Thirty-six adult male Wistar rats were randomly allocated into six groups (n = 6/group). The control group received distilled water (2 mL/kg), while the Pb group received lead acetate (120 mg/kg). A positive control group (Pb+Vit C) was co-administered lead acetate (120 mg/kg) and ascorbic acid (100 mg/kg). Three treatment groups (Pb+375, Pb+750, and Pb+1500) received concurrent administration of lead acetate (120 mg/kg) alongside graded doses of EECl (375, 750, and 1500 mg/kg, respectively) daily. Administrations of all substances lasted for 14 days via oral gavage. Following the 14-day treatment period, the animals were humanely euthanized. Brains were rapidly excised and hemisected; one hemisphere was homogenized for the neurochemical quantification of calcium (Ca²⁺) and zinc (Zn²⁺), while the contralateral hemisphere was fixed in Bouin's fluid. Histopathological evaluation of the hippocampus was conducted using Congo red staining to assess β-amyloid plaque deposition. Co-administration of EECl significantly attenuated Pb-induced neurochemical disruptions. Hippocampal Ca²⁺ and Zn²⁺ levels were significantly preserved in all EECl-treated groups compared to the Pb-only group (p <0.05). Furthermore, histological analysis revealed a marked reduction in Pb-induced β-amyloid deposition in the hippocampus of EECl-treated rats relative to the untreated Pb group. These findings demonstrate that Curcuma longa ethanol extract confers significant neuroprotection against lead-induced hippocampal toxicity. This protective effect is likely mediated by the preservation of essential divalent cations (Ca²⁺ and Zn²⁺) and the suppression of Congo Red-positive amyloid-like deposits.