Cell-Mediated Immunomodulatory and Neuroprotective Effects of Moringa oleifera Leaf Extract Against Aluminum Chloride-Induced Hypothalamic Toxicity in Adult Male Wistar Rats.
Abstract
Background: Aluminum chloride (AlCl₃) is a well-established neurotoxin implicated in oxidative stress, immune dysregulation, and hypothalamic dysfunction. The search for plant-based therapeutic agents with immunomodulatory and neuroprotective properties remains critical in toxicological research. Objective: This study evaluated the cell-mediated immunomodulatory and neuroprotective effects of Moringa oleifera leaf extract (MOLE) against AlCl₃-induced hypothalamic toxicity in adult male Wistar rats. Methods: Thirty-six adult male Wistar rats (180g – 220g) were randomly assigned into six groups (n=6) and treated orally for 28 days. Aluminum chloride (100mg/kg) was administered to induce toxicity. Immunological parameters (CD4⁺ and CD8⁺ T-cells by flow cytometry, serum IL-2, IFN-γ and TNF-α by ELISA), delayed-type hypersensitivity (DTH) response, oxidative stress markers (MDA, SOD, CAT, GPx) in hypothalamic tissue, histopathology, immunohistochemistry, and RT-PCR gene expression analyses were performed. Results: AlCl₃ exposure significantly suppressed CD4⁺ and CD8⁺ T-cell populations, reduced IL-2 and IFN-γ levels, elevated TNF-α (P < 0.05), induced oxidative stress, and caused severe hypothalamic neuronal degeneration and vacuolation. Treatment with MOLE significantly reversed these alterations in a dose-dependent manner, with the 400 mg/kg dose showing effects comparable to the Vitamin E positive control. Gene expression analysis confirmed restoration of IL-2 and IFN-γ mRNA levels. Histological and immunohistochemical examinations demonstrated marked preservation of neuronal architecture and reduced astroglia activation. Conclusion: Moringa oleifera leaf extract exhibits potent neuroprotective and immunomodulatory effects mediated through enhancement of cell-mediated immunity and antioxidant defense systems, suggesting its potential as a therapeutic candidate against heavy metal-induced neurotoxicity.