Neuroinflammatory Response and Redox-regulation Activity of Hyperoside in Manganese-induced Neurotoxicity Model of Wistar Rats.

Abstract

Background: Excessive manganese exposure can lead to neurotoxicity with detrimental effects on the brain. Neuroinflammatory responses and redox regulation play pivotal roles in this process. Exploring the impact of hyperoside in a Wistar rat model offers insights into potential neuroprotective strategies against manganese-induced neurotoxicity.

Objective: The study investigated the neuroprotective efficacy of hyperoside isolated from the ethanol leaf extract of Gongronema latifolium (HELEGL), in the brain tissue of Wistar rats following 15 consecutive days of exposure to 30 mg/L of MnCl2.

Methods: Control animals in Group 1 had access to regular drinking water, while animals in groups 2-4 were exposed to MnCl₂ in their drinking water. Groups 3 and 4 also received additional HELEGL at doses of 100 mg/kg and 200 mg/kg of body weight, respectively. In Group 5, HELEGL at a dose of 100 mg/kg of body weight was administered alone. Treatment with HELEGL commenced on day 8 via oral administration.

Results: HELEGL effectively mitigated MnCl₂-induced memory impairment, organ-body weight discrepancies, and fluid intake deficits. Exposure to MnCl₂ increased the activities or levels of various markers such as acyl peptide hydrolase, tumour necrosis factor-α, dipeptidyl peptidase IV, nitric oxide, IL-1β, prolyl oligopeptidase, caspase-3, myeloperoxidase, H₂O₂, and malondialdehyde, while it decreased the activities or levels of others, including AChE, BChE, DOPA, serotonin, epinephrine, norepinephrine, GST, GPx, CAT, SOD, GSH, and T-SH (p < 0.05). In contrast, HELEGL effectively counteracted the adverse effects of MnCl₂ by alleviating oxidative stress, inflammation, apoptosis, mitochondrial dysfunction, cognitive deficits, and bolstering the antioxidant status. Moreover, HELEGL restored the normal histoarchitecture of the brain, which had been distorted by MnCl₂.

Conclusion: In summary, HELEGL reversed the causative factors of neurodegenerative diseases induced by MnCl₂ exposure, suggesting its potential for further exploration as a prospective therapeutic agent in the management of Alzheimer's disease and related forms of dementia.