Effect of alpha-mangostin in the prevention of behavioural and neurochemical defects in methylmercury-induced neurotoxicity in experimental rats

Rakesh Sahu; Sidharth Mehan; Sumit Kumar; Aradhana Prajapati; Abdulrahman Alshammari; Metab Alharbi; Mohammed A Assiri; Acharan S Narula

doi:10.1016/j.toxrep.2022.04.023

Effect of alpha-mangostin in the prevention of behavioural and neurochemical defects in methylmercury-induced neurotoxicity in experimental rats

Toxicol Rep. 2022 Apr 22:9:977-998. doi: 10.1016/j.toxrep.2022.04.023. eCollection 2022.

Authors

Rakesh Sahu¹, Sidharth Mehan¹, Sumit Kumar¹, Aradhana Prajapati¹, Abdulrahman Alshammari², Metab Alharbi², Mohammed A Assiri², Acharan S Narula³

Affiliations

¹ Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India.
² Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh 11451, Saudi Arabia.
³ Narula Research, LLC, 107 Boulder Bluff, Chapel Hill, NC 27516, USA.

Abstract

Methylmercury (MeHg+) is a known neurotoxin that causes progressive motor neuron degeneration in the central nervous system. Axonal degeneration, oligodendrocyte degeneration, and myelin basic protein (MBP) deficits are among the neuropathological abnormalities caused by MeHg+ in amyotrophic lateral sclerosis (ALS). This results in demyelination and motor neuron death in both humans and animals. Previous experimental studies have confirmed that overexpression of the extracellular signalling regulated kinase (ERK1/2) signalling contributes to glutamate excitotoxicity, inflammatory response of microglial cells, and oligodendrocyte (OL) dysfunction that promotes myelin loss. Alpha-mangostin (AMG), an active ingredient obtained from the tree "Garcinia mangostana Linn," has been used in experimental animals to treat a variety of brain disorders, including Parkinson's and Huntington's disease memory impairment, Alzheimer's disease, and schizophrenia, including Parkinson's disease and Huntington's disease memory impairment, Alzheimer's disease, and schizophrenia. AMG has traditionally been used as an antioxidant, anti-inflammatory, and neuroprotective agent.Accordingly, we investigated the therapeutic potential of AMG (100 and 200 mg/kg) in experimental rats with methylmercury (MeHg+)-induced neurotoxicity. The neuroprotective effect of AMG on behavioural, cellular, molecular, and other gross pathological changes, such as histopathological alterations in MeHg+ -treated rat brains, is presented. The neurological behaviour of experimental rats was evaluated using a Morris water maze (MWM), open field test (OFT), grip strength test (GST), and force swim test (FST). In addition, we investigate AMG's neuroprotective effect by restoring MBP levels in cerebral spinal fluid and whole rat brain homogenate. The apoptotic, pro-inflammatory, and oxidative stress markers were measured in rat blood plasma samples and brain homogenate. According to the findings of this study, AMG decreases ERK-1/2 levels and modulates neurochemical alterations in rat brains, minimising MeHg+ -induced neurotoxicity.

Keywords: Alpha-mangostin; Amyotrophic lateral sclerosis; ERK-1/2; Methylmercury; Neuroprotection; Oligodendrocytes.