Neuroprotection by arbutin against haloperidol-induced Tardive Dyskinesia in rats and reducing neurotoxicity in SHSY-5Y cells

Abstract

Abstract Background: Schizophrenia is a psychological condition, and its primary treatment is an antipsychotic medication. However, long-term use of typical antipsychotics often causes irregular involuntary movements, targeting the orofacial region. Due to its complex pathophysiology, there is no appropriate cure for Tardive Dyskinesia (TD). Arbutin, is a natural polyphenol, which is well known for neuroprotection. Therefore, this study evaluated the neuroprotective potential of arbutin against haloperidol induced neurotoxicity and orofacial dysfunction in TD rats. Methods & results: SH-SY5Y cells were treated with 1 mM concentration of haloperidol and arbutin (5, 10, 15, and 20 µM) for 48 hours, arbutin significantly reduced haloperidol-induced neurotoxicity. Other side, Wistar rats were treated with haloperidol (1 mg/kg/for 21 days) for induced TD like symptoms and treatment with arbutin (50 and 100 mg/kg i.p.) for 21 days show significant decrease in vacuous chewing movements, tongue protrusions, and facial jerking and improved locomotor activity and motor coordination in haloperidol-treated rats. Further, arbutin treatment causes a significant reduction in nitric oxide, MDA, TNF-α, IL-β, and increases SOD, GSH and catalase levels in the striatum region in contrast to haloperidol-treated rats. Conclusion: In-vitro and In-vivo experimental outcomes suggest that arbutin has the neuroprotective potential that limit TD progression. Their results indicate that arbutin has anti-inflammatory and antioxidant properties that strengthen motor activity and could be explored for cellular and molecular pathways for possible use in the treatment of TD.