Glucagon-like Peptide-1 Boosts Plumbagin’s Neuroprotection AgainstRotenone-Induced Motor Deficits

INTRODUCTION: Parkinson's disease (PD), a condition that involves neural degeneration, develops due to dopaminergic neuronal death in the substantia nigra pars compacta, resulting in reduced striatal dopamine levels. This shortage causes problems with movement and thinking. The neurodefensive response of GLP-1 is especially important in PD. Assessments have demonstrated the neuroprotective advantages of activating GLP-1 receptors in distinct models of PD, resulting in enhancements in motor as well as non-motor behaviour. These characteristics suggest that GLP-1 signalling could be a promising target for PD treatment. Moreover, plumbagin is the primary active component of Plumbago zeylanica L., a medicinal herb that is clinically used in China. Also, plumbagin is reported to have significant neuroprotective efficacy. METHODS: In this study, male rats received rotenone (1.5 mg/kg; subcutaneously), followed by plumbagin (20 mg/kg; p.o.). The rats' motor abilities were assessed using the actophotometer, beam walk, rotarod, gait analysis, open field, grip strength, as well as bar catalepsy evaluation. In addition, the levels of dopamine, RAGE, and GLP-1 were measured. RESULTS: Plumbagin improved movement issues caused by rotenone, boosted dopamine and GLP-1 levels, as well as lowered RAGE levels in the brains of rats. DISCUSSION: The study highlights plumbagin's potential in treating PD by improving motor function, increasing dopamine and GLP-1 levels, and reducing RAGE levels in a rotenone-induced rat model. These findings suggest that plumbagin may offer neuroprotective effects through GLP-1 pathway activation, making it a promising candidate for future PD therapies. CONCLUSION: These outcomes imply that agents that activate GLP-1, such as plumbagin, present a promising strategy for creating treatments to safeguard against rotenone-induced motor disorders.