Protective effect of alpha mangostin on rotenone induced toxicity in rat model of Parkinson's disease.

Parkinson's disease (PD) is a progressive, late-onset, and degenerative disorder that affects the central nervous system with an unknown etiology. Due to its incredible complexity in disease nature, many of the existing treatment approaches show a vain recovery in Parkinson's patients. Therefore, an in search of disease-modifying therapeutics for an effective recovery is essential. Alpha mangostin is an important polyphenolic xanthone reported for its neuroprotective effect against rotenone-induced α-synuclein aggregation and loss of tyrosine hydroxylase positive (TH⁺)-neurons in SHSY-5Y cells. Hence, the current study aims to test its protective effect in managing the in-vivo rat model of PD. To justify this aim, adult male Sprague Dawley rats (250 ± 20 g) were subjected to chronic treatment of rotenone (2 mg/kg/day, s.c.) for 21 days. In parallel alpha mangostin treatment (10 mg/kg, i.p) was administered along with rotenone for 21 days. Chronic rotenone treatment for 21 days increased lipid peroxidation, nitrite concentration, and decreased glutathione levels. Further, depletion of TH⁺-dopaminergic neuron expression in substantia nigra pars compacta (SNc), and the development of motor and behavioral deficits in rotenone treated animals like cognitive impairment, muscle incoordination, and neuromuscular weakness were observed. Moreover, western blot studies ascertained the reduced normal alpha-synuclein levels and increased phosphorylated α-synuclein levels in comparison to the vehicle-treated group. Treatment with alpha mangostin significantly restored the locomotor activity, memory deficits, and improved the levels of antioxidant enzymes. It also significantly reduced the levels of phosphorylated α-synuclein which in turn gave protection against TH⁺-dopaminergic neuronal loss in SNc, suggesting it's anti-oxidant and anti-aggregatory potential against α-synuclein. In conclusion through our current results, we could suggest that alpha mangostin has a potential neuroprotective effect against rotenone-induced PD and might be used as a neuroprotective agent. Further mechanistic studies on preclinical and clinical levels are required to be conducted with alpha mangostin to avail and foresee it as a potential agent in the treatment and management of PD.