Effects of a (alpha)-mangostin on a cellular model of Parkinson's diseasePrachya Janhom
( M.Sc. )
Parkinson’s disease (PD) is a progressive neurodegenerative disorder of the central nervous system due to the death of dopaminergic neurons in the substantia nigra pars compacta resulting in movement disorders. Moreover, PD is recognized as the second most common neurodegenerative disorder, affecting 6 million individuals worldwide after the age of 65 years. Exploration into molecular mechanisms underlying this disease is needed. MPP+, the active metabolite of the neurotoxin called MPTP, is widely used for generation of in vitro models for PD as its effect causes permanent PD-like symptoms. α-Mangostin, a xanthone in mangosteen fruit (Garcinia mangostana), has been previously found to have involvement in cell protection, according to its antioxidant properties. This study aimed to evaluate the effects of α-mangostin on MPP+-induced apoptosis of the human neuroblastoma SH-SY5Y cell line. The results showed that treatment with MPP+ (1000 M) decreased cell viability, but co-treatment with α-mangostin (10 M) significantly increased cell viability in a concentration- and time-dependent manner. α-Mangostinhas been shown to decrease intracellular ROS production, composed of hydrogen peroxide (H2O2), peroxynitrite (ONOO-), and superoxide anions (O2-) induced by MPP+. α-mangostin significantly reduced the Bax/Bcl-2 ratio and p53 gene expression after exposure to MPP+. Treatment with MPP+ lead to an increase in cleaved, cadpase-3 protein activity. The combined treatment with α-mangostin effectively suppressed MPP+-induced caspase-3 activation, contributing to prevention of DNA fragmentation and phosphatidylserine externalization, which were proportional to the number of apoptotic cells. The results from the present study reveal that α-mangostin can protect against MPP+-induced toxicity in a human neuroblastoma SH-SY5Y cellular model of PD through its anti-oxidant and anti-apoptotic activity.