Protective effects of γ-mangostin on 6-OHDA-induced toxicity in SH-SY5Y cells.

γ-Mangostin is a xanthone with hydroxyl groups that confer the substance-free radical scavenging effects. As opposed to the other more extensively studied mangostins, scarce research has been conducted on neuroprotective effects of γ-mangostin on models of Parkinson's disease (PD). Therefore, this investigation aimed to elucidate its antioxidant and neuroprotective effects on 6-OHDA-induced toxicity in SH-SY5Y cells. 6-OHDA treatment, an inducer of PD pathology in vitro studies, decreased cell viability and increased the level of intracellular ROS production. Furthermore, the substance-induced the expression of phosphorylated p38 MAPK, negatively affected the Bax/Bcl-2 ratio and increased caspase-3 activity; all of which were factors that are associated with apoptosis. Pretreatment of cells with γ-mangostin at concentrations of 0.5, 1, and 2.5μM markedly increased cell survival and reduced the level of intracellular ROS formation as shown by DPPH radical scavenging activity of the compound. Furthermore, a significant suppression of p-p38, improved Bax/Bcl-2 ratio expression, and reduced caspase-3 activity was exhibited in the cells after γ-mangostin pretreatment. The reduction of apoptosis was further supported by the reduction of pyknotic nuclei indicated by Hoescht 33342 staining. These findings indicate that γ-mangostin could attenuate 6-OHDA-induced neuronal cell death and that the protective effect of γ-mangostin is associated with its antioxidative potential and through the modulation of the apoptotic signalling pathway. Therefore, γ-mangostin may be an effective xanthone among other mangostins for preventing neurodegeneration in PD caused by oxidative stress.