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

摘要

gamma-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 gamma-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 gamma-mangostin at concentrations of 0.5, 1, and 2.5 mu M 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 gamma-mangostin pretreatment. The reduction of apoptosis was further supported by the reduction of pyknotic nuclei indicated by Hoescht 33342 staining. These findings indicate that gamma-mangostin could attenuate 6-OHDA-induced neuronal cell death and that the protective effect of gamma-mangostin is associated with its antioxidative potential and through the modulation of the apoptotic signalling pathway. Therefore, gamma-mangostin may be an effective xanthone among other mangostins for preventing neurodegeneration in PD caused by oxidative stress.