Neuroprotective effects of xanthone derivative of Garcinia mangostana against lead-induced acetylcholinesterase dysfunction and cognitive impairment

Lead poisoning is a common environmental toxicity and low level of lead exposure is responsible for neurobehavioral or intelligence defects. This study was designed to investigate the protective effect of a xanthone derivative of Garcinia mangostana against lead-induced acetycholinesterase (AChE) dysfunction and cognitive impairment in mice. ICR mice were exposed to lead acetate (Pb) in drinking water (1%) with or without xanthone co-administration (100 and 200 mg/kgBW/day) for 38 days. Xanthone possesses a high phenolic content, which is positive correlation with its antioxidant activity (R2 = 0.98). The IC50 of xanthone on scavenging free radical activities, hydroxyl radical, superoxide radical, hydrogen peroxide and nitric oxide in cell-free system were 0.48 ± 0.08, 1.88 ± 0.09, 2.20 ± 0.03 and 0.98 ± 0.40 mg/mL, respectively. We found that Pb induced AChE dysfunction and memory deficit in a dose dependent manner, indicated by in vitro and in vivo studies. However, xanthone significantly restored AChE activity in the blood and brains of mice and prevented Pb-induced neurobehavioral defect indicators with Forced Swimming and Morris water maze tests. Xanthone treatment improved all indicators compared to the Pb-treated group. In conclusion, xanthone alleviates Pb-induced neurotoxicity, in part, by suppression of oxidative damage and reversing AChE activity with a reduction in learning deficit and memory loss.