title: Neuroprotective effects of xanthone derivative of Garcinia mangostana against lead-induced acetylcholinesterase dysfunction and cognitive impairment.
abstract: 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 200mg/kgBW/day) for 38days. Xanthone possesses a high phenolic content, which is positive correlation with its antioxidant activity (R(2)=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±0.40mg/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.
authors.affiliation: Biomedical Sciences, School of Allied Health Sciences and Public Health, Walailak University, Nakhon Si Thammarat 80160, Thailand.
authors.forename: Moe Pwint
authors.initials: MP
authors.lastname: Phyu
authors.affiliation: Biomedical Sciences, School of Allied Health Sciences and Public Health, Walailak University, Nakhon Si Thammarat 80160, Thailand. Electronic address: njibjoy@yahoo.com.
authors.forename: Jitbanjong
authors.initials: J
authors.lastname: Tangpong
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects; D002474:Cell-Free System / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy*; D029762:Garcinia mangostana / Q000737:chemistry*; D007854:Lead / Q000633:toxicity*; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy; D051379:Mice; D008813:Mice, Inbred ICR; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy / Q000209:etiology; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D010936:Plant Extracts; D044004:Xanthones; D007854:Lead; C009689:xanthone; D000110:Acetylcholinesterase
keywords: Acetylcholinesterase (AChE); Antioxidant activity; Cognitive impairment; Lead (Pb); Xanthone