Abstract

BACKGROUNDCurrently, there are no drugs that can reverse or delay the progression of Alzheimer's disease (AD).1 Neuroinflammation could be one of the major underlying mechanisms of AD.2 Oxidative stress can directly potentiate neurodegeneration via neuron cell damage3 or indirectly activate the neuroinflammation process.4 Additionally, pro‐inflammatory cytokines, for example, interleukin 6 (IL‐6), are upregulated in the brain of patients with AD, producing amyloid plaque and hyperphosphorylated tau, which are hallmark pathologies of AD,5 and vice versa.6 Thus, antioxidants may thwart or impede the injury of neuron cells.Mangosteen pericarp extract is a potent natural antioxidant. The primary bioactive substances from pericarp extraction contain xanthones and derivatives (less polar substances) together with polyphenolic groups such as catechins and anthocyanidins (more polar substances).8,9 Among the xanthone groups, the most abundant was α‐mangostin. It showed both antioxidant activities10,11 and a cytotoxic effect (by inducing apoptosis7,12 and increasing reactive oxygen species [ROS] levels in various tumor cells).7,13,14 Furthermore, investigations of mouse models reported colitis from α‐mangostin.15 A mangosteen extract dose not exceeding 200 mg/kg was safe in mice.16 These controversial results could not exclude the possibility that α‐mangostin might harm viable neuron cells. Consequently, the water‐soluble ethyl acetate partitioned mangosteen pericarp ethanol extract (WME) should focus