Schisandrin B, an active substance, is derived from Chinese herb fruit Wuweizi, which exerts various pharmacological activities and has displayed significant beneficial effects in ameliorating Alzheimer's disease (AD). The aim of this study was to further extend our examination for the use of schisandrin B extract in the potential treatment of AD effects by investigating DNA methylation (DNMT), known to be modified in this disease using SH-SY5Y neuronal cell line exposed to β-amyloid protein (Aβ1-42). In particular, the purpose of this investigation was to examine alterations in mRNA and protein expression of DNMT. Data demonstrated that schisandrin B blocked Aβ1-42-mediated injury in SH-SY5Y neuronal cell line as evidenced by a restoration of cellular morphology and cell viability to approximate control levels at the highest 10 μg/ml Schisandrin B. Incubation with Aβ1-42 significantly decreased mRNA and protein expression of DNMT3A and DNMT1 in SH-SY5Y neuronal cell line. Incubation with Aβ1-42 followed by 24 treatment with schisandrin B significantly inhibited the Aβ1-42 -induced changes in mRNA and protein expression of DNMT3A and DNMT3B in a concentration-dependent manner. It is of interest that the mRNA expression of DNMT3A and DNMT1 were significantly higher than control. Data thus indicate schisandrin B was effective in inhibiting the actions of Aβ1-42 on cell survival and morphology and that DNA methylation may be associated with the beneficial findings.