Esculentoside A suppresses Aβ1–42-induced neuroinflammation by down-regulating MAPKs pathwaysin vivo

Esculentoside A (EsA) is a saponin isolated from the roots of Phytolacca esculenta. Previous studies have demonstrated that EsA exerts strong anti-inflammatory effects in peripheral immune inflammation. This study is to determine whether EsA is effective in inflammation-related neurodegenerative diseases, such as Alzheimer's disease (AD).Male C57BL/6(B6) mice were divided into three groups of six mice as follows: (1) control group; (2) AD model group (Aβ(1-42)-induced AD mice with saline); (3) EsA group (Aβ(1-42)-induced AD mice with EsA, 5 mg/kg/day, i.p. for 15 days). Behavioural testing was performed after 15 days of EsA treatment. Real time PCR and Western blot were used to assess the level of inflammation factors and mitogen-activated protein kinases (MAPKs). Immunostaining was used to determine the level of activated microglia and astrocyte.The results showed that EsA attenuated memory deficits in Aβ(1-42)-induced AD mice. Esculentoside A decreased the pro-inflammatory factors and microglia and astrocyte activation in the hippocampi of Aβ(1-42)-induced AD mice. Moreover, Aβ(1-42) activated phosphorylation of ERK, JNK and p38 MAPKs in the hippocampi of mice in the AD model group, while EsA significantly decreased the phosphorylation levels.These findings indicate that EsA provides protective effects against neuroinflammation triggered by β-amyloid.