(E)-2-Methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) Phenol Ameliorates LPS-Mediated Memory Impairment by Inhibition of STAT3 Pathway

Ji Yeon Choi, Chul Ju Hwang, Do Yeon Lee, Sun Mi Gu, Hee Pom Lee, Dong Young Choi, Ki Wan Oh, Sang-Bae Han, Jin Tae Hong

Alzheimer's disease (AD) is pathologically characterized by an excessive accumulation of amyloid-beta (Aβ) fibrils within the brain. We tested the anti-inflammatory and anti-amyloidogenic effects of (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP), a selective signal transducer and activator of transcription 3 (STAT3) inhibitor. We examined whether MMPP (5 mg/kg in drinking water for 1 month) prevents amyloidogenesis and cognitive impairment on AD model mice induced by intraperitoneal LPS (250 μg/kg daily 7 times) injections. Additionally, we investigated the anti-neuroinflammatory and anti-amyloidogenic effect of MMPP (1, 5, and 10 μg/mL) in LPS (1 μg/mL)-treated cultured astrocytes and microglial BV-2 cells. MMPP treatment reduced LPS-induced memory loss. This memory recovery effect was associated with the reduction of LPS-induced inflammatory proteins; cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as well as activation of microglial cells and astrocytes in the brain. Furthermore, MMPP reduced LPS-induced β-secretase and Aβ generation. In in vitro study, LPS-induced expression of inflammatory proteins and amyloidogenic proteins was decreased in microglial BV-2 cells and cultured astrocytes by MMPP treatment. Moreover, MMPP treatment suppressed DNA binding activities of the activation of STAT3 in in vivo and in vitro. These results indicated that MMPP inhibits LPS-induced amyloidogenesis and neuroinflammation via inhibition of STAT3.