Protective effects of a dimeric derivative of ferulic acid in animal models of Alzheimer's disease

• Published in: European journal of pharmacology 2016-07, Vol.782, p.30-34
• Main Authors: Jung, Jun-Sub, Yan, Ji-Jing, Li, Hong-Mei, Sultan, Md. Tipu, Yu, Jaehoon, Lee, Hee-Sul, Shin, Kye-Jung, Song, Dong-Keun
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - physiopathology; Amyloid beta-Peptides - pharmacology; Animal models of Alzheimer's disease; Animals; Coumaric Acids - chemistry; Coumaric Acids - pharmacology; Coumaric Acids - therapeutic use; Dimerization; Disease Models, Animal; Ferulic acid-derivative; Male; Maze Learning - drug effects; Memory - drug effects; Mice; Mice, Transgenic; Peptide Fragments - pharmacology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2016.04.047

Ferulic acid is a compound with potent anti-oxidant and anti-inflammatory activities. We previously reported the protective effects of ferulic acid administration against two animal models of Alzheimer's disease (AD): intracerebroventricular (i.c.v.) injection of Aß1-42 in mice and APP/PS1 mutant transgenic mice. In this study using the same AD animal models, we examined the effect of KMS4001, one of dimeric derivatives of ferulic acid. Intragastric pretreatment of mice with KMS4001 (30mg/kg/day) for 5 days significantly attenuated the Aß1-42 (i.c.v.)-induced memory impairment both in passive avoidance test and in Y-maze test. APP/PS1 mutant transgenic mice at KMS4001 doses of 3 and 30mg/kg/day via drinking water showed the significantly enhanced novel-object recognition memory at both 1.5 and 3 months after the start of KMS4001 treatment. Treatment of APP/PS1 mutant transgenic mice with KMS4001 for 3 months at the doses of 3 and 30mg/kg/day markedly decreased Aβ1-40 and Aβ1-42 levels in the frontal cortex. The KMS4001 dose-response relationships for Aβ decrease and for improvement in novel-object recognition test corresponded to each other. Taken together, these results suggest that KMS4001 could be an effective drug candidate against AD.