Protective effects of a dimeric derivative of ferulic acid in animal models of Alzheimer's disease.
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.
Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Chuncheon, Gangwon-do 24252, Republic of Korea.
Jun-Sub
JS
Jung
Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Chuncheon, Gangwon-do 24252, Republic of Korea.
Ji-Jing
JJ
Yan
Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Chuncheon, Gangwon-do 24252, Republic of Korea.
Hong-Mei
HM
Li
Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Chuncheon, Gangwon-do 24252, Republic of Korea.
Md Tipu
MT
Sultan
Department of Chemistry and Education, Seoul National University, Seoul 08826, Republic of Korea.
Jaehoon
J
Yu
Scigenic Co., Ltd., Seoul, Republic of Korea.
Hee-Sul
HS
Lee
College of Pharmacy, The Catholic University of Korea, Bucheon, Gyeonggi-do 14662, Republic of Korea. Electronic address: kyejung@catholic.ac.kr.
Kye-Jung
KJ
Shin
Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Chuncheon, Gangwon-do 24252, Republic of Korea. Electronic address: dksong@hallym.ac.kr.
Dong-Keun
DK
Song
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D003373:Coumaric Acids / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D019281:Dimerization; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D003373:Coumaric Acids; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C004999:ferulic acid
Animal models of Alzheimer's disease; Ferulic acid-derivative