Journal of Neuroscience Research
Volume 88 Issue 4, Pages 896 - 904

Effect of rosmarinic acid in motor dysfunction and life span in a mouse model of familial amyotrophic lateral sclerosis
Yosuke Shimojo 1, Kunio Kosaka 1, Yoshihiro Noda 2, Takahiko Shimizu 2 *, Takuji Shirasawa 3 *
1Beauty Care Product Developing Team, Research and Development Center, Nagase & Co., Ltd.,Hyogo, Japan
2Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
3Department of Ageing Control Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
email: Takahiko Shimizu (shimizut@tmig.or.jp) Takuji Shirasawa (shirasawa@shirasawa-acl.net)
*Correspondence to Takahiko Shimizu, Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0015, Japan

*Correspondence to Takuji Shirasawa, Department of Ageing Control Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo 113-0033, Japan

KEYWORDS
amyotrophic lateral sclerosis • SOD1 • rosemary • rosmarinic acid • antioxidant • antiinflammation

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a late-onset progressive neurodegenerative disease affecting motor neurons. About 2% of patients with the disease are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). The purpose of this study is to assess the effect of rosemary extract and its major constituents, rosmarinic acid (RA) and carnosic acid (CA), in human SOD1 G93A transgenic mice, which are well-established mouse models for ALS. The present study demonstrates that intraperitoneal administration of rosemary extract or RA from the presymptomatic stage significantly delayed motor dysfunction in paw grip endurance tests, attenuated the degeneration of motor neurons, and extended the life span of ALS model mice. In addition, RA administration significantly improved the clinical score and suppressed body weight loss compared with a vehicle-treated group. In conclusion, this study provides the first report that rosemary extract and, especially, RA have preventive effects in the mouse model of ALS. © 2009 Wiley-Liss, Inc.
Received: 25 February 2009; Revised: 8 July 2009; Accepted: 13 July 2009