Journal of Ethnopharmacology 134 (2011) 1028–1032 Contents lists available at ScienceDirect Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jethpharm Ethnopharmacological communication Neuroprotective effect of SuHeXiang Wan in Drosophila models of Alzheimer’s disease Yoon Ki Hong a,1 , Seung Hwan Park a,1 , Soojin Lee a , Soojin Hwang a , Min Jung Lee a , Darae Kim a , Jang Ho Lee a , Seung Yeop Han a , Sang Tae Kim b , Young-Kyoon Kim c , Songhee Jeon d , Byung-Soo Koo e , Kyoung Sang Cho a,∗ a Department of Biological Sciences, Konkuk University, Seoul 143-701, Republic of Korea b Division of Life & Pharmaceutical, Ewha womans University, Seoul 120-750, Republic of Korea c Department of Forest Products & Biotechnology, Kookmin University, Seoul 136-702, Republic of Korea d Dongguk University Research Institute of Biotechnology, Dongguk University, Seoul 100-715, Republic of Korea e Department of Neuropsychiatry, Graduate School of Dongguk University, Seoul 100-715, Republic of Korea article info Article history: Received 25 September 2010 Received in revised form 10 January 2011 Accepted 11 February 2011 Available online 17 February 2011 Keywords: Alzheimer’s disease apoptosis Drosophila SuHeXiang Wan JNK abstract Aim of the study: SuHeXiang Wan (SHXW) is a Chinese traditional medicinal prescription that consists of 15 crude herbs. SHXW has been used to treat central nervous depression, seizures, infantile convulsion and stroke, and its essential oil has been shown to have anticonvulsant and antioxidative activity. The goal of this study was to investigate the beneficial effects of SHXW on the neurological phenotypes of Drosophila AD models. Materials and methods: We evaluated the effects of a modified SHXW (called KSOP1009) intake on the AD-like phenotypes of Drosophila AD models, which express human A42 in their developing eyes or neurons. Results: When the flies were kept on the media containing 5 g/ml of KSOP1009 extract, A42-induced eye degeneration, apoptosis, and the locomotive dysfunctions were strongly suppressed. However, A42 fibril deposits in the A42 overexpressing model were not affected by treatment with KSOP1009 extract. Conversely, KSOP1009 extract intake significantly suppressed the constitutive active form of hemipter- ous, a JNK activator, while it induced eye degeneration and JNK activation, which has been recognized as an important mediator of A42-associated neuro-cytotoxicity. Conclusions: In conclusion, the results of this study suggest that KSOP1009 confers a therapeutic potential to AD-like pathology of A42 overexpressing Drosophila model via suppression of the hyperactivation of JNK activity and apoptosis. © 2011 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Alzheimer’s disease (AD) is a common neurodegenerative dis- ease that causes progressive cognitive deficits, plaques, tangles, and neural loss (Ashe and Zahs, 2010). The most well studied cause of AD is deposition of A42 plaques, which are generated from amyloid precursor protein via gamma- and alpha secretase (Wirths et al., 2004). Many studies have shown that A42 overexpression in neu- rons results in apoptosis via JNK activation, and that inhibition of JNK activity protects cells from A42 toxicity (Borsello and Forloni, Abbreviations: AD, Alzheimer’s disease; SHXW, SuHeXiang Wan; JNK, c-Jun-N- terminal kinase. ∗ Corresponding author. Tel.: +82 2 450 3424; fax: +82 2 3436 5432. E-mail address: kscho@konkuk.ac.kr (K.S. Cho). 1 Both these authors contributed equally to this work. 2007; Braithwaite et al., 2010). In addition to human cell studies, various AD animal models have been used to identify methods of treating this disease. One powerful genetic and cell biological sys- tem, Drosophila, has often been used to study neurodegenerative diseases, and many Drosophila AD models have been generated (Iijima-Ando and Iijima, 2010). Several drug candidates have been developed to cure AD to date (Mangialasche et al., 2010). For example, given the charac- teristics of AD, loss of cholinergic neurons and reduced activity of choline acetyltransferase in the cerebral cortex and hippocampus, acetylcholinesterase inhibitors such as donepezil hydrochloride have been used to reduce the symptoms of AD (Dong et al., 2005). However, the neuroprotective activity of current drugs used for the treatment of AD is still the subject of debate (Mangialasche et al., 2010). SuHeXiang Wan (SHXW) is a Chinese traditional medicinal pre- scription that consists of 15 crude herbs (Bensky and Gamble, 0378-8741/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2011.02.012