Research Report SK-PC-B70M confers anti-oxidant activity and reduces Aβ levels in the brain of Tg2576 mice Ji-Seon Seo a,1 , Tae-Kyung Kim a,1 , Yea-Hyun Leem a , Kang-Woo Lee a , Sun-Kyu Park a , In-Sun Baek a , Kyoung-Shim Kim a , Guang-Jin Im b , Soo Min Lee b , Yang Hae Park b , Pyung-Lim Han a, ⁎ a Department of Chemistry and Nano Science, and Brain Disease Research Institute, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemoon-Gu, Seoul, 120-750, Republic of Korea b Life Science R&D Center, SK Chemicals, Suwon, Gyungki-do, 440-745, Republic of Korea ARTICLE INFO ABSTRACT Article history: Accepted 12 January 2009 Available online 21 January 2009 SK-PC-B70M is an oleanolic-glycoside saponin-enriched fraction derived from the root of Pulsatilla koreana. Recently, it was reported that hederacolchiside-E is an active ingredient of SK-PC-B70M that confers a neuroprotective effect against the cytotoxicity induced by Aβ(1–42) in SK-N-SH neuroblastoma cells. SK-PC-B70M improves scopolamine-induced impairments of spatial working memory in rats. In the present study, we investigated whether SK-PC-B70M has a beneficial effect on the Tg2576 murine model of Alzheimer's disease. ELISA analysis revealed that the levels of soluble and insoluble forms of Aβ(1–42) in Tg2576 mice fed SK-PC-B70M (2000 ppm) from 11 months to 16 months of age were reduced to, respectively, 66% and 79% of the control Tg2576 mice. Anti-Aβ antibody-stained brain sections of Tg2576 mice with SK-PC-B70M (2000 ppm) consistently showed a reduction in plaque formation in the brain. Western blot analyses showed altered expressions of various cellular factors, such as up-regulation of transthyretin, phospho-ERK, and phospho-CREB in the brain treated with SK-PC-B70M. SK-PC-B70M suppressed the neuronal toxicity induced by H 2 O 2 in primary cortical culture. Moreover, biochemical and immunohistochemical analyses showed that the levels of malondialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE), oxidized by-products of lipid peroxidation, were notably reduced in the hippocampus of Tg2576 mice treated with SK-PC-B70M compared with the Tg2576 control. These results suggest that SK-PC-B70M attenuates AD-like pathology in the brain of Tg2576 mice. © 2009 Elsevier B.V. All rights reserved. Keywords: Natural compound Alzheimer disease Aβ Plaque ROS 1. Introduction Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by histopathologic hallmarks, including senile plaque deposition in the space outside neurons, neurofibrillary tangle formation within neurons, and neuronal loss. These pathologic processes are usually accompanied by marked changes in gene expression and biochemical states of various cellular factors. Because mutations in genes encoding BRAIN RESEARCH 1261 (2009) 100 – 108 ⁎ Corresponding author. Fax: +82 2 3277 3419. E-mail address: plhan@ewha.ac.kr (P.-L. Han). 1 These authors contributed equally to this work. 0006-8993/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2009.01.019 available at www.sciencedirect.com www.elsevier.com/locate/brainres