SK-PC-B70M confers anti-oxidant activity and reduces Abeta levels in the brain of Tg2576 mice.
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 Abeta(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 Abeta(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-Abeta 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.
Seo
Ji-Seon
JS
Department of Chemistry and Nano Science, and Brain Disease Research Institute, Ewha Womans University, Seodaemoon-Gu, Seoul, Republic of Korea.
Kim
Tae-Kyung
TK
Leem
Yea-Hyun
YH
Lee
Kang-Woo
KW
Park
Sun-Kyu
SK
Baek
In-Sun
IS
Kim
Kyoung-Shim
KS
Im
Guang-Jin
GJ
Lee
Soo Min
SM
Park
Yang Hae
YH
Han
Pyung-Lim
PL
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000975:Antioxidants; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C527801:SK-PC-B70M; D012503:Saponins; D008315:Malondialdehyde; D006861:Hydrogen Peroxide