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In this study, we investigated the protective effects of saikosaponin C (<jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c), one of the main bioactive components produced by the traditional Chinese herb, <jats:italic>radix bupleuri,<\/jats:italic> the root of <jats:italic>Bupleurum falcatum<\/jats:italic>, against <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> in various neuronal models. Interestingly, we found that <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c has dual effects on <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> by targeting amyloid beta (A\u03b2) and tau, two key proteins in <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c significantly suppressed the release of both A\u03b2 peptides 1\u201340 and 1\u201342 into cell culture supernatants, though it does not affect <jats:styled-content style=\"fixed-case\">BACE<\/jats:styled-content>1 activity and expression. <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c also inhibited abnormal tau phosphorylation at multiple <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>\u2010related residues. Moreover, <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c seems to have beneficial effects on cellular tau function; it accelerated nerve growth factor\u2010mediated neurite outgrowth and increased the assembly of microtubules. In addition, <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c increased synaptic marker proteins such as synaptophysin and <jats:styled-content style=\"fixed-case\">PSD<\/jats:styled-content>\u201095. Considering its various biological activities, our results suggest that <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c might be a novel therapeutic tool for treating human <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> and other neurodegenerative diseases.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13515-fig-0009-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nTau and amyloid beta are two key features in Alzheimer's disease. Saikosaponin C, an active component of Bupleuri Radix, inhibits abnormal tau phosphorylation and amyloid beta production, thereby promoting synaptic integrity. Saikosaponin C also prevents amyloid beta\u2010induced apoptosis in brain vascular endothelial cells. Therefore, Saikosaponin C may provide a new therapeutic strategy for treatment of neurodegenerative diseases, including Alzheimer's disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13515","type":"journal-article","created":{"date-parts":[[2015,12,28]],"date-time":"2015-12-28T14:58:47Z","timestamp":1451314727000},"page":"1232-1245","source":"Crossref","is-referenced-by-count":33,"title":["A potential therapeutic effect of saikosaponin C as a novel dual\u2010target anti\u2010Alzheimer agent"],"prefix":"10.1111","volume":"136","author":[{"given":"Tae Ho","family":"Lee","sequence":"first","affiliation":[{"name":"Division of Gerontology Department of Medicine Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sungha","family":"Park","sequence":"additional","affiliation":[{"name":"Severance Integrative Research Institute for Cerebral &amp; Cardiovascular Diseases (SIRIC) Yonsei University College of Medicine Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi\u2010Hyeon","family":"You","sequence":"additional","affiliation":[{"name":"Division of Gerontology Department of Medicine Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji\u2010Hong","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Chemistry College of Biomedical and Health Science Konkuk University Chungju Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang\u2010Hyun","family":"Min","sequence":"additional","affiliation":[{"name":"New Drug Development Center DGMIF Daegu Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byeong Mo","family":"Kim","sequence":"additional","affiliation":[{"name":"Severance Integrative Research Institute for Cerebral &amp; Cardiovascular Diseases (SIRIC) Yonsei University College of Medicine Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,1,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.56.6.673"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/156720206778792948"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.68051870.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90057-X"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.59.8.1267"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/S0021-9258(18)48529-8","article-title":"Assembly and aggregation properties of synthetic Alzheimers A4\/beta amyloid peptide analogs","volume":"267","author":"Burdick D.","year":"1992","journal-title":"J. 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