{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T22:56:01Z","timestamp":1790981761235,"version":"4.1.0"},"reference-count":24,"publisher":"Georg Thieme Verlag KG","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Planta Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Alzheimer\u2019s disease is characterized by the accumulation of cerebral amyloid beta (A\u03b2) peptides, making the inhibition of A\u03b2 production a key therapeutic strategy. We screened a plant extract library for A\u03b242 inhibitors using human neural progenitor cells and identified a Ruscus aculeatus extract as a potential candidate. Although rhizome extracts of R. aculeatus exhibit vasotonic, and anti-inflammatory properties, their effects on amyloid-\u03b2 precursor protein (APP) processing have not been investigated. We aimed to elucidate how R. aculeatus extract influences A\u03b2 production and its underlying mechanisms. R. aculeatus extract significantly reduced A\u03b240 and A\u03b242 production and the pathogenic A\u03b242\/A\u03b240 ratio in both human neural progenitor (ReNcell VM) and mouse neuroblastoma (Neuro2a) cells in concentration-dependent manner. The extract enhanced non-amyloidogenic APP pathway processing, evidenced by increased levels of ADAM10 active form, soluble APP\u03b1 and C-terminal fragment \u03b1 levels. Despite increasing BACE1 protein levels, the extract reduced soluble APP\u03b2 production, suggesting inhibition of BACE1-mediated APP cleavage. RNA-seq analysis revealed Notch signaling pathway downregulation, implying \u03b3-secretase activity modulation. In conclusion, the R. aculeatus extract suppresses A\u03b2 production by modulating multiple APP processing pathways, primarily through enhancing non-amyloidogenic pathway via ADAM10 activation. By reducing amyloidogenic peptides levels, R. aculeatus extract may contribute to decreased amyloid plaques formation. These findings identify R. aculeatus extract as a modulator of APP metabolism.<\/jats:p>","DOI":"10.1055\/a-2943-8874","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T22:40:11Z","timestamp":1790980811000},"source":"Crossref","is-referenced-by-count":0,"title":["Ruscus aculeatus Extract Inhibits Amyloid Beta Production and Upregulates the Active form of ADAM10 in Human Neural Progenitor Cells"],"prefix":"10.1055","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6751-049X","authenticated-orcid":false,"given":"Kenta","family":"Murata","sequence":"additional","affiliation":[{"name":"Kobayashi Pharmaceutical Co Ltd R&D Headquarters, Osaka, Japan","place":["Minoh-City"],"department":["Saito R&D and Manufacturing Lab"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Mizushina","sequence":"additional","affiliation":[{"name":"Kobayashi Pharmaceutical Co Ltd R&D Headquarters, Osaka, Japan","place":["Minoh-City"],"department":["Saito R&D and Manufacturing Lab"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Izawa","sequence":"additional","affiliation":[{"name":"Kobayashi Pharmaceutical Co Ltd R&D Headquarters, Osaka, Japan","place":["Minoh-City"],"department":["Saito R&D and Manufacturing Lab"]},{"name":"Graduate School of Medicine, The University of Tokyo, Tokyo, Japan","place":["Bunkyo"],"department":["Department of Innovative Dementia Prevention"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunori","family":"Matsui","sequence":"additional","affiliation":[{"name":"Kobayashi Pharmaceutical Co Ltd R&D Headquarters, Osaka, Japan","place":["Minoh-City"],"department":["Saito R&D and Manufacturing Lab"]},{"name":"Graduate School of Medicine, The University of Tokyo, Tokyo, Japan","place":["Bunkyo"],"department":["Department of Innovative Dementia Prevention"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Wakabayashi","sequence":"additional","affiliation":[{"name":"Graduate School of Medicine, The University of Tokyo, Tokyo, Japan","place":["Bunkyo"],"department":["Department of Innovative Dementia Prevention"]},{"name":"Graduate School of Medicine, The University of Tokyo, Tokyo, Japan","place":["Bunkyo"],"department":["Department of Neuropathology"]},{"name":"Meiji Pharmaceutical University, Tokyo, Japan","place":["Kiyose"],"department":["Department of Pathophysiology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadafumi","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Graduate School of Medicine, The University of Tokyo, Tokyo, Japan","place":["Bunkyo"],"department":["Department of Innovative Dementia Prevention"]},{"name":"Graduate School of Medicine, The University of Tokyo, Tokyo, Japan","place":["Bunkyo"],"department":["Department of Neuropathology"]},{"name":"National Center of Neurology and Psychiatry, Tokyo, Japan","place":["Kodaira"],"department":["Department of Degenerative Neurological Diseases"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Iwatsubo","sequence":"additional","affiliation":[{"name":"Graduate School of Medicine, The University of Tokyo, Tokyo, Japan","place":["Bunkyo"],"department":["Department of Neuropathology"]},{"name":"National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan","place":["Kodaira"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Matsushima","sequence":"additional","affiliation":[{"name":"Kobayashi Pharmaceutical Co Ltd R&D Headquarters, Osaka, Japan","place":["Minoh-City"],"department":["Saito R&D and Manufacturing Lab"]},{"name":"Graduate School of Medicine, The University of Tokyo, Tokyo, Japan","place":["Bunkyo"],"department":["Department of Innovative Dementia 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