{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T23:15:48Z","timestamp":1783379748905,"version":"3.54.6"},"reference-count":38,"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>Forgetting and memory formation are 2 distinct processes, both essential for the survival of humans and other animals. The protein Musashi2 (MSI2) was recently discovered as a key regulator of forgetting in the model organism Caenorhabditis elegans, making it an attractive therapeutic target for drug discovery and development.<\/jats:p>\n                  <jats:p>Here, we report a fluorescence polarization assay-based screening campaign aimed at identifying MSI2 inhibitors from 2,844 plant extracts. The dichloromethane extract of the aerial parts of Huperzia serrata, a plant traditionally used in Chinese medicine for the treatment of memory dysfunction, was identified as a hit and subsequently subjected to HPLC-based activity profiling. Scale-up isolation identified fatty acids, namely linoleic acid (11) and palmitoleic acid (12), both eluting within the main active window. As other fractions also seem to display activity, although weaker, their minor constituents were also investigated, revealing 1 new serratane triterpenoid (1) and 7 known serratene triterpenoids 2-8, their biosynthetic precursor \u03b1-onocerin (9), as well as an abietane diterpene (10). The absolute configuration of compound 1 was established by X-ray crystallography. All isolated compounds were evaluated for their activity, revealing that linoleic acid (11) and palmitoleic acid (12) inhibited MSI2 with IC50 values of 14.6 and 23.1\u2009\u00b5M, respectively, while compound 10 only showed moderate activity (IC50 of 34.4\u2009\u00b5M).<\/jats:p>","DOI":"10.1055\/a-2900-3049","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T22:54:37Z","timestamp":1783378477000},"source":"Crossref","is-referenced-by-count":0,"title":["New Serratane Triterpenoid and Musashi2 inhibitors from Huperzia serrata"],"prefix":"10.1055","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5288-5317","authenticated-orcid":false,"given":"Tamara","family":"Balsiger","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malik","family":"Rakhmanov","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Prescimone","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalena","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim-Dung","family":"Huynh","sequence":"additional","affiliation":[{"name":"Research Cluster Molecular and Cognitive Neurosciences, Department of Biomedicine, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Papassotiropoulos","sequence":"additional","affiliation":[{"name":"Research Cluster Molecular and Cognitive Neurosciences, Department of Biomedicine, University of Basel, Basel, Switzerland"},{"name":"University Psychiatric Clinics, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Teufel","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"Stetak","sequence":"additional","affiliation":[{"name":"Research Cluster Molecular and Cognitive Neurosciences, Department of Biomedicine, University of Basel, Basel, Switzerland"},{"name":"University Psychiatric Clinics, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3497-2524","authenticated-orcid":false,"given":"Eliane","family":"Garo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1016\/j.neuron.2012.04.007","article-title":"Dopamine Is required for learning and forgetting in Drosophila","volume":"74","author":"J A Berry","year":"2012","journal-title":"Neuron"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/j.cell.2009.12.044","article-title":"Forgetting is regulated through rac activity in Drosophila","volume":"140","author":"Y Shuai","year":"2010","journal-title":"Cell"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1016\/j.celrep.2013.02.019","article-title":"Forgetting in C. elegans is accelerated by neuronal communication via the TIR-1\/JNK-1 pathway","volume":"3","author":"A Inoue","year":"2013","journal-title":"Cell Rep"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e1010420;","DOI":"10.1371\/journal.pgen","article-title":"Phosphorylation of MSI-1 is implicated in the regulation of associative memory in Caenorhabditis elegans","volume":"18","author":"P Mastrandreas","year":"2022","journal-title":"PLoS Genet"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1007\/s12035-022-03116-7","article-title":"(\u2212)- gossypol inhibition of musashi-mediated forgetting improves memory and age-dependent memory decline in Caenorhabditis elegans","volume":"60","author":"P Mastrandreas","year":"2023","journal-title":"Mol Neurobiol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1016\/j.cell.2014.01.054","article-title":"Forgetting is regulated via musashi-mediated translational control of the Arp2\/3 complex","volume":"156","author":"N Hadziselimovic","year":"2014","journal-title":"Cell"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"15194","DOI":"10.1073\/pnas.232087499","article-title":"RNA-binding protein Musashi family: Roles for CNS stem cells and a subpopulation of ependymal cells revealed by targeted disruption and antisense ablation","volume":"99","author":"S I Sakakibara","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"8091","DOI":"10.1523\/JNEUROSCI.21-20-08091.2001","article-title":"RNA-binding protein Musashi2: Developmentally regulated expression in neural precursor cells and subpopulations of neurons in mammalian CNS","volume":"21","author":"S I Sakakibara","year":"2001","journal-title":"J Neurosci"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1080\/15476286.2018.1539607","article-title":"Luteolin inhibits Musashi1 binding to RNA and disrupts cancer phenotypes in glioblastoma 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Medica"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2900-3049.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T22:54:38Z","timestamp":1783378478000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2900-3049"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,6]]},"references-count":38,"URL":"https:\/\/doi.org\/10.1055\/a-2900-3049","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0032-0943","1439-0221"],"issn-type":[{"value":"0032-0943","type":"print"},{"value":"1439-0221","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,6]]}}}