{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:12:30Z","timestamp":1790709150942,"version":"4.1.0"},"reference-count":100,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: This study evaluated the antifungal, enzyme inhibitory, and anticancer properties of the ethyl acetate (EtOAc) leaves extract of Rubus ulmifolius Schott using in vitro assays and in silico analysis. Methods: Antifungal activity was assessed against five fungal strains by measuring inhibition zones. Enzyme inhibition assays were conducted for acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and urease. Antiproliferative effects were tested against HT-29 colorectal, SK-OV-3 ovarian, and A549 lung cancer cells using the MTT assay. Network pharmacology and molecular docking analyses were performed on major compounds previously identified by GC\u2013MS (gallic acid, caffeic acid, catechin, and fructofuranose) to uncover the potential mechanisms of the plant in colorectal and ovarian cancers. Results: The extract displayed notable antifungal activity, particularly against Penicillium sp., Aspergillus fumigatus, and Candida albicans, with inhibition zones of 22.5 \u00b1 0.7 to 26.8 \u00b1 1.3 mm. Enzyme assays revealed moderate inhibition of AChE (IC50 = 92.94 \u00b1 1.97 \u00b5g\/mL), weaker activity against BChE (IC50 = 274.93 \u00b1 2.32 \u00b5g\/mL), and modest inhibition of urease (IC50 = 262.60 \u00b1 1.41 \u00b5g\/mL). The extract exhibited strong antiproliferative effects against HT-29 and SK-OV-3 cells (IC50 = 2.41 \u00b1 0.13 and 4.63 \u00b1 0.26 \u00b5g\/mL, respectively), whereas activity against A549 lung cancer cells was limited. Network pharmacology predicted 52 and 44 overlapping target genes between the major compounds and colorectal and ovarian cancers, respectively. Protein\u2013protein interaction networks identified hub genes for each cancer type, with key shared targets including EGFR, ESR1, PTGS2, and STAT3. Molecular docking confirmed favorable binding between these targets and the compounds, particularly catechin, which showed interactions comparable to those of reference inhibitors. Conclusions: These findings suggest that R. ulmifolius may possess multi-target antifungal, neuroprotective, and anticancer potential, warranting further in vitro pharmacological and preclinical validation.<\/jats:p>","DOI":"10.3390\/ph18101563","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T16:33:22Z","timestamp":1760632402000},"page":"1563","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Therapeutic Insights into Rubus ulmifolius Schott Leaf Extract: In Vitro Antifungal, Enzyme Inhibition, and Anticancer Activities Integrated with Network Pharmacology and Molecular Docking Analyses of Colorectal and Ovarian Cancer"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6572-4489","authenticated-orcid":false,"given":"Amina","family":"Bramki","sequence":"first","affiliation":[{"name":"Higher National School of Biotechnology, Taoufik Khaznadar, Nouveau P\u00f4le Universitaire Ali Mendjeli, BP E66, Constantine 25100, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8281-1723","authenticated-orcid":false,"given":"Ghozlane","family":"Barboucha","sequence":"additional","affiliation":[{"name":"Higher National School of Biotechnology, Taoufik Khaznadar, Nouveau P\u00f4le Universitaire Ali Mendjeli, BP E66, Constantine 25100, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7946-219X","authenticated-orcid":false,"given":"Ouided","family":"Benslama","sequence":"additional","affiliation":[{"name":"Department of Natural and Life Sciences, Faculty of Exact Sciences and Natural and Life Sciences, Larbi Ben M\u2019Hidi University, Oum El Bouaghi 04000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatiha","family":"Seglab","sequence":"additional","affiliation":[{"name":"Biomedical Research Center (BRC), QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5739-5048","authenticated-orcid":false,"given":"Fatima Zohra","family":"Makhlouf","sequence":"additional","affiliation":[{"name":"Higher National School of Biotechnology, Taoufik Khaznadar, Nouveau P\u00f4le Universitaire Ali Mendjeli, BP E66, Constantine 25100, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirine","family":"Nessah","sequence":"additional","affiliation":[{"name":"Higher National School of Biotechnology, Taoufik Khaznadar, Nouveau P\u00f4le Universitaire Ali Mendjeli, BP E66, Constantine 25100, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4612-4642","authenticated-orcid":false,"given":"Chawki","family":"Bensouici","sequence":"additional","affiliation":[{"name":"Biotechnology Research Center, UV 03, BP. E73, Ali Mendjeli, Constantine 25016, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0609-8902","authenticated-orcid":false,"given":"Marco","family":"Masi","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3524-7962","authenticated-orcid":false,"given":"Abdullah A.","family":"Shaito","sequence":"additional","affiliation":[{"name":"Biomedical Research Center (BRC), QU Health, Qatar University, Doha P.O. Box 2713, Qatar"},{"name":"Biomedical Sciences Department, College of Health Sciences, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"},{"name":"College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tabarki, S., Aouadhi, C., Mechergui, K., Hammi, K.M., Ksouri, R., Raies, A., and Toumi, L. (2017). Comparison of Phytochemical Composition and Biological Activities of Rubus ulmifolius Extracts Originating from Four Regions of Tunisia. Chem. Biodivers., 14.","DOI":"10.1002\/cbdv.201600168"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"El-Saadony, M.T., Saad, A.M., Mohammed, D.M., Korma, S.A., Alshahrani, M.Y., Ahmed, A.E., Ibrahim, E.H., Salem, H.M., Alkafaas, S.S., and Saif, A.M. (2025). Medicinal plants: Bioactive compounds, biological activities, combating multidrug-resistant microorganisms, and human health benefits\u2014A comprehensive review. Front. 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