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
<b>Background/Objectives:</b> This study evaluated the antifungal, enzyme inhibitory, and anticancer properties of the ethyl acetate (EtOAc) leaves extract of <i>Rubus ulmifolius</i> Schott using in vitro assays and in silico analysis. <b>Methods:</b> 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-MS (gallic acid, caffeic acid, catechin, and fructofuranose) to uncover the potential mechanisms of the plant in colorectal and ovarian cancers. <b>Results:</b> The extract displayed notable antifungal activity, particularly against <i>Penicillium</i> sp., <i>Aspergillus fumigatus</i>, and <i>Candida albicans</i>, with inhibition zones of 22.5 ± 0.7 to 26.8 ± 1.3 mm. Enzyme assays revealed moderate inhibition of AChE (IC<sub>50</sub> = 92.94 ± 1.97 µg/mL), weaker activity against BChE (IC<sub>50</sub> = 274.93 ± 2.32 µg/mL), and modest inhibition of urease (IC<sub>50</sub> = 262.60 ± 1.41 µg/mL). The extract exhibited strong antiproliferative effects against HT-29 and SK-OV-3 cells (IC<sub>50</sub> = 2.41 ± 0.13 and 4.63 ± 0.26 µg/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-protein interaction networks identified hub genes for each cancer type, with key shared targets including <i>EGFR</i>, <i>ESR1</i>, <i>PTGS2</i>, and <i>STAT3</i>. Molecular docking confirmed favorable binding between these targets and the compounds, particularly catechin, which showed interactions comparable to those of reference inhibitors. <b>Conclusions:</b> These findings suggest that <i>R. ulmifolius</i> may possess multi-target antifungal, neuroprotective, and anticancer potential, warranting further in vitro pharmacological and preclinical validation.
Authors
- Ouided Benslama (ORCID: https://orcid.org/0000-0002-7946-219X)
- Chawki Bensouıcı (ORCID: https://orcid.org/0000-0003-4612-4642)
- Fatima Zohra Makhlouf (ORCID: https://orcid.org/0000-0001-5739-5048)
- Abdullah A. Shaito (ORCID: https://orcid.org/0000-0003-3524-7962)
- Fatiha Seglab (ORCID: https://orcid.org/0000-0002-5558-4811)
- Marco Masi (ORCID: https://orcid.org/0000-0003-0609-8902)
- Amina Bramki (ORCID: https://orcid.org/0000-0001-6572-4489)
- Ghozlane Barboucha
- Sirine Nessah
Institutions
- Larbi Ben M'hidi University of Oum El Bouaghi (DZ)
- Higher National Veterinary School (DZ)
- Biotechnology Research Center (IR)
- Qatar University (QA)
- University of Naples Federico II (IT)
Publication Details
- Journal
- Pharmaceuticals
- Published
- 2025-10-16
- DOI
- https://doi.org/10.3390/ph18101563
- Citations
- 3
- Primary Topic
- Phytochemicals and Antioxidant Activities
- Type
- article
- Field-Weighted Citation Impact
- 2.32
Funders
- Qatar University
- Direction Générale de la Recherche Scientifique et du Développement Technologique