{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T14:50:18Z","timestamp":1792248618926,"version":"4.4.0"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Antimicrobial resistance (AMR) represents a critical global health issue, prompting the urgent exploration of alternative plant-derived antimicrobial therapies. In this context, the present study evaluates the therapeutic efficacy and safety profiles of <jats:italic>Olea europaea<\/jats:italic> and <jats:italic>Ficus carica<\/jats:italic> leaf extracts against multidrug-resistant pathogens, integrating <jats:italic>in vitro<\/jats:italic> antimicrobial assays, <jats:italic>in vivo<\/jats:italic> toxicity assessments, and <jats:italic>in silico<\/jats:italic> modeling approaches.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Leaf extracts from <jats:italic>O. europaea<\/jats:italic> and <jats:italic>F. carica<\/jats:italic> were prepared by solvent-based maceration using methanol, acetone, and distilled water. Their antimicrobial properties were evaluated through disk and well diffusion assays to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against clinically relevant pathogens. Toxicological assessments were performed <jats:italic>in vivo<\/jats:italic> using the BALB\/c mice model, including histopathological examinations, hematological profiling, and biochemical analyses. A complementary <jats:italic>in vitro<\/jats:italic> toxicogenomic screening was conducted using a cell-based reporter assay to profile nuclear receptor signaling and cellular stress responses. Furthermore, computational modeling and molecular docking were employed to predict the possible interactions of selected phytochemicals with <jats:italic>E. coli<\/jats:italic> cytochrome c peroxidase.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Methanolic extracts of <jats:italic>O. europaea<\/jats:italic> exhibited potent antimicrobial activity against multidrug-resistant isolates, whereas <jats:italic>F. carica<\/jats:italic> extracts showed minimal efficacy across all experimental contexts. <jats:italic>In silico<\/jats:italic> molecular docking analyses revealed high-affinity interactions between olive-derived phenolic compounds and <jats:italic>E. coli<\/jats:italic> cytochrome c peroxidase, suggesting a plausible mechanistic basis for the observed antibacterial effects. <jats:italic>In vivo<\/jats:italic>, toxicological evaluation in BALB\/c mice administered aqueous formulations of the methanolic olive extract demonstrated dose-dependent hepatic and renal histopathological alterations, accompanied by dysregulation of the immunological profiles and elevated hepatic enzyme levels. These findings were consistent with outcomes from the cell reporter assays and computational toxicology models, which indicated potential nephrotoxic and immunotoxic risks at higher concentrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings validate the promising antimicrobial activity of <jats:italic>O. europaea<\/jats:italic> and <jats:italic>F. carica<\/jats:italic> leaf extracts against multidrug-resistant pathogens. However, further investigations on precise dosage optimization and long-term safety evaluations are essential before these extracts are implemented in clinical practice.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2025.1567921","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T05:15:02Z","timestamp":1747631702000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Overall in vitro, in vivo, and in silico evaluation of Olea europaea and Ficus carica leaf extracts for antimicrobial activity against multidrug-resistant pathogens"],"prefix":"10.3389","volume":"16","author":[{"given":"Mahmoud","family":"Aloriby","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Elkawafi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salem","family":"Aldrsy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Sweker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadeel","family":"Elabdeli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisha","family":"Elbarghathi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Benhasouna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madiha","family":"El-Awamie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nariman","family":"Elsharif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Alqabbasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salmin","family":"Alshalmani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabiea","family":"Algazal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farag","family":"Bleiblo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"615","DOI":"10.3390\/foods9050615","article-title":"Potential activity of aqueous fig leaves extract, olive leaves extract and their mixture as natural preservatives to extend the shelf life of pasteurized Buffalo milk","volume":"9","author":"Abdel-Aziz","year":"2020","journal-title":"Foods"},{"key":"B2","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.sajb.2021.04.019","article-title":"The therapeutic effects of Ficus carica extract as an antioxidant and anticancer agent","volume":"141","author":"Abdel-Rahman","year":"2021","journal-title":"South Afr. 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