{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:03:15Z","timestamp":1789984995145,"version":"4.0.1"},"reference-count":66,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004410","name":"TUBITAK 2209-A","doi-asserted-by":"publisher","award":["1919B012216140"],"award-info":[{"award-number":["1919B012216140"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Ficus carica L., a widely cultivated member of the Moraceae family, is recognized for its rich phytochemical composition and diverse biological activities; however, the influence of harvest season and extraction solvent on its bioactive profile remains insufficiently explored. In this context, leaves collected from Dalaman (Mu\u011fla, T\u00fcrkiye) in April and November were comparatively evaluated in terms of phenolic profiles, antioxidant capacity, enzyme inhibitory potential, molecular docking interactions, and preliminary ADMET properties. Eight extracts were prepared using ethyl acetate, methanol, aqueous ethanol, and water, and phenolic composition was characterized by HPLC-DAD using 42 reference standards. Major contributors to bioactivity included hesperidin, rutin, chlorogenic acid, cynarin, naringenin, and 4-hydroxyresorcinol. Antioxidant activity was assessed via DPPH\u02d9, ABTS\u02d9+, CUPRAC, and \u03b2-carotene\u2013linoleic acid assays, while enzyme inhibitory activities against acetylcholinesterase, butyrylcholinesterase, and tyrosinase were determined. Hesperidin reached its highest concentration in the water extract FC14 (80.06 mg\/g). FC14 showed the strongest DPPH\u02d9 (IC50: 54.46 \u00b1 0.94 \u03bcg\/mL), ABTS\u02d9+ (IC50: 10.75 \u00b1 0.17 \u03bcg\/mL), and CUPRAC (A0.5: 95.38 \u00b1 1.69 \u03bcg\/mL) activities, whereas the ethyl acetate extract FC11 showed the strongest \u03b2-carotene\u2013linoleic acid activity (IC50: 37.77 \u00b1 2.11 \u03bcg\/mL). The water extract FC24 showed the strongest AChE (IC50: 135.52 \u00b1 0.77 \u03bcg\/mL) and tyrosinase (IC50: 34.46 \u00b1 1.05 \u03bcg\/mL) inhibition. The results demonstrated that both harvesting season and extraction solvent significantly influenced the phytochemical composition and biological activities. Principal component analysis revealed clear discrimination among extracts, and molecular docking supported these findings by highlighting strong interactions of hesperidin and rutin with target enzymes. PCA explained 50.30% of the total variance. Molecular docking analysis revealed the strongest binding affinities for hesperidin toward AChE (\u22129.3 kcal\/mol), hesperidin and rutin toward BChE (both \u221210.8 kcal\/mol), and rutin toward tyrosinase (\u221210.3 kcal\/mol). ADMET predictions suggested favorable oral drug-likeness for selected compounds, whereas others may require further optimization. Overall, these findings indicate that F. carica leaves represent a promising source of natural phenolics with multifunctional bioactivity.<\/jats:p>","DOI":"10.3390\/life16091518","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T14:39:24Z","timestamp":1789137564000},"page":"1518","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Phytochemical Profiling, In Vitro Bioactivity, Molecular Docking, and Pharmacokinetic\u2013Toxicity Evaluation of Ficus carica Leaf Extracts"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8657-052X","authenticated-orcid":false,"given":"Bihter","family":"\u015eahin","sequence":"first","affiliation":[{"name":"Department of Chemistry and Chemical Processing Technologies, Susurluk Agriculture and Forest Vocational School, Band\u0131rma Onyedi Eyl\u00fcl University, 10600 Bal\u0131kesir, T\u00fcrkiye"},{"name":"Department of Chemistry and Chemical Processing Technologies, Susurluk Agriculture and Forest Vocational School, Bal\u0131kesir University, 10602 Bal\u0131kesir, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Zafer","family":"Ma\u015flakc\u0131","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Processing Technologies, Susurluk Agriculture and Forest Vocational School, Band\u0131rma Onyedi Eyl\u00fcl University, 10600 Bal\u0131kesir, T\u00fcrkiye"},{"name":"Department of Chemistry and Chemical Processing Technologies, Susurluk Agriculture and Forest Vocational School, Bal\u0131kesir University, 10602 Bal\u0131kesir, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"G\u00fcl\u015fah","family":"Kani","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Processing Technologies, Susurluk Agriculture and Forest Vocational School, Band\u0131rma Onyedi Eyl\u00fcl University, 10600 Bal\u0131kesir, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"project-administration","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2093-4949","authenticated-orcid":false,"given":"\u00d6zge","family":"Tokul \u00d6lmez","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Mu\u011fla S\u0131tk\u0131 Ko\u00e7man University, 48121 Mu\u011fla, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"software","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.2147\/DDDT.S436446","article-title":"Physicochemistry, nutritional, and therapeutic potential of Ficus carica\u2014A promising nutraceutical","volume":"18","author":"Fazel","year":"2024","journal-title":"Drug Des. 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