{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T15:57:33Z","timestamp":1785513453164,"version":"3.56.0"},"reference-count":73,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Silybum marianum (SM) is a rich source of flavonolignans with promising antioxidant and antidiabetic properties; however, its therapeutic application is limited by poor stability and bioavailability. This study combined experimental and computational approaches to develop and evaluate SM-loaded chitosan nanoparticles (CS\u2013SM nanoparticles). Microwave-assisted extraction followed by LC-MS\/MS profiling identified eleven metabolites, including major flavonolignans characteristic of SM. Nanoparticles prepared by ionic gelation exhibited favorable physicochemical properties, including a particle size of 173\u2013189 nm, a polydispersity index of 0.23, a zeta potential of +41.5 mV, an encapsulation efficiency of 98%, and a drug loading capacity of 50%, indicating the formation of a stable colloidal delivery system. CS\u2013SM nanoparticles showed enhanced antioxidant, anti-inflammatory, and \u03b1-amylase inhibitory activities compared with crude extracts. The formulation exhibited an \u03b1-amylase IC50 value of approximately 0.40 mg\/mL and maintained low hemolytic activity, suggesting favorable preliminary biocompatibility. Molecular docking demonstrated favorable interactions of neosilyhermin A, silibinin, and silyhermin with \u03b1-amylase and \u03b1-glucosidase active sites. Short-timescale molecular dynamics simulations revealed ligand-dependent behavior within the chitosan\u2013TPP matrix, indicating different release tendencies among the investigated flavonolignans. Overall, the results support CS\u2013SM nanoparticles as a promising platform for the delivery of bioactive phytochemicals with antioxidant and antidiabetic potential.<\/jats:p>","DOI":"10.3390\/molecules31152677","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T15:02:01Z","timestamp":1785510121000},"page":"2677","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Eco-Friendly Synthesis, Physicochemical Characterization, and In Vitro Biological Evaluation of Plant-Derived Bioactive-Loaded Chitosan Nanoparticles Supported by Molecular Modeling Studies"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7779-6344","authenticated-orcid":false,"family":"Ajwa","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Agriculture, Faisalabad 38040, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8520-2503","authenticated-orcid":false,"given":"Fatma","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Agriculture, Faisalabad 38040, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4039-4166","authenticated-orcid":false,"given":"Amer","family":"Jamil","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Agriculture, Faisalabad 38040, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilal","family":"Aslam","sequence":"additional","affiliation":[{"name":"Institute of Physiology and Pharmacology, University of Agriculture Faisalabad, Faisalabad 38040, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Weber","sequence":"additional","affiliation":[{"name":"Institute of Physics and Applied Computer Science, Faculty of Applied Physics and Mathematics, Gda\u0144sk University of Technology, 11\/12G. 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