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This study evaluated the in vitro effects of its aqueous extract on human T lymphocyte proliferation, cytokine secretion (IL\u20102, interferon\u2010\u03b3 [IFN\u2010\u03b3], and IL\u20104), and redox balance. T lymphocytes were isolated by differential centrifugation using a Histopaque gradient and cultured with concanavalin A and various extract concentrations (1\u2013100\u00a0\u00b5g\/mL). Key assessments included proliferation 3\u2010(4,5\u2010dimethylthiazol\u20102\u2010yl)\u20102,5\u2010diphenyltetrazolium bromide (MTT) assay, cytokine levels (ELISA), ATP content, cytotoxicity (micronucleus test), and oxidative stress markers (glutathione, SOD, catalase, hydroperoxides, and protein carbonyls) after 48\u00a0h. The extract enhanced lymphocyte proliferation and showed immunostimulatory effects. Molecular modeling revealed strong binding of chlorogenic acid and caffeine to the active site of IFN\u2010\u03b3 (PDB ID: 6E3K), confirmed by higher negative energy values and also the existence of different types of interactions, namely, hydrogen bonding and hydrophobic interactions. At higher concentrations, the extract increased oxidative activity, whereas at lower concentrations (1\u201325\u00a0\u00b5g\/mL), it activated antioxidant defenses and improved redox homeostasis. Thus, coffee parchment aqueous extract at low doses modulated immune activity and oxidative balance, supporting antioxidant defenses and immune functions. It represents a potential source of nutraceuticals with cell\u2010protective effects.<\/jats:p>","DOI":"10.1002\/cbdv.202502274","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T19:39:33Z","timestamp":1763753973000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Harnessing the Potential of Coffee Parchment as a Source of Bioactive Compounds to Modulate T Lymphocyte Proliferation, Activity, and Oxidative Stress"],"prefix":"10.1002","volume":"23","author":[{"given":"Amel","family":"Medjdoub","sequence":"first","affiliation":[{"name":"Laboratory of Physiology, Physiopathology and Biochemistry of Nutrition, Department of Biology, Faculty of Natural and Life Sciences, Earth and Universe Abou\u2010BekrBelka\u00efd University  Tlemcen Algeria"},{"name":"Department of Biology, Faculty of Natural and Life Sciences University of Oran1 Ahemd Ben Bella  Oran Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmahan","family":"Imessaoudene","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, Physiopathology and Biochemistry of Nutrition, Department of Biology, Faculty of Natural and Life Sciences, Earth and Universe Abou\u2010BekrBelka\u00efd University  Tlemcen Algeria"},{"name":"Department of Natural and Life Sciences, Institute of Nature and Life Sciences Tissemsilt University  Tissemsilt Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Chelihi","sequence":"additional","affiliation":[{"name":"Laboratoire de Catalyse et Synth\u00e8se en Chimie Organique, Facult\u00e9 des Sciences Universit\u00e9 De Tlemcen Abou\u2010Bekr Belka\u00efd  Tlemcen Algeria"},{"name":"Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology Silesian University of Technology  Gliwice Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9116-1608","authenticated-orcid":false,"given":"Ismail","family":"Daoud","sequence":"additional","affiliation":[{"name":"Department of Matter Sciences University Mohamed Khider  Biskra Algeria"},{"name":"Laboratory of Natural and Bio\u2010actives Substances. 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