Harnessing the Potential of Coffee Parchment as a Source of Bioactive Compounds to Modulate T Lymphocyte Proliferation, Activity, and Oxidative Stress

Coffee parchment, a by‐product of coffee processing, is rich in phenolic compounds but remains underexplored. This study evaluated the in vitro effects of its aqueous extract on human T lymphocyte proliferation, cytokine secretion (IL‐2, interferon‐γ [IFN‐γ], and IL‐4), and redox balance. T lymphocytes were isolated by differential centrifugation using a Histopaque gradient and cultured with concanavalin A and various extract concentrations (1–100 µg/mL). Key assessments included proliferation 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, cytokine levels (ELISA), ATP content, cytotoxicity (micronucleus test), and oxidative stress markers (glutathione, SOD, catalase, hydroperoxides, and protein carbonyls) after 48 h. 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‐γ (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 (1–25 µg/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‐protective effects.