Biphasic Regulation of Human Lymphocyte Redox Status and Cytokine Secretion by Algerian Propolis Extract: In Vitro and In Silico Evaluations.

Propolis has long been used in Algerian folk medicine to strengthen immunity and treat infections. This work investigated the immunomodulatory effects of an ethanolic extract of propolis (EEP) on human lymphocytes. Brown propolis samples were collected from the Tlemcen region of Algeria. Human peripheral blood lymphocytes from healthy donors were cultured with increasing concentrations of EEP (0.25-2 mg/mL). Cell proliferation, cytotoxicity, ATP, cytokine secretion (IL-2, IFN-γ, and IL-4), and redox markers (MDA, carbonylated proteins, GSH, catalase, and NO) were assessed. EPP exhibited a biphasic response: moderate concentrations enhanced lymphocyte proliferation, cytokine secretion, and antioxidant defenses, while higher concentrations induced cytotoxicity, Th1-dominant response and oxidative stress associated to decreased catalase activity. Molecular modeling revealed that caffeic acid, quercetin, and catechin, the major EPP compounds, exhibit strong binding affinity of toward catalase and interact with critical residues involved in enzymatic activity suggesting their potential involvement in catalase-related redox modulation with favorable pharmacokinetic properties.