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Symptoms and complications associated with severe SARS‐CoV‐2 infection such as acute respiratory distress syndrome (ARDS) and organ damage have been linked to SARS‐CoV‐2 spike protein S1‐induced increased production of pro‐inflammatory cytokines by immune cells. In this study, the effects of an extract of Garcinia kola seeds and garcinoic acid were investigated in SARS‐CoV‐2 spike protein S1‐stimulated human PBMCs. Results of ELISA experiments revealed that Garcinia kola extract (6.25, 12.5, and 25 μg/ml) and garcinoic acid (1.25, 2.5, and 5 μM) significantly reduced SARS‐CoV‐2 spike protein S1‐induced secretion of TNFα, IL‐6, IL‐1β, and IL‐8 in PBMCs. In‐cell western assays showed that pre‐treatment with Garcinia kola extract and garcinoic acid reduced expressions of both phospho‐p65 and phospho‐IκBα proteins, as well as NF‐κB DNA binding capacity and NF‐κB‐driven luciferase …