Abstract: To investigate the anti-inflammatory effect of manuka honey, its impact on cell viability and the expression of genes involved in the nuclear factor kappa-B (NF-κB) signaling pathway in HepG2 and Caco-2 cells with inflammation induced by lipopolysaccharide (LPS) was assessed by the CCK-8 method, microscopic observation, quantitative polymerase chain reaction (PCR), and enzyme linked immunosorbent assay (ELISA). The results showed that LPS treatment at 1.00 and 2.00 μg/mL caused significant nuclear deformation and disruption of tight junctions in HepG2 and Caco-2 cells, respectively. Despite these morphological changes, cell viability did not decrease significantly. In addition, the expression of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and cyclooxygenase (COX-2) was significant upregulated via the NF-κB signaling pathway. At concentrations above 20.00 mg/mL, manuka honey markedly inhibited cell viability, and manuka honey concentrations in the range of 2.50–20.00 mg/mL significantly inhibited the expression of pro-inflammatory cytokines induced by LPS, the effect being most pronounced at 10.00 mg/mL, bringing cytokine expression back to levels close to the control group. This study suggests that manuka honey has a significant inhibitory effect on inflammatory responses and can effectively alleviate LPS-induced cellular inflammation, indicating its potential as an adjunctive therapeutic strategy. This study offers new insights for the clinical treatment of inflammatory diseases.

Key words: manuka honey, pro-inflammatory cytokines, lipopolysaccharide-induced inflammation, HepG2 cells, Caco-2 cells