Unveiling Stingless Bee Honey Anti-inflammatory Potential Through the Polarization of LPS-induced J774 Macrophages

Macrophages play an important role during the inflammatory process. These cells can adopt either the pro- or anti-inflammatory phenotypes. While stingless bee honeys have demonstrated evidence of anti-inflammatory potential, their capacity to induce a shift from a pro-inflammatory state to an inflammation-resolution state has not been thoroughly investigated. In this study, the anti-inflammatory activity of two stingless bees (Scaptotrigona bicunctata-honey A and Melipona quadriasciata-honey G) honeys in J774 macrophages induced by LPS was evaluated. Both honeys exhibited non-cytotoxic effects and reduced nitrite and IL-4 levels. However, only honey G increased the levels of the anti-inflammatory cytokine IL-13, by 163.1 ± 14.8% (p < 0.05) and was further investigated for its immunomodulatory effect. This honey reduced the expression of TLR4 by 59.3 ± 3.5% (p < 0.001) and increased the mannose receptor levels by 67.3 ± 2.4% (p < 0.001). Moreover, it increased the phagocytic activity by 25.0 ± 7.7% (p < 0.01) and decreased the death of the macrophages by 32.1 ± 1.7% (p < 0.001). Collectively, these findings highlight stingless bee honey from Melipona quadriasciata bee has an important immunomodulatory effect, as it reduces the markers of the pro-inflammatory state of J774 cells and increases the markers of resolution or anti-inflammatory responses.