10-HDA attenuates inflammatory responses in LPS-activated RAW264.7 cells

Background: Inflammation is implicated in the pathogenesis of various diseases, including cancer, diabetes, and diseases caused by bacterial infections. Macrophages, as key regulators of inflammatory responses, can polarize into distinct phenotypes such as pro-inflammatory M1 and anti-inflammatory M2 macrophages. Trans-10-hydroxy-2-decenoic acid (10-HDA), a bioactive component of royal jelly (RJ), exhibits potent anti-inflammatory properties; however, its influence on macrophage polarization remains poorly understood. Methods: 10-HDA was used to uncover the mechanisms for LPS-induced inflammatory response in RAW264.7 cells. CCK8 assay, ELISA assay, western blot analysis, real-time PCR, immunofluorescence assay were performed to evaluate the protective effects of 10-HDA. Results: Our findings demonstrated that 10-HDA treatment upregulated M2 macrophage markers, enhanced the secretion of anti-inflammatory cytokines, and modulated multiple signaling pathways. Mechanistically, 10-HDA exerted its anti-inflammatory effects by targeting the NUR77/NF-κB pathway, suppressing the expression of inducible nitric oxide synthase (iNOS) while promoting the anti-inflammatory marker CD206. Additionally, 10-HDA significantly inhibited the production of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α. Furthermore, 10-HDA influenced mitochondrial metabolism, suggesting a protective role in maintaining mitochondrial function. Conclusion: These results indicate that 10-HDA promotes M2 macrophage polarization through the NUR77/NF-κB signaling pathway and by mitigating mitochondrial dysfunction, highlighting its potential role in modulating innate immunity and its potential application in anti-inflammatory therapy.