Anti-Inflammatory Activities of Zophobas morio Larvae Lipids on Lipopolysaccharide-Induced Activated Macrophages: Reprogramming Macrophage Polarization and Attenuating Oxidative Stress

This study investigated the structural and anti-inflammatory properties of Zophobas morio lipids (ZMLs). The fatty acid (FAs) composition showed a higher proportion of unsaturated FAs, mainly consisting of oleic (30.30%) and linoleic acids (20.05%), than saturated FAs, including palmitic (24.80%) and stearic acids (12.96%). In addition, FT-IR and 1H-NMR analyses confirmed that ZML possessed a typical triglyceride structure, with long-chain alkyl groups. Thermogravimetric analysis (TGA) indicated that ZML exhibited high thermal stability, with a degradation peak at 369 °C. Differential scanning calorimetry (DSC) displayed a thermal transition at −8 °C, corresponding to the crystallization of unsaturated FAs in ZML. ZML significantly inhibits lipopolysaccharide (LPS)-induced pro-inflammatory M1 macrophage polarization by suppressing nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, thereby attenuating the expression of inflammatory mediators. Additionally, ZML alleviated inflammatory oxidative stress by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant pathway. Notably, ZML not only induced M2 macrophage polarization in quiescent macrophages but also reprogrammed M1 macrophages toward the anti-inflammatory M2 phenotype. These findings suggest that ZML is a natural nutritional lipid source and a potential therapeutic agent for modulating inflammatory response.