Astaxanthin and kaempferol, renowned natural compounds, possess potent antioxidant properties and exhibit remarkable biological activities. However, their poor water solubility, low stability, and limited bioavailability are the primary bottlenecks that restrict their utilization in pharmaceuticals and functional foods. To overcome these drawbacks, this study aims to fabricate astaxanthin/kaempferol co-encapsulated nanoparticles and investigate their synergistic effects on reducing the risk of stress oxidation, chronic inflammation, and lipid accumulation in RAW264.7 and HepG2 cells. The synthesized astaxanthin/kaempferol nanoparticles exhibited well-defined spherical morphology with an average particle diameter ranging from 74 to 120 nm. These nanoparticles demonstrated excellent stability with the remaining astaxanthin content ranging from 82.5% to 92.1% after 6 months of storage at 4 °C. Nanoastaxanthin/kaempferol displayed high dispersibility and stability in aqueous solutions, resulting in a significant enhancement of their bioactivity. In vitro assessments on cell lines revealed that nanoastaxanthin/kaempferol enhanced the inhibition of H2O2-induced oxidative stress in HepG2 and LPS-induced NO production in RAW264.7 compared to nanoastaxanthin. Additionally, these nanoparticles reduced the expression of genes involved in inflammation (iNOS, IL-6 and TNF-α). Moreover, hepatocytes treated with nanoastaxanthin/kaempferol showed a reduction in lipid content compared to those treated with nanoastaxanthin, through enhanced regulation of lipid metabolism-related genes. Overall, these findings suggest that the successful fabrication of co-encapsulated nanoparticles containing astaxanthin and kaempferol holds promising therapeutic potential in the treatment of non-alcoholic fatty liver disease.
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