Natural Nanoparticles Derived from Chenopodium quinoa Willd. Alleviate Metabolic Dysfunction-associated Steatotic Liver Disease via Inhibiting TNF-α/TNFR1-Mediated Apoptosis.

Plant-derived nanoparticles, as an emerging natural bioactive substance with potential health benefits, have a potential application prospect in the prevention and control of metabolic dysfunction-associated steatotic liver disease (MASLD). Quinoa serves as a promising resource for screening active ingredients for improving MASLD. In present study, the quinoa-derived nanoparticles (QDNPs) were firstly extracted by ultracentrifugation and sucrose density gradient centrifugation. Notably, we demonstrated that QDNPs exhibited outstanding stability in the gastrointestinal tract, facilitating their enrichment in target organ to the release of their active ingredients. Further, we observed that upon uptake by hepatocytes, QDNPs displayed significant anti-MASLD effects both in vitro and in vivo, characterized by histological improvements, with reductions in lipid accumulation, lipid degeneration, non-alcoholic steatohepatitis score (NAS), and inflammatory index levels. Transcriptome and KEGG analysis revealed enrichment of the apoptosis pathway, and further experiments confirmed that the anti-MASLD activity triggered by QDNPs mainly be attributed to the inhibition of TNF-α/TNFR1-mediated apoptosis. This study reveals the promising application of QDNPs as a natural bioactive nanomaterial in functional food supplements or a nutritious candidate for alleviating MASLD.