Lupiwighteone exerts anti-aging effects by suppressing NF-κB and activating the MAPKs/Nrf2 signaling pathway

Lupiwighteone (Lup), a natural isoflavonoid, phytochemical, exhibits potential anti-inflammatory properties; however, its impacts on inflammation, oxidative stress, and aging processes remain insufficiently characterized. The present study systematically investigated the anti-inflammatory and anti-aging effects of Lup using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and Caenorhabditis elegans (C. elegans), aiming to elucidate its underlying molecular mechanisms and biological significance. The study employed cell culture, animal experiments, and molecular biology techniques, combined with molecular docking, to evaluate Lup's modulatory effects on NF-κB and MAPK signaling cascades and the Nrf2 pathway. Our results indicated that Lup treatment significantly extended lifespan, reduced reactive oxygen species (ROS) levels, and slowed age-related physiological decline in the C. elegans model. Mechanistically, we found that Lup activated the MAPKs/Nrf2 pathway, enhanced antioxidant stress responses, and reduced oxidative damage, thereby delaying the aging process. Additionally, Lup treatment significantly suppressed the production and secretion of key pro-inflammatory mediators, including TNF-α, IL-6, and nitric oxide, while inhibiting NF-κB signaling activation in LPS-stimulated RAW264.7 cells. This inhibition was mediated by impeding IκBα degradation, thereby preventing NF-κB translocation to the nucleus. Collectively, these findings demonstrated that Lup exerts significant anti-aging, anti-inflammatory, and antioxidant activities through the dual regulation of oxidative stress and inflammation. These results not only strengthen the theoretical basis of plant-derived medicines in anti-inflammation and anti-aging but also provide new insights and practical guidance for the future development of natural pharmaceuticals.