Ethyl Acetate Extract of Cynanchi Auriculati Radix Inhibits LPS-Induced M1 Polarization of RAW264.7 Macrophages and Prolongs the Lifespan of Caenorhabditis elegans by Regulating NF-κB and PMK-1/SKN-1 Signaling Pathways

Extracts of Cynanchi Auriculati Radix (RCA), derived from the roots of Cynanchum auriculatum Royle ex Wight. (CA), have been documented to possess anti-inflammatory and antioxidant properties. However, the molecular mechanisms of their anti-aging action remain unclear. The present study aimed to explore the potential anti-aging components and mechanisms of RCA. LC-MS/MS and network pharmacology were used to identify components and targets. In vitro, LPS-induced RAW264.7 macrophages were used to assess anti-inflammatory effects. In vivo, Caenorhabditis elegans models were employed to evaluate lifespan and stress resistance. Five bioactive components were identified. The ethyl acetate extract of RCA (RCAEA) inhibited LPS-induced M1 macrophage polarization by suppressing the expression of NO, PGE2, IL-1β, iNOS, COX-2, TNF-α, and IL-6 via the NF-κB pathway. In C. elegans, RCAEA extended lifespan and enhanced oxidative and heat stress resistance, without affecting reproduction. These benefits were mediated by the PMK-1/SKN-1 pathway, as confirmed using mutant strains. RCAEA is a promising anti-aging and anti-inflammatory agent, acting through NF-κB and PMK-1/SKN-1 signaling pathways.