Artemisia indica Willd. Extract Regulate NLRP3 Inflammasome and ENaC Trafficking in Angiotensin II-Stimulated Renal Tubular Cells

Artemisia indica Willd. is widely used in traditional medicine and dietary practices. Phytochemical analysis of Artemisia indica Willd. aqueous extract (AAE) by HPLC–ESI–MS/MS identified isochlorogenic acid C (ICAC) as a major constituent. Angiotensin II (Ang II) disrupts renal tubular epithelial cell homeostasis and contributes to renal injury. In this study, we evaluated the protective effects of AAE and ICAC in Ang II-stimulated NRK52E cells. Both AAE and ICAC significantly reduced reactive oxygen species (ROS) production, mitochondrial dysfunction, and proinflammatory cytokine release. Mechanistic analyses showed that AAE inhibited Ang II type 1 receptor (AT1R)-mediated NF-κB activation and suppressed NLRP3 inflammasome signaling, thereby alleviating inflammatory responses and pyroptosis. In addition, AAE and ICAC restored sodium homeostasis by reactivating neural precursor cell expressed developmentally downregulated gene 4-like (Nedd4-2), promoting epithelial sodium channel (ENaC) ubiquitination and reducing its apical membrane accumulation. Molecular docking suggested that ICAC interacts with the extracellular domain of α-ENaC, supporting its regulatory role. Overall, AAE and ICAC protect renal tubular epithelial cells against Ang II-induced injury by reducing oxidative stress, inflammation, and dysregulated sodium transport, highlighting their potential as plant-derived therapeutic agents for hypertension-associated renal dysfunction.