Research Progress on Anti-Inflammatory and Antioxidant Mechanism of Artemether Based on MAPK/NF-κB Signaling Pathway

Artemether, a derivative of the natural compound artemisinin, is increasingly recognized for its multi-target anti-inflammatory and antioxidant properties. This review systematically elucidates the molecular mechanisms underlying these effects, focusing on artemether's dual modulation of the MAPK/NF-κB and Nrf2 signaling pathways. We detail how artemether concurrently inhibits the MAPK/NF-κB axis-suppressing IKKβ phosphorylation and IκBα degradation to block NF-κB nuclear translocation-and downregulates p38/contextually modulates ERK phosphorylation. This leads to a significant reduction in key inflammatory mediators, including TNF-α, IL-6, and COX-2. Simultaneously, artemether activates the Nrf2 antioxidant pathway, upregulating HO-1 expression and enhancing the activity of SOD and GSH-Px, which effectively scavenges free radicals and reduces markers of oxidative damage such as MDA and 8-OHdG. The core therapeutic synergy arises from artemether's disruption of the ROS-NF-κB positive feedback loop, which inhibits neutrophil infiltration and lipid peroxidation, thereby ameliorating tissue injury in experimental models of arthritis and neurodegenerative diseases. Compared to conventional NSAIDs and glucocorticoids, artemether exhibits a favorable safety profile, particularly regarding gastrointestinal effects, and demonstrates unique immunomodulatory potential. Future research directions should prioritize the development of nano-targeted delivery systems and the elucidation of pathway crosstalk at the single-cell level to advance the clinical translation of artemether for chronic inflammatory diseases.