Artemisinin and its derivatives throughout the therapeutic mechanisms and clinical potential

Artemisinin (ART), a sesquiterpene lactone, was first isolated from Artemisia annua by Youyou Tu, contributing significantly to antimalarial therapy. Beyond its antimalarial effects, ATZ and its derivatives exhibit broad pharmacological activities, including anticancer, antiviral, anti-inflammatory, and renoprotective properties. Recent research has expanded its therapeutic applications to metabolic syndrome, fibrosis, and as a potential treatment for SARS-CoV-2. This review delves into the multifaceted therapeutic potential of Artemisinin, focusing on its diverse applications in treating various pathologies, including cancer, fibrosis, metabolic disorders, and viral infections. Additionally, it explores the underlying molecular mechanisms, particularly the roles of reactive oxygen species (ROS), autophagy, and ferritinophagy in mediating therapeutic effects. Artemisinin’s efficacy stems largely from its unique endoperoxide bridge, which, upon activation, generates carbon-centered radicals and ROS that damage cellular components, particularly in parasites and cancer cells. In metabolic disorders, ATZ derivatives modulate ER stress and autophagy, offering protective effects against obesity and diabetes. Notably, Artemisinin's ability to induce ferritinophagy and ferroptosis in hepatic stellate cells highlights its potential in mitigating fibrosis. Furthermore, Artemisinin has emerged as a promising candidate for inhibiting SARS-CoV-2 replication, with ongoing clinical trials exploring its efficacy. However, the full spectrum of its molecular mechanisms, especially in non-malarial contexts, remains incompletely understood. Artemisinin holds remarkable therapeutic versatility beyond its traditional antimalarial role, with promising applications in cancer, fibrosis, metabolic disorders, and viral infections. Continued research into optimizing its dosage and understanding its molecular pathways is essential to fully harness its potential across diverse diseases.