Artemisinin and its derivatives for metabolic syndrome: From multi-target mechanisms to translational opportunities (Review)

Abstract

Metabolic syndrome (MetS) is a complex of disorders, characterized by insulin resistance accompanied by abdominal obesity, dyslipidemia, hypertension and impaired glucose metabolism. This group of conditions notably increases the risk of type 2 diabetes mellitus and cardiovascular or cerebrovascular diseases and has become a major global public health challenge. Current treatments for MetS often fail to meet clinical needs owing to the limitations associated with single-target therapies and notable side effects. Artemisinin-based drugs are primarily used as antimalarial drugs but have garnered widespread attention for their broad biological activities. Preclinical evidence suggests that artemisinin and its derivatives improve insulin sensitivity, regulate lipid metabolism, alleviate chronic inflammation and reshape the gut microbiota by modulating multiple metabolism-related signaling pathways, including AMP-activated protein kinase, PI3K/Akt, NF-κB and Toll-like receptor 4, indicating a potential therapeutic avenue for MetS. However, most of these findings are derived from cell-based and animal studies, while direct clinical evidence in patients with MetS remains limited. In the present review, the therapeutic potential and core molecular mechanisms of artemisinin and its derivatives for MetS are summarized and the challenges and opportunities for their future clinical translation are discussed.