New Roles of Artemisinins in Atherosclerosis Progression

Artemisinin is a natural compound derived from the Chinese plant Artemisia annua , which was officially approved by the FDA for its antimalarial effects. In recent years, a growing body of studies has shown the novel function of artemisinin in atherosclerosis therapy. In vivo studies have shown that artemisinin can inhibit the progression of atherosclerosis plaque. In the present review, the evidence showing the inhibitory effects of artemisinin on the progression of atherosclerosis plaque and its underlying mechanisms is discussed. Mechanistically, artemisinin and its derivatives act by modulating various atherosclerosis-mediating risk factors, including hyperlipidemia, inflammation, oxidative stress, and malfunctioning vascular smooth muscle cells (VSMCs). Notably, artesunate, but not artemisinin, can attenuate the plasma levels of TG, TC, VLDL-C, and LDL-c, along with a substantial decline in arterial lipid deposition through enhancing the LDPL activity via inducing the KFL2/NRF2/TCF7L2 axis. Artemisinin was found to ameliorate the atherosclerosis plaque inflammation by reducing monocyte adhesion and subsequent transmigration to the intima, via inhibiting the expression of ICAM-1 and VCAM-1, diminishing NLRP3 inflammasome activation, and reducing the expression of inflammatory factors such as IL-1β, IL-18, TNF-α, MCP-1, and TGF-β1 mechanistically and mainly via suppressing the by NF-κB activity. Artemisinin could exert antioxidant effects through activating the PI3K/Akt/eNOS signaling pathway and suppressing the ROS-mediated NF-κB signal pathway. Artemisinin could also improve the VSMC function in the atherosclerosis plaque. These findings can suggest artemisinin as a new therapeutic agent for treating atherosclerosis; however, future clinical trials are warranted to validate its therapeutic efficiency in patients with atherosclerosis.