Dihydroartemisinin alleviates steatosis and inflammation in nonalcoholic steatohepatitis by decreasing endoplasmic reticulum stress and oxidative stress

Nonalcoholic steatohepatitis (NASH) is a severely inflammatory subtype of nonalcoholic fatty liver. Endoplasmic reticulum stress (ERS) and oxidative stress (OS) cause metabolic abnormalities, promote liver steatosis and inflammation, and are central to the development of NASH. Dihydroartemisinin (DHA) is a compound extracted from Artemisia annua that is often used in the treatment of malaria. Recent studies have shown that DHA also has a wide range of pharmacological effects, acting on various organs throughout the body to exert anti-inflammatory, antioxidant, and anti-fibrotic effects. In this study, we demonstrated in vitro that the anti-inflammatory effect of DHA is effective against NASH and reduces liver steatosis. DHA treatment decreased the synthesis of lipids, such as cholesterol and free fatty acids, and the expression of nuclear factor kappa-B. This is accomplished by inhibiting the unfolded protein response and reducing the production of reactive oxygen species, thereby inhibiting OS and ERS. This study reveals DHA's therapeutic effect and potential mechanism in NASH, implying that DHA could be a new and promising candidate for NASH therapy.