Mitoflaxone

Artemisia argyi, a globally recognized plant widely used in medicine and food, has become an important and popular food additive in Asia and other parts of the world. However, its edible safety has always been controversial. Herein, we aimed to evaluate the safety and health benefits of A. argyi as a dietary additive. Fresh and dried A. argyi water extracts (FAA and DAA, respectively) were prepared by simulating two processing methods for edible tender A. argyi. And chemical composition analysis showed that both FAA and DAA were rich in nutritional and functional components, including polysaccharides, proteins, and polyphenols. UHPLC-TQ-MS analysis showed that tender A. argyi mainly contained 11 polyphenol components (mainly flavonoids and phenolic acids). Then, an acute toxicity study, based on the maximum limit method, showed that single administrations of FAA and DAA at doses of 40 and 133 g/kg, respectively (crude drug dosage), induced no signs of poisoning and no mortality. In a sub-chronic toxicity study, FAA and DAA treated at 3.42 and 6.83 g/kg (crude drug dosage) induced no significant toxic reactions, hematological abnormalities, or impairments in organ structure and function. Serum metabolomic analysis revealed the presence of only 46 and 52 differential metabolites in the FAA and DAA groups, respectively. Functional enrichment analysis revealed that tender A. argyi did not induce toxicity by altering metabolism from an overall perspective; however, it may have induced beneficial effects by regulating lipid metabolism. Furthermore, dual consideration of chemical abundance and network pharmacological analyses indicated that eupatilin was the most promising active ingredient among the polyphenols for treating metabolic syndrome. In mice with metabolic syndrome, eupatilin reversed changes in body weight, reduced blood glucose levels, and improved dysregulated lipid metabolism and intestinal barrier damage. Mechanistically, the gut microbiome analysis showed 9 differential genera were significantly restored after eupatilin intervention. And metabolomic analysis showed that 4 key differential metabolites were identified from the feces of Eup-treated mice. In addition, integrated analysis revealed that eupatilin mainly promoted L-phenylalanine metabolism by increasing the abundance of Akkermansia and decreasing the abundance of Helicobacter and Rikenella. Briefly, these findings systematically elucidated the safety of tender A. argyi as a dietary additive and its health benefits in metabolic syndrome via gut microbiota and metabolites. Importantly, this study will provide essential scientific support for the dual application of A. argyi in medicine and nutrition.