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.

Candida albicans ranks as one of the most common causes of fungal sepsis in hospitalized patients around the world with an increasing mortality rate. The current antifungal drugs in use face several limitations including fungal resistance due to biofilm formation. This has complicated the treatment landscape, necessitating the need for continued search for effective therapeutic options against drug-resistant C. albicans threats. Therefore, this study investigated eighteen fluorene derivatives for their antifungal and antibiofilm potential against C. albicans. Two fluorene derivatives namely: 9,9-bis(4-hydroxyphenyl) fluorene (BHPF) and fluorene-9-acetic acid (FAA) were identified as potential inhibitors of Candida biofilms, achieving 97 % and 89 % inhibition at 10 μg/mL. Microscopic studies also confirmed their antibiofilm efficacy, with BHPF demonstrating activities comparable to amphotericin B. Furthermore, BHPF inhibited planktonic cell growth at concentration as low as 5 μg/mL. Both BHPF and FAA exhibited fungicidal activity and also inhibited C. albicans virulence factors such as cell aggregation and hyphal formation. Notably, neither compound showed propensity for resistance development over 15 passages. Additionally, toxicity evaluations in both plant and Caenorhabditis elegans model revealed non-to mild toxicity, and the ADMET prediction also satisfied the criteria for drug-likeliness. The results of this multifaceted investigation highlight the potential of BHPF and FAA as novel antifungal agents targeting C. albicans infections and biofilm-related challenges.