Exploring the glucose-lowering and anti-inflammatory immune mechanism of artemether by AMPK/mTOR pathway and microbiome based on multi-omics

作者：Tao Jiang, Peipei Du, Dongxia Liu, Hetao Chen, Yujin Ma, Bin Hu, Jingna Li, Hongwei� Jiang, Xuejiao Li · 发表于：Frontiers in Pharmacology · 年份：2025 · DOI：10.3389/fphar.2025.1520439 · 被引用次数：11 · 研究领域：Metabolism, Diabetes, and Cancer、Natural Antidiabetic Agents Studies、Adipokines, Inflammation, and Metabolic Diseases

Background Diabetes mellitus (DM) is a metabolic disease with high morbidity, which significantly affects human life and health expenditures. Previous studies have demonstrated that artemether (ATM) has anti-diabetes and anti-inflammation activities, but its mechanism has not been fully elucidated. This research aimed to elucidate the impact of ATM on glucolipid metabolism in a type 2 diabetes mellitus (T2DM) model db/db mice and what kind of role the gut microbiota played, and explored the underlying mechanisms involved. Methods C57BL/KsJ-db/db mice were treated with 80 and 160 mg/kg of ATM for 8 weeks, with metformin as a positive control. Results ATM treatment (160 mg/kg) observably ameliorated insulin resistance (IR), hyperglycemia, hyperlipemia and pathological injury in the liver and pancreas. In addition, ATM significantly decreased the expression of TNF-α, IL-1β, IL-6, NF-κB and IL-17A, and significantly increased the level of IL-10 in diabetic mice. 16S rRNA sequencing and targeted GC-MS metabolomics result indicated that ATM restored gut microbiota dysbiosis based on increasing beneficial bacteria Lactobacillus and reducing pathogenic bacteria Helicobacter and Prevotella leading to the accumulation of propionic and valeric acids and the reduction of lipopolysaccharides (LPS) release, intestinal inflammation and intestinal barrier damage. Network pharmacology and metabolomics identified the AMPK/mTOR pathway as the main signaling involved in ATM improves glucolipid m...