<p>Artemether Regulates Metaflammation to Improve Glycolipid Metabolism in db/db Mice</p>

Abstract

Background: Artemether, a commonly used artemisinin derivative, has been shown to possess potential antidiabetic activities. However, only limited information is available on the mechanisms of artemether in type 2 diabetes. Therefore, in this study, we examined some of the possible mechanisms of artemether (ATM) upon glycolipid metabolism in the db/db mouse model of diabetes. Materials and Methods: Male C57BL/KsJ-db/db and C57BL/KsJ-db/+ mice at 4 weeks of age were divided into four groups (N=6/group): ( 1) NC (normal controldb/+ mice, 1% methylcellulose, intragastric administration), ( 2) DM (diabetic modeldb/db mice, 1% methylcellulose, intragastric administration), (3) ATM 100 (DM + 100 mg/kg of artemether) and ( 4) ATM 200 (DM + 200 mg/kg of artemether). A number of assays related to diabetes were then performed following a 4-week period of these treatments.Results: Artemether at both doses significantly reduced rates of weight gain and fasting blood glucose levels, improved islet function and insulin resistance and reduced serum lipid levels to varying degrees in db/db mice. Artemether exerted a positive effect on islet vacuolar degeneration and hepatic steatosis, and increased expressions of AMP-activated protein kinase, glucose transporter 4 and Insulin receptor β protein in the liver of these db/db mice. With the use of liver protein chip detection, we found that artemether significantly improved the immune microenvironment, downregulated the expression of inflammatory factors and activated the cytokine-mediated signaling pathway through cytokine-cytokine receptor interactions. Conclusion:Artemether may regulate glycolipid metabolism in db/db mice by improving the immune microenvironment. The results of this study provide important new information that can serve as the foundation for future research into the use of artemether as a means to improve glycolipid metabolism.

The Potential Roles of Artemisinin and Its Derivatives in the Treatment of Type 2 Diabetes Mellitus

“…Rates of weight gain↓food and water intake↓ fasting blood glucose levels↓GTT and ITT (improved) islet function, insulin resistance and insulin sensitivity (improved) serum lipid levels (TC, TG and FFA)↓ islet vacuolar degeneration and hepatic steatosis (improved) AMPK↑ GLUT-4↑ IRβ↑ expression of inflammatory factors↓ Fu et al (Fu et al, 2020) Frontiers in Pharmacology | www.frontiersin.org…”

“…Therefore, the crucial goals for treating T2DM are mainly to improve IR and islet cell function. In Fu’s research, islet function and IR were significantly improved in male db/db mice treated for 4 weeks with 100 mg/kg or 200 mg/kg artemether ( Fu et al, 2020 ). Many studies have shown that artemisinin and its derivatives have great potential in the treatment of T2DM, whether in the early stage or late stage of the disease.…”

“…Notably, many studies have reported that artemisinin and its derivatives can increase insulin sensitivity and improve IR. Artemisinin and its derivatives can also reduce food intake and the rate of body weight increases caused by a high-fat diet (HFD) ( Lu et al, 2016 ; Guo et al, 2018 ; Fu et al, 2020 ). It seems that the antiobesity effect of artemisinins may be one of the most important ways they alleviate IR.…”

“…Kim’s team found that A. annua leaf extract significantly improved ITT and GTT results and decreased COX-2 levels in HFD-fed mice ( Kim et al, 2016 ). Recently, investigators also found that artemether can promote AMP-activated protein kinase (AMPK) activity and downregulate the expression of inflammatory factors to reverse the pathological state in db/db mice ( Fu et al, 2020 ). NF-κB plays a key role.…”

“…In summary, through a literature review, we found that artemisinins have anti-inflammatory effects and relieve IR. Based on the common pathological state of chronic inflammation in diabetes and IR, it is speculated that the anti-inflammatory effects of artemisinins have a causal relationship with attenuated IR ( Fu et al, 2020 ).…”