HM-chromanone alleviates hyperglycemia and inflammation in mice with endotoxin-induced insulin resistance

This study was designed to investigate whether (E)-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone alleviates inflammation and hyperglycemia in mice with endotoxin-induced insulin resistance. (E)-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone (10, 30, and 50 mg/kg bodyweight) was orally pre-administered to C57BL/6 J mice. An hour later, lipopolysaccharides (20 mg/kg bodyweight) was administered intraperitoneally to induce endotoxins. Blood samples were collected from the tail vein of the mice every 0, 30, and 90 min. The results indicated that (E)-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone effectively regulated blood glucose levels in mice with endotoxin-induced insulin resistance. Furthermore, (E)-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone significantly reduced the phosphorylation of mammalian target of rapamycin, ribosomal protein S6 kinase 1, and protein kinase C θ. Additionally, (E)-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone suppressed the phosphorylation of c-Jun-NH2-terminal kinase and IkB kinase β, thereby decreasing the phosphorylation of inhibitor of nuclear factor kappa-B α and activating the nuclear factor-κB and activator protein-1 in the liver. Therefore, the expression of tumor necrosis factor-α, interleukin-6, and interleukin-1β was significantly reduced by suppressing the nuclear factor-κB and activator protein 1 activity. Suppression of mammalian target of rapamycin, S6 kinase 1, protein kinase C θ, c-Jun-NH2-terminal kinase, and IkB kinase β also ameliorated insulin resistance by reducing the phosphorylation of insulin receptor substrate-1 serine 307, thereby decreasing hyperglycemia. These findings suggest that (E)-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone can alleviate hyperglycemia and inflammation in mice with endotoxin-induced insulin resistance.