Improvement of hyperglycemia in a murine model of insulin resistance and high glucose- and inflammasome-mediated IL-1β expressions in macrophages by silymarin
Journal
Chemico-Biological Interactions
Journal Volume
290
Pages
12-18
Date Issued
2018
Author(s)
Abstract
Macrophages and inflammasome pathway are involved in high-glucose toxicity and development of insulin resistance. Silymarin (SMR) was known to modulate glucose homeostasis and reduce inflammation. However, it is still unknown whether SMR possess anti-hyperglycemic effects in diabetic-like knockout mice (Hnf-1αkin/?/Ins.cre mice) with insulin resistance and also unclear how SMR regulates LPS induced stress markers and pro-inflammatory cytokines under stresses of high glucose (HG) or NLRP3 inflammasome activation. Current results show that oral administration of SMR (100 mg/kg) reduced hyperglycemia in the mouse model of maturity-onset diabetes of the young type 3-like mice. In cultured macrophages, SMR (5–20 μg/ml) reduces high glucose (HG)-enhanced expressions of inducible nitric oxide synthase, nitric oxide generation stimulated by LPS; however, no effects on COX-2 expressions. The enhanced interleukin-1β (ΙL-1β) secretions in the presence of HG or palmitate were also significantly down regulated by SMR in dose-dependent manner in LPS-treated macrophages. Such observations may result from the decreased extracellular signal-regulated kinase 1/2 phosphorylation, while without affecting protein kinase C-α phosphorylation and nuclear factor-κB activation. These findings together show that SMR acts as a protector against HG-related stresses not only by lowering hyperglycemia but also suppressing HG- and inflammasome-mediated IL-1β expressions to improve insulin resistance. ? 2018 Elsevier B.V.
SDGs
Other Subjects
cryopyrin; cyclooxygenase 2; immunoglobulin enhancer binding protein; inflammasome; insulin; interleukin 1beta; interleukin 6; mitogen activated protein kinase 1; mitogen activated protein kinase 3; nitric oxide synthase; protein kinase C alpha; s 0292; silymarin; tumor necrosis factor; glucose; hepatocyte nuclear factor 1alpha; inducible nitric oxide synthase; inflammasome; interleukin 1beta; lipopolysaccharide; mitogen activated protein kinase 1; mitogen activated protein kinase 3; nitric oxide; silymarin; animal experiment; animal model; animal tissue; antidiabetic activity; Article; controlled study; drug effect; enzyme activation; extracellular matrix; glucose homeostasis; glucose intake; human; human cell; hyperglycemia; insulin blood level; insulin resistance; knockout mouse; macrophage; mouse; mouse model; nonhuman; protein expression; protein phosphorylation; protein secretion; RAW 264.7 cell line; signal transduction; THP-1 cell line; animal; cell line; cytology; deficiency; disease model; down regulation; genetics; hyperglycemia; insulin resistance; macrophage; metabolism; pathology; phosphorylation; Animals; Cell Line; Disease Models, Animal; Down-Regulation; Glucose; Hepatocyte Nuclear Factor 1-alpha; Hyperglycemia; Inflammasomes; Insulin Resistance; Interleukin-1beta; Lipopolysaccharides; Macrophages; Mice; Mice, Knockout; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Nitric Oxide; Nitric Oxide Synthase Type II; Phosphorylation; RAW 264.7 Cells; Silymarin
Type
journal article