anagliptin and Inflammation

Sepsis is a multiple organ dysfunction syndrome (MODS) induced by infection, which significantly threatens public health. The overactivation of inflammatory reactions and oxidative stress participate in the pathogenesis of sepsis. Anagliptin, a novel anti-diabetic agent widely applied for the treatment of type II diabetes, has been recently claimed to possess anti-inflammatory properties. Here, the protective effects of anagliptin on lipopolysaccharide (LPS)- stimulated macrophages will be checked to explore the possible pharmacological property of anagliptin on sepsis. The state of oxidative stress was dramatically activated by LPS, accompanied by the upregulation of toll-like receptor 4 (TLR4) and high mobility group box-1 (HMGB-1), as well as the elevated expression of inducible nitric oxide synthase (iNOS) and production of nitric oxide (NO). After treatment with anagliptin, the state of oxidative stress in macrophages was alleviated, with the downregulation of TLR4, HMGB-1, iNOS, and the declined release of NO. The excessive secretion of inflammatory factors, activation of the NF-κB pathway, and promoted expression level of receptor-interacting protein 1 (RIP1) were observed in LPS- stimulated macrophages, all of which were greatly reversed by the introduction of anagliptin. Lastly, the protective properties of anagliptin on LPS- treated macrophages, including the inhibitory effects on inflammation and the NF-κB pathway, were dramatically abolished by the overexpression of RIP1 in macrophages. Collectively, anagliptin prevented LPS-induced inflammation and activation of P338D1 macrophages by repressing the expression level of RIP1.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Dipeptidyl-Peptidase IV Inhibitors; GTPase-Activating Proteins; Inflammation; Interleukin-6; Lipopolysaccharides; Macrophages; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Pyrimidines; Toll-Like Receptor 4; Transcription Factor RelA; Tumor Necrosis Factor-alpha

Chronic psychosocial stress is a risk factor for cardiovascular disease. In view of the important role of dipeptidyl peptidase-4 (DPP-4) in human pathophysiology, we studied the role of DPP-4 in stress-related vascular aging in mice, focusing on oxidative stress and the inflammatory response.. DPP-4 inhibition can improve vascular aging in stressed mice, possibly by improving oxidative stress production and vascular inflammation. Our results suggest that DPP-4 may become a new therapeutic target for chronic stress-related vascular aging in metabolic cardiovascular diseases.

Topics: Animals; Aorta; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Down-Regulation; Human Umbilical Vein Endothelial Cells; Humans; Hydrogen Peroxide; Inflammation; Male; Mice; Mice, Inbred BALB C; Nitric Oxide Synthase; Oxidative Stress; Pyrimidines; Sirtuin 1; Stress, Physiological

Treatment with the dipeptidyl peptidase-4 inhibitor, anagliptin, or with the α-glucosidase inhibitor, miglitol, reduced the oral sucrose load-inducible expression of interleukin (IL)-1β, IL-18, tumor necrosis factor-α, S100a8, S100a9, S100a11, IL-1R2, IL-1Rn and tumor necrosis factor receptor 2 genes in peripheral leukocytes of Otsuka Long-Evans Tokushima fatty (OLETF) rats at the stage of impaired glucose tolerance. Inhibiting postprandial hyperglycemia reduced the expression of genes related to inflammation in peripheral leukocytes of OLETF rats.

Topics: 1-Deoxynojirimycin; alpha-Glucosidases; Animals; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Gene Expression; Hyperglycemia; Hypoglycemic Agents; Inflammation; Insulin; Interleukin-18; Interleukin-1beta; Leukocytes, Mononuclear; Male; Pyrimidines; Rats; Rats, Inbred OLETF; Receptors, Interleukin-1; S100 Proteins; Sucrose; TNF Receptor-Associated Factor 2