Animal Models Of Chronic Disease Research Articles

Anti-diabetic activity of field cricket glycosaminoglycan by ameliorating oxidative stress

BackgroundField cricket (Gryllus bimaculatus) is newly emerged as an edible insect in several countries. Anti-inflammatory effect of glycosaminoglycan derived from this cricket on chronic disease animal model such as diabetic mouse has not been fully investigated yet. Thus, the objective of this study was to determine the anti-oxidative effect of such glycosaminoglycan on diabetic mouse.MethodsTo discover potential therapeutic agents, field cricket glycosaminoglycan (GbG) was tested in the present study. Its anti-oxidative activities in diabetic mice were determined based on its abilities to reduce glucose, ALT, AST, ALP, LDL-cholesterol and BUN levels. Dung beetle (C. molossus) glycosaminoglycan (CaG) was used as a positive control. Db mice were intraperitoneally administered for 1 month according to their group assignments: 1) normal (DB-Hetero); 2) control (DB-Homo); 3) 5 mg/kg treatment of CaG (CaG5); 4) 5 mg/kg treatment of GbG (GbG5); and 5) 10 mg/kg treatment of metformin (Metformin 10).ResultsBlood glucose level decreased after 1st week of treatment with GbG. LDL-cholesterol and alkaline phosphatase levels were also inhibited by GbG. Markers of oxidative damage, such as protein carbonyl content and levels of hepatocellular biomarkers, were reduced in db mice treated with GbG. Especially anti-oxidative activities of catalase, superoxide dismutase and glutathione peroxidase were significantly increased in GbG treated group compared to those in the control (Db Homo). GbG was composed of heparin disaccharides. Its main N-glycan was identified as Hex9GlcNAc2 (m/z 1905.7) with neutral mono-sugar mainly comprising of hexose and L (+) rhamnose by mass spectroscopy.ConclusionsSero-biochemical and hepatocellular anti-oxidant assay results in db mice suggest that cricket (G. bimaculatus) glycosaminoglycan might possess anti-oxidative effect in diabetic state.

Potent, Selective, Water Soluble, Brain-Permeable EP2 Receptor Antagonist for Use in Central Nervous System Disease Models.

Activation of prostanoid EP2 receptor exacerbates neuroinflammatory and neurodegenerative pathology in central nervous system diseases such as epilepsy, Alzheimer's disease, and cerebral aneurysms. A selective and brain-permeable EP2 antagonist will be useful to attenuate the inflammatory consequences of EP2 activation and to reduce the severity of these chronic diseases. We recently developed a brain-permeable EP2 antagonist 1 (TG6-10-1), which displayed anti-inflammatory and neuroprotective actions in rodent models of status epilepticus. However, this compound exhibited moderate selectivity to EP2, a short plasma half-life in rodents (1.7 h) and low aqueous solubility (27 μM), limiting its use in animal models of chronic disease. With lead-optimization studies, we have developed several novel EP2 antagonists with improved water solubility, brain penetration, high EP2 potency, and selectivity. These novel inhibitors suppress inflammatory gene expression induced by EP2 receptor activation in a microglial cell line, reinforcing the use of EP2 antagonists as anti-inflammatory agents.

Advanced Glycation End Product Receptor‐Mediated Cellular Dysfunction

Advanced glycation end products (AGEs), S100/calgranulins, and HMGB1 proteins supposedly play a pivotal role in diabetes mellitus and other chronic inflammatory diseases by promoting cellular dysfunction via binding to cellular surface receptors. Particularly, engagement of the receptor for AGEs (RAGE) has gained major attention because it converts short-lasting cellular activation in sustained cellular dysfunction. Consistently, blockade of ligand-RAGE interaction with soluble RAGE (sRAGE) suppresses chronic cellular activation and dysfunction in animal models of chronic diseases. RAGE-/- mice, however, demonstrate that the protection conferred by RAGE deficiency is lower than that mediated by sRAGE. Furthermore, RAGE-/- mice can be protected by sRAGE in certain settings of the adaptive immune response. This finding implies that abounding RAGE ligands overworking the RAGE pathway might also activate other receptors.