Coagonist of glucagon-like peptide-1 and glucagon receptors ameliorates kidney injury in murine models of obesity and diabetes mellitus

AIM To investigate the role of glucagon-like peptide-1(GLP-1)/glucagon receptors coagonist on renal dysfunction associated with diabetes and obesity. METHODS Chronic high-fat diet fed C57 BL/6 J mice, streptozotocintreated high-fat diet fed C57 BL/6 J mice and diabeticC57 BLKS/J db/db mice were used as models of diabetes-induced renal dysfunction. The streptozotocintreated high-fat diet fed mice and db/db mice were treated with the GLP-1 and glucagon receptors coagonist(Aib2 C24 Chimera2, 150 μg/kg, sc) for twelve weeks, while in chronic high-fat diet fed mice, coagonist(Aib2 C24 Chimera2, 150 μg/kg, sc) treatment was continued for forty weeks. Kidney function, histology, fibrosis, inflammation, and plasma biochemistry were assessed at the end of the treatment. RESULTS Coagonist treatment decreased body weight, plasma lipids, insulin resistance, creatinine, blood urea nitrogen, urinary albumin excretion rate and renal lipids. In kidney, expression of lipogenic genes(SREBP-1 C, FAS, and SCD-1) was decreased, and expression of genes involved in β-oxidation(CPT-1 and PPAR-α) was increased due to coagonist treatment. In plasma, coagonist treatment increased adiponectin and FGF21 and decreased IL-6 and TNF-?. Coagonist treatment reduced expression of inflammatory(TNF-α, MCP-1, and MMP-9) and pro-fibrotic(TGF-β, COL1 A1, and α-SMA) genes and also improved histological derangement in renal tissue.CONCLUSION Coagonist of GLP-1 and glucagon receptors alleviated diabetes and obesity-induced renal dysfunction by reducing glucose intolerance, obesity, and hyperlipidemia.

Celastrus paniculatus oil ameliorates synaptic plasticity in a rat model of attention deficit hyperactivity disorder

Objective:To explore the effect and mechanism of action of Celastrus paniculatus oil on the treatment of perinatal rats with attention deficit hyperactivity disorder.Methods:In the perinatal stage,the rats were either isolated or administered with lead acetate to establish an animal model of attention deficit hyperactivity disorder.Atomoxetine served as the reference standard.Animals’behaviours were assessed through Y-maze,novel object preference,fear conditioning and residentintruder aggression tests.Oxidative stress parameters,bioamine concentration(dopamine,noradrenaline and 5-hydroxytryptamine),nerve growth factor,interleukin-6,nuclear factor-κB,and tumour necrosis factor(TNF)-αwere estimated.Synaptophysin immunohistochemical assay was performed.Results:Celastrus paniculatus oil significantly improved behavioural parameters in Y maze,novel object preference,discrimination index,fear conditioning and resident intruder aggressive tests.The treatment groups showed a decrease in malondialdehyde level.Changes in the levels of dopamine,noradrenaline,and serotonin were restored by Celastrus paniculatus oil.Celastrus paniculatus oil increased nerve growth factor and decreased interleukin-6,nuclear factor-κB,and TNF-α.Synaptophysin immunoreactivity was also improved by Celastrus paniculatus oil with alleviated reactive gliosis,degeneration,and vascular proliferation.Conclusions:This research shows the therapeutic potential of Celastrus paniculatus oil for the treatment of attention deficit hyperactivity disorder.

Lepidium sativum Linn.种子的脱脂乙醇提取物体外自由基清除活性(英文)

AIM:The objective of the present study was to evaluate the antioxidant potential of the defatted ethanolic extract of the seeds of Lepidium Sativum Linn.METHODS:Different in vitro chemical assays viz.DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging,ABTS (2,2-azinobis-(3-ethylbenzothiazoline-6-sulphonate) radical scavenging,iron chelation,lipid peroxidation,super-oxide scavenging and non-enzymatic haemoglobin glycosylation assay were used.The total antioxidant capacity of the extract was determined spectrophotometrically by phosphomolybdic acid method.RESULT & CONCLUSION:The defatted lepidium seed extract showed significant free radical scavenging activity in ABTS and non-enzymatic glycosylation assays,and a moderate activity in all the other assays.IC50 of the extract in the DPPH,ABTS,iron chelation,lipid peroxidation and super oxide scavenging assays were found to be 171.13,38.64,128.94,71.39 and 206.09 μg·mL-1 respectively.The haemoglobin glycosylation assay of the extract showed a percentage scavenging of 46.60% and 74.88%,at 0.5 and 1.0 μg·mL-1,concentrations,respectively.Total antioxidant capacity of ethanolic extract of L.sativum (10 mg·mL-1) was found to be equivalent to 58.38 μg·mL-1 of ascorbic acid.