scholarly journals A propolis-derived small molecule ameliorates metabolic syndrome in obese mice by targeting the CREB/CRTC2 transcriptional complex

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Yaqiong Chen ◽  
Jiang Wang ◽  
Yibing Wang ◽  
Pengfei Wang ◽  
Zan Zhou ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Fasting Blood Glucose ◽  
Obese Mice ◽  
Glucose Levels ◽  
Diet Induced Obesity ◽  
Blood Glucose Levels ◽  
Suitable Target ◽  
Artepillin C ◽  
Transcriptional Complex

AbstractThe molecular targets and mechanisms of propolis ameliorating metabolic syndrome are not fully understood. Here, we report that Brazilian green propolis reduces fasting blood glucose levels in obese mice by disrupting the formation of CREB/CRTC2 transcriptional complex, a key regulator of hepatic gluconeogenesis. Using a mammalian two-hybrid system based on CREB-CRTC2, we identify artepillin C (APC) from propolis as an inhibitor of CREB-CRTC2 interaction. Without apparent toxicity, APC protects mice from high fat diet-induced obesity, decreases fasting glucose levels, enhances insulin sensitivity and reduces lipid levels in the serum and liver by suppressing CREB/CRTC2-mediated both gluconeogenic and SREBP transcriptions. To develop more potential drugs from APC, we designed and found a novel compound, A57 that exhibits higher inhibitory activity on CREB-CRTC2 association and better capability of improving insulin sensitivity in obese animals, as compared with APC. In this work, our results indicate that CREB/CRTC2 is a suitable target for developing anti-metabolic syndrome drugs.

scholarly journals Immunomodulatory Role of an Ayurvedic Formulation on Imbalanced Immunometabolics during Inflammatory Responses of Obesity and Prediabetic Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Kamiya Tikoo ◽  
Shashank Misra ◽  
Kanury V. S. Rao ◽  
Parul Tripathi ◽  
Sachin Sharma
Keyword(s):  
Inflammatory Responses ◽  
Fasting Blood Glucose ◽  
Normal Diet ◽  
Immunological Parameters ◽  
Glucose Levels ◽  
Inflammatory Conditions ◽  
Diet Induced Obesity ◽  
Blood Glucose Levels ◽  
Sugar Levels ◽  
Major Factors

Kal-1 is a polyherbal decoction of seven different natural ingredients, traditionally used in controlling sugar levels, inflammatory conditions particularly regulating metabolic and immunoinflammatory balance which are the major factors involved in obesity and related diseases. In the present study, we aimed to investigate the effect of Kal-1 (an abbreviation derived from the procuring source) on diet-induced obesity and type II diabetes using C57BL/6J mice as a model. The present study was performed with two experimental groups involving obese and prediabetic mice as study animals. In one, the mice were fed on high-fat with increased sucrose diet, and different amounts (5, 20, and 75 μL) of Kal-1 were administered with monitoring of disease progression over a period of 21 weeks whereas in the second group the mice were first put on the same diet for 21 weeks and then treated with the same amounts of Kal-1. A significant reduction in body weight, fat pads, fasting blood glucose levels, insulin levels, biochemical parameters, immunological parameters, and an array of pro- and anticytokines was observed in obese and diabetic mice plus Kal-1 than control (lean) mice fed on normal diet. In conclusion, Kal-1 has immunomodulatory potential for diet-induced obesity and associated metabolic disorders.

Parenteral 17beta-estradiol decreases fasting blood glucose levels in non-obese mice with short-term ovariectomy

Life Sciences ◽  
2010 ◽  
Vol 87 (11-12) ◽  
pp. 358-366 ◽  
Author(s):  
Ju-Young Kim ◽  
Kyung-Jin Jo ◽  
Ok-Soon Kim ◽  
Byung-Joon Kim ◽  
Dong-Wook Kang ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Fasting Blood Glucose ◽  
Obese Mice ◽  
Short Term ◽  
Glucose Levels ◽  
Blood Glucose Levels

scholarly journals Rhein Reduces Fat Weight indb/dbMouse and Prevents Diet-Induced Obesity in C57Bl/6 Mouse through the Inhibition of PPARγSignaling

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Yu Zhang ◽  
Shengjie Fan ◽  
Na Hu ◽  
Ming Gu ◽  
Chunxiao Chu ◽  
...  
Keyword(s):  
Target Genes ◽  
Fasting Blood Glucose ◽  
Peroxisome Proliferator ◽  
Brown Adipocytes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Levels ◽  
Rheum Palmatum ◽  
Diet Induced Obesity ◽  
Blood Glucose Levels ◽  
Underlying Mechanisms

Rheum palmatumhas been used most frequently in the weight-reducing formulae in traditional Chinese medicine. However, the components ofRheum palmatumthat play the antiobesity role are still uncertain. Here, we tested the weight-reducing effect of two majorRheum palmatumcompounds ondb/dbmouse. We found that rhein (100 mg kg−1 day−1), but not emodin, reduced the fat weight indb/dbmouse. Using diet-induced obese (DIO) C57BL/6 mice, we identified that rhein blocked high-fat diet-induced obesity, decreased fat mass and the size of white and brown adipocytes, and lowered serum cholesterol, LDL cholesterol, and fasting blood glucose levels in the mice. To elucidate the underlying mechanisms, we used reporter assay and gene expression analysis and found that rhein inhibited peroxisome proliferator-activated receptorγ(PPARγ) transactivity and the expression of its target genes, suggesting that rhein may act as a PPARγantagonist. Our data indicate that rhein may be a promising choice for antiobesity therapy.

Abstract 397: HMOX1 Ameliorates Fatty Liver and Metabolic Syndrome by Reduction of Hepatic Heme and PGC1a

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Komal Sodhi ◽  
Wade G Douglas ◽  
Stephen J Peterson ◽  
Larry Dial ◽  
Imran T Khawaja ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Body Weight ◽  
Blood Glucose ◽  
Fatty Liver ◽  
Obese Mice ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Lipid Droplet Size

Introduction: Nonalcoholic fatty liver (NAFLD) occurs in a setting of high fat diets, insulin resistance, obesity and dyslipidemia. Individuals with NAFLD have an increased risk of developing metabolic syndrome. Heme oxygenase-1 (HMOX1), a major cytoprotective enzyme, attenuates oxidative stress and obesity and increases insulin sensitivity. The antioxidant effect of HMOX1 is due to an increase in ferritin, and bilirubin and a decrease in heme, a pro-oxidant. The aim of this study was to examine the role of increased hepatic HMOX activity in decreasing steatosis, adiposity and vascular dysfunction and to determine the mechanism underlying these metabolic changes in obese mice. Methods: Obese mice were administered cobalt protoporphyrin (CoPP) and HMOX activity inhibitor stannous mesoporphyrin (SnMP) for 6 weeks. Blood pressure, body weight and blood glucose levels were measured in all the groups. Glycogen content, hepatic fibrosis, heme levels, fatty acid synthase (FAS) and lipid droplet size in liver were also assessed. Results: CoPP administration increased hepatic HMOX1 protein levels and HMOX activity, decreased blood pressure, body weight, blood glucose levels, hepatic heme content (p<0.05) as compared to obese mice. Our results also showed that HMOX1 induction causes a significant decrease in lipid steatosis ( lipid droplet size and FAS levels; p<0.01) as compared to obese mice. Densitometry analysis showed increased expression of PPARα and Glut 1 along with decreased expression of PGC1α in hepatic tissue. These beneficial effects were reversed by administration of SnMP. Conclusion: This novel study demonstrates the role of hepatic HMOX1 in attenuating the fatty liver and metabolic homeostasis by decreasing PGC1α and heme content and enhancing glycogen levels. Pharmacological agents that increase HMOX1 levels or gene targeting of HMOX1 offer a promising therapeutic target for NAFLD and suggest the existence of a significant link between the heme-HMOX system and the extent and severity of heme-dependent fatty liver.

scholarly journals Defatted Hydroethanolic Extract of Ammodaucus leucotrichus Cosson and Durieu Seeds: Antidiabetic and Anti-Inflammatory Activities

2020 ◽  
Vol 10 (24) ◽  
pp. 9147
Author(s):  
Imane Es-Safi ◽  
Hamza Mechchate ◽  
Amal Amaghnouje ◽  
Anna Calarco ◽  
Smahane Boukhira ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Fasting Blood Glucose ◽  
Diabetic Mice ◽  
North African ◽  
Glucose Levels ◽  
The North ◽  
Blood Glucose Levels ◽  
Anti Inflammatory ◽  
Hydroethanolic Extract ◽  
Inflammatory Effect

The seeds of Ammodaucus leucotrichus Cosson and Durieu have been used in the North African Sahara as a traditional medicine to treat diabetes. The present study investigates the antidiabetic, antihyperglycemic, and anti-inflammatory properties of the defatted hydroethanolic extract of Ammodaucus leucotrichus (DHEAM). The antidiabetic and the antihyperglycemic studies were assessed on alloxan-induced diabetic with orally administered doses of DHEAM (100 and 200 mg/kg). At the same time, its anti-inflammatory propriety was evaluated by measuring edema development in the Wistar rats paw induced with carrageenan. Treatment of diabetic mice with DHEAM for four weeks managed their high fasting blood glucose levels, improved their overall health, and also revealed an excellent antihyperglycemic activity. Following the anti-inflammatory results, DHEAM exhibited a perfect activity. HPLC results revealed the presence of seven molecules (chlorogenic acid, 3-p-coumaroylquinic acid, gallic acid, ferulic acid, myricetin, quercetin, luteolin). This work indicates that the DHEAM has an important antidiabetic, antihyperglycemic, and anti-inflammatory effect that can be well established as a phytomedicine to treat diabetes.

scholarly journals Effects of Apocynin on Heart Muscle Oxidative Stress of Rats with Experimental Diabetes: Implications for Mitochondria

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 335
Author(s):  
Estefanía Bravo-Sánchez ◽  
Donovan Peña-Montes ◽  
Sarai Sánchez-Duarte ◽  
Alfredo Saavedra-Molina ◽  
Elizabeth Sánchez-Duarte ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Sensitivity ◽  
Cardiac Tissue ◽  
Diabetic Rats ◽  
Oxidase Inhibitor ◽  
Beneficial Effects ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Transport Chain ◽  
Male Wistar Rats

Diabetes mellitus (DM) constitutes one of the public health problems today. It is characterized by hyperglycemia through a defect in the β-cells function and/or decreased insulin sensitivity. Apocynin has been tasted acting directly as an NADPH oxidase inhibitor and reactive oxygen species (ROS) scavenger, exhibiting beneficial effects against diabetic complications. Hence, the present study’s goal was to dissect the possible mechanisms by which apocynin could mediate its cardioprotective effect against DM-induced oxidative stress. Male Wistar rats were assigned into 4 groups: Control (C), control + apocynin (C+A), diabetes (D), diabetes + apocynin (D+A). DM was induced with streptozotocin. Apocynin treatment (3 mg/kg/day) was applied for 5 weeks. Treatment significantly decreased blood glucose levels and insulin resistance in diabetic rats. In cardiac tissue, ROS levels were higher, and catalase enzyme activity was reduced in the D group compared to the C group; the apocynin treatment significantly attenuated these responses. In heart mitochondria, Complexes I and II of the electron transport chain (ETC) were significantly enhanced in the D+A group. Total glutathione, the level of reduced glutathione (GSH) and the GSH/ oxidized glutathione (GSSG) ratio were increased in the D+A group. Superoxide dismutase (SOD) and the glutathione peroxidase (GSH-Px) activities were without change. Apocynin enhances glucose uptake and insulin sensitivity, preserving the antioxidant defense and mitochondrial function.

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