scholarly journals The Caprine Casein-Alpha-S2 Protein Modulates the Molecular Mechanism 2 of Insulin Signal Transduction in Type2 Diabetes Rat

2020 ◽  
Author(s):  
Fatchiyah Fatchiyah ◽  
Rista Nikmatu Rohmah ◽  
Lidwina Faraline Triprisila ◽  
Takeshi Ohta ◽  
Hazna Noor Meidinna
Keyword(s):  
Body Weight ◽  
Diabetes Management ◽  
Diabetic Rats ◽  
The Body ◽  
Therapeutic Effects ◽  
Mrna Levels ◽  
Caprine Milk ◽  
Type2 Diabetes ◽  
Tnf Α ◽  
Protein Treatment

This study purpose was to investigate the association of casein-alpha-S2 protein of Caprine milk and molecular mechanismofinsulin signaltransduction in type2 diabetes mellitus (T2DM). The Caprine milk CSN1S2 protein treatment of 0, 375, 750, and 1500mg/kg BW were conducted to the control and T2DM rats. We observed several physiological parameters of all rats. The levels of insulin and TNF-α in the plasma were measured using ELISA.The expressions of proteins and mRNA levels of diabetes-related genes in the pancreas tissues were analyzed using Western Blotting and Real-Time PCR, respectively. Our study found that diabetic rats had lower body weight, food intake, and fecal weight compared with control rats. The Caprine milk CSN1S2 protein consumption affected the body weight of diabetic rats to increase, especially at the dose of 750mg/kg BW.Interestingly, the genes associated with insulin signaling were improved by the CSN1S2 protein treatment in diabetic rats, although their blood glucose and cholesterol level were not affected. The diabetic rats showed an elevated insulin level and GLUT4 protein expression after treatment. We also reported that the CSN1S2-treated diabetic rats had a gradually reduced expression of TNF-α and VCAM-1 in dose-dependent. Moreover, the 750mg/kg BW of CSN1S2 treatment enhanced the mRNA expressions of INS-receptor, GLUT4, IGF-1, CAMKK, and CAMKIV in diabetic rats. The ability of Caprine milk CSN1S2 protein to regulate the molecular mechanisms in the diabetes-signaling pathway indicated its potential therapeutic effects on diabetes management.

scholarly journals Metformin-Mg2+ adjunct therapy synergistically modulates insulin and PDX-1 gene signatures in STZ-NAD induced diabetic model

2020 ◽  
Vol 8 (3) ◽  
pp. 66-71
Author(s):  
Oluwaseun FAPOHUNDA ◽  
Femi Abiola OGUNLEYE ◽  
Tomisin Happy OGUNWA ◽  
Idowu Olaposi OMOTUY ◽  
Titilola Titilayoaderonke SAMUEL ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Treated Group ◽  
Diabetic Rats ◽  
The Body ◽  
Distilled Water ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Magnesium Supplementation ◽  
Adjunct Therapy

Diabetes mellitus (DM) is a multi-factorial debilitating disorder of metabolism, usually due to a combination of hereditary and environmental causes, resulting in abnormally high blood sugar levels (hyperglycemia) as a result of defects in either insulin secretion or insulin action in the body. DM is usually accompanied by hypomagnesemia. This study was aimed at investigating the effect of oral magnesium supplementation on pancreatic gene expression of insulin and PDX-1 in type-2 streptozotocin-nicotinamide induced Sprague dawley diabetic rats. A total of 24Sprague dawleyrats (Four groups of six rats each), were used for this study; Group 1: Normal rats (CONTROL) given distilled water for 4weeks; Group 2: Metformin + Magnesium treated rats (DMM) orally given 100mg/kg and 1000mg/kg body weight respectively for 4weeks; Group 3: Metformin treated diabetic rats (DM), orally given 100mg/kg body weight for 4weeks; Group 4: Diabetic untreated control rats (DU) given distilled water for 4weeks. Measured data were analyzed statistically. The result revealed that there was significant (p<0.05) increase in the feed and water intake of the treated rats but the metformin-magnesium supplement treated group showed more increase when compared with only metformin treated group. PDX-1 and insulin gene expression levels were significantly (p<0.05) higher in the control when compared with all the diabetic groups. However, PDX-1 and insulin mRNA levels were significantly (p<0.05) higher in DMM, when compared with DM. DMM showed improvements when compared with DM which suggests magnesium supplementation as an adjunct therapy with metformin may help inthe regeneration of the beta cells of the pancreas.

scholarly journals Mesenchymal stem cells significantly improved treatment effects of Linezolid on severe pneumonia in a rabbit model

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Dexiao Kong ◽  
Xia Liu ◽  
Xiaomei Li ◽  
Jianting Hu ◽  
Xiaoyan Li ◽  
...  
Keyword(s):  
Body Weight ◽  
Rabbit Model ◽  
Lower Lobe ◽  
The Body ◽  
Inflammatory Factors ◽  
Individual Treatment ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Chest Imaging ◽  
Tnf Α

Abstract The present study aimed to investigate whether co-administration of mesenchymal stromal cells (MSC) and linezolid (LZD) into a rabbit model of methicillin-resistant Staphylococcus aureus (MRSA)-infected pneumonia would bring a synergistic therapeutic effect. Human umbilical cord-derived MSCs (hUMSCs) were isolated and characterized. A rabbit model of pneumonia was constructed by delivering 1 × 1010 CFU MRSA via a bronchoscope into the basal segment of lower lobe of right lung. Through analyzing vital sign, pulmonary auscultation, SpO2, chest imaging, bronchoscopic manifestations, pathology, neutrophil percentage, and inflammatory factors, we verified that a rabbit model of MRSA-induced pneumonia was successfully constructed. Individual treatment with LZD (50 mg/kg for two times/day) resulted in improvement of body weight, chest imaging, bronchoscopic manifestations, histological parameters, and IL-10 concentration in plasma (P<0.01), decreasing pulmonary auscultation, and reduction of IL-8, IL-6, CRP, and TNF-α concentrations in plasma (P<0.01) compared with the pneumonia model group at 48 and 168 h. Compared with LZD group, co-administration of hUMSCs (1 × 106/kg for two times at 6 and 72 h after MRSA instillation) and LZD further increased the body weight (P<0.05). The changes we observed from chest imaging, bronchoscopic manifestations and pathology revealed that co-administration of hUMSCs and LZD reduced lung inflammation more significantly than that of LZD group. The plasma levels of IL-8, IL-6, CRP, and TNF-α in combined group decreased dramatically compared with the LZD group (P<0.05). In conclusion, hUMSCs administration significantly improved therapeutic effects of LZD on pneumonia resulted from MRSA infection in a rabbit model.

scholarly journals Tailored Hydrogels as Delivery Platforms for Conditioned Medium from Mesenchymal Stem Cells in a Model of Acute Colitis in Mice

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1127
Author(s):  
Juan Sendon-Lago ◽  
Lorena Garcia-del Rio ◽  
Noemi Eiro ◽  
Patricia Diaz-Rodriguez ◽  
Leandro Avila ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Body Weight ◽  
Conditioned Medium ◽  
Local Treatment ◽  
Histopathological Analysis ◽  
Mrna Levels ◽  
Acute Colitis ◽  
Tnf Α ◽  
Ifn Γ

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is increasingly prevalent and current therapies are not completely effective. Mesenchymal stem cells are emerging as a promising therapeutic option. Here, the effect of local hydrogel application loaded with conditioned medium (CM) from human uterine cervical stem cells (hUCESC-CM) in an experimental acute colitis mice model has been evaluated. Colitis induction was carried out in C57BL/6 mice by dissolving dextran sulfate sodium (DSS) in drinking water for nine days. Ulcers were treated by rectal administration of either mesalazine (as positive control) or a mucoadhesive and thermosensitive hydrogel loaded with hUCESC-CM (H-hUCESC-CM). Body weight changes, colon length, and histopathological analysis were evaluated. In addition, pro-inflammatory TNF-α, IL-6, and IFN-γ mRNA levels were measured by qPCR. Treatment with H-hUCESC-CM inhibited body weight loss and colon shortening and induced a significant decrease in colon mucosa degeneration, as well as TNF-α, IFN-γ, and IL-6 mRNA levels. Results indicate that H-hUCESC-CM effectively alleviated DSS-induced colitis in mice, suggesting that H-hUCESC-CM may represent an attractive cell-free therapy for local treatment of IBD.

scholarly journals Carbohydrate response element binding protein (ChREBP) modulates the inflammatory response of mesangial cells in response to glucose

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Yan Chen ◽  
Yan-Jun Wang ◽  
Ying Zhao ◽  
Jin-Cheng Wang
Keyword(s):  
Diabetes Mellitus ◽  
Inflammatory Response ◽  
Mesangial Cells ◽  
Binding Protein ◽  
The Body ◽  
Mrna Levels ◽  
Diabetic Mice ◽  
Response Element ◽  
Tnf Α ◽  
Element Binding Protein

Diabetic nephropathy (DN) is one of the most devastating complications of diabetes mellitus. Carbohydrate response element binding protein (ChREBP) is a basic helix–loop–helix leucine zipper transcription factor that primarily mediates glucose homeostasis in the body. The present study investigated the role of ChREBP in the pathogenesis of DN. The expression of ChREBP was detected in patients with type 2 diabetes mellitus (T2DM), diabetic mice, and mesangial cells. ELISA was used to measure cytokine production in mesangial cells. Flow cytometry analysis was performed to detect the apoptosis of mesangial cells in the presence of high glucose. The expression levels of ChREBP and several cytokines (TNF-α, IL-1β, and IL-6) were up-regulated in T2DM patients. The mRNA and protein levels of ChREBP were also significantly elevated in the kidneys of diabetic mice. Moreover, glucose treatment promoted mRNA levels of TNF-α, IL-1β, and IL-6 in mesangial cells. Glucose stimulation induced significant apoptosis of SV40 MES 13 cells. In addition, transfection with ChREBP siRNA significantly inhibited ChREBP expression. Consequently, the inflammatory responses and apoptosis were inhibited in SV40 MES 13 cells. These results demonstrated that ChREBP could mediate the inflammatory response and apoptosis of mesangial cells, suggesting that ChREBP may be involved in the pathogenesis of DN.

scholarly journals Absence of antidiabetic and hypolipidemic effect of Gymnema sylvestre in non-diabetic and alloxan-diabetic rats

2004 ◽  
Vol 47 (4) ◽  
pp. 545-551 ◽  
Author(s):  
Ricardo Galletto ◽  
Vera Lúcia Dias Siqueira ◽  
Edilene Bega Ferreira ◽  
Arildo José Braz Oliveira ◽  
Roberto Barbosa Bazotte
Keyword(s):  
Body Weight ◽  
Blood Level ◽  
Serum Lipids ◽  
Body Weight Gain ◽  
Acute Effect ◽  
Diabetic Rats ◽  
The Body ◽  
Hypolipidemic Effect ◽  
Gymnema Sylvestre ◽  
Water Ingestion

In this study we investigated the antidiabetic and hypolipidemic potential of dried powdered leaves of Gymnema sylvestre (GS). The acute effect of GS administered by oral gavage on glucose blood level of and lipids in non-diabetic and alloxan-diabetic rats were investigated in the following conditions: a) after a balanced meal; b) after the ingestion of 1000 mg/kg amylose or 1000 mg/kg glucose; c) after the ingestion of a mixture of 12 mL/kg soybean oil + 1% cholesterol (SOC). In addition, the effect of the treatment with GS during two (sub-acute) or four weeks (chronic) on body weight, food and water ingestion, glucose blood level and lipids in non-diabetic and alloxan-diabetic rats were measured. The dose of GS utilized in the majority of the experiments, i.e., 30 mg/kg, corresponds to that given to treat diabetes in Brazil. GS acutely did not influence the elevation of glycemia promoted by a balanced meal or by the administration of amylose or glucose; but promoted more intense (P<0.05) elevation of serum lipids after the administration of SOC. Moreover, the sub-acute and chronic treatment with GS in non-diabetic and alloxan-diabetic rats did not change: a) the body weight gain; b) food and water ingestion; c) the blood level of glucose and lipids. Thus we concluded that GS, at least in the form commercialized in the Brazil, i.e., dried powdered leaves, require further experimental and clinical trials before being recommended to treat diabetes and hyperlipidemia.

Hepatoproective Nature of Aerial parts of Caesalpinia pulcherrima in STZ Induced Diabetic Rat Model

2021 ◽  
pp. 3716-3720
Author(s):  
Pooja Pooja ◽  
Mazumder Avijit ◽  
Soumya Das
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Diabetic Rats ◽  
The Body ◽  
Marker Enzymes ◽  
Metabolizing Enzymes ◽  
Standard Drug ◽  
Liver Marker Enzymes

Diabetes is a chronic disease which characterized by hyperglycemia (elevated or abnormally high blood sugar levels) and other metabolic disturbances, including metabolism of lipids and haemostasis. Caesalpinia pulcherrima has previously showed strong anti-diabetic and hepatoprotective potential. The present research work was to investigate the anti-diabetic activity and hepatoprotective activity Caesalpinia pulcherrima in streptozotocin-induced (STZ) diabetic rats. The dose-dependent effects of 45days oral treatment with methanol extract of plant (200 and 300mg/kg) of CPAE on body weight, blood glucose level, total protein, albumin, liver marker enzymes and carbohydrate metabolizing enzymes were evaluated in STZ-induced diabetic rats. Oral administration methanolic extract of Caesalpinia pulcherrima of showed significant restoration of the body weight and decrease in the blood glucose level, liver marker enzymes (ALT, AST ALP) and carbohydrate metabolizing enzymes were observed in diabetic rats. These results suggest that fruit extract of Caesalpinia pulcherrima has valuable anti-diabetic activity in STZ-induced diabetic rats which is comparable to the standard drug metformin and hence might be of use in the management of diabetes.

Therapeutic effects of different treatment periods against ischemic stroke and toxicology study of Angong Niuhuang Pill in rats

2020 ◽  
Author(s):  
Jianzhao Chen ◽  
Yushuang Chai ◽  
Yuanfeng He ◽  
Jisheng Huang ◽  
Ting Wan ◽  
...  
Keyword(s):  
Body Weight ◽  
Ischemic Stroke ◽  
Protective Effect ◽  
Toxic Effect ◽  
Treatment Period ◽  
Ischemia Reperfusion ◽  
Neurological Function ◽  
The Body ◽  
Therapeutic Effects ◽  
Toxicology Study

Abstract Background : Angong Niuhuang Pill (ANP) is one of the most famous drugs to treat stroke in China, but there is no definite treatment period in drug instruction. In this study, we used middle cerebral artery occlusion (MCAO) model to evaluate its therapeutic effects of different treatment periods and studied its toxic effect in rats. Methods : Protective effect of ANP was observed in the cerebral ischemia-reperfusion model in rats; ANP (270 mg/kg) three different treatment period included 1 day, 4 days and 7 days. The observation period was 30 days. Therapeutic effect was evaluated by detecting neurological function, cerebral infraction volume, brain histology and cytokines. Three dose including 550, 1640, 4910 mg/kg were studied in toxicology study. The administration period was 30 days. Toxic effect was evaluated by detecting appearance, behavior, excrement character, food-intake, body weight, hematological parameters and biomarkers such as TBA, GSTα, Cystatin C, clusterin, GSH, S-100B and MBP. Results : Seven days treatment period of ANP had better effect than 1 day and 4 days treatment periods in rat MCAO model from neurological function scores, the volume of cerebral infarction, brain histology and the serum content of IL-1β, TNF-α and NO; the brain content of IL-1β and NO. The results of 30 days multiple dose toxicology study showed no animal death in all groups; in ANP 4910 mg/kg group, the kidney and liver coefficient increased about 10%, the body weight grew more slowly, the TBA increased slightly. There was no abnormal change in histology. These all recovered after drug withdraw for 8 weeks. Conclusion: Seven days treatment period of ANP had more protective effect than 1 day and 4 days treatment periods in ischemic stroke rat. No observed adverse effect level (NOAEL) of ANP was 1640 mg/kg; the safety margin of ANP was 270-1640 mg/kg. These data provided reference to modify drug instruction.

scholarly journals Antihyperglycemic and Antihyperlipidemic of Karala (Momordica charantia) Fruits in Streptozotocin Induced Diabetic Rats

2012 ◽  
Vol 5 (1) ◽  
pp. 29-37 ◽  
Author(s):  
MA Hossain ◽  
M Mostofa ◽  
D Debnath ◽  
AKMR Alam ◽  
Z Yasmin ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Body Weight ◽  
Total Cholesterol ◽  
Aqueous Extract ◽  
Diabetic Rats ◽  
Momordica Charantia ◽  
The Body ◽  
Control Group ◽  
Albino Rats ◽  
Higher Doses

To investigate the antihyperglycemic and antihyperlipidemic effect of Momordica charantia (Karala), the aqueous extract of the Karala fruit was tested on streptozotocin (STZ)-induced diabetic rats. Thirty six albino rats were used in the experiment, 30 diabetic and the remaining six as negative control (T1). Diabetes was induced by administering (injecting) STZ at dose of 55mg/kg body weight. Thirty diabetic animals were randomly divided into five groups such as diabetic control group (T2) without any application of treatment, and groups T3,T4,T5 and T6 were treated with aqueous extract of Karala fruits daily at the doses of 250,    500 and 750mg/kg and glibenclamide (at a dose of 5mg/kg body weight) respectively. The body weight was taken and blood samples were collected from individual animal to determine glucose levels at 15 day interval up to 90 days. In addition, Asparate  Transaminenase(AST), Alanine Transaminenase(ALT), Alkaline Phosphatase(ALP), Total cholesterol (TCh) and Triglyceride (TGA) were determined at day 15 and at the end of the experiment. All three doses of Karala extracts reduced diabetic induced blood sugar and the reduction is comparable with standard glibenclamide (GLM) dose particularly with higher doses Karala extracts (500 and 750mg). Karala also prevented body weight loss due to induced diabetes as did by GLM treatment.. The treatment also resulted in a significant reduction of Asparate Transaminenase(AST), Alanine Transaminenase(ALT), Alkaline Phosphatase(ALP), Total cholesterol (TCh) and Triglyceride (TGA) activities of treated rats when compared to the STZ induced  diabetic rats. Higher doses of Karala (500 and 750mg/kg) are as effective as standard GLM dose on measured variables. This study demonstrated that Karala has hyperglycemia and antihyperlipidemic effect against STZ induced diabetic rats. These findings open the possibility of using Karala extract to treat diabetic animal and human patients although further research is warranted. DOI: http://dx.doi.org/10.3329/jesnr.v5i1.11550 J. Environ. Sci. & Natural Resources, 5(1): 29 - 37, 2012  

SH2B1 CpG-SNP Is Associated with Body Weight Reduction in Obese Subjects Following a Dietary Restriction Program

2014 ◽  
Vol 66 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Maria Luisa Mansego ◽  
Fermin Ignacio Milagro ◽  
Maria Angeles Zulet ◽  
José Alfredo Martinez
Keyword(s):  
Dna Methylation ◽  
Body Weight ◽  
Weight Reduction ◽  
Molecular Mechanisms ◽  
White Blood Cells ◽  
The Body ◽  
Mrna Levels ◽  
Bdnf Mrna ◽  
Body Weight Reduction ◽  
Obese Subjects

The objective of this study was to examine whether 7 SNPs previously associated with obesity-related traits that add or remove potential sites of DNA methylation are accompanied by differential DNA methylation and subsequently affect adiposity variables or body weight reduction in WBC from obese subjects under an energy-restricted program. Material and Methods: Anthropometric measurements were assessed in 47 volunteers recruited within the RESMENA study (Spain). At baseline, DNA from white blood cells was isolated and 7 obesity-related trait CpG-SNPs were genotyped by TaqMan-PCR. Then, methylation levels of CpG-SNP sites were quantified by MassArray® EpiTyper™ or MS-HRM approaches. Results: Differential DNA methylation levels were observed by genotypes in all of the CpG-SNPs analyzed. The FTO and BDNF methylation levels were further correlated with baseline body weight and, BDNF mRNA levels and body weight change, respectively. Moreover, the rs7359397 (SH2B1) was associated with the body weight, body mass index, and truncal fat mass reduction. Conclusions: Our results reveal the interaction of epigenetic and genetic variations in CpG-SNPs, especially in BDNF and SH2B1 genes, and how allele-specific methylation may contribute to elucidate the possible molecular mechanisms as these SNPs are affecting the decrease of mRNA levels and contributing to a lower body weight reduction. © 2014 S. Karger AG, Basel

Pterostilbene Ameliorates Nephropathy Injury in Streptozotocin-Induced Diabetic Rats

Pharmacology ◽  
2019 ◽  
Vol 104 (1-2) ◽  
pp. 71-80 ◽  
Author(s):  
Ying Zhang ◽  
Shaoyu Ren ◽  
Ying Ji ◽  
Yafeng Liang
Keyword(s):  
High Fat Diet ◽  
Nuclear Factor Κb ◽  
Diabetic Rats ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Tnf Α ◽  
Necrosis Factor ◽  
Different Doses

Background: Our study investigated the therapeutic role and potential mechanisms of pterostilbene (PS) in diabetic nephropathy (DN) rats. Methods: DN models were established by high-fat diet after streptozotocin injection. A total of 50 Sprague-Dawley rats were randomly divided into control, DN, PS-treated groups (PS-H, PS-M, PS-L). PS was administered to rats by gavage for 8 weeks at 3 different doses (25, 10, and 5 mg/kg/day). The levels of oxidative stress activity (superoxide dismutase [SOD], malondialdehyde [MDA], glutathione peroxidase [GSH-PX]) and inflammatory factors (tumor necrosis factor [TNF]-α, interleukin (IL)-6, IL-1β, monocyte chemoattractant factor [MCP]-1) were detected by ­ELISA. TGF-β, Smad1, and fibronectin (FN) were measured through immunohistochemistry. The relative expressions of phospho-IκBα/IκBα, phospho-IκB kinases (IKK)β/IKKβ, phospho-nuclear factor-κB (NF-κB) p65/NF-κB p65 were detected by western blot. Results: Compared with DN group, the levels of TNF-α, IL-6, IL-1β, and MCP-1 were decreased in the PS-H group (p < 0.05). Meanwhile, the levels of SOD, MDA, GSH-PX improved in kidney and serum in PS-H groups (p< 0.05). PS also significantly decreased the level of phospho-NF-κB p65 and increased the levels of phospho- IKKβ and phospho-Iκ-Bα (p < 0.05). The results showed that PS treatment decreased TGF-β, Smad1, and FN expressions. Conclusion: PS had potential therapeutic effects on DN, which may be related to the regulation of NF-κB pathway.

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