scholarly journals Farrerol ameliorates diabetic hepatopathy in rat model of type 2 diabetes mellitus via modulation of oxidativeinflammatory stress

2020 ◽  
Vol 19 (1) ◽  
pp. 71-76
Author(s):  
Li Dong ◽  
Lixia Yang ◽  
Fengsui Liu ◽  
Haitao Zhan ◽  
Xinwei Chen

Purpose: To investigate the effect of farrerol on diabetic hepatopathy in a rat model of type 2 diabetes mellitus (T2DM).Methods: Adult male Wistar rats (n = 40) were randomly assigned to four groups of ten rats each: normal control, diabetic control, farrerol control and treatment groups. With the exception of normal control and farrerol control groups, the rats were fed high-fat diet (HFD) for four weeks, and thereafter injected streptozotocin (STZ) at a dose of 30 mg/kg body weight intraperitoneally (i.p.) for induction of T2DM. Rats in farrerol control and treatment groups received 50 mg/kg farrerol orally/day. Serum levels of triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein  cholesterol (HDL-C) and lowdensity lipoprotein cholesterol (LDL-C) were determined. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were assessed in liver homogenate while mRNA and protein expressions of glucose transporter 2 (GLUT2) were assayed in liver using real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also determined using qRT-PCR.Results: Diabetes mellitus (DM) led to significant reductions in rat body weight and SOD activity, while increasing fasting blood glucose (FBG) and MDA levels (p < 0.05). However, treatment with farrerol significantly reversed the effect of DM on these parameters (p < 0.05). The mRNA expressions of TNF-α and IL-1β were significantly higher in diabetic control group than in normal control group, but were significantly reduced after farrerol treatment (p < 0.05). Treatment with farrerol also significantly reversed the effect of DM on rat lipid profile (p < 0.05). The expression of GLUT2 protein was significantly downregulated in the liver of diabetic control rats, when compared with normal control rats, but was significantly upregulated after treatment with farrerol (p < 0.05).Conclusion: The results of this study show that farrerol alleviates STZ-induced hyperglycemia and dyslipidemia via reduction in oxidative stress and inflammation, and upregulation of GLUT2 protein expression. Thus, farrerol has antidiabetic and hepatoprotective potentials for clinical use in  humans. Keywords: Diabetes mellitus, Dyslipidemia, Farrerol, Hepatopathy, High-fat diet

Author(s):  
L. C. Chuku ◽  
N. C. Chinaka

The influenceof antioxidant supplementation on high fat diet-streptozotocin (HFD-STZ) induced type 2 diabetes mellitus in Wistar albino rats was investigated. Appropriate (RDA) proportions of some antioxidant rich substances which includes; vitamins (A, B3, B6, B12, C and E), minerals (calcium, selenium, chromium, magnesium, potassium and zinc), α-lipoic acid, cinnamon powder, curcumin (Meriva®), cordyceps, resveratrol, quercetin, D-ribose-L-cysteine were pulled together in corn oil and stored at 4°C for use. Serum glutathione (GSH) and malondialdehyde (MDA) levels, as well as activities of antioxidant enzymes: superoxide dismutases (SOD), catalase (CAT), glutathione-s-transferase (GST), glutathione peroxidise (GPx) and glutathione reductase (GR) were measured using standard methods. Data analysis was done with SPSS version 20.0 and significant level was set at P≤0.05. Results of in vitro oxidative stress indices and antioxidant enzyme activity indicate that after 4 weeks of treatment, there was no significant change (p≥0.05) in serum FBS levels of treated groups compared to the normal control group, but there was a significant decrease (p≤0.05) after 8 and 12 weeks of treatment when compared to the diabetic control group. There was no significant difference (p≥0.05) in the activities of antioxidant enzymes when compared to the normal control group, while in the diabetic control there was significant increase (p≤0.05) compared to the other groups. The results after 4, 8 and 12 weeks of treatment showed a significant increase (p≤0.05) in serum GSH level of normal and treated groups compared to diabetic control group, whereas there was a significant decline (p≤0.05) in serum MDA level of treated and normal control groups when compared to diabetic control. The results therefore suggest that the supplement may possess significant (p≤0.05) free radical scavenging potentials which could be beneficial to health.


2020 ◽  
Vol 21 (5) ◽  
pp. 1870
Author(s):  
Do Yeon Kim ◽  
Sang Ryong Kim ◽  
Un Ju Jung

To test the hypothesis that myricitrin (MYR) improves type 2 diabetes, we examined the effect of MYR on hyperglycemia, glucose intolerance, hepatic steatosis, and inflammation in high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetic mice. Male C57BL/6J mice were randomly divided into three groups: non-diabetic, diabetic control, and MYR (0.005%, w/w)-supplemented diabetic groups. Diabetes was induced by HFD and STZ, and MYR was administered orally for 5 weeks. Myricitrin exerted no significant effects on food intake, body weight, fat weight, or plasma lipids levels. However, MYR significantly decreased fasting blood glucose levels, improved glucose intolerance, and increased pancreatic β-cell mass compared to the diabetic control group. Myricitrin administration also markedly increased glucokinase mRNA expression and activity as well as lowered glucose-6-phosphatase and phosphoenolpyruvate carboxykinase mRNA expression and activity in the liver. In addition, liver weight, hepatic triglyceride content, and lipid droplet accumulation were markedly decreased following MYR administration. These changes were seemingly attributable to the suppression of the hepatic lipogenic enzymes—fatty acid synthase and phosphatidate phosphohydrolase. Myricitrin also significantly lowered plasma MCP-1 and TNF-α levels and the mRNA expression of hepatic pro-inflammatory genes. These results suggest that MYR has anti-diabetic potential.


Author(s):  
Hui-Li Lin ◽  
Pei-Wen Cheng ◽  
Yi-Chen Tu ◽  
Bor-Chun Yeh ◽  
Bin-Nan Wu ◽  
...  

Abstract Objectives Eugenosedin-A (Eu-A), an adrenergic and serotonergic antagonist, is known to have anti-metabolic syndrome effects. In this study, we evaluated its protective effects against diabetes mellitus (DM) in spontaneous hypertensive rats (SHR) and compared it with two anti-diabetes medications, glibenclamide (Gli) and pioglitazone (Pio). Methods We divided 10-week-old SHRs into five groups: a control group fed a normal diet; an untreated DM group induced by injecting the SHRs with STZ/NA and feeding them a high-fat diet (HFD); and three treated groups (after giving STZ/NA and HFD) gavage given with Eu-A, Gli or Pio (5 mg/kg per day) for 4 weeks. Key findings The untreated DM group weighed less and had hyperglycaemia, hypoinsulinemia and hyperlipidemia. They were also found to have aberrant glucose-dependent insulin pathways, glucose metabolism and lipid synthesis proteins, while the controls did not. Eu-A, Gli and Pio ameliorated the above biochemical parameters in the treatment groups. Eu-A and Pio, but not Gli, improved hypertension and tachycardia. Conclusions Taken together, Eu-A ameliorated DM, hypertension and tachycardia by improving glucose, lipid homeostasis and anti-adrenergic, serotonergic activities. We concluded that Eu-A could be used in the development of an effective agent for controlling DM and its complications.


2018 ◽  
Vol 19 (9) ◽  
pp. 2706 ◽  
Author(s):  
Cristina Sena ◽  
Maria Cipriano ◽  
Maria Botelho ◽  
Raquel Seiça

Prevention of hepatic fat accumulation may be an important approach for liver diseases due to the increased relevance of hepatic steatosis in this field. This study was conducted to investigate the effects of the antioxidant α-lipoic acid (α-LA) on hepatic steatosis, hepatocellular function, and oxidative stress in a model of type 2 diabetes fed with a high fat diet (HFD). Goto-Kakizaki rats were randomly divided into four groups. The first group received only a standard rat diet (control GK) including groups 2 (HFD), 3 (vehicle group), and 4 (α-LA group), which were given HFD, ad libitum during three months. Wistar rats are the non-diabetic control group. Carbohydrate and lipid metabolism, liver function, plasma and liver tissue malondialdehyde (MDA), liver GSH, tumor necrosis factor-α (TNF-α) and nuclear factor E2 (erythroid-derived 2)-related factor-2 (Nrf2) levels were assessed in the different groups. Liver function was assessed using quantitative hepatobiliary scintigraphy, serum aspartate, and alanine aminotransferases (AST, ALT), alkaline phosphatase, gamma-glutamyltranspeptidase, and bilirubin levels. Histopathologically steatosis and fibrosis were evaluated. Type 2 diabetic animals fed with HFD showed a marked hepatic steatosis and a diminished hepatic extraction fraction and both were fully prevented with α-LA. Plasma and liver tissue MDA and hepatic TNF-α levels were significantly higher in the HFD group when compared with the control group and significantly lower in the α-LA group. Systemic and hepatic cholesterol, triglycerides, and serum uric acid levels were higher in hyperlipidemic GK rats and fully prevented with α-LA. In addition, nuclear Nrf2 activity was significantly diminished in GK rats and significantly augmented after α-LA treatment. In conclusion, α-LA strikingly ameliorates steatosis in this animal model of diabetes fed with HFD by decrementing the inflammatory marker TNF-α and reducing oxidative stress. α-LA might be considered a useful therapeutic tool to prevent hepatic steatosis by incrementing antioxidant defense systems through Nrf2 and consequently decreasing oxidative stress and inflammation in type 2 diabetes.


Author(s):  
O. N. Briggs ◽  
K. N. Elechi-Amadi ◽  
F. C. Ezeiruaku ◽  
R. E. Teme

The scourge of diabetes has led to an increase in the use of complementary and alternative medicine. The lack of regulation and control leads to the indiscriminate use of these herbals, with potential risk to patients. Aim: This study evaluates the lipidaemic and hepatic status of type 2 diabetic rats treated with the polyherbal capsule glucoblock. Methodology: A total of 35 male Wistar albino rats weighing between 120-220 g were used for this study. The rats were placed on high fat diet and diabetes was induced by a single intraperitoneal injection of freshly prepared streptozotocin (STZ) (45 mg/kg body wt). Fasting plasma glucose (FPG) was determined using the glucose oxidase method. Total Cholesterol (TC), Triglyceride (TG) and High Density Lipoprotein Cholesterol (HDL-C) were determined using enzymatic methods. Low Density Lipoprotein Cholesterol (LDL-C) was calculated using the Friedewald’s equation. Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) were determined using Reitman-Frankel method, while alkaline phosphatase (ALP) was determined using the colorimetric phenolphthalein method. Liver sections were stained using haematoxylin and eosin (H&E) staining technique, and phytochemical analysis was also done on the herbal capsule. Results: The results show no significant differences in TC levels in all groups compared to the negative control. TG level was significantly higher in the diabetic control group when compared to the negative control. TG level in the singular treatment groups were significantly lower, but the combination group (glibenclamide + glucoblock) showed no significant difference compared to the diabetic control. The negative control had significantly higher HDL-C compared to the diabetic control and treatment groups. There were no significant differences in HDL-C levels in all the treatment groups, when compared to the diabetic control. The negative control had significantly lower LDL-C compared to the diabetic control and treatment groups. There were no significant differences in LDL-C levels in all the treatment groups, when compared to the diabetic control. ALT, AST and ALP levels were significantly higher in the diabetic control, but was significantly reduced to normal levels by the treatments. Liver sections of the negative control showed normal histoarchitecture. The diabetic control showed inflammation and fatty deposition. The treatment groups showed a nearly normal histoarchitecture, with fatty deposits. Conclusion: High fat diet in combination with a sub-diabetic dose of streptozotocin produced significant diabetes in the Wistar rats with dyslipidaemia and elevated liver enzyme levels. The anti-diabetic treatments, glibenclamide and glucoblock did not correct the dyslipidaema caused by diabetes. However, the treatments had equipotent hepatoprotective effect and restored liver enzyme levels to normal as well as improving liver histology.


2021 ◽  
Author(s):  
Xuetao Sun ◽  
Sara S Nunes

People with diabetes mellitus (DM) are at an increased risk for myocardial infarction (MI) than age matched people without DM. However, assays for pre-clinical therapy are performed in animal models of ischemia that lack the co-morbid conditions present in patients with MI, such as DM. This contributes to the failure to translate pre-clinical trials results to the clinic. Thus, to increase the clinical relevance of xenograft studies in pre-clinical models, it is important to have a DM model in animals that are immunodeficient. Here, we developed a type 2 diabetes mellitus (T2D) model in nude athymic rats using high-fat diet and streptozotocin (HFD-STZ). Nude athymic rats were randomized into a control group (normal chow) or a HFD (45% fat, 20% protein and 35% carbohydrate)-STZ group. STZ (35 mg/kg i.v.) or vehicle was administered 8 weeks after HFD feeding started. Assessments were done longitudinally and at week 9 (endpoint). The HFD-STZ group showed mild hyperglycemia pre STZ administration (7.7 ± 0.3 mM vs 5.8 ± 0.2 mM in control) by week 8. In addition, plasma insulin levels were increased and the HOMA index was 2.5-times higher in the HFD-STZ. The HFD-STZ group showed increased fasting (147%) triglycerides. After STZ-administration, blood glucose levels increased substantially (23.6 ± 1.4 mM vs 5.5 ± 0.3 mM in control). The HFD-STZ treated animals also showed increased left ventricular wall thickness, cardiac hypertrophy and fibrosis, reduced cardiac function compared to normal chow control. In line with the HFD-STZ model in immunocompetent rats, the HFD-STZ treatment of athymic rats recapitulates key features of T2D, including aspects of established clinical diabetic cardiomyopathy and should be suitable for xenograft studies in the context of T2D.


Author(s):  
A. T. Nnadiukwu ◽  
C. C. Monago-Ighorodje ◽  
L. C. Chuku

Aim: This study was carried out to evaluate the effect of ethanol extract of Aju Mbaise herbal mixture on some haematological indices of diabetic Wistar albino rats. Sample: Packed cell volume (PCV) and haemoglobin (Hb) concentration was estimated in diabetic rats treated with ethanol extract of Aju Mbaise herbal mixture. Study Design: In the course of the experiment, fifty-four (54) rats with initial weight range of 30 – 40 g were grouped into 6 of 9 rats per group. The first group served as the normal control (NC) while the remaining five groups were induced with diabetes type 2 using high-fat diet for 8 weeks and streptozotocin at 35 mg/kg body weight. Group II served as the diabetic control while the remaining groups (III, IV, V & VI) were treated with metformin and three different concentrations of the plant extract respectively. Place and Duration of Study: The study was carried out in the Animal house of the Department of Pharmacology, Faculty of Basic Clinical Sciences, University of Port Harcourt, between July 2018 and January 2019. Methodology: The haemoglobin and packed cell volume were estimated after 4th, 8th and 12th week of treatment using MINDRAY Auto-Haematology analyzer. Results: From the results obtained, it was observed that the diabetic control group has a PCV and haemoglobin concentration that is significantly (P<.05) lower when compared to that of the normal control group and the other treated groups. Conclusion: The study has shown that Aju Mbaise herbal mixture is a haematopoietic agent as it had the tendency to synthesize blood cells.


2021 ◽  
Author(s):  
nannan liu ◽  
Xuefeng Chen ◽  
Juanna Song ◽  
Mengyin Chen ◽  
Pin Gong ◽  
...  

This study evaluated the hypoglycemic effect of Auricularia auricula polysaccharides (AAPs) on streptozotocin-induced type 2 diabetes mellitus (T2DM) male mice (C57BL/6J) using a metabolomic approach based on ultrahigh-performance liquid chromatography–Q...


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