scholarly journals Effect of the Total Extract of Averrhoacarambola (Oxalidaceae) Root on the Expression Levels of TLR4 and NF-κB in Streptozotocin-Induced Diabetic Mice

2015 ◽  
Vol 36 (6) ◽  
pp. 2307-2316 ◽  
Author(s):  
Xiaohui Xu ◽  
Tao Liang ◽  
Xing Lin ◽  
Qingwei Wen ◽  
Xingmei Liang ◽  
...  

Background: Averrhoacarambola L., which is a folk medicine used in diabetes mellitus (DM) in ancient China, has been reported to have anti-diabetic efficacy. Aims: The aim of this study was to evaluate the hypoglycemic effect of the extract of Averrhoacarambola L. root (EACR) on the regulation of the Toll-like receptor 4 (TLR4)-Nuclear-factor kappa B (NF-κB) pathway in B) pathway in streptozotocin (STZ)-induced diabetic mice. Methods: the mice were injected with STZ (120 mg/kg body weight) via a tail vein. After 72 h, the mice with FBG = 11.1 mmol/L were confirmed as having diabetes. Subsequently, the mice were treated intragastrically with EACR (300, 600, 1200 mg/kg body weight/d) and metformin (320 mg/kg body weight/d) for 14 days. Results: As a result the serum fasting blood glucose (FBG), interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) levels were decreased following EACR administration. Immunohistochemical analysis revealed that the pancreatic tissue expression levels of TLR4 and NF-κB were downregulated after EACR administration. EACR suppressed pancreatic mRNA expression level of TLR4 and blocked the downstream NF-κB pathway in the pancreas. According to Western blot analysis EACR suppressed pancreatic TLR4 and NF-κB protein expression levels. Histopathological examination of the pancreas showed that STZ-induced pancreas lesions were alleviated by the EACR treatment. Conclusion: These findings suggest that the modulation of the IL-6 and TNF-a inflammatory cytokines and the suppression of the TLR4-NF-κB pathway are most likely involved in the anti-hyperglycemic effect of EACR in STZ-induced diabetic mice.

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256140
Author(s):  
Kongphop Parunyakul ◽  
Krittika Srisuksai ◽  
Sawanya Charoenlappanit ◽  
Narumon Phaonakrop ◽  
Sittiruk Roytrakul ◽  
...  

Type 1 Diabetes mellitus (T1DM) is associated with abnormal liver function, but the exact mechanism is unclear. Cordycepin improves hepatic metabolic pathways leading to recovery from liver damage. We investigated the effects of cordycepin in streptozotocin-induced T1DM mice via the expression of liver proteins. Twenty-four mice were divided into four equal groups: normal (N), normal mice treated with cordycepin (N+COR), diabetic mice (DM), and diabetic mice treated with cordycepin (DM+COR). Mice in each treatment group were intraperitoneally injection of cordycepin at dose 24 mg/kg for 14 consecutive days. Body weight, blood glucose, and the tricarboxylic acid cycle intermediates were measured. Liver tissue protein profiling was performed using shotgun proteomics, while protein function and protein-protein interaction were predicted using PANTHER and STITCH v.5.0 software, respectively. No significant difference was observed in fasting blood glucose levels between DM and DM+COR for all time intervals. However, a significant decrease in final body weight, food intake, and water intake in DM+COR was found. Hepatic oxaloacetate and citrate levels were significantly increased in DM+COR compared to DM. Furthermore, 11 and 36 proteins were only expressed by the N+COR and DM+COR groups, respectively. Three unique proteins in DM+COR, namely, Nfat3, Flcn, and Psma3 were correlated with the production of ATP, AMPK signaling pathway, and ubiquitin proteasome system (UPS), respectively. Interestingly, a protein detected in N+COR and DM+COR (Gli3) was linked with the insulin signaling pathway. In conclusion, cordycepin might help in preventing hepatic metabolism by regulating the expression of energy-related protein and UPS to maintain cell survival. Further work on predicting the performance of metabolic mechanisms regarding the therapeutic applications of cordycepin will be performed in future.


Author(s):  
Syed Akif Raza Kazmi ◽  
Muhammad Zahid Qureshi ◽  
Sadia . ◽  
Saleh S Alhewairini ◽  
Shaukat Ali ◽  
...  

Diabetes is a life-threatening disease and chronic diabetes affects the parts of the body including the liver, kidney and pancreas. The root cause of diabetes is mainly associated with oxidative stress produced by reactive oxygen species. The minocycline is a polyphenolic drug with excellent antioxidant activities. The objective of the present study was to investigate the antidiabetic potential of minocycline modified silver nanoparticles (Mino/AgNPs) against alloxan-induced diabetic mice. The Mino/AgNPs were synthesized using minocycline as reducing and stabilizing agents. UV-vis, FTIR, X-ray diffraction (XRD) and transmission electron microscopy (TEM) were applied for the characterization of Mino/AgNPs. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay was conducted to determine the antioxidant potential of newly synthesized Mino/AgNPs. The results revealed that the Mino/AgNPs showed higher radical scavenging activity (IC50 = 19.7 µg/mL) as compared to the minocycline (IC50 = 26.0 µg/mL) and ascorbic acid (IC50 = 25.2 µg/mL). Further, the Mino/AgNPs were successfully employed to examine their antidiabetic potential against Alloxan-induced diabetic mice. Hematological results showed that the mice treated with Mino/AgNPs demonstrated a significant decrease in fasting blood glucose level and lipid profile as compared to the diabetic group. The histopathological examination confirmed that the diabetic mice treated with Mino/AgNPs showed significant recovery and revival of histo-morphology of kidney, central vein of liver and islet cells of the pancreas compared to the diabetic mice. Hence Mino/AgNPs have good antidiabetic potential and could be an appropriate nanomedicine to prevent the development of diabetes.


2018 ◽  
Vol 46 (7) ◽  
pp. 2883-2897 ◽  
Author(s):  
Gaofeng Song ◽  
Pengxun Han ◽  
Huili Sun ◽  
Mumin Shao ◽  
Xuewen Yu ◽  
...  

Objective The aim of this study was to investigate the renoprotective effects and molecular mechanisms of astragaloside IV (AS-IV) in streptozotocin (STZ)-induced diabetic mice. Methods Male C57BL/6 mice were injected intraperitoneally with STZ at 200 mg/kg body weight. AS-IV was administered for 8 consecutive weeks, beginning 1 week after STZ injection. Body weight, 24-hour urinary albumin excretion, and fasting blood glucose were measured. Kidney tissues were examined by histopathological analyses. Total levels and phosphorylation of mitogen-activated protein kinase 1/2 (MEK1/2), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and ribosomal S6 kinase 2 (RSK2) were determined by Western blotting analysis. Results AS-IV treatment significantly reduced albuminuria and serum creatinine levels, ameliorated mesangial matrix expansion and greater foot process width, and decreased the levels of urinary N-acetyl-beta-D-glucosaminidase, neutrophil gelatinase-associated lipocalin, and transforming growth factor-beta 1 in STZ-induced diabetic mice. AS-IV also inhibited renal cortical phosphorylation of MEK1/2, ERK1/2 and RSK2. Conclusion Our results suggest that AS-IV attenuates renal injury in STZ-induced diabetic mice. This effect might be partially associated with inhibition of the activation of the MEK1/2-ERK1/2-RSK2 signaling pathway.


2015 ◽  
Vol 8 (2) ◽  
pp. 103-111 ◽  
Author(s):  
Ankita Bhattacharjee ◽  
Shilpi Kumari Prasad ◽  
Swagata Pal ◽  
Bithin Maji ◽  
Alak Kumar Syamal ◽  
...  

Abstract Although cigarette smoking is associated with insulin resistance and an increased risk for type 2 diabetes, few studies have examined the effect of nicotine on the adult endocrine pancreas. In this study, male Wister rats were treated with nicotine (3 mg/kg body weight/day) with or without supplementation of folic acid (36 μg/kg body weight/day) or vitamin B12 (0.63 μg/kg body weight/day) alone or in combination. Fasting blood glucose, insulin and HBA1C level and different oxidative and anti-oxidative stress parameters were measured and pancreatic tissue sections were stained with eosin-haematoxylene. Data were analysed by nonparametric statistics. The results revealed that nicotine induced prediabetes condition with subsequent damage to pancreatic islets in rats. Nicotine also caused oxidative stress in pancreatic tissue as evidenced by increased nitric oxide and malondialdehyde level and decreased superoxide dismutase, catalase and reduced glutathione level. Compared to vitamin B12 supplementation, folic acid blunted the nicotine-induced toxicity in pancreatic islets with higher efficacy. Further, folic acid and vitamin B12 in combination were able to confer significant protection on pancreatic islets against nicotine induced toxicity. These results suggest that supplementation of folic acid and vitamin B12 in combination may be a possible strategy of detoxification against nicotine-induced toxicity in pancreatic islets of the rat.


2020 ◽  
Author(s):  
Shahrear Biozid ◽  
Mohammad Nazmul Alam ◽  
Jainul Abeden ◽  
Faruk ◽  
Ahmad Ibtehaz Chowdhury ◽  
...  

Objective: To evaluate the anti-diabetic and anti-diarrheal activity of methanol extract of Flemingia stricta Roxb. (Fabaceae) leaf.Methods: In anti-diabetic study, the extract was administered to alloxan-induce diabetic mice at two concentrations (200mg/kg and 400mg/kg body weight) for acute (12 hours) and prolong treatments (15 days) and blood glucose levels (Blood glucose level) of diabetic mice were monitored at intervals of hours and days throughout the duration of treatment. Antidiarrheal test was conducted by castor oil induced diarrhea and enteropooling as well as intestinal motility in mice at three different concentration (100mg/kg, 200mg/kg and 400mg/kg body weight).Results: Treatment of alloxan induce diabetic mice with the extract caused a significant reduction in fasting blood glucose level of the diabetic mice both in acute (12 hours) and prolong treatment (15 days) and it was determined that the extract at both concentration (200mg/kg and 400mg/kg) showed the significant (P<0.05) hypoglycemic effect in comparison to the standard drug Metformin (10mg/kg). In the case of castor oil induced diarrheal test, enteropooling test and gastrointestinal motility test, the extract of F. stricta at 100mg/kg, 200mg/kg and 400mg/kg has given significant effect (P<0.05) in comparing to standard drug Loperamide (5mg/kg). Conclusion: These result suggested that the methanol extract of F. stricta Roxb. possess promising anti-diabetic effect on alloxan-induced mice and significant antidiarrheal effect on castor oil induced diarrheal mice.


2017 ◽  
Vol 16 (10) ◽  
pp. 2425-2430
Author(s):  
Huma Aslam ◽  
Arif-ullah Khan ◽  
Najeeb-ur- Rehman ◽  
Fawad Ali ◽  
Humaira Nadeem ◽  
...  

Purpose: To investigate Heliotropium strigosum whole plant extract for its potential to reduce the blood glucose level of alloxan-induced diabetic mice.Methods: Preliminary phytochemical analysis was carried out using standard  procedures. Diabetes was induced in Balb/c mice by injecting alloxan (200 mg/kg i.p.). The crude methanol extract of Heliotropium strigosum (Hs.Cr, 30, 100 and 300 mg/kg doses) was administered daily to alloxan-induced diabetic mice for 15 days and its effect on fasting blood glucose levels, body weight and oral glucose tolerancewas evaluated. Two control groups (non-diabetic control and diabetic control)  received normal saline (0.2 ml). Metformin (500 mg/kg) was used as reference standard.Results: Heliotropium strigosum showed positive for the presence of alkaloids, tannins and flavonoids. The extract (30, 100 and 300 mg/kg) caused significant reduction in the fasting blood glucose level of alloxan-induced diabetic mice on days 5, 10 and 15 compared to diabetic control (p < 0.001). In this regard, the  anti-hyperglycemic effect compared to the reference (metformin). The extract also timedependently decreased the body weight of the treated animals as well as improved tolerance of the oral glucose overload.Conclusion: These results indicate that Heliotropium strigosum possesses  anti-hyperglycemic effect, reduces body weight and enhances the tolerance of  glucose overload in mice. Further studies are therefore required to determine its  feasiilty as an alternate herbal medicine in the management of diabetes in humans.Keywords: Heliotropium strigosum, Anti-hyperglycemic, Alloxan-induced diabetic mice, Blood glucose, Oral glucose tolerance, Body weight


Author(s):  
Karima Sayah ◽  
Hanae Naceiri Mrabti ◽  
Badia Belarj ◽  
Faouzi Kichou ◽  
Yahia Cherrah ◽  
...  

AbstractObjectivesCistus salviifoluis L. is a shrub from Cistaceae family used in many traditional medicines for the treatment of various diseases including diabetes mellitus. The aim of this study was to evaluate the in vivo antidiabetic potential of the aerial parts aqueous extract of Cistus salviifolius L. (CSA).MethodsExperimental diabetes was induced in adult male mice by intra-peritoneal injection of Streptozotocin-nicotinamide (STZ-NC). CSA at a dose of 500 mg/kg was administered daily to the diabetic mice for four weeks. The effect of the extract on hyperglycemia, body weight, serum total cholesterol, triglycerides, hepatic and renal functional markers were determined. Histopathological examination of the mice pancreas was also performed. The diabetic animals treated with CSA were compared with animals treated by the standard drug metformin.ResultsTreatment with CSA showed a significant reduction in blood glucose, total triglycerides and creatinine levels and prevented the reduction of body weight caused by diabetes. Furthermore, histopathological analysis of the mice pancreas showed that the group treated with CSA reduced damage induced by STZ-NC on islets of Langerhans cells when compared to the diabetic control.ConclusionsThe results suggest that the aqueous extract of Moroccan C. salviifolius L. possesses beneficial effect on treatment of diabetes.


2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Yanyan Song ◽  
Wei Liu ◽  
Ke Tang ◽  
Junting Zang ◽  
Dong Li ◽  
...  

Renal interstitial fibrosis is considered to be the typical manifestation of diabetic nephropathy (DN). Mangiferin has shown positive effect on the prevention or treatment of diabetes and its complications. The aim of this study was to explore the inhibitive effect and mechanism of mangiferin on renal interstitial fibrosis in diabetic mice. Streptozotocin- (STZ-) induced diabetic mice were treated with mangiferin (15, 30, and 60 mg/kg/d) for 4 weeks. The morphology of kidneys was observed by Masson’s trichrome staining, and the biochemical parameters (fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), blood urea nitrogen (BUN), serum creatinine (SCr), and urine protein) were determined by kits. In addition, the levels of inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin- (IL-) 6, and IL-1β), antioxidant enzymes (SOD, CAT, and GSH-Px), MDA, and ROS were assessed. Furthermore, the expressions of fibronectin (FN), collagen I (Col I), and α-SMA were measured by immunohistochemistry. Regulations of TGF-β1 and the PTEN/PI3K/Akt pathway were detected by Western blotting. Treatment with mangiferin significantly ameliorated renal dysfunction in diabetic mice, as evidenced by the increase in body weight and decreases in FBG, TG, TC, BUN, SCr, urine protein, and the kidney to body weight ratio (KW/BW). Furthermore, mangiferin treatment prevented renal interstitial fibrosis evidenced by decreases in the positive expression of FN, Col I, and α-SMA, in comparison with morphological changes in the renal tissue. Meanwhile, mangiferin increased antioxidant enzymes, reduced the TNF-α, IL-6, and IL-1β, as well as MDA and ROS. Additionally, mangiferin administration also downregulated TGF-β1, upregulated PTEN, and decreased the phosphorylation of both PI3K and Akt. These findings demonstrate that mangiferin may reduce inflammation and oxidative stress in DN, thereby inhibiting the renal interstitial fibrosis by reducing the TGF-β1-mediated elevation of Col I, FN, and α-SMA through the PTEN/PI3K/Akt pathway.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Nancy R Webb ◽  
Xia Li ◽  
Kathy Forrest ◽  
William Bailey ◽  
Boris B Boyanovsky ◽  
...  

Introduction: Of the 10 secretory phospholipase A 2 (sPLA 2 ) enzymes expressed in humans, Group X (GX) sPLA 2 is the most potent in hydrolyzing phospholipids on cell membranes. In addition to its lipolytic activity, GX sPLA 2 is also a high affinity ligand for the M-type sPLA 2 receptor. Although numerous studies have implicated GX sPLA 2 in important biological processes in vitro , data from studies in vivo are lacking. To elucidate the physiological functions of this enzyme we recently developed C57BL/6 mice with targeted deletion of the GX sPLA 2 gene. Results : Analysis by real time RT-PCR showed that GX sPLA 2 mRNA is widely distributed in mouse tissues, with highest expression in intestine, testes, brain, thymus, spleen, fat, lung, and heart. Unlike some of the other members of the sPLA 2 family, tissue expression of GX sPLA 2 was not highly upregulated in mice injected with lipopolysaccharide. However, GX sPLA 2 was induced almost 5-fold in retroperitoneal fat of mice fed a high-fat (60 kcal%) diet for 17 weeks.Targeted disruption of GX sPLA 2 resulted in increased body weight in 1.5 year-old mice fed a normal laboratory diet (male GX sPLA 2 +/+ mice: 35.8±0.4 g; male GX sPLA 2 −/− mice: 45.033.2 g; p<0.05). The increase in body weight was associated with significantly increased percent body fat (GX sPLA 2 +/+ mice: 16.0±1.0%; GX sPLA 2 −/− mice: 19.6±1%; p<0.05), increased adipocyte size (GX sPLA 2 +/+ mice: 1300±26 um 2 GX sPLA 2 −/− mice: 2700±78 um 2 ; p<0.001), and decreased fasting plasma triglyceride levels (GX sPLA 2 +/+ mice: 46.3±4.9 mg/dl; GX sPLA 2 −/− mice: 33.8±2.9 mg/dl; p<0.05) at 3 months of age. Food consumption, fasting blood glucose, and plasma total cholesterol levels were not significantly different between GX sPLA 2 −/− and GX sPLA 2 +/+ mice. Compared to 3 month old GX sPLA 2 +/+ mice, the relative expression of IL-6 and F4/80 mRNAs in adipose tissue of age-matched GX sPLA 2 −/− mice was increased 9- and 4-fold, respectively, suggesting that the increased adiposity in GX sPLA 2 −/− mice was associated with an increase in the inflammatory profile of adipose tissue Conclusions: Our data points to a previously unrecognized role for Group X sPLA 2 in the development of obesity and associated adipose tissue inflammation.


2020 ◽  
Vol 10 (2) ◽  
pp. 129-139
Author(s):  
Uchenna Collins Abonyi ◽  
Moses A Omoiri ◽  
Peter A Akah

This study evaluated the anti-diabetic properties of the methanol extract and fractions of Dennettia tripetala leaves in alloxan diabetic rats. The crude  methanol extract (ME), n-hexane  (NF), ethyl acetate  (EAF), butanol  (BF) and water  (WF) fractions,  were tested for anti-diabetic activity in  alloxan-induced diabetic mice. The extracts and its fractions were screened for phytochemical constituents. Glibenclamide was used as the standard anti-diabetic treatment   Fasting blood glucose (FBG) levels were determined using a glucometer.  Lipid profile parameters were also assessed.  Histopathological examination of the pancreas was performed. The presence of glycosides, saponins, reducing sugars, fats and oil, alkaloids, carbohydrates, flavonoids, proteins and tannins were detected in ME, and the fractions. Treatment of the rats with the extract and its fractions reduced FBG levels significantly (p < 0.05) within 10 hours of acute treatment and 14 days short term treatment.  The highest reduction was by the crude extract,( ME 500 mg/kg) with percentage reduction of 62.89 %. The study revealed  significant (p < 0.05) reductions in serum triglyceride, serum cholesterol and LDL levels  by the extracts and its fractions  while a significant (p <  0.05) increase  in HDL levels was evident .  The effect of the extract and fractions on body weight indicated a moderate weight gain. Treatment with high dose of the extract and fractions (500 mg/kg) resulted in marked rejuvenation of the pancreatic β cells. The results of this study suggest that the leaves of Dennetia tripetala are endowed with potent anti-diabetic and antilipidemic properties.   Keywords: Dennetia tripetala, Antidiabetic, Alloxan, Lipid profile, Histopathplogy.


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