In vivo antioxidant and anti-inflammatory effects of soluble dietary fiber Konjac glucomannan in type-2 diabetic rats

Abstract Context: Withania coagulans (Stocks) Dunal fruits are used in the therapeutics of several ailments due to possessing of potent phytoconstituents which is also used traditionally for curing the diabetes. Objective: The present study was assessing the amelioration potential of the phytochemicals of an ethanol fruit extract of Withania coagulans (Stocks) Dunal in the HOMA (Homeostatic model assessment) indices and pancreatic endocrinal tissues by inhibition of DPP-4 and antioxidants activities.Material and methods: The identification of phytoconstituents of the test extract was performed by LCMS. Further, assessments of in-vitro, in-vivo and in-silico were achieved by following standard methods. In-vivo studies were conducted on type-2 diabetic ratsResults: The chosen extract inhibited DPP-4 activity by 63.2% in an in vitro assay as well as significantly inhibit serum DPP-4 levels. Accordingly, the administration of the ethanol fruit extract resulted in a significant (𝑃≤ 0.001) alterations in the lipid profile, antioxidant levels, and HOMA indices. Moreover, pancreatic endocrinal tissues (islet of Langerhans) appeared to have the restoration of normal histoarchitecture as evidenced by increased cellular mass. Molecular docking (Protein - ligands) of identified phytoconstituents with DPP-4 (target enzyme) shown incredibly low binding energy (Kcal/mol) as required for ideal interactions. ADMET analysis of the pharmacokinetics of the identified phytoconstituents indicated an ideal profile as per Lipinski laws. Conclusion: It can be concluded that the phytoconstituents of an ethanol fruit extract of Withania coagulans have the potential to inhibit DPP-4 which result in improved glucose homeostasis and restoration of pancreatic endocrinal tissues in type-2 diabetic rats.

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Improvements in HOMA Indices and Pancreatic Endocrinal Tissues in Type -2 Diabetic Rats by DPP-4 Inhibition and Antioxidant Potential of an Ethanol Fruit Extract of Withania Coagulans

10.21203/rs.3.rs-69981/v1 ◽

2020 ◽

Author(s):

Heera Ram ◽

Pramod Kumar ◽

Ashok Purohit ◽

Priya Kashyap ◽

Suresh Kumar ◽

...

Keyword(s):

Diabetic Rats ◽

Model Assessment ◽

Fruit Extract ◽

Withania Coagulans ◽

Homeostatic Model Assessment ◽

Docking Protein ◽

Type 2 Diabetic

Abstract Context: Withania coagulans (Stocks) Dunal fruits are used in the therapeutics of several ailments due to possessing of potent phytoconstituents which is also used traditionally for curing the diabetes. Objective: The present study was assessing the amelioration potential of the phytochemicals of an ethanol fruit extract of Withania coagulans (Stocks) Dunal in the HOMA (Homeostatic model assessment) indices and pancreatic endocrinal tissues by inhibition of DPP-4 and antioxidants activities.Material and methods: The identification of phytoconstituents of phytochemicals of the test extract was performed by LCMS. Further, assessments of in-vitro, in-vivo and in-silico were achieved by following standard methods. In-vivo studies were conducted on type-2 diabetic ratsResults: The chosen extract inhibited DPP-4 activity by 63.2% in an in vitro assay. Accordingly, the administration of the ethanol fruit extract resulted in a significant (𝑃≤ 0.001) alterations in the lipid profile, antioxidant levels, and HOMA indices. Moreover, pancreatic endocrinal tissues (islet of Langerhans) appeared to have the restoration of normal histoarchitecture as evidenced by increased cellular mass. Molecular docking (Protein - ligands) of identified phytoconstituents with DPP-4 (target enzyme) shown incredibly low binding energy (Kcal/mol) as required for ideal interactions. ADMET analysis of the pharmacokinetics of the identified phytoconstituents indicated an ideal profile as per Lipinski laws. Conclusion: It can be concluded that the phytoconstituents of an ethanol fruit extract of Withania coagulans have the potential to inhibit DPP-4 which result in improved glucose homeostasis and restoration of pancreatic endocrinal tissues in type-2 diabetic rats.

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Antidiabetic, antihyperlipidemic and in vivo antioxidant potential of aqueous extract of Anogeissus latifolia bark in type 2 diabetic rats

Asian Pacific Journal of Tropical Disease ◽

10.1016/s2222-1808(12)60229-1 ◽

2012 ◽

Vol 2 ◽

pp. S596-S602 ◽

Cited By ~ 9

Author(s):

Subramaniam Ramachandran ◽

Koikaramparambil Robert Naveen ◽

Baskaran Rajinikanth ◽

Mohammad Akbar ◽

Aiyalu Rajasekaran

Keyword(s):

Aqueous Extract ◽

Diabetic Rats ◽

Antioxidant Potential ◽

Type 2 Diabetic

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Acute regulation of pancreatic islet microcirculation and glycaemia by telmisartan and ramipril: discordant effects between normal and Type 2 diabetic rats

Clinical Science ◽

10.1042/cs20120635 ◽

2013 ◽

Vol 125 (9) ◽

pp. 433-438 ◽

Cited By ~ 3

Author(s):

Anna Olverling ◽

Zhen Huang ◽

Thomas Nyström ◽

Åke Sjöholm

Keyword(s):

Blood Flow ◽

Insulin Secretion ◽

Wistar Rats ◽

Serum Insulin ◽

Diabetic Rats ◽

Angiotensin Receptor ◽

Angiotensin Receptor Antagonist ◽

Type 2 Diabetic

Diabetic patients are often treated with an ACEi (angiotensin-converting enzyme inhibitor) or angiotensin receptor antagonist against hypertension or albuminuria. These drugs also have a positive impact on glucose tolerance, but the mechanism for this remains elusive. Hypothesizing a positive non-additive effect, we studied whether the angiotensin receptor antagonist telmisartan or the ACEi ramipril acutely influence insulin secretion and glycaemia in vivo in healthy and Type 2 diabetic rats through effects on islet blood perfusion. Telmisartan and ramipril were injected intravenously into anaesthetized non-diabetic Wistar rats or Type 2 diabetic GK (Goto–Kakizaki) rats. In non-diabetic Wistar rats, neither whole PBF (pancreatic blood flow) nor IBF (islet blood flow) were significantly influenced by telmisartan and ramipril, alone or in combination. Renal blood flow was enhanced significantly by telmisartan and ramipril when used in combination, whereas ABF (adrenal blood flow) was not affected by any of the drugs. Telmisartan and ramipril both significantly increased serum insulin levels, but did not influence glycaemia. In Type 2 diabetic GK rats, both whole PBF and IBF were significantly decreased by telmisartan and ramipril, but only when used in combination. Renal blood flow was enhanced significantly by telmisartan and ramipril alone, but not when used in combination, whereas ABF was not affected by any of the drugs. Telmisartan and ramipril both significantly decreased serum insulin levels, and non-additively elevated blood glucose levels. In conclusion, the present study suggests that a local pancreatic RAS (renin–angiotensin system), sensitive to acute administration of telmisartan and ramipril, controls pancreatic IBF and insulin secretion and thereby has an impact on glucose tolerance. Our findings indicate unexpected significant differences in the effects of these agents on islet microcirculation, in vivo insulin secretion and glycaemia between healthy and Type 2 diabetic rats.

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Arginase inhibition restores in vivo coronary microvascular function in type 2 diabetic rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00560.2010 ◽

2011 ◽

Vol 300 (4) ◽

pp. H1174-H1181 ◽

Cited By ~ 47

Author(s):

Julia Grönros ◽

Christian Jung ◽

Jon O. Lundberg ◽

Ruha Cerrato ◽

Claes-Göran Östenson ◽

...

Keyword(s):

Vascular Function ◽

Wistar Rats ◽

Diabetic Rats ◽

Microvascular Function ◽

Vascular Integrity ◽

Gk Rats ◽

Type 2 Diabetic ◽

Coronary Microvascular Function

Nitric oxide (NO) is crucial for maintaining normal endothelial function and vascular integrity. Increased arginase activity in diabetes might compete with NO synthase (NOS) for their common substrate arginine, resulting in diminished production of NO. The aim of this study was to evaluate coronary microvascular function in type 2 diabetic Goto-Kakizaki (GK) rats using in vivo coronary flow velocity reserve (CFVR) and the effect of arginase inhibition to restore vascular function. Different groups of GK and Wistar rats were given vehicle, the arginase inhibitor Nω-hydroxy-nor-l-arginine (nor-NOHA), l-arginine, and the NOS inhibitor NG-monomethyl -l-arginine (l-NMMA). GK rats had impaired CFVR compared with Wistar rats (1.31 ± 0.09 vs. 1.87 ± 0.05, P < 0.001). CFVR was restored by nor-NOHA treatment compared with vehicle in GK rats (1.71 ± 0.13 vs. 1.23 ± 0.12, P < 0.05) but remained unchanged in Wistar rats (1.88 ± 0.10 vs. 1.79 ± 0.16). The beneficial effect of nor-NOHA in GK rats was abolished after NOS inhibition. CFVR was not affected by arginine compared with vehicle. Arginase II expression was increased in the aorta and myocardium from GK rats compared with Wistar rats. Citrulline-to-ornithine and citrulline-to-arginine ratios measured in plasma increased significantly more in GK rats than in Wistar rats after nor-NOHA treatment, suggesting a shift of arginine utilization from arginase to NOS. In conclusion, coronary artery microvascular function is impaired in the type 2 diabetic GK rat. Treatment with nor-NOHA restores the microvascular function by a mechanism related to increased utilization of arginine by NOS and increased NO availability.

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Pioglitazone attenuates diabetic nephropathy through an anti-inflammatory mechanism in type 2 diabetic rats

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfn157 ◽

2008 ◽

Vol 23 (9) ◽

pp. 2750-2760 ◽

Cited By ~ 78

Author(s):

G. J. Ko ◽

Y. S. Kang ◽

S. Y. Han ◽

M. H. Lee ◽

H. K. Song ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Diabetic Rats ◽

Inflammatory Mechanism ◽

Anti Inflammatory ◽

Type 2 Diabetic

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In vivo multi-tissue efficacy of peroxisome proliferator-activated receptor-γ therapy on glucose and fatty acid metabolism in obese type 2 diabetic rats

Obesity ◽

10.1002/oby.20378 ◽

2013 ◽

Vol 21 (12) ◽

pp. 2522-2529 ◽

Cited By ~ 8

Author(s):

Samuel Nemanich ◽

Sudheer Rani ◽

Kooresh Shoghi

Keyword(s):

Fatty Acid ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Diabetic Rats ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Type 2 Diabetic

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Anti-inflammatory and insulin secretory activity in experimental type-2 diabetic rats treated orally with magnesium

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2017-0104 ◽

2018 ◽

Vol 29 (5) ◽

pp. 507-514 ◽

Cited By ~ 1

Author(s):

Abayomi Oluwatosin Ige ◽

Olanrewaju Amos Ajayi ◽

Eunice Olufunke Adewoye

Keyword(s):

Insulin Resistance ◽

Serum Insulin ◽

Density Lipoprotein ◽

Diabetic Rats ◽

Low Grade ◽

Control Serum ◽

Experimental Type ◽

Anti Inflammatory ◽

Type 2 Diabetic

Abstract Background Diabetes mellitus causes low-grade chronic inflammation which leads to the development of long-term complications. Oral magnesium (Mg) intake amongst other effects was reported to reduce the levels of inflammatory markers. This study investigated the anti-inflammatory and insulin secretory activities in experimental type-2 diabetic rats (n=32) orally treated with Mg. Methods Experimental type-2 diabetic rats were induced with high fat diet and alloxan (50 mg/kg, single i.p.) for over 10 weeks prior to the experimental procedures. Male Wistar rats were divided into 4 equal groups: control, untreated experimental diabetics, and experimental diabetics treated orally with either metformin (Met) (250 mg/kg), or Mg (250 mg/kg), respectively, for 14 days. The blood glucose (BG) levels were monitored before experimental induction of diabetes and thereafter on days 1, 7, 10, and 14, respectively. Serum insulin, C-reactive protein (CRP), interleukin-6 (IL-6), and lipid profile were assessed using laboratory kits while pancreatic beta cell function (BCF) and insulin resistance were estimated using homeostasis model assessment equations. Results Significant increase in the BG level was observed in all experimental diabetic groups on day 1 compared to controls. On day 14, BG, BCF, triglyceride, cholesterol, and low-density lipoprotein levels were increased while the high-density lipoprotein level was reduced in untreated diabetics compared to other groups. Insulin and insulin resistance were increased in all groups compared to control. Serum insulin and IL-6 were reduced while CRP was elevated in diabetic treated groups (Met and Mg) compared to untreated diabetics. Conclusions This study shows a hypoglycemic, lipid regulatory, insulin stimulatory, and anti-inflammatory effect of oral Mg treatment in experimental type-2 diabetic rats.

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