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      Antidiabetic, antihyperlipidemic activities and herb–drug interaction of a polyherbal formulation in streptozotocin induced diabetic rats

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          Abstract

          Background

          Ojamin (OJ), a polyherbal antidiabetic formulation, is extensively used as a food supplement to control diabetes alone or along with synthetic antidiabetic agents. However, it's phytochemical and pharmacological investigations are lacking.

          Objective

          The present study was undertaken to study antidiabetic and antihyperlipidemic potentials of OJ and its interaction with Metformin in streptozotocin (STZ)-induced diabetic rats.

          Materials and methods

          Diabetes was induced in Wistar rats by single intraperitoneal (i.p.) injection of streptozotocin (60 mg/kg). Antidiabetic, antihyperlipidemic activities of OJ were evaluated at dose of 0.28 ml/kg by estimating biochemical changes in urine, serum and liver tissue homogenate and histological changes in liver and pancreatic tissues. Metformin (100 mg/kg, p.o.) was used as reference standard drug.

          Results

          Results indicate that STZ administration caused hyperglycemia, increased serum glycosylated hemoglobin content, altered serum lipid profile, polyuria, decreased liver glycogen content and histological changes in liver and pancreatic tissues. This elevated serum glucose level and urine volume was significantly decreased by OJ. Supplementation with OJ produced significant improvement in serum lipid profile and glycosylated hemoglobin content along with significant increase in the liver glycogen content. OJ treatment also restored histological changes in liver and pancreatic tissue near to the normal. The observed antidiabetic and hypolipidemic effects of OJ were superior to Metformin. Co-treatment of diabetic rats with OJ and Metformin failed to control blood glucose levels.

          Conclusion

          It is concluded that the OJ possesses significant antidiabetic and antihyperlipidemic activities in rats. However, co-administration of OJ and Metformin is cautioned.

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          Oxidative stress: the vulnerable beta-cell.

          Sigurd Lenzen (2008)
          Antioxidative defence mechanisms of pancreatic beta-cells are particularly weak and can be overwhelmed by redox imbalance arising from overproduction of reactive oxygen and reactive nitrogen species. The consequences of this redox imbalance are lipid peroxidation, oxidation of proteins, DNA damage and interference of reactive species with signal transduction pathways, which contribute significantly to beta-cell dysfunction and death in Type 1 and Type 2 diabetes mellitus. Reactive oxygen species, superoxide radicals (O(2)(*-)), hydrogen peroxide (H(2)O(2)) and, in a final iron-catalysed reaction step, the most reactive and toxic hydroxyl radicals (OH(*)) are produced during both pro-inflammatory cytokine-mediated beta-cell attack in Type 1 diabetes and glucolipotoxicity-mediated beta-cell dysfunction in Type 2 diabetes. In combination with NO(*), which is toxic in itself, as well as through its reaction with the O(2)(*-) and subsequent formation of peroxynitrite, reactive species play a central role in beta-cell death during the deterioration of glucose tolerance in the development of diabetes.
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            Induction of diabetes by Streptozotocin in rats.

            Ahmad B. Rad, D Norouzian, M Mehrabi … (2007)
            The objective of this study is to induce experimental diabetes mellitus by Streptozotocin in normal adult Wistar rats via comparison of changes in body weight, consumption of food and water, volume of urine and levels of glucose, insulin and C-peptide in serum, between normal and diabetic rats. Intra-venous injection of 60mg/kg dose of Streptozotocin in adult wistar rats, makes pancreas swell and at last causes degeneration in Langerhans islet beta cells and induces experimental diabetes mellitus in the 2-4 days. Induction of experimental diabetes mellitus is indeed the first step in the plan of purification of pancreatic Langerhans islet cells of normal rats for transplanting under the testis subcutaneous of experimentally induced diabetic rats. Streptozotocin induces one type of diabetes which is similar to diabetes mellitus with non-ketosis hyperglycemia in some animal species. For induction of experimental diabetes in male adult rats weighted 250-300 grams (75-90 days), 60mg/kg of Streptozotocin was injected intravenously. Three days after degeneration of beta cells, diabetes was induced in all animals. The diabetic and normal animals were kept in the metabolic cages separately and their body weight, consumption of food and water, urine volume, the levels of serum glucose, insulin and C-peptide quantities in all animals were measured and then these quantities were compared. For a microscopic study of degeneration of Langerhans islet beta cells of diabetic rats, sampling from pancreas tissue of diabetic and normal rats, staining and comparison between them, were done. Induction of diabetes with Streptozotocin decreases Nicotinamide-adenine dinucleotide (NAD) in pancreas islet beta cells and causes histopathological effects in beta cells which probably intermediates induction of diabetes. In this study, we used Streptozotocin for our experiments in induction of experimental diabetes mellitus. After Induction of diabetes, consumption of food and water, volume of urine and glucose increased in the diabetic animals in comparison with normal animals, but the weight of body and the volume of insulin and C-peptide decreased in the diabetic animals. Sampling and staining of pancreas tissue of diabetic and normal rats showed that the Langerhans islet beta cells of diabetic rats have been clearly degenerated. In three days, Streptozotocin makes pancreas swell and at last causes degeneration in Langerhans islet beta cells and induces experimental diabetes. It also changes normal metabolism in diabetic rats in comparison with normal rats. Consumption of water and food, volume of urine, serum glucose increases in diabetic animals in comparison with normal rats but the levels of serum insulin, C-peptide and body weight decreases.
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              LDL cholesterol as a strong predictor of coronary heart disease in diabetic individuals with insulin resistance and low LDL: The Strong Heart Study.

              Barbara Howard, David Robbins, Maurice L. Sievers … (2000)
              Diabetes has been shown to increase the risk of coronary heart disease in all populations studied. However, there is a lack of information on the relative importance of diabetes-associated risk factors for cardiovascular disease (CVD), especially the role of lipid levels, because low density lipoprotein (LDL) cholesterol often is not elevated in diabetic individuals. The objective of this analysis was to evaluate CVD risk factors in a large cohort of diabetic individuals and to compare the importance of dyslipidemia (ie, elevated triglycerides and low levels of high density lipoprotein [HDL] cholesterol) and LDL cholesterol in determining CVD risk in diabetic individuals. The Strong Heart Study assesses coronary heart disease and its risk factors in American Indians in Arizona, Oklahoma, and South/North Dakota. The baseline clinical examinations (July 1989 to January 1992) consisted of a personal interview, physical examination, and drawing of blood samples for 4549 study participants (2034 with diabetes), 45 to 74 years of age. Follow-up averaged 4.8 years. Fatal and nonfatal CVD events were confirmed by standardized record review. Participants with diabetes, compared with those with normal glucose tolerance, had lower LDL cholesterol levels but significantly elevated triglyceride levels, lower HDL cholesterol levels, and smaller LDL particle size. Significant independent predictors of CVD in those with diabetes included age, albuminuria, LDL cholesterol, HDL cholesterol (inverse), fibrinogen, and percent body fat (inverse). A 10-mg/dL increase in LDL cholesterol was associated with a 12% increase in CVD risk. Thus, even at concentrations well below the National Cholesterol Education Program target of 130 mg/dL, LDL cholesterol is a strong independent predictor of coronary heart disease in individuals with diabetes, even when components of diabetic dyslipidemia are present. These results support recent recommendations for aggressive control of LDL cholesterol in diabetic individuals, with a target level of <100 mg/dL.
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                Author and article information

                Contributors
                Vishnu P. Choudhari
                Journal
                Journal ID (nlm-ta): J Ayurveda Integr Med
                Journal ID (iso-abbrev): J Ayurveda Integr Med
                Title: Journal of Ayurveda and Integrative Medicine
                Publisher: Elsevier
                ISSN (Print): 0975-9476
                ISSN (Electronic): 0976-2809
                Publication date PMC-release: 11 November 2017
                Publication date (Print): Oct-Dec 2017
                Publication date (Electronic): 11 November 2017
                Volume: 8
                Issue: 4
                Pages: 218-225
                Affiliations
                [1]MAEER's Maharashtra Institute of Pharmacy, MIT Campus, Paud Road, Kothrud, Pune, Maharashtra 411038, India
                Author notes
                [∗ ]Corresponding author. vishnu.choudhari@ 123456mippune.edu.in
                Article
                Publisher ID: S0975-9476(16)30193-0
                DOI: 10.1016/j.jaim.2016.11.002
                PMC ID: 5747493
                PubMed ID: 29137853
                SO-VID: efd0b68b-b86e-44d8-a1a5-6b59aa879492
                Copyright © © 2016 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Publishing Services by Elsevier B.V.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 13 July 2016
                Date revision received : 24 October 2016
                Date accepted : 7 November 2016
                Categories
                Subject: Original Research Article (Experimental)

                ScienceOpen disciplines: Complementary & Alternative medicine
                Keywords: antidiabetic,antihyperlipidemic,herb–drug interaction,metformin,ojamin,polyherbal formulation
                Data availability:
                ScienceOpen disciplines: Complementary & Alternative medicine
                Keywords: antidiabetic, antihyperlipidemic, herb–drug interaction, metformin, ojamin, polyherbal formulation

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