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      Antihyperglycemic and hypolipidemic effects of α, β-amyrin, a triterpenoid mixture from Protium heptaphyllum in mice

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          Abstract

          Background

          Pentacyclic triterpenes in general exert beneficial effects in metabolic disorders. This study investigated the effects of α, β-amyrin, a pentacyclic triterpene mixture from the resin of Protium heptaphyllum on blood sugar level and lipid profile in normal and streptozotocin (STZ)-induced diabetic mice, and in mice fed on a high-fat diet (HFD).

          Findings

          Mice treated with α, β-amyrin (10, 30 and 100 mg/kg, p.o.) or glibenclamide (10 mg/kg, p.o.) had significantly reduced STZ-induced increases in blood glucose (BG), total cholesterol (TC) and serum triglycerides (TGs). Unlike glibenclamide that showed significant reductions in BG, TC and TGs in normoglycemic mice, α, β-amyrin did not lower normal blood sugar levels but at 100 mg/kg, manifested a hypolipidemic effect. Also, α, β-amyrin effectively reduced the elevated plasma glucose levels during the oral glucose tolerance test. Moreover, the plasma insulin level and histopathological analysis of pancreas revealed the beneficial effect of α, β-amyrin in the preservation of beta cell integrity. In mice treated orally with α, β-amyrin (10, 30 and 100 mg/kg) or fenofibrate (200 mg/kg), the HFD-associated rise in serum TC and TGs were significantly less. The hypocholesterolemic effect of α, β-amyrin appeared more prominent at 100 mg/kg with significant decreases in VLDL and LDL cholesterol and an elevation of HDL cholesterol. Besides, the atherogenic index was significantly reduced by α, β-amyrin.

          Conclusions

          These findings reflect the potential antihyperglycemic and hypolipidemic effects of α, β-amyrin mixture and suggest that it could be a lead compound for drug development effective in diabetes and atherosclerosis.

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          Most cited references28

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          Increased very low density lipoprotein (VLDL) secretion, hepatic steatosis, and insulin resistance.

          Insulin resistance (IR) affects not only the regulation of carbohydrate metabolism but all aspects of lipid and lipoprotein metabolism. IR is associated with increased secretion of VLDL and increased plasma triglycerides, as well as with hepatic steatosis, despite the increased VLDL secretion. Here we link IR with increased VLDL secretion and hepatic steatosis at both the physiologic and molecular levels. Increased VLDL secretion, together with the downstream effects on high density lipoprotein (HDL) cholesterol and low density lipoprotein (LDL) size, is proatherogenic. Hepatic steatosis is a risk factor for steatohepatitis and cirrhosis. Understanding the complex inter-relationships between IR and these abnormalities of liver lipid homeostasis will provide insights relevant to new therapies for these increasing clinical problems. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Synthesis, biology and clinical significance of pentacyclic triterpenes: a multi-target approach to prevention and treatment of metabolic and vascular diseases.

            This review (with 335 references cited) is devoted to pentacyclic triterpenes. The total synthesis, semi-synthesis, structural modification, and metabolic behavior of naturally occurring pentacyclic triterpenes are described. We also cover the in vivo evidence, mechanistic studies, and clinical significance of pentacyclic triterpenes as multi-target therapeutic agents for the prevention and treatment of metabolic and vascular diseases.
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              Diabetes-induced oxidative stress and low-grade inflammation in porcine coronary arteries.

              Multiple pathways contribute to accelerated coronary atherosclerosis in diabetics, including increased oxidative stress and inflammatory burden. Accordingly, the mechanisms of abnormal formation of reactive oxygen species and the changes in inflammatory gene expression were examined in diabetic coronary arteries. In pigs with streptozotocin-induced diabetes, superoxide formation was augmented in coronary media and adventitia because of increased NAD(P)H oxidase activity (3 months) accompanied by upregulated expression of its cytosolic subunit, p22phox. Diabetes-induced oxidative stress resulted in the inflammatory response in the adventitia (increased expression of interleukin-6, tumor necrosis factor-alpha, monocyte chemotactic protein-1, vascular cell adhesion molecule-1 [VCAM-1]) and in the media (VCAM-1). To examine the mechanisms of these changes, studies with isolated coronary fibroblasts were undertaken. Advanced glycation end products (AGEs), rather than glucose itself, upregulated expression of interleukin-6, VCAM-1, and monocyte chemotactic protein-1 mRNAs. These results were paralleled by increased interleukin-6 secretion (P<0.01) and augmented leukocyte adhesion to AGE-stimulated coronary cells (P<0.001). AGEs increased expression of phosphorylated forms of mitogen-activated protein kinases in coronary cells (ERK1/2 and JNK) and resulted in redox-sensitive expression of inflammatory genes that was inhibited by several inhibitors of oxidative pathways [NAD(P)H oxidase inhibitors, N-acetylcysteine, and pyrrolidine dithiocarbamate]. Diabetes increased NAD(P)H oxidase activity and oxidative stress, producing inflammatory responses in porcine coronary media and adventitia. AGEs activated ERK1/2 and JNK signaling pathways and induced the expression of several inflammatory genes in coronary cells in a redox-sensitive manner. These results suggest the involvement of AGEs in the development of accelerated coronary atherosclerosis in diabetes.
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                Author and article information

                Journal
                Lipids Health Dis
                Lipids Health Dis
                Lipids in Health and Disease
                BioMed Central
                1476-511X
                2012
                6 August 2012
                : 11
                : 98
                Affiliations
                [1 ]Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
                [2 ]Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Odontology and Nurse, Federal University of Ceará, Fortaleza, Ceará, Brazil
                [3 ]Department of Chemistry, Federal University of Piauí, Teresina, Piauí, Brazil
                [4 ]Department of Morphology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
                Article
                1476-511X-11-98
                10.1186/1476-511X-11-98
                3484111
                22867128
                7f243959-4098-4719-868b-dc952129a2f9
                Copyright ©2012 Santos et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 November 2011
                : 24 July 2012
                Categories
                Short Report

                Biochemistry
                protium heptaphyllum,pentacyclic triterpene,α,β-amyrin,mice,antihyperglycemic and hypolipidemic effects

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