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      Gynura divaricata rich in 3, 5−/4, 5-dicaffeoylquinic acid and chlorogenic acid reduces islet cell apoptosis and improves pancreatic function in type 2 diabetic mice

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          Abstract

          Background

          Diabetes mellitus is one of the most common chronic diseases that accompanied by severe complications. Gynura divaricata (GD), a medicinal and edible plant that is usually used for the treatment of diabetes. Therefore, this study investigates the chemical components of GD with hypoglycemic effect and the possible mechanism lowering blood sugar in T2D diabetic mice.

          Methods

          The methanol extract of GD was analysed by HPLC-DAD. And then mice with type 2 diabetes induced by a high-fat diet in combination with streptozotocin feed the diet containing lyophilized GD powder for 4 weeks. During this period, fasting blood glucose (FBG) levels and body weight were measured.

          Results

          GD was rich in four bioactive components of dicaffeoylquinic acid and chlorogenic acid. These components occupied about 2.37% in the GD powder in which the highest level was 3, 5-dicaffeoylquinic acid. Oral GD significantly reduced FBG, fasting serum insulin, and glycosylated serum protein levels, and enhanced antioxidative activities. HE-staining showed that the pathological damage in pancreatic β-cells was ameliorated. An immunohistochemical assay also showed that GD promoted marked pancreatic β-cell regeneration. GD also caused notable increase in GLUT2, GK, MafA, PDX-1, and Bcl-2 as well as reduction in Bax and caspase-3 expression as shown by western blot analysis.

          Conclusions

          GD exerts the pronounced hypoglycaemic effect by inhibiting islet cell apoptosis and improving pancreatic function. Therefore, GD might have a potential to improve diabetes.

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          Most cited references41

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          Anti-diabetic and anti-lipidemic effects of chlorogenic acid are mediated by ampk activation.

          Chlorogenic acid (CGA) has been shown to stimulate glucose uptake in skeletal muscle through the activation of AMPK. However, its effect on other metabolic pathways and likewise its effects after long-term consumption have yet to be understood. We investigated the effects of CGA on glucose tolerance, insulin sensitivity, hepatic gluconeogenesis, lipid metabolism and skeletal muscle glucose uptake in Lepr(db/db) mice. Hepatoma HepG2 was used to investigate CGA's effect on hepatic glucose production and fatty acid synthesis. Subsequently, we attempted to evaluate whether these effects of CGA are associated with the activation of AMPK. In Lepr(db/db) mice, acute treatment with CGA lowered AUCglucose in an OGTT. Chronic administration of CGA inhibited hepatic G6Pase expression and activity, attenuated hepatic steatosis, improved lipid profiles and skeletal muscle glucose uptake, which in turn improved fasting glucose level, glucose tolerance, insulin sensitivity and dyslipidemia in Lepr(db/db) mice. CGA activated AMPK, leading to subsequent beneficial metabolic outcomes, such as suppression of hepatic glucose production and fatty acid synthesis. Inhibition and knockdown of AMPK abrogated these metabolic alterations. In conclusion, CGA improved glucose and lipid metabolism, via the activation of AMPK. Copyright © 2013 Elsevier Inc. All rights reserved.
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            Chlorogenic Acid Stimulates Glucose Transport in Skeletal Muscle via AMPK Activation: A Contributor to the Beneficial Effects of Coffee on Diabetes

            Chlorogenic acid (CGA) has been shown to delay intestinal glucose absorption and inhibit gluconeogenesis. Our aim was to investigate the role of CGA in the regulation of glucose transport in skeletal muscle isolated from db/db mice and L6 skeletal muscle cells. Oral glucose tolerance test was performed on db/db mice treated with CGA and soleus muscle was isolated for 2-deoxyglucose transport study. 2DG transport was also examined in L6 myotubes with or without inhibitors such as wortmannin or compound c. AMPK was knocked down with AMPKα1/2 siRNA to study its effect on CGA-stimulated glucose transport. GLUT 4 translocation, phosphorylation of AMPK and Akt, AMPK activity, and association of IRS-1 and PI3K were investigated in the presence of CGA. In db/db mice, a significant decrease in fasting blood sugar was observed 10 minutes after the intraperitoneal administration of 250 mg/kg CGA and the effect persisted for another 30 minutes after the glucose challenge. Besides, CGA stimulated and enhanced both basal and insulin-mediated 2DG transports in soleus muscle. In L6 myotubes, CGA caused a dose- and time-dependent increase in glucose transport. Compound c and AMPKα1/2 siRNA abrogated the CGA-stimulated glucose transport. Consistent with these results, CGA was found to phosphorylate AMPK and ACC, consistent with the result of increased AMPK activities. CGA did not appear to enhance association of IRS-1 with p85. However, we observed activation of Akt by CGA. These parallel activations in turn increased translocation of GLUT 4 to plasma membrane. At 2 mmol/l, CGA did not cause any significant changes in viability or proliferation of L6 myotubes. Our data demonstrated for the first time that CGA stimulates glucose transport in skeletal muscle via the activation of AMPK. It appears that CGA may contribute to the beneficial effects of coffee on Type 2 diabetes mellitus.
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              Comparison of the Antioxidative Activity of Some Acid-phenols: Structure-Activity Relationship

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                Author and article information

                Contributors
                yinxiaolu1881992@163.com
                2544711675@qq.com
                086-0512-65880181 , sericult@suda.edu.cn
                Journal
                Nutr Metab (Lond)
                Nutr Metab (Lond)
                Nutrition & Metabolism
                BioMed Central (London )
                1743-7075
                10 October 2018
                10 October 2018
                2018
                : 15
                : 73
                Affiliations
                ISNI 0000 0001 0198 0694, GRID grid.263761.7, Silk Biotechnology Laboratory, School of Biology and Basic Medical Sciences, , Soochow University, ; RM702-2303, No. 199, Renai Road, Dushuhu Higher Edu. Town, Suzhou, 215123 People’s Republic of China
                Article
                310
                10.1186/s12986-018-0310-y
                6180593
                95573a5b-b5ef-4722-905b-33e405c72552
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 12 July 2018
                : 1 October 2018
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Nutrition & Dietetics
                diabetes mellitus,gynura divaricata,type 2 diabetes,fasting blood glucose,serum insulin,pancreatic β-cell

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