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      Global gene expression analysis in liver of db/db mice treated with catalpol

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          Abstract

          Catalpol, a major bioactive component from Rehmannia glutinosa, which has been used to treat diabetes. The present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db mice. The db/db mice were randomly divided into six groups (10/group) according to their blood glucose levels: db/db control, metformin (positive control), and four dose levels of catalpol treatment (25, 50, 100, and 200 mg·kg -1), and 10 db/m mice were used as the normal control. All the groups were administered orally for 8 weeks. The levels of fasting blood glucose (FBG), random blood glucose (RBG), glucose tolerance, insulin tolerance, and glycated serum protein (GSP) and the globe gene expression in liver tissues were analyzed. Our results showed that catalpol treatment obviously reduced water intake and food intake in a dose-dependent manner. Catalpol treatment also remarkably reduce fasting blood glucose (FBG) and random blood glucose (RBG) in a dose-dependent manner. The RBG-lowering effect of catal-pol was better than that of metformin. Furthermore, catalpol significantly improved glucose tolerance and insulin tolerance via increasing insulin sensitivity. Catalpol treatment significantly decreased GSP level. The comparisons of gene expression in liver tissues among normal control mice, db/db mice and catalpol treated mice (200 and 100 mg·kg -1) indicated that there were significant increases in the expressions of 287 genes, whichwere mainly involved in lipid metabolism, response to stress, energy metabolism, and cellular processes, and significant decreases in the expressions of 520 genes, which were mainly involved in cell growth, death, immune system, and response to stress. Four genes expressed differentially were linked to glucose metabolism or insulin signaling pathways, including Irs1 (insulin receptor substrate 1), Idh2 (isocitrate dehydrogenase 2 (NADP +), mitochondrial), G6pd2 (glucose-6-phosphate dehydrogenase 2), and SOCS3 (suppressor of cytokine signaling 3). In conclusion, catalpol ecerted significant hypoglycemic effect and remarkable therapeutic effect in db/db mice via modulating various gene expressions.

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          Most cited references 16

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          Natural medicines used in the traditional Chinese medical system for therapy of diabetes mellitus.

          The rapidly increasing diabetes mellitus is becoming a serious threat to mankind health in all parts of the world. The control and treatment of diabetes and its complications mainly depend on the chemical or biochemical agents, but the fact is that it has never been reported that someone had recovered totally from diabetes. With the distinctive traditional medical opinions and natural medicines mainly originated in herbs, the traditional Chinese medicine performed a good clinical practice and is showing a bright future in the therapy of diabetes mellitus and its complications. Based on a large number of chemical and pharmacological research work, numerous bioactive compounds have been found in Chinese medicinal plants for diabetes. The present paper reviews 86 natural medicines with regards to their origin, anti-diabetic active principles and/or pharmacological test results, which are commonly used in the traditional Chinese medical system and have demonstrated experimental or/and clinical anti-diabetic effectiveness. Among these natural medicines, 82 originate from plants and 4 from animals or insects, which covers 45 families. It is strongly significant to pay close attention to traditional Chinese medical therapeutics and natural medicines for treatment of diabetes mellitus and its complications. Copyright 2004 Elsevier Ireland Ltd.
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            Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis.

            Clinicians and patients need updated evidence on the comparative effectiveness and safety of diabetes medications to make informed treatment choices.
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              Central role of ceramide biosynthesis in body weight regulation, energy metabolism, and the metabolic syndrome.

              Although obesity is associated with multiple features of the metabolic syndrome (insulin resistance, leptin resistance, hepatic steatosis, chronic inflammation, etc.), the molecular changes that promote these conditions are not completely understood. Here, we tested the hypothesis that elevated ceramide biosynthesis contributes to the pathogenesis of obesity and the metabolic syndrome. Chronic treatment for 8 wk of genetically obese (ob/ob), and, high-fat diet-induced obese (DIO) mice with myriocin, an inhibitor of de novo ceramide synthesis, decreased circulating ceramides. Decreased ceramide was associated with reduced weight, enhanced metabolism and energy expenditure, decreased hepatic steatosis, and improved glucose hemostasis via enhancement of insulin signaling in the liver and muscle. Inhibition of de novo ceramide biosynthesis decreased adipose expression of suppressor of cytokine signaling-3 (SOCS-3) and induced adipose uncoupling protein-3 (UCP3). Moreover, ceramide directly induced SOCS-3 and inhibited UCP3 mRNA in cultured adipocytes suggesting a direct role for ceramide in regulation of metabolism and energy expenditure. Inhibition of de novo ceramide synthesis had no effect on adipose tumor necrosis factor-alpha (TNF-alpha) expression but dramatically reduced adipose plasminogen activator inhibitor-1 (PAI-1) and monocyte chemoattactant protein-1 (MCP-1). This study highlights a novel role for ceramide biosynthesis in body weight regulation, energy expenditure, and the metabolic syndrome.
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                Author and article information

                Journal
                CJNM
                Chinese Journal of Natural Medicines
                Elsevier
                1875-5364
                20 August 2018
                : 16
                : 8
                : 590-598
                Affiliations
                1Tianjin Institute of Pharmaceutical Research Co., Ltd., Tianjin 300301, China
                2Tianjin Institute of Pharmaceutical Research Drug Safety Assessment Co., Ltd., Tianjin 300301, China
                3Qinghai Yangzong Pharmaceutical Co., Ltd., Xining 810003, China
                Author notes
                *Corresponding author: SHEN Xiu-Ping, Tel: 86-22-84845266, E-mail: shenxp@ 123456tjipr.com

                These authors have no conflict of interest to declare.

                Article
                S1875-5364(18)30096-7
                10.1016/S1875-5364(18)30096-7
                Copyright © 2018 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

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