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      Network Pharmacology Studies on the Bioactive Compounds and Action Mechanisms of Natural Products for the Treatment of Diabetes Mellitus: A Review

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          Abstract

          Diabetes mellitus (DM) is a kind of chronic and metabolic disease, which can cause a number of diseases and severe complications. Network pharmacology approach is introduced to study DM, which can combine the drugs, target proteins and disease and form drug-target-disease networks. Network pharmacology has been widely used in the studies of the bioactive compounds and action mechanisms of natural products for the treatment of DM due to the multi-components, multi-targets, and lower side effects. This review provides a balanced and comprehensive summary on network pharmacology from current studies, highlighting different bioactive constituents, related databases and applications in the investigations on the treatment of DM especially type 2. The mechanisms related to type 2 DM, including α-amylase and α-glucosidase inhibitory, targeting β cell dysfunction, AMPK signal pathway and PI3K/Akt signal pathway are summarized and critiqued. It suggests that the network pharmacology approach cannot only provide a new research paradigm for natural products, but also improve the current antidiabetic drug discovery strategies. Furthermore, we put forward the perspectives on the reasonable applications of network pharmacology for the therapy of DM and related drug discovery.

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          Innate immunity and intestinal microbiota in the development of Type 1 diabetes

          Type 1 diabetes (T1D) is a debilitating autoimmune disease that results from T cell-mediated destruction of insulin-producing β cells. Its incidence has increased during the past several decades in developed countries 1, 2, suggesting that changes in the environment (including human microbial environment) may influence disease pathogenesis. The incidence of spontaneous T1D in non-obese diabetic (NOD) mice can be affected by the microbial environment in the animal housing facility3 or by exposure to microbial stimuli, such as injection with mycobacteria or various microbial products 4,5. Here we show that specific-pathogen free (SPF) NOD mice lacking MyD88 protein (an adaptor for multiple innate immune receptors that recognize microbial stimuli) do not develop T1D. The effect is dependent on commensal microbes as germ-free (GF) MyD88-negative NOD mice develop robust diabetes, whereas colonization of these GF NOD.MyD88-negative mice with a defined microbial consortium (representing bacterial phyla normally present in human gut) attenuates T1D. We also find that MyD88-deficiency changes the composition of the distal gut microbiota, and that exposure to the microbiota of SPF NOD.MyD88-negative donors attenuates T1D in GF NOD recipients. Together, these findings indicate that interaction of the intestinal microbes with the innate immune system is a critical epigenetic factor modifying T1D predisposition.
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            Anticancer polysaccharides from natural resources: a review of recent research.

            Taking into account the rising trend of the incidence of cancers of various organs, effective therapies are urgently needed to control human malignancies. However, almost all of the chemotherapy drugs currently on the market cause serious side effects. Fortunately, several previous studies have shown that some non-toxic biological macromolecules, including polysaccharides and polysaccharide-protein complexes, possess anti-cancer activities or can increase the efficacy of conventional chemotherapy drugs. Based on these encouraging observations, a great deal of effort has been focused on discovering anti-cancer polysaccharides and complexes for the development of effective therapeutics for various human cancers. This review focuses on the advancements in the anti-cancer efficacy of various natural polysaccharides and polysaccharide complexes in the past 5 years. Most polysaccharides were tested using model systems, while several involved clinical trials. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              Signalling by insulin and IGF receptors: supporting acts and new players.

              The signalling pathways utilised by insulin receptor (IR) and IGF receptor to transduce their diverse effects on cellular metabolism, growth and survival are well established in broad outline, but many details remain to be elucidated. Tyrosine phosphorylation of IR substrates and Shc initiates signalling via canonical phosphoinositide 3-kinase/Akt and Ras/MAP kinase pathways, which together mediate many of the actions of insulin and IGFs. However, a variety of additional substrates and scaffolds have been described that may play roles in modulating the canonical pathways or in specific biological responses. This review will focus on recent studies that have extended our understanding of insulin/IGF signalling pathways, and the elements that may contribute to specificity.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                23 February 2017
                2017
                : 8
                : 74
                Affiliations
                Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University Tianjin, China
                Author notes

                Edited by: Jianbo Xiao, University of Macau, Macau

                Reviewed by: Ake Sjoholm, University of South Alabama, USA; Alessandro Martorana, University of Rome Tor Vergata, Italy

                *Correspondence: Haixia Chen, chenhx@ 123456tju.edu.cn

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2017.00074
                5322182
                28154535
                832a294d-9b23-455f-a8f5-7c0f4b6feb41
                Copyright © 2017 Li, Yuan, Pan, Wang and Chen.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 14 December 2016
                : 06 February 2017
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 110, Pages: 10, Words: 0
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                network pharmacology,diabetes mellitus,natural products,database,mechanism

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