For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
7
views
40
references
 Top references
cited by
2
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
1 collections
    0
    shares
      296
      similar
       All similar

      Drug Design, Development and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the design and development of drugs, as well as the clinical outcomes, patient safety, and programs targeted at the effective and safe use of medicines. Sign up for email alerts here.

      88,007 Monthly downloads/views I 4.319 Impact Factor I 6.6 CiteScore I 1.12 Source Normalized Impact per Paper (SNIP) I 0.784 Scimago Journal & Country Rank (SJR)

       

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Immunoregulatory Effect of Acanthopanax trifoliatus (L.) Merr. Polysaccharide on T1DM Mice

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Acanthopanax trifoliatus (L.) Merr. is a medicinal plant found in Southeast Asia, and its young leaves and shoots are consumed as a vegetable. The main bioactive components of this herb are polysaccharides that have significant anti-diabetic effects. The aim of this study was to evaluate the immunoregulatory effect of A. trifoliatus (L.) Merr. polysaccharide (ATMP) on a mouse model of type 1 diabetes mellitus (T1DM).

          Methods

          The monosaccharide composition and mean molecular mass of ATMP were determined by HPLC and HPGPC. T1DM was induced in mice using STZ, and 35, 70 and 140mg/kg ATMP was administered daily via the intragastric route for six weeks. Untreated and metformin-treated positive control groups were also included. The body weight of the mice, food and water intake and fasting glucose levels were monitored throughout the 6-week regimen. Histological changes in the pancreas and spleen were analyzed by H&E staining. Oral glucose tolerance was evaluated with the appropriate test. Peroxisome proliferator-activated receptor γ (PPARγ) mRNA and protein levels in the spleen were measured by quantitative real time PCR and Western blotting. IL-10, IFN-γ and insulin levels in the sera were determined by ELISA. The CD4 + and CD8 +T cells in spleen tissues were detected by immunohistochemistry (IHC).

          Results

          ATMP and metformin significantly decreased fasting blood glucose, and the food and water intake after 6 weeks of treatment. In contrast, serum insulin levels, glucose tolerance and body weight improved considerably in the high and medium-dose ATMP and metformin groups. T1DM was associated with pancreatic and splenic tissue damage. The high dose (140mg/kg) of ATMP reduced infiltration of inflammatory cells into the pancreas and restored the structure of islet β-cells in the diabetic mice. Consistent with this, 35, 70 and 140mg/kg ATMP increased IL-10 levels and decreased that of IFN-γ, thereby restoring the CD4 +/CD8 + and Th1/Th2 cytokine ratio. At the molecular level, high-dose ATMP up-regulated PPARγ in the splenic cells.

          Conclusion

          ATMP exerts a hypoglycemic effect in diabetic mice by restoring the immune balance in the spleen.

          Most cited references40

          • Record: found
          • Abstract: found
          • Article: not found

          PPARγ and the global map of adipogenesis and beyond.

          Martina Lefterova, Anders K Haakonsson, Mitchell A. Lazar … (2014)
          Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor (NR) superfamily of ligand-dependent transcription factors (TFs) and function as a master regulator of adipocyte differentiation and metabolism. We review recent breakthroughs in the understanding of PPARγ gene regulation and function in the chromatin context. It is now clear that multiple TFs team up to induce PPARγ during adipogenesis, and that other TFs cooperate with PPARγ to ensure adipocyte-specific genomic binding and function. We discuss how this differs in other PPARγ-expressing cells such as macrophages and how these genome-wide mechanisms are preserved across species despite modest conservation of specific binding sites. These emerging considerations inform our understanding of PPARγ function as well as of adipocyte development and physiology. Published by Elsevier Ltd.
          Article 0 comments Cited 224 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            PPARgamma and PPARdelta negatively regulate specific subsets of lipopolysaccharide and IFN-gamma target genes in macrophages.

            Hannah Glass, John Welch, Luis Gonzalez … (2003)
            Natural and synthetic agonists of the peroxisome proliferator-activated receptor gamma (PPARgamma) regulate adipocyte differentiation, glucose homeostasis, and inflammatory responses. Although effects on adipogenesis and glucose metabolism are genetically linked to PPARgamma, the PPARgamma dependence of antiinflammatory responses of these substances is less clear. Here, we have used a combination of mRNA expression profiling and conditional disruption of the PPARgamma gene in mice to characterize programs of transcriptional activation and repression by PPARgamma agonists in elicited peritoneal macrophages. Natural and synthetic PPARgamma agonists, including the thiazolidinedione rosiglitazone (Ro), modestly induced the expression of a surprisingly small number of genes, several of which were also induced by a specific PPARdelta agonist. The majority of these genes encode proteins involved in lipid homeostasis. In contrast, Ro inhibited induction of broad subsets of lipopolysaccharide and IFN-gamma target genes in a gene-specific and PPARgamma-dependent manner. At high concentrations, Ro inhibited induction of lipopolysaccharide target genes in PPARgamma-deficient macrophages, at least in part by activating PPARdelta. These studies establish overlapping transactivation and transrepression functions of PPARgamma and PPARdelta in macrophages and suggest that a major transcriptional role of PPARgamma is negative regulation of specific subsets of genes that are activated by T helper 1 cytokines and pathogenic molecules that signal through pattern recognition receptors. These findings support a physiological role of PPARgamma in regulating both native and acquired immune responses.
            Article 0 comments Cited 83 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              PPARγ signaling and emerging opportunities for improved therapeutics

              Robert Danner, Edward Dougherty, Shuibang Wang (2016)
              Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated nuclear receptor that regulates glucose and lipid metabolism, endothelial function and inflammation. Rosiglitazone (RGZ) and other thiazolidinedione (TZD) synthetic ligands of PPARγ are insulin sensitizers that have been used for the treatment of type 2 diabetes. However, undesirable side effects including weight gain, fluid retention, bone loss, congestive heart failure, and a possible increased risk of myocardial infarction and bladder cancer, have limited the use of TZDs. Therefore, there is a need to better understand PPARγ signaling and to develop safer and more effective PPARγ-directed therapeutics. In addition to PPARγ itself, many PPARγ ligands including TZDs bind to and activate G protein-coupled receptor 40 (GPR40), also known as free fatty acid receptor 1. GPR40 signaling activates stress kinase pathways that ultimately regulate downstream PPARγ responses. Recent studies in human endothelial cells have demonstrated that RGZ activation of GPR40 is essential to the optimal propagation of PPARγ genomic signaling. RGZ/GPR40/p38 MAPK signaling induces and activates PPARγ co-activator-1α, and recruits E1A binding protein p300 to the promoters of target genes, markedly enhancing PPARγ-dependent transcription. Therefore in endothelium, GPR40 and PPARγ function as an integrated signaling pathway. However, GPR40 can also activate ERK1/2, a proinflammatory kinase that directly phosphorylates and inactivates PPARγ. Thus the role of GPR40 in PPARγ signaling may have important implications for drug development. Ligands that strongly activate PPARγ, but do not bind to or activate GPR40 may be safer than currently approved PPARγ agonists. Alternatively, biased GPR40 agonists might be sought that activate both p38 MAPK and PPARγ, but not ERK1/2, avoiding its harmful effects on PPARγ signaling, insulin resistance and inflammation. Such next generation drugs might be useful in treating not only type 2 diabetes, but also diverse chronic and acute forms of vascular inflammation such as atherosclerosis and septic shock.
              Article 0 comments Cited 57 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Drug Des Devel Ther
                Journal ID (iso-abbrev): Drug Des Devel Ther
                Journal ID (publisher-id): dddt
                Journal ID (pmc): dddt
                Title: Drug Design, Development and Therapy
                Publisher: Dove
                ISSN (Electronic): 1177-8881
                Publication date (Electronic): 18 June 2021
                Publication date Collection: 2021
                Volume: 15
                Pages: 2629-2639
                Affiliations
                [1 ]School of Pharmacy, Guangdong Pharmaceutical University , Guangzhou, 510006, People’s Republic of China
                [2 ]Department of Pharmacy, Xiamen Children's Hospital, Children's Hospital of Fudan University at Xiamen , Xiamen, 361006, People’s Republic of China
                Author notes
                Correspondence: Yufang Pan; Huiwen Yang School of Pharmacy, Guangdong Pharmaceutical University , Guangzhou, 510006, People’s Republic of China Email p39352011@163.com; halleyyang@163.com
                Article
                Publisher ID: 309851
                DOI: 10.2147/DDDT.S309851
                PMC ID: 8219122
                SO-VID: ee1a0b65-1c13-4a39-baf3-ebc570c33c1d
                Copyright statement: © 2021 Li et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 06 March 2021
                Date accepted : 04 May 2021
                Page count
                Figures: 7, Tables: 2, References: 40, Pages: 11
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: acanthopanax trifoliatus (l.) merr,type 1 diabetes mellitus,pparγ,cd4+ t cells,cd8+ t cells,immunoregulation
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: acanthopanax trifoliatus (l.) merr, type 1 diabetes mellitus, pparγ, cd4+ t cells, cd8+ t cells, immunoregulation

                Comments

                Comment on this article

                scite_

                Similar content296

                See all similar

                Cited by2

                See all cited by

                Most referenced authors395

                See all reference authors