Astragalus Polysaccharides: An Effective Treatment for Diabetes Prevention in NOD Mice

Abstract

Background: Type 1 diabetes mellitus (DM) is a chronic autoimmune disease that is related to the disequilibrium state of Th1 and Th2 subgroups of helper T lymphocyte (Th) and their cytokines. Astragalus polysaccharides (APS) are bioactive components extracted from one of the traditional Chinese herbs, used to enhance the function of human immune system.

Objective: To investigate the effects of APS on preventing type 1 DM and Th1/Th2-subtype cytokines, we compared the results of administration of APS and normal saline (NS) on non-obese diabetic (NOD) mice.

Subjects and Methods: APS or NS was administered to 4-week-old mice at a dose of 2.0 g/kg per day for 10 weeks. At 40 weeks, blood glucose, serum C-peptide (C-P) and GAD antibody were measured; pancreas was examined histologically; the intra-islet lymphocyte infiltration and T lymphocyte subsets in the spleen were analysed; the gene expression of IL-1β, IL-2, IL-6, IL-12, TNF-α, INF-γ, IL-4, IL-5, IL-10, TGF-β, Bcl-2, SOD, Fas and iNOS were measured by RT-PCR.

Results: The results showed that APS-administered NOD mice had a lower incidence rate of type 1 DM, lower serum C-P level, better histologic findings of pancreatic islets, and a lower D4+/CD8+ ratio of T lymphocytes from the spleen and the infiltrated islets. RT-PCR analysis showed gene expression levels are lower in IL-1β, IL-2, IL-6, IL-12, TNF-α, INF-γ, Fas, iNOS, and higher in IL-4, IL-5, IL-10, TGF-β, Bcl-2, SOD in the pancreatic tissue from APS-administered NOD mice as compared to the NS group.

Conclusions: These results demonstrated the effects of Astragalus polysaccharides on the prevention of type 1 DM in NOD mice by correcting the imbalance between the Th1/Th2 cytokines.

Key words

astragalus polysaccharides - diabetes - immunology - gene expression

References

• 1 Ahraham RS, Wen L, Marientta EV. Type 1 diabetes-predisposing MHC alleles influence the selection of glutamic acid decarboxylase 65-specific T cells in a transgenic model.  J Immunol. 2001;  166 1370-1389
• 2 Chen W, Li YM, Yu MH. Immunoloregulation effects of astragalus polysaccharides on T Helper lymphocyte subgroups in nonobese diabetic mice.  Chinese J Modern Medicine. 2007;  17 ((1)) 28-31
• 3 Chen W, Li YM, Yu MH. Effects of Astragalus polysaccharides on chymase, angiotensin- converting enzyme and angiotensin II in diabetic cardiomyopathy in hamsters.  J Int Med Res. 2007;  35 ((6)) 873-877
• 4 Choquet KG, Ducluzeau M, Nicolas TR. Increased production of interferon-gamma, but not IL-4 mRNA, by streptozotocin in the popliteal lymph node assay.  J Appl Toxicol. 2000;  20 175-187
• 5 Christen U, Wolfe T, Mohrle U. A dual role for TNF-α in type 1 diabetes: islet-specific expression abrogates the ongoing autoimmune process when induced late but not early during pathogenesis.  J Immunol. 2001;  166 ((2)) 7023-7032
• 6 Cong L, Li YM, Yu MH. Effect of Astragalus polysaccharides on the expression of myocardial collagen in hamsters with diabetic cardiomyopathy.  Chinese J Clinical rehabilitation. 2006;  10 ((7)) 64-66
• 7 Farilla L, Dotta F, Mario U Di. Presence of interleukin 4 or interleukin 10, but not both cytokines, in pancreatic tissue of two patients with recently diagnosed diabetes mellitus typeI.  Autoimmunity. 2000;  32 1161-1186
• 8 Glowacka E, Banasik M, Lewkowicz P. The effect of LPS on neutrophils from patients with high risk of type 1 diabetes mellitus in relation to IL-8, IL-10 and IL-12 production and apoptosis in vitro.  Scand J Immunol. 2002;  55 ((2)) 210-217
• 9 Grewal IS, Grewal KD, Wong FS. Expression of transgene encoded TGF-beta in islets prevents autoimmune diabetes in NOD mice by a local mechanism.  J Autoimmun. 2002;  19 ((1-2)) 9-22
• 10 Heitmeirer MR, Arnush M, Scarim AL. Pancreatic beta cell damage mediated by beta-cell production of interleukin-1: A novel mechanism for virus-induced diabetes.  J Biol Chem. 2001;  276 ((14)) 1151-1158
• 11 Hill NJ, Gunst K Van, Sarvetnick N. Th1 and Th2 pancreatic inflammation differentially affects homing of islet- reactive CD4 cells in nonobese diabetic mice.  J Immunol. 2003;  170 ((4)) 1649-1658
• 12 Hirai H, Kaino Y. Analysis of cytokine mRNA expression in pancreatic islets if nonobese diabetic mice.  J Pediatr Endocrinol Metab. 2000;  13 91-114
• 13 Karlsson MG, Lawesson SS, Ludvigsson J. Th1-like dominance in high-risk first-degree relatives f type 1 diabetic patients.  Diabetologia. 2000;  43 742-766
• 14 Liu J, Beller DI. Distinct pathways for NF-kappa B regulation are associated with aberrant macrophage IL-12 production in lupus- and diabetes-prone mouse strains.  J Immunol. 2003;  170 ((9)) 4489-4496
• 15 Ni Y, Su Q, Liu X. Experimental study of potimized techniques of water decoction extraction of Astragalus polysaccharide.  China J Chin Medicine. 1998;  23 ((6)) 284-286
• 16 Phillips JM, Browe GL, Chancey AL, Thanigaraj S. Nondepleting Anti-CD4 has an immediate action on diabetogenic effector cells, halting their destruction of pancreatic β cells.  J Immunol. 2000;  165 ((4)) 1949-1958
• 17 Rajagopalan G, Kudva YC, Flavell RA. Accelerated diabetes in rat insulin promoter-tumor necrosis factor-alpha transgenic nonobese diabetic mice lacking major histocompatibility class II molecules.  Diabetes. 2003;  52 ((2)) 342-327
• 18 Sparre T, Christensen UB, Mose Larsen P. IL-1beta induced protein changes in diabetes prone BB rat islets of Langerhans identified by proteome analysis.  Diabetologia. 2002;  45 ((11)) 1550-1561
• 19 Ventura OD, Vilella CA, Zanin ME. Kinetics of TNF-alpha and IFN-gamma mRNA expression in islets and spleen of NOD mice.  Braz J Med Biol Res. 2002;  35 ((11)) 1347-1355
• 20 Wu Y, Ou-Yang JP, Wu K, Wang Y, Zhou YF, Wen CY. Hypoglycemic effect of Astragalus polysaccharide and its effect on PTP1B.  Acta Pharmacol Sin. 2005;  26 ((3)) 345-352
• 21 Zhang YC, Pileggi A, Agarwal A. Adeno-associated virus-mediated IL-10 gene therapy inhibits diabetes recurrence in syngeneic islet cell transplantation of NOD mice.  Diabetes. 2003;  52 ((3)) 708-716

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