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
Correspondence
Y.-M. Li
No.12 Wu-Lu-Mu-Qi Middle Road
200040 Shanghai
China
eMail: yimingli@fudan.edu.cn