The immunotherapeutic effects of Astragalus polysaccharide in type 1 diabetic mice.
The present study investigated whether Astragalus polysaccharide (APS) possessed immunotherapeutic effects on type 1 diabetes mellitus. Diabetic mice induced by multiple low dose streptozotocin (MLD-STZ) were administered either APS (100, 200, 400 mg/kg body weight) or saline intraperitoneally daily, and sacrificed after 15 or 30 d of treatment. Meanwhile normal mice not treated with STZ nor with APS were offered into non-diabetic group. Blood glucose and serum insulin levels were measured, histologic and morphometric analyses of the pancreas were performed to determine the effect of APS on pancreatic islets. Further investigations on immune changes in spleens were tested by ELISA, semi-quantitative RT-PCR and Western blot. Downregulated blood glucose level, upregulated serum insulin concentration, increased beta cell mass, decreased apoptotic beta cell percentage, downregulation of Th1/Th2 cytokine ratio and upregulation of peroxisome proliferator-activated receptor gamma (PPARgamma) gene expression in spleens were significantly time- and dose-dependent on APS treatment, when compared to saline controls. These results show that APS seems to be helpful to attenuate insulitis and preserve beta cells from apoptosis, but it can't entirely rescue type 1 diabetes mellitus. APS ameliorates both the clinical and histological parameters of the MLD-STZ induced diabetic mice in a long-lasting fashion, most likely through immunoregulatory actions on Th1/Th2 cytokine ratio, strongly associated with PPARgamma gene expression in spleens.
Li
Ru-Jiang
RJ
Department of Histology and Embryology, Key Laboratory of Environment and Genes Related to Disease (Ministry of Education), Medical School of Xi'an Jiaotong University, Xi'an 710061, China.
Qiu
Shu-Dong
SD
Chen
Hong-Xia
HX
Tian
Hong
H
Wang
Hai-Xu
HX
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D027885:Astragalus propinquus / Q000737:chemistry*; D001786:Blood Glucose / Q000032:analysis; D015153:Blotting, Western; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D011134:Polysaccharides / Q000276:immunology / Q000302:isolation & purification / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D000276:Adjuvants, Immunologic; D001786:Blood Glucose; D047495:PPAR gamma; D011134:Polysaccharides; D012333:RNA, Messenger; D003208:Concanavalin A; D015847:Interleukin-4; D007371:Interferon-gamma