Biol. Pharm. Bull. 30(3) 470—476 (2007)

quently occurring chronic diseases in puberty. It afflicts millions of individuals worldwide, and its prevalence and incidence continue to rise annually. This disease results from selective destruction of the insulin-producing b cells in the pancreatic islets, and is primarily a T cell-mediated autoimmune disease directed against one or more b cell autoantigens. T cells specific for islet b cell autoantigens may exist normally but are restrained by immunoregulatory mechanisms (the self-tolerant state). However, T1DM develops when one or another immunoregulatory mechanism fails, allowing b cell autoreactive T cells to become activated, expand clonally and entrain a cascade of immune and inflammatory processes in the islets. This autoimmune inflammatory process is caused by a switch of the immune balance between T helper 1 and 2 (Th1 and Th2) lymphocytes towards Th1 response, initiated and propagated by the effect of Th1 cells and their secreted cytokines (e.g. interferon g), and suppressed by Th2-secreted anti-inflammatory cytokines (e.g. IL-4, IL-10). Usual clinical treatment for T1DM, such as insulin or insulin replacement, may ameliorate the symptoms of the endocrine disease, but it does not affect the autoimmune process. To successfully recover from T1DM, concomitant immunosuppressive therapy is indispensable to protect b cells from immune-mediated destruction. However, the broad spectrum immunosuppressive diabetic therapy is not completely free of islet toxic side effects and is associated with deleterious systemic complications. Although new immunomodulatory therapeutic regimens focused on GAD and heat shock protein 60 (Diapep277), which is designed to inhibit b cell destruction specifically, are in the early clinical trial phase, they are used only in new-onset of T1DM or in individuals with latent autoimmune diabetes of the adult, and appear to have marginal efficacy in the inhibition of insulitis and in decreasing insulin requirements. Therefore, today, there is an urgent need to search for alternative therapies that may have a similar degree of efficacy on the protection of exogenously or endogenously expanded b cell mass from the prevailing anti-b cell leukocyte population without undesirable side effects. The identification of compounds with immunomodulatory activity from medicinal plants may provide an opportunity to develop a new class of antidiabetic agents. According to previous reports, Astragalus polysaccharide (APS) is one of the most important and valuable compounds with immunomodulatory properties. Polysaccharides from natural sources are a class of macromolecules that can profoundly affect the immune system and therefore have the potential as immunomodulators with wide clinical applications. Astragalus polysaccharide (APS) is extracted from Astragalus membranaceus (Huangqi). Scientific investigation in the last two decades has revealed much insight into the pharmacological functions of different components of Huangqi, especially its polysaccharide fractions. Astragalus polysaccharide (APS) is reported to have antioxidant, antidiabetic, and immunomodulatory activities. In vivo studies, administering APS or Huangqi extract markedly decreases normal murine Th1/Th2 cytokine ratio. This immunopharmacological profile of APS may be related to its beneficial effects in the diseases with imbalance of Th1/Th2 cytokine ratio, such as T1DM. Although APS may improve the metabolism of streptozotocin (STZ) induced diabetic rats, enable insulin-sensitizing and antihyperglycemic activity in fat-fed STZ-treated rats, and before onset of T1DM in NOD mice pretreated with APS, diabetes mellitus can be partly prevented, there is no data on immunotherapeutic effects of APS on T1DM after the disease 470 Vol. 30, No. 3