Preventive Effect of Ninjin-to (Ren-Shen-Tang), a Kampo (Japanese Traditional) Formulation, on Spontaneous Autoimmune Diabetes in Non-Obese Diabetic (NOD) Mice

J-STAGE
  • Kobayashi Takao
    Department of Bioregulatory Function, Graduate School of Medicine, The University of Tokyo
  • Song Qing-Hua
    Department of Bioregulatory Function, Graduate School of Medicine, The University of Tokyo
  • Hong Tie
    Department of Bioregulatory Function, Graduate School of Medicine, The University of Tokyo
  • Kitamura Hajime
    Department of Pathology, Yokohama Minami Kyosai Hospital
  • Cyong Jong-Chol
    Department of Bioregulatory Function, Graduate School of Medicine, The University of Tokyo

抄録

We previously found that ingestion of an extract of Ninjin-to (NJT; Ren-Shen-Tang) suppressed the development of autoimmune diabetes in C57BL/KsJ mice induced by multiple low doses of streptozotocin. To verify this effects on spontaneous autoimmune diabetes, the effects of NJT on NOD mice were investigated in the present study. NJT, provided in drinking water (0.25%, 450mg/kg/day) from 6 weeks of age, significantly prevented the incidence of spontaneous diabetes in female NOD mice at 30 weeks of age (2/10) compared with that of the controls (7/10), with no effects on body growth or food intake. Even in nondiabetic mice, the blood glucose levels of the NOD controls gradually increased with age, while such increase in NJT treated mice was significantly suppressed by preventing any deficiency of glucose tolerance. NJT also significantly suppressed the progression of insulitis, which causes insulin deficiency and diabetes. It is well known that NOD mice develop insulitis and diabetes because of their Th1-dominant autoimmune response. IFN-γ production from splenic T lymphocytes stimulated with anti-CD3 monoclonal antibodies was increased, whereas IL-4 production was decreased in NOD controls compared to age- and sex-matched normal ICR mice. NJT treatment reduced these deviations of cytokine production in NOD mice. These data all suggest that NJT can prevent spontaneous insulitis and diabetes by the modification of deviated cytokine production in NOD mice.

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