Preventive effect of Ninjin-to (Ren-Shen-Tang), a Kampo (Japanese traditional) formulation, on spontaneous autoimmune diabetes in non-obese diabetic (NOD) mice

We previously found that ingestion of an extract of Ninjin-to (NJT; Ren-She n-Tang) suppressed the development of autoimmune diabetes in C57BL/KsJ mice induced by multiple low doses of strepto-zotocin, To verify this effects o n spontaneous autoimmune diabetes, the effects of NJT on NOD mice were inve stigated in the present study. NJT, provided in drinking water (0.25 %, 450 mg/kg/day) from 6 weeks of age, significantly prevented the incidence of s pontaneous diabetes in female NOD mice at 30 weeks of age (2/10) compared w ith that of the controls (7/10), with no effects on body growth or food int ake. 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 caus es insulin deficiency and diabetes. It is well known that NOD mice develop insulitis and diabetes because of their Th1-dominant autoimmune response. I FN-gamma production from splenic T lymphocytes stimulated with anti CD3 mon oclonal antibodies was increased, whereas IL-4 production was decreased in MOD controls compared to age- and sex-matched normal ICR mice. NJT-treatmen t reduced these deviations of cytokine production in NOD mice. These data a ll suggest that NJT can prevent spontaneous insulitis and diabetes by the m odification of deviated cytokine production in NOD mice.