Reversal effects of Kampo medicine on pathogenesis of diabetes

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Jong-Chol Cyong. Department of Bioregulatory Function, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. Reveral effects of Kampo medicine on pathogenesis of diabetes. Proceedings of International Symposium on East-West Medicine. 110-116, 1999.-purpose Traditional medicine has defined an exhausted condition with polyuria due to over-drinking, over-eating. And as "shoukatsu<消渴>"(emaciation-thirst) from the ancient times. It is considered that "shou-katsu" would obviously correspond to diabetes mellitus in modern medicine. We have attempted bridge building by the common understanding of the pathogenesis of diabetes in Kampo medicine and modern medicine. Material and Method We have selected six formulae, Mao-to(痲黃湯), Shimbu-to(眞武湯), Ninjin-to(人蔘湯), Shigyaku-san (四逆散), Keishi-to(桂枝湯)and Shimotsu-to(四物湯), which contain relatively fewer kinds of crude drugs. We consider these formulae to be the basis of various herbal combinations. We administered these six formulae to three different types of experimental mice affected by type ` diabetes. 1)BALB/C diabetic mice with destruction of pancreatic islet inducedby single high doses of streptozotocin(STZ); 2) C57BL/Ks mice with T cell mediated autoimmune diabetes induced by single low doses of STZ(MLDSTZ); 3)NOD/Shi spontaneously diabetic mice. In addition, we clinically Investigated outpatients with type 2 diabetes who received the combination therapy of Kampo medicines. Results and Discussion. The Ninjin-to(人蔘湯) could reverse the decrease of weight in MLDSTZ induced diabetes mice, improve their general status, and significantly inhibit the development of diabetes. But we observed lymphatic infiltration of the pancreatic islets in both the control group and the Ninjin-to treated group. We found great changes in the Ninjin-to reated group when we analyzed the functions of the lymphocytes in detail. The Ninjin-to reated group when we analyzed the functions of the lymphocytes in detail. The Ninjin-to treatment could reduce the increase of INF□-producing cells, measurement of the expression of INFγand IL-4 in the CD4 cells stimulated by anti-CD3/CD28. Type 1 diabetes causes an augment in the Th¹ helper function, and the Ninjin-to may control the balance of Th¹and Th²by suppressing of Th1 function. We found that the incidence of diabetes could be prevented in NOD mice by the administration of the Ninjin-to for 24 weeks. We also observed a significant improvement in glucose tolerance and the regression of insulitis. It has not yet been reported that a preventive drug for diabetes has been developed in Western medicine. Anti-heat shock protein(HSP) antibodies are produced before the expression of advanced glycation endproduct(AGE) in human type 1 diabetes. The values of anti-HSP antibodies have been increased in untreated NOD mice, according to the progression of diabetes. However, the expression of anti-HSP antibodies was significantly decreased in the group of mice treated by the Ninjin-to, We also observed artherosclerosis in the main arteries when normal mice immunized by bacterial HSP took the lipid loading diet, It is suggested that anti-HSP protein antibodies may be expressed both in diabetes and in artheroslerosis. Anti-HSP antibodies were frequently found in the serum of patients with diabetes. The administration of Hachimi-jio-gan(八味地黃丸)for two weeks could reduce this expression of anti-HSP antibodies. The destroyed islet cells in STZ-induced diabetic mice were observed to be regenerated in an extremely short time after the administration of Mao-to(麻黃湯)to these mice. In addition, Zokumei-to(統命湯), which has the combined formulae of Ninjin-to and Mao-to could significantly decrease HbA1c in the patient with diabetes. Conclusion We found that simple Kampo formulae such as Ninjin-to or Mao-to may have potent preventive effects against diabetes and artherosclerosis, and may restore thepancreatic islets. Advanced research in Kampo medicnes may show novel ways for the prevention and treatment of diabetes mellitus.