Herbal flavonoids inhibit the development of autoimmune diabetes in NOD mice: proposed mechanisms of action in the example of PADMA 28

Padma 28 is a multicompound herbal preparation based on the camphor formulas from traditional tibetan medicine (TTM). It contains a variety of different secondary plant substances, which include terpenes and polyphenols such as flavonoids and tannins. The formula is used in various chronic inflammatory diseases. The aim of this study was to investigate whether secondary plant substances as present in Padma 28 are able to prevent the development of autoimmune diabetes. Female NOD mice were administered an aqueous Padma 28 extract intraperitonneally (i.p.), subcutaneously (s.c.) or per os (p.o.) over a period of 13 weeks. The development of autoimmune diabetes mellitus type 1 was monitored over 24 weeks. Untreated and saline treated mice served as controls. After 24 weeks, 20% of the control groups were free of diabetes while 100% and 80% of the animals administered aqueous extracts from Padma 28 i.p. or s.c., respectively, were diabetes-free. In the p.o. group, 33% were diabetes-free. In controls, only a few pancreatic islets had survived. Animals treated i.p. with Padma 28 had preserved islets with minimal lymphocyte infiltrations. Spleen cells from animals treated i.p. or s.c. with Padma 28 and stimulated with concanavalin A showed significant elevations in the levels of interleukins (IL)-10, IL-6 and IL-4. In the plasma, the level of the Th1 cytokine IL-12 was decreased in the i.p. group. Padma 28 treatment by the i.p. route of administration showed a significant decrease in CD8 cytotoxic cells, which have been implicated in the destruction of the islets. The findings support the use of secondary plant substances such as flavonoids in inflammatory autoimmune diseases. The results suggest that Padma 28 has immuno-modulatory effects associated with a shift from Th1 to Th2 immune response and may have protective effects against autoimmune diabetes.