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

Abstract

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 immuno­modulatory effects associated with a shift from Th1 to Th2 immune response and may have protective effects against autoimmune diabetes

The Herbal Preparation Padma® 28 Protects Against Neurotoxicity in PC12 Cells

“…The decrease in oxidative activity induced by Padma 28 may be attributed either to a direct scavenging of reactive oxygen species generated in the PC12, or to the interference with the generation of hydroxyl radicals by chelating divalent transitional metals such as Fe IIII + which might participate in the Fenton reaction (Halliwell and Gutteridge, ). However, the effect of Padma 28 against oxidative capacity may be also indirect by stimulating the antiinflammatory cytokine IL‐10 (Weiss et al , ) and inhibiting the proinflammatory cytokine production (Barak et al , ).…”

“…The study investigated the neuroprotective potential of Padma 28, a herbal multi‐component formula based on Tibetan medicine, which is rich in polyphenols and in addition, antioxidant components (Ginsburg et al , ). Padma 28 has been reported to have protective effects in a wide spectrum of conditions, including arterial diseases, inflammatory conditions as well as diabetes (Aslam et al , ; Barak et al , ; Bowling and Stewart, ; Matzner and Sallon, ; Melzer et al , ; Navab et al , ; Weiss et al , ), but much less is known about its effect on neurodegenerative diseases. The study investigated the effect of Padma 28, as well as of certain polyphenols, in a PC12 neuronal cell line derived from rat pheochromocytoma, which displays phenotypic characteristics of sympathetic neurons.…”

Tibetan Medicine for Diabetes Mellitus: Overview of Pharmacological Perspectives

“…This multi-herbal preparation is rich in secondary plant substances including essential oils, flavonoids, and tannins ( Samochowiec and Wieland, 1983 ). Herbal flavonoids isolated from Padma 28 was investigated to explore the protective effect on the autoimmune disorder in non-obese diabetic mice ( Weiss et al, 2011 ). The destruction of β-cells in autoimmune DM involves an imbalanced Th1/Th2 polarization and Th1/Th2 cytokines ( Rabinovitch and Suarez-Pinzon, 1998 ).…”

“…The destruction of β-cells in autoimmune DM involves an imbalanced Th1/Th2 polarization and Th1/Th2 cytokines ( Rabinovitch and Suarez-Pinzon, 1998 ). The aqueous extract of Padma 28 containing abundant flavonoids was found to suppress the development of autoimmune DM in female NOD mice ( Weiss et al, 2011 ). The levels of Th2 cytokines IL-10 and IL-6 were increased whereas Th1 cell-derived IL-12 was decreased after intraperitoneal administration of aqueous Padma 28 extract.…”

Camphor (Cinnamomum camphora), a traditional remedy with the history of treating several diseases

“…Padma 28 is another multi compound herbal preparation, based on camphor formula which has shown to be effective against chronic inflammatory diseases. The result of a study indicates that Padma 28 has the ability to suppress the development of autoimmune diabetes in female non obese diabetic (NOD) mice which could be an experimental model for type 1 diabetes mellitus in humans [15].…”