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.

OBJECTIVE: To determine the effect of blue light on cultured splenocyte viability and secretion of cytokines involved in the regulation of immune responses in the inflammatory process. BACKGROUND DATA: Previous studies showed that red light has various effects on lymphocyte proliferation and production of cytokines. MATERIALS AND METHODS: Cultured mouse splenocytes were exposed to visible light (wavelengths, 450-490 nm) using 2-108 J/cm(2), with and without scavengers of reactive oxygen species (ROS). One half of the samples were stimulated by the heat-killed periopathogenic bacterium Porphyromonas gingivalis. Following incubation for 48 h, the levels of the cytokines interleukin-10 (IL-10), tumor necrosis factor alpha (TNFα), and interferon gamma (IFNγ) were analyzed, and the viability of the cells was tested using the XTT assay. The total oxidant-scavenging capacity of the nonexposed and exposed splenocytes to light was determined by a chemiluminescence assay, and the temperature of the cell culture medium was measured after light exposure. RESULTS: Exposure to blue light at fluences of 27-108 J/cm(2) caused a decrease in splenocyte viability. Lower fluences increased the secretion of cytokine IL-10, which was abolished by ROS scavengers. Exposure to light had no effect on the secretion of cytokines TNFα and IFNγ. Following exposure to light, more ROS were detected and the temperature measured did not exceed 30.7°C. CONCLUSIONS: Blue light had a stimulatory effect on cell secretion of IL-10, mediated by ROS. Therefore, an increase in IL-10 might be a potential method for modulating the inflammatory processes of local disorders, such as periodontitis and arthritis.

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. As a rich source of antioxidant polyphenols, this herbal Padma 28 preparation seems to be a promising candidate for the treatment of degenerative diseases such as Alzheimer's disease (AD), a condition involving oxidative stress. Moreover, polyphenols have also been shown to mitigate AD neuropathology. The study investigated the protective effect of Padma 28 and of certain polyphenols on the neurotoxicity of PC12 cells induced by the neurotoxins: amyloid-beta (Aβ), glutamate, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 3-nitropropionate (3-NP), known to be involved in AD, Parkinson's disease (PD), amyotrophic-lateral-sclerosis (ALS) and Huntington's disease (HD), respectively. The decrease in cell viability induced by each of the toxins was significantly attenuated by Padma 28 treatment. Also, a decrease in the oxidative capacity of PC12 cells treated with Padma 28 was noted, indicating that the decrease in cell viability induced by the toxins might have been the result of an oxidative stress which could be attenuated by Padma 28 acting as a potent antioxidant. Padma 28, which is available in Europe and USA, seems to be a promising candidate for the treatment of CNS diseases.

Screening the voluminous literature describing the quantifications of antioxidant levels in patients with various clinical disorders and after the administration of supplements has revealed that nearly all the studies have exclusively involved measurements in plasma. Since the classic tests have mainly quantified levels of low-molecular- weight antioxidants and albumin in human plasma but not those associated with erythrocyte enzymes and hemoglobin, such studies have not taken into account the roles of circulating cells, all laden with catalase and additional enzymes. This finding raises serious doubt as to whether reports on antioxidant quantifications exclusively in plasma can be trusted to represent true oxidant-scavenging abilities. Using a new chemiluminescence assay and an assay involving the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) (which are adapted to quantify antioxidants in whole blood),1 we have shown that erythrocytes, platelets, and lymphocytes not only rapidly scavenge reactive oxygen species but also avidly bind to their surfaces a large variety of antioxidant polyphenols, which further enhance their oxidantscavenging abilities.2,3 Such complexes could further act synergistically with low-molecular-weight antioxidants in plasma and with albumin to decompose reactive oxygen species. The synergistic scavenging effect of reactive oxygen species can be induced by a combination of human erythrocytes, plasma, and the representative polyphenol, epicatechin (Fig. 1). The advantage of the luminescence assay over the other classic methods is that it can quantify antioxidants in whole blood and that only 2 to 3 mm3 are needed to rapidly assess its oxidantscavenging ability. As proposed by Richards et al.4 and by Minetti and Malorni,5 erythrocytes have potent antioxidant properties that can act as sinks and as protectors against reactive oxygen species but may also act as pro-oxidant cells. It has been suggested that the genuine oxidant-scavenging ability of blood is most probably a result of the synergistic effects exerted by the antioxidants associated with blood cells, mostly due to catalase, superoxide dismutase, glutathione peroxidase, oxidoreductase, and hemoglobin, cells that are coated in an accumulative manner by dietary polyphenols, free circulating polyphenols, and low-molecular-weight antioxidants and albumin in plasma.2,3 The ability of blood cells to bind antioxidant polyphenols may be an important phenomenon with far-reaching in vivo consequences. With all these factors taken together, it is paramount that antioxidants be measured in whole blood and not in plasma alone in clinical settings.

The dilemma whether supplementations of dietary antioxidants might prevent the adverse consequences of oxidative stress, the inadequacy of the analytical methods employed to quantify oxidant scavenging ability (OSA) levels in whole blood and the distribution and fate of polyphenols and their metabolites in various body compartments following oral consumption are discussed. While none-metabolized polyphenols might exert their antioxidant effects mainly in the oral cavity, metabolized polyphenols might be beneficial in the gastrointestinal tract to counteract the toxicity of oxidants and also of the sequelae of inflammatory processes. Although only micromolar amounts of polyphenols and their metabolites eventually reach the blood circulation, these may nevertheless still be highly effective as scavengers of reactive oxygen and nitrogen species because of their ability to synergize with plasma low molecular-weight antioxidants and with albumin. Polyphenols can avidly bind to surfaces of microorganisms and of blood cells to markedly enhance their OSA, therefore the routine quantifications of antioxidant levels conducted in clinical settings should always use catalase-rich whole blood but not as customary, plasma alone. In addition to their antioxidant and metal chelating properties, polyphenols may also act as signaling agents capable of affecting metabolic, inflammatory, autoimmune, carcinogenic and aging processes.