Dioscorea Extract (DA-9801) Modulates Markers of Peripheral Neuropathy in Type 2 Diabetic db/db Mice

The purpose of this study was to investigate the therapeutic effects of DA-9801, an optimized extract of Dioscorea species, on diabetic peripheral neuropathy in a type 2 diabetic animal model. In this study, db/db mice were treated with DA-9801 (30 and 100 mg/kg, daily, p.o.) for 12 weeks. DA-9801 reduced the blood glucose levels and increased the withdrawal latencies in hot plate tests. Moreover, it prevented nerve damage based on increased nerve conduction velocity and ultrastructural changes. Decrease of nerve growth factor (NGF) may have a detrimental effect on diabetic neuropathy. We previously reported NGF regulatory properties of the Dioscorea genus. In this study, DA-9801 induced NGF production in rat primary astrocytes. In addition, it increased NGF levels in the sciatic nerve and the plasma of type 2 diabetic animals. DA-9801 also increased neurite outgrowth and mRNA expression of Tieg1/Klf10, an NGF target gene, in PC12 cells. These results demonstrated the attenuation of diabetic peripheral neuropathy by oral treatment with DA-9801 via NGF regulation. DA-9801 is currently being evaluated in a phase II clinical study.

Enhancement of Antigen-specific Antibody and CD8(+) T Cell Responses by Codelivery of IL-12-encapsulated Microspheres in Protein and Peptide Vaccination

BACKGROUND: Although IL-12 has been widely accepted to play a central role in the control of pathogen infection, the use of recombinant IL-12 (rIL-12) as a vaccine adjuvant has been known to be ineffective because of its rapid clearance in the body. METHODS: To investigate the effect of sustained release of IL-12 in vivo in the peptide and protein vaccination models, rIL-12 was encapsulated into poly (DL-lactic-co-glycolic acid) (PLGA). RESULTS: We found that codelivery of IL-12-encapsulated microspheres (IL-12EM) could dramatically increase not only antibody responses, but also antigen-specific CD4(+) and CD8(+) T cell responses. Enhanced immune responses were shown to be correlated with protective immunity against influenza and respiratory syncytial virus (RSV) virus challenge. Interestingly, the enhancement of CD8(+) T cell response was not detectable when CD4(+) T cell knockout mice were subjected to vaccination, indicating that the enhancement of the CD8(+) T cell response by IL-12EM is dependent on CD4(+) T cell "help". CONCLUSION: Thus, IL-12EM could be applied as an adjuvant of protein and peptide vaccines to enhance protective immunity against virus infection.