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.

Calcium Ion Dynamics after Dexamethasone Treatment in Organotypic Cultured Hippocampal Slice

It is imperative to analyse brain injuries directly in real time, so as to find effective therapeutic compounds to protect brain injuries by stress. We established a system which could elucidate the real time Ca2+ dynamics in an organotypic cultured hippocampal slice by the insults of artificial stress hormone, dexamethasone. The real time Ca2+ dynamics could continuously be detected in cornus ammonis 3 (CA3) of the organotypic hippocampus for 8 hours under confocal microscopy. When dexamethasone concentration was increased, the Ca2+ was also increased in a dose dependent manner at 1~100 microM concentrations. Moreover, when the organotypic cultured hippocampal slice was treated with a glutamate receptor antagonist together with dexamethasone, the real time Ca2+ dynamics were decreased. Furthermore, we confirmed by PI uptake study that glutamate receptor antagonist reduced the hippocampal tissue damage caused by dexamethasone treatment. Therefore, our new calcium ion dynamics system in organotypic cultured hippocampal slice after dexamethasone treatment could provide real time analysis method for investigation of brain injuries by stress.