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Neurodegenerative diseases, including Alzheimer’s disease, are prevalent in diabetic patients. DA-9801 is a standardized extract of Dioscorea japonica Thunb. and Dioscorea nipponica Makino, which has been shown to reduce blood glucose levels and exert protective effects against diabetic peripheral neuropathy. Here, we aimed to investigate whether DA-9801 could protect hyperglycemia-induced central neuropathy and to elucidate the underlying mechanisms. DA-9801 protected rat cortical primary neurons against hyperglycemia-induced neurotoxicity by lowering the levels of reactive oxygen species. In addition, we identified the genes whose expression in high glucose-treated primary neurons was significantly altered by DA-9801 treatment. Moreover, the major saponins of DA-9801, dioscin and protodioscin, protected neurons from hyperglycemia-induced toxicity, suggesting that these may be the most important active neuroprotective components of DA-9801. Our results showed that DA-9801 protects neurons derived from the central nervous system and that it may be useful to treat and delay the development of neurodegenerative diseases in diabetic patients.

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.