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

Abstract

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. www.biomolther.orgThe 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.

Combined Application of UHPLC‐QTOF/MS, HPLC‐ELSD and 1H–NMR Spectroscopy for Quality Assessment of DA‐9801, A Standardised Dioscorea Extract

“…However, most of the currently available treatments for diabetic neuropathy only relieve the symptoms (Edwards et al, 2008). Drugs commonly used to ameliorate the symptoms, such as gabapentin and α-lipoic acid, are reported to cause various side effects; thus, the development of safer treatments for diabetic neuropathy is of upmost importance (Moon et al, 2014).…”

“…10-1341692-0000). Several preclinical studies have been done to evaluate the therapeutic efficacy and mechanism of DA-9801 in vitro and in vivo (Kim et al, 2011a;Ji et al, 2013;Jin et al, 2013;Lee et al, 2013;Moon et al, 2014;Song et al, 2014;Won et al, 2015). Recently, in January 2015, DA-9801 ended its US phase II clinical trial for assessing the safety and effectiveness in the treatment of subjects with diabetic neuropathy (ClinicalTrials.gov identifier NCT01822925).…”