Dioscorea Extract (DA-9801) Modulates Markers of Peripheral Neuropathy in Type 2 Diabetic db/db Mice.
10.4062/biomolther.2014.051
- Author:
Eunjung MOON
1
;
Sung Ok LEE
;
Tong Ho KANG
;
Hye Ju KIM
;
Sang Zin CHOI
;
Mi Won SON
;
Sun Yeou KIM
Author Information
1. College of Pharmacy, Gachon University, Incheon 406-799, Republic of Korea. sunnykim@gachon.ac.kr
- Publication Type:Original Article
- Keywords:
DA-9801;
Dioscorea japonica Thunb;
Dioscorea nipponica Makino;
Diabetic peripheral neuropathy;
Nerve growth factor;
Type 2 diabetes mellitus
- MeSH:
Animals;
Astrocytes;
Blood Glucose;
Diabetes Mellitus, Type 2;
Diabetic Neuropathies;
Dioscorea*;
Mice*;
Models, Animal;
Nerve Growth Factor;
Neural Conduction;
Neurites;
PC12 Cells;
Peripheral Nervous System Diseases*;
Plasma;
Rats;
RNA, Messenger;
Sciatic Nerve
- From:Biomolecules & Therapeutics
2014;22(5):445-452
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.