Characteristics of Antidiabetic Effect of Dioscorea rhizoma(2) - Prevention of Diabetic Neuropathy by NGF Induction -

산약의 항당뇨 특성 연구(2) - NGF 유도 신경병증예방 -

  • Kang, Tong-Ho (Dept. of Oriental Pharmaceutical Development, Nambu University) ;
  • Choi, Sang-Zin (R&D Center, Dong-A Pharm. Co, Ltd) ;
  • Lee, Tae-Ho (R&D Center, Dong-A Pharm. Co, Ltd) ;
  • Son, Mi-Won (R&D Center, Dong-A Pharm. Co, Ltd) ;
  • Park, Ji-Ho (East-West Medical Science Integrated Research Center, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Kim, Sun-Yeou (East-West Medical Science Integrated Research Center, Graduate School of East-West Medical Science, Kyung Hee University)
  • Published : 2008.12.31


The main cause of diabetic neuropathy, one of the most debilitating complications, is the chronic hyperglycemia, the increase sorbitol or the decrease of nerve growth factor(NGF). NGF, a protein, plays a major role in the development and maintenance of peripheral nervous system. Systemic administration of NGF prevents manifestations of neuropathy in rodent models of diabetic neuropathy. In the previous investigation, we report the hypoglycemia effect of Dioscorea rhizoma extract(DRE) in diabetic mice. The present study shows protective effect of DRE on diabetic neuropathy by induction of NGF protein. We investigated the NGF level in salivary gland and sciatic nerve of normal mouse and the effect of DRE on sciatic nerve conductivity and thermal hyperalgesia test in Type 2 db/db mouse. DRE increased endogenous NGF level in salivary gland and sciatic nerve of mouse. And sensory nerve conductivity velocity(SNCV), motor nerve conductivity velocity(MNCV) and thermal hyperalgesia increased in DRE treatment mice compared with control group. On the basis of our results, we conclude that DRE increase induction of endogenous NGF level and have protective effect on diabetic neuropathy by induction of NGF. Therefore, we propose that long-term use of DRE might help prevention of diabetes-associated complication; diabetic neuropathy.



  1. James, R. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 26 Suppl. 1:S5-20. 2003
  2. Caputo, GM, Cavanagh, PR, Ulbrecht, JS and Gibbons, GW. Assessment and management of foot disease in patients with diabetes. N. Engl. J. Med. 331:854-860. 1994
  3. Pittenger, G and Vinik, A. Nerve growth factor and diabetic neuropathy. Exp. Diabesity Res. 4:271-285. 2003
  4. Singh, NP, Puqazhendhi, V, Das, AK, Prakash, A and Aqarwal, SK. Clinical and laboratory profile of diabetes in elderly. J. Indian Med. Assoc. 97:124-128. 1999
  5. Steinbacher, BC, Jr and Nadelhaft, I. Increased levels of nerve growth factor in the urinary bladder and hypertrophy of dorsal root ganglion neurons in the diabetic rat. Brain Res. 782:255-260. 1998
  6. Zhao, G, Kan, J, Li, Z and Chen, Z. Structural features and. immunological activity of a polysaccharide from Dioscorea opposita Thunb roots. Carbohyd. Polymers. 61:125-131. 2005
  7. Kim, MJ, Kim, HN, Kang, KS, Baek, NI, Kim, DK, Kim, YS, Jeon, BH and Kim, SH. Methanol extract of Dioscoreae rhizoma inhibits pro-inflammatory cytokines and mediators in the synoviocytes of rheumatoid arthritis. Int. Immunopharmacol. 4:1489-1497. 2004
  8. Hu, K and Yao, X. The cytotoxicity of methyl protodioscin against human cancer cell lines in vitro. Cancer Invest. 21: 389-393. 2003
  9. Yin, J, Tezuka, Y, Kouda, K, Tran, QL, Miyahara, T, Chen, Y and Kadota, S. Antiosteoporotic activity of the water extract of Dioscorea spongiosa. Biol. Pharm. Bull. 27:583-586. 2004
  10. McAnuff, MA, Harding, WW, Omoruyi, FO, Jacobs, H, Morrison, EY and Asemota, HN. Hypoglycemic effects of steroidal sapogenins isolated from Jamaican bitter yam, Dioscorea polygonoides. Food Chem. Toxicol. 43:1667-1672. 2005
  11. Kwon, CS, Sohn, HY, Kim, SH, Kim, JH, Son, KH, Lee, JS, Lim, JK and Kim, JS. Anti-obesity effect of Dioscorea nipponica Makino with lipase-inhibitory activity in rodents. Biosci. Biotechnol. Biochem. 67:1451-1456. 2003
  12. Zettler, C, Bridges, DCM, Zhou, X and Rush, RA. Detection of increased tissue concentrations of nerve growth factor with an improved extraction procedure. J. Neurosci. Res. 46:581-594. 1996<581::AID-JNR7>3.0.CO;2-F
  13. Hellweg, R and Hartung, HD. Endogenous levels of nerve growth factor(NGF) are altered in experimental diabetes mellitus: a possible role for NGF in the pathogenesis of diabetic neuropathy. J. Neurosci. Res. 26:258-267. 1990
  14. Hellweg, R, Wohrle, M, hartung, HD, Stracke, H, Hock, C and Fegerlin, K. Diabetes mellitus associated decrease in nerve growth factor levels is reversed by allogenic pancreatic islet transplantation. Neurosci. Lett. 125:1-4. 1991
  15. Kasayama, S and Oka, T. Impaired production of nerve growth factor in the submandibular gland of diabetic mice. Am. J. Physiol. 257:E400-E404. 1989
  16. Apfel, SC, Lipton, RB, Arezzo, JC and Kessler, JA. Nerve growth factor prevents toxic neuropathy in mice. Ann. Neurol. 29:87-90. 1991
  17. Apfel, SC, Arezzo, JC, Lipson, L and Kessler, JA. Nerve growth factor prevents experimental cisplastin neuropathy. Ann. Neurol. 31:76-80. 1992
  18. Calcutt, NA, Tomlinson, DR, Willars, GB and Keen, P. Axonal transport of substance P-like immunoreactivity in gangliosidetreated diabetic rats. J. Neurol. Sci. 96:283-291. 1990
  19. Robinson, JP, Willars, GB, Tomlinson, DR and Keen, P. Axonal transport and tissue contents of substance P in rats with longterm streptozotocin-diabetes. Effects of the aldose reductase inhibitor 'statil'. Brain Res. 426:339-348. 1987
  20. Tomlinson, DR, Robinson, JP, Willars, GB and Keen, P. Deficient axonal transport of substance P in streptozotocin-induced diabetic rats. Effects of sorbinil and insulin. Diabetes. 37: 488-493. 1988
  21. Willars, GB, Calcutt, NA, Compton, AM, Tomlinson, DR and Keen, P. Substance P levels in peripheral nerve, skin, atrial myocardium and gastrointestinal tract of rats with long-term diabetes mellitus. Effects of aldose reductase inhibition. J. Neurol. Sci. 91:153-164. 1989
  22. Diemel, LT, Stevens, EJ, Willars, GB and Tomlinson, DR. Depletion of substance P and calcitonin gene-related peptide in sciatic nerve of rats with experimental diabetes: effects of insulin and aldose reductase inhibition. Neurosci. Lett. 137:253-256. 1992
  23. Archer, AG, Watkins, PJ, Thomas, PK, Sharma, AK and Payan, J. The Natural history of acute painful diabetic neuropathy in diabetes mellitus. J. Neurol. Neurosurg. Psychiat. 46: 491-499. 1983
  24. Boulton, AJ, Worthy, RC, Drury, J, Hardisty, CA, Wolf, E, Cudworth, AG and Ward, JD. Metabolic and genetic studies in diabetic neuropathy. Diabetologia. 26:15-19. 1984
  25. Thomas, PK and Eliasson, SG. Diabetic Neuropathy. pp.1773- 810. Saunders. Philadelphia, USA. 1984
  26. Singleton, JR, Smith, AG and Bromberg, MB. Painful sensory polyneuropathy associated with impaired glucose tolerance. Muscle Nerve. 24:1225-1228. 2001