title: Neurotrophic activity of DA-9801, a mixture extract of Dioscorea japonica Thunb. and Dioscorea nipponica Makino, in vitro.
abstract: BACKGROUND
  Dioscorea japonica Thunb. has been traditionally used to treat polyuria and diabetes in Korea.
  
  
  OBJECTIVE
  We previously report the effects of Dioscorea japonica Thunb. extract on glucose control, NGF induction, and neuroprotection in a rodent diabetic model. Since the most potent fraction, DA-9801, was identified from a mixture of Dioscorea japonica Thunb. (DJ) and Dioscorea nipponica Makino (DN) following bioactivity-guided fractionation, here, we investigated the potential mechanism of the extract activity against diabetic peripheral neuropathy (DPN).
  
  
  METHODS
  A 1:3 mixture of DJ and DN was extracted with ethanol (DA-9801) and further fractionated into an ethylacetate-soluble fraction (DA-9801E). Effects of these extracts on neurite outgrowth were measured in PC-12 cells and DRG neurons. Effects on cell viability and TrkA phosphorylation were evaluated in PC-12 cells. NGF induction effect was determined in primary Schwann cells as well as IMS32 cells (immortalized Schwann cells).
  
  
  RESULTS
  No cytotoxicity was observed in PC-12 cells at the concentration below 500 μg/ml of either DA-9801 or DA-9801E. DA-9801 and DA-9801E at 100 μg/ml and 10 μg/ml, respectively, showed a significant effect on neurite outgrowth in PC-12 cells and DRG neurons in the presence of or absence a low concentration of NGF (2 ng/ml). The Trk-A phosphorylation effect of DA9801 was confirmed in PC-12 cells. An NGF induction effect of these extracts was not detected in either IMS-32 cells, or primary Schwann cells.
  
  
  CONCLUSIONS
  The NGF agonistic activity of DA-9801 and DA-9801E was demonstrated, which may contribute to their neuroprotective effect against DPN. Studies of the detailed mechanism of these extracts as well as identification of the active components are warranted for the development of an anti-DPN drug from DJ and DN.
authors.affiliation: Department of Biomedical Sciences, College of Medicine, The Catholic University of Korea, 505 Banpo-4-dong, Seocho-ku, Seoul 137-701, Republic of Korea.
authors.forename: Namho
authors.initials: N
authors.lastname: Kim
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Yu-Jin
authors.initials: YJ
authors.lastname: Kim
authors.forename: Jeong-Ki
authors.initials: JK
authors.lastname: Kim
authors.forename: Min-Kyung
authors.initials: MK
authors.lastname: Nam
authors.forename: Hyangshuk
authors.initials: H
authors.lastname: Rhim
authors.forename: Sungjoo Kim
authors.initials: SK
authors.lastname: Yoon
authors.forename: Sang-Zin
authors.initials: SZ
authors.lastname: Choi
authors.forename: Miwon
authors.initials: M
authors.lastname: Son
authors.forename: Sun-Yeou
authors.initials: SY
authors.lastname: Kim
authors.forename: Hyo-Jeong
authors.initials: HJ
authors.lastname: Kuh
mesh_terms: D000085:Acetates / Q000737:chemistry; D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000187:drug effects; D005591:Chemical Fractionation; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D027742:Dioscorea / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000737:chemistry; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009414:Nerve Growth Factors / Q000378:metabolism; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016716:PC12 Cells; D010766:Phosphorylation; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000378:metabolism; D012583:Schwann Cells / Q000187:drug effects; D012584:Sciatic Nerve / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012997:Solvents / Q000737:chemistry; D015854:Up-Regulation
chemical_list: D000085:Acetates; D009414:Nerve Growth Factors; D010936:Plant Extracts; D012997:Solvents; D000431:Ethanol; C007650:ethyl acetate; D020917:Receptor, trkA