title: Phenolic derivatives from the rhizomes of Dioscorea nipponica and their anti-neuroinflammatory and neuroprotective activities.
abstract: BACKGROUND
  Dioscorea nipponica (Dioscoreaceae) have been used as traditional medicines for diabetes, inflammatory and neurodegenerative diseases in Korea. The aim of the study was to isolate the bioactive components from the rhizomes of Dioscorea nipponica and to evaluate their anti-neuroinfalmmatory and neuroprotective activities.
  
  
  METHODS
  The phytochemical investigation of 50% EtOH extract of Dioscorea nipponica using successive column chromatography over silica gel, Sephadex LH-20, and preparative high performance liquid chromatography (HPLC) resulted in the isolation and identification of 17 phenolic derivatives, including four new phenolic compounds (1-4). The structural elucidation of these compounds was based on spectroscopic methods, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy techniques, mass spectrometry, and optical rotation. All isolated compounds were evaluated for their effects on nerve growth factor (NGF) secretion in a C6 rat glioma cell line and nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV2 cells. The neurite outgrowth of compound 16 was further evaluated by using mouse neuroblastoma N2a cell lines.
  
  
  RESULTS
  Three new stilbene derivatives, diosniponol C (1), D (2) and diosniposide A (3) and one new phenanthrene glycoside, diosniposide B (4), together with 13 known compounds were isolated from the rhizomes of Dioscorea nipponica. Of the tested compounds (1-17), phenanthrene, 3,7-dihydroxy-2,4,6-trimethoxy-phenanthrene (16) was the most potent NGF inducer, with 162.35±16.18% stimulation, and strongly reduced NO levels with an IC50 value of 19.56 μM in BV2 microglial cells. Also, it significantly increased neurite outgrowth in N2a cells.
  
  
  CONCLUSIONS
  This study supports the ethnopharmacological use of Dioscorea nipponica rhizomes as traditional medicine.
authors: Natural Products Laboratory, School of Pharmacy, Sungkyunkwan University, 300 Chonchon-dong, Jangan-ku, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors: Kyeong Wan
authors: KW
authors: Woo
authors: Graduate School of East-West Medical Science, Kyung Hee University Global Campus, Yongin 446-701, Republic of Korea.
authors: Oh Wook
authors: OW
authors: Kwon
authors: College of Pharmacy, Gachon University, Incheon 406-799, Republic of Korea; Gachon Institute of Pharmaceutical Science, Gachon University, Incheon 406-799, Republic of Korea; Gachon Medical Research Institute, Gil Medical Center, Inchon 405-760, Republic of Korea.
authors: Sun Yeou
authors: SY
authors: Kim
authors: Dong-A Pharm Institute, Kiheung, Yongin 449-905, Republic of Korea.
authors: Sang Zin
authors: SZ
authors: Choi
authors: Dong-A Pharm Institute, Kiheung, Yongin 449-905, Republic of Korea.
authors: Mi Won
authors: MW
authors: Son
authors: Natural Products Laboratory, School of Pharmacy, Sungkyunkwan University, 300 Chonchon-dong, Jangan-ku, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors: Ki Hyun
authors: KH
authors: Kim
authors: Natural Products Laboratory, School of Pharmacy, Sungkyunkwan University, 300 Chonchon-dong, Jangan-ku, Suwon, Gyeonggi-do 440-746, Republic of Korea. Electronic address: krlee@skku.edu.
authors: Kang Ro
authors: KR
authors: Lee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D027742:Dioscorea / Q000737:chemistry*; D005910:Glioma / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D020128:Inhibitory Concentration 50; D008070:Lipopolysaccharides / Q000008:administration & dosage; D055670:Medicine, Korean Traditional; D051379:Mice; D020932:Nerve Growth Factor / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010636:Phenols / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D027343:Rhizome
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D010636:Phenols; D010936:Plant Extracts; D009569:Nitric Oxide; D020932:Nerve Growth Factor
keywords: Dioscorea nipponica; Dioscoreaceae; N(G)-monomethyl-L-arginine (PubChem CID: 135242); NGF induction; Phenanthrene; Stilbene