title: Lignans from the stems of Clematis armandii ("Chuan-Mu-Tong") and their anti-neuroinflammatory activities.
abstract: BACKGROUND
  The dried stems of Clematis armandii (Caulis clematidis armandii), named "Chuan-Mu-Tong" in Chinese Pharmacopoeia, have been traditionally used as an herbal remedy mainly for inflammation-associated diseases. The Aim of the study is to identify the potential anti-neuroinflammatory components from Clematis armandii.
  
  
  METHODS
  The ethanol extract of "Chuan-Mu-Tong" was suspended in H₂O and exhaustively extracted with CH₂Cl₂. The CH₂Cl₂ fraction was successively subjected to column chromatography (CC) over silica gel, Sephadex LH-20, and semi-preparative HPLC. The structures of the isolated compounds were identified by spectroscopic methods and by comparison with those reported in the literature. Their anti-neuroinflammatory activities were evaluated by inhibitory effects on pro-inflammatory mediators [e.g. nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α)] in lipopolysaccharide (LPS)-activated BV-2 cells.
  
  
  RESULTS
  One new and sixteen known lignans were isolated and characterized. The absolute configuration of the new lignan, (7R,8S)-9-acetyl-dehydrodiconiferyl alcohol (1), was elucidated by a combination of 1D/2D NMR techniques and the Electronic Circular Dichroism (ECD) spectroscopy based on the empirical helicity rules. The anti-neuroinflammatory bioassay showed that compounds 1, (7R,8S)-dehydrodiconiferyl alcohol (2), erythro-guaiacylglycerol-β-coniferyl ether (5), and threo-guaiacylglycerol-β-coniferyl ether (6) displayed significant inhibitory effects on NO production. Among them, neolignans 1 and 2 exhibited more potent activities than the positive control (N(G)-monomethyl-L-arginine, L-NMMA), with an IC₅₀ value of 9.3 and 3.9 μM, respectively. Moreover, both 1 and 2 were also found to concentration-dependently suppress the TNF-α release in LPS-stimulated BV-2 cells.
  
  
  CONCLUSIONS
  The results revealed that lignans are the major components of "Chuan-Mu-Tong", and their anti-neuroinflammatory activities strongly support the traditional application of this herb medicine on inflammation. Moreover, the dihydrobenzo[b]furan neolignans 1 and 2 as well as Caulis clematidis armandii could be further exploited as new therapeutic agents to treat inflammation-mediated neurodegenerative and aging-associated diseases.
authors.affiliation: Department of Natural Products Chemistry, Fudan University, Shanghai 201203, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Department of Chemistry, School of Science & Engineering, No. 3663 Zhongshan Road N, East China Normal University, Shanghai 200062, China; Department of Chemistry, Hoa Lu University, No. 491C Xuanthanh Road, Ninh Binh 40000, Vietnam.
authors.forename: Van-Binh
authors.initials: VB
authors.lastname: Bui
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, No. 826 Zhangheng Road, Shanghai 201203, China. Electronic address: liuxinhua@fudan.edu.cn.
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Liu
authors.affiliation: Department of Natural Products Chemistry, Fudan University, Shanghai 201203, China.
authors.forename: Zhi-Lai
authors.initials: ZL
authors.lastname: Hong
authors.affiliation: Department of Natural Products Chemistry, Fudan University, Shanghai 201203, China.
authors.forename: Guo-Xun
authors.initials: GX
authors.lastname: Yang
authors.affiliation: Department of Natural Products Chemistry, Fudan University, Shanghai 201203, China; Department of Chemistry, School of Science & Engineering, No. 3663 Zhongshan Road N, East China Normal University, Shanghai 200062, China. Electronic address: jfhu@brain.ecnu.edu.cn.
authors.forename: Jin-Feng
authors.initials: JF
authors.lastname: Hu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D039324:Clematis / Q000737:chemistry; D017705:Lignans / Q000302:isolation & purification / Q000494:pharmacology*; D008070:Lipopolysaccharides; D051379:Mice; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D017705:Lignans; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide
keywords: Anti-neuroinflammation; Clamatis armandii; Lignans; NO; Ranunculaceae; TNF-α