title: Lariciresinol-4-O-β-D-glucopyranoside from the root of Isatis indigotica inhibits influenza A virus-induced pro-inflammatory response.
abstract: BACKGROUND
  Isatis indigotica is a traditional Chinese medicine. Its dried roots named "ban lan gen" in Chinese, are used for clinical treatment of virus infection, tumor, inflammation with a long history. However, its anti-influenza active ingredient and the underlying mechanism remain unclear. In this study, the anti-influenza and anti-inflammatory effects of a lignan glycoside: lariciresinol-4-O-β-D-glucopyranoside isolated from the root of I. indigotica on human alveolar epithelial cell line A549 infected with influenza A virus were investigated.
  
  
  METHODS
  Chemical and spectroscopic methods were employed to identify the structure of the lignan glycoside. Cytotoxicity of the lignan glycoside was analyzed using methylthiazolyltetrazolium (MTT) assay. The inhibitory activity against influenza virus of the lignan was determined by CPE inhibition assay. HEK-293 cells stably co-transfected with NF-κB responsive firefly luciferase and constitutively expressing GFP were employed for monitoring the effect of the lignan on NF-κB signal pathway activation. Nuclear export of viral ribonucleoprotein (RNP) complexes was monitored by indirect immunofluorescence. Quantitative real-time PCR was used to quantify the expression profiling of cytokines and chemokines after infection with influenza virus.
  
  
  RESULTS
  We showed that the lignan glycoside treatment was effective against the influenza A virus-induced cytopathic effect (CPE) in MDCK cells. Further study demonstrated the lignan glycoside attenuated virus-induced NF-κB activation, but did not affect export of viral ribonucleoprotein (RNP) complexes from the nucleus in late stages of infection. We revealed that the lignan glycoside suppressed influenza A virus (H1N1)-induced expression of the pro-inflammatory molecules IL-6, TNF-α, IL-8, MCP-1, IP-10 and IFN-α. Moreover, the cytokines and chemokines profiles induced by H9N2 virus resembled those of influenza virus H1N1, but the lignan glycoside reduced the expression of IP-10 and TNF-α.
  
  
  CONCLUSIONS
  Our results suggest that the lignan glycoside is a bioactive component of I. indigotica which may contribute an adjunct to pharmacotherapy for influenza virus infection.
authors: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, China.
authors: Jing
authors: J
authors: Li
authors: Macau University of Science and Technology, Taipa, Macau S.A.R.
authors: Beixian
authors: B
authors: Zhou
authors: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, China.
authors: Chufang
authors: C
authors: Li
authors: Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors: QiaoYan
authors: Q
authors: Chen
authors: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, China.
authors: Yutao
authors: Y
authors: Wang
authors: Guangzhou Medical University, Guangzhou 510182, China.
authors: Zhengtu
authors: Z
authors: Li
authors: Guangzhou Medical University, Guangzhou 510182, China.
authors: Tingting
authors: T
authors: Chen
authors: Guangzhou Medical University, Guangzhou 510182, China.
authors: Chunguang
authors: C
authors: Yang
authors: Macau University of Science and Technology, Taipa, Macau S.A.R.
authors: Zhihong
authors: Z
authors: Jiang
authors: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, China; Macau University of Science and Technology, Taipa, Macau S.A.R.
authors: Nanshan
authors: N
authors: Zhong
authors: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, China; Macau University of Science and Technology, Taipa, Macau S.A.R.. Electronic address: jeffyah@163.com.
authors: Zifeng
authors: Z
authors: Yang
authors: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, China. Electronic address: chenrc@vip.163.com.
authors: Rongchang
authors: R
authors: Chen
mesh_terms: D000818:Animals; D004285:Dogs; D005960:Glucosides / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000378:metabolism; D053127:Influenza A Virus, H9N2 Subtype / Q000187:drug effects* / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots
chemical_list: D005960:Glucosides; D018836:Inflammation Mediators; D010936:Plant Extracts; C528933:lariciresinol-4'-O-glucopyranoside
keywords: 45027869; Inflammation; Influenza virus; Lariciresinol-4-O-β-D-glucopyranoside; PubChem CID:; Root of Isatis indigotica