title: Andrographolide as an anti-H1N1 drug and the mechanism related to retinoic acid-inducible gene-I-like receptors signaling pathway.
abstract: OBJECTIVE
  To observe the anti-virus effects of andrographolide (AD) on the retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) signaling pathway when immunological cells were infected with H1N1.
  
  
  METHODS
  Leukomonocyte was obtained from umbilical cord blood by Ficoll density gradient centrifugation, and immunological cells were harvested after cytokines stimulation. Virus infected cell model was established by H1N1 co-cultured with normal human bronchial epithelial cell line (16HBE). The optimal concentration of AD was defined by methyl-thiazolyl-tetrazolium (MTT) assay. After the virus infected cell model was established, AD was added into the medium as a treatment intervention. After 24-h co-culture, cell supernatant was collected for interferon gamma (IFN-γ) and interleukin-4 (IL-4) enzyme-linked immunosorbent assay (ELISA) detection while immunological cells for real-time polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  The optimal concentration of AD for anti-virus effect was 250 μg/mL. IL-4 and IFN-γ in the supernatant and mRNA levels in RLRs pathway increased when cells was infected by virus, RIG-I, IFN-β promoter stimulator-1 (IPS-1), interferon regulatory factor (IRF)-7, IRF-3 and nuclear transcription factor κB (NF-κB) mRNA levels increased significantly (P<0.05). When AD was added into co-culture medium, the levels of IL-4 and IFN-γ were lower than those in the non-interference groups and the mRNA expression levels decreased, RIG-I, IPS-1, IRF-7, IRF-3 and NF-κB decreased significantly in each group with significant statistic differences (P<0.05).
  
  
  CONCLUSIONS
  The RLRs mediated viral recognition provided a potential molecular target for acute viral infections and andrographolide could ameliorate H1N1 virus-induced cell mortality. And the antiviral effects might be related to its inhibition of viral-induced activation of the RLRs signaling pathway.
authors: Department of Traditional Chinese Medicine, School of Medicine, Jinan University, Guangzhou, 510632, China.
authors: Bin
authors: B
authors: Yu
authors: Cong-qi
authors: CQ
authors: Dai
authors: Zhen-you
authors: ZY
authors: Jiang
authors: En-qing
authors: EQ
authors: Li
authors: Chen
authors: C
authors: Chen
authors: Xian-lin
authors: XL
authors: Wu
authors: Jia
authors: J
authors: Chen
authors: Qian
authors: Q
authors: Liu
authors: Chang-lin
authors: CL
authors: Zhao
authors: Jin-xiong
authors: JX
authors: He
authors: Da-hong
authors: DH
authors: Ju
authors: Xiao-yin
authors: XY
authors: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000821:virology; D004224:Diterpenes / Q000494:pharmacology*; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000276:immunology; D007251:Influenza, Human / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D008264:Macrophages / Q000187:drug effects / Q000821:virology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000998:Antiviral Agents; D004224:Diterpenes; C508598:IL4 protein, human; C505371:MAVS protein, human; D016328:NF-kappa B; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D015847:Interleukin-4; C030419:andrographolide; D016899:Interferon-beta; D007371:Interferon-gamma; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases