title: Gan-Lu-Siao-Du-yin, a prescription of traditional Chinese medicine, inhibited enterovirus 71 replication, translation, and virus-induced cell apoptosis.
abstract: BACKGROUND
  Gan-Lu-Siao-Du-yin (GLSDY) is a prescription of traditional Chinese medicine. GLSDY contains 11 ingredients and is commonly used for endemic diseases. Enterovirus 71 (EV71) is an endemic disease that can cause meningoencephalitis with mortality and neurologic sequelae without any effective management. It is unknown whether GLSDY is effective against EV71 infection.
  
  
  OBJECTIVE
  To test the hypothesis that GLSDY can protect cell from EV71-induced injury.
  
  
  METHODS
  Effects of a hot water extract of GLSDY on EV71 were tested in human foreskin fibroblast cells (CCFS-1/KMC) and human rhabdomyosarcoma cells (RD cells) by plaque reduction assay and flow cytometry respectively. Inhibition of viral replication was further examined by reverse quantitative RT-PCR (qRT-PCR). Its effect on viral protein translation and virus-induced apoptosis were examined by western blot.
  
  
  RESULTS
  GLSDY was dose-dependently effective against EV71 infection (p<0.0001) in both CCFS-1/KMC cells and RD cells. GLSDY was highly effective when supplemented after viral inoculation (P<0.0001) with an IC50 of 8.7μg/mL. GLSDY inhibited viral RNA replication (P<0.0001), formation of viral structural proteins (VP0, VP1, VP2 and VP3) and non-structural proteins (protease 2B and 3AB). Furthermore, 300μg/mL GLSDY is effective to inhibit virus-induced apoptosis possibly through direct inhibition of caspase-8 and indirectly by inhibition of Bax.
  
  
  CONCLUSIONS
  GLSDY is cheap and readily available to manage EV71 infection by inhibiting viral replication, viral protein formations, and EV71-induced apoptosis.
authors.affiliation: Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ya Ju
authors.initials: YJ
authors.lastname: Hsieh
authors.affiliation: School of Pharmacy and Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Taiwan.
authors.forename: Ming Hong
authors.initials: MH
authors.lastname: Yen
authors.affiliation: Department of Renal Care, College of Medicine, Kaohsiung Medical University, Taiwan.
authors.forename: Ya Wen
authors.initials: YW
authors.lastname: Chiang
authors.affiliation: Department of Renal Care, College of Medicine, Kaohsiung Medical University, Taiwan.
authors.forename: Chia Feng
authors.initials: CF
authors.lastname: Yeh
authors.affiliation: Department of Microbiology, School of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan.
authors.forename: Lien Chai
authors.initials: LC
authors.lastname: Chiang
authors.affiliation: Department of Food Science and Technology, Tajen University of Technology, Ping-Tung, Taiwan.
authors.forename: Den En
authors.initials: DE
authors.lastname: Shieh
authors.affiliation: Division of Internal Medicine, Department of Emergency Medicine, Kaohsiung Medical University Hospital, Taiwan.
authors.forename: IJeng
authors.initials: I
authors.lastname: Yeh
authors.affiliation: Department of Renal Care, College of Medicine, Kaohsiung Medical University, Taiwan; Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan. Electronic address: cjs@kmu.edu.tw.
authors.forename: Jung San
authors.initials: JS
authors.lastname: Chang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D029821:Enterovirus A, Human / Q000187:drug effects*; D005347:Fibroblasts / Q000821:virology*; D006801:Humans; D012208:Rhabdomyosarcoma / Q000821:virology*; D046888:Tissue Array Analysis; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D004365:Drugs, Chinese Herbal; C000614379:gan-lu-siao-du-yin
keywords: Antiviral; Baicalein (PubChem CID: 5281605); Baicalin (PubChem CID: 64982); Chlorogenic acid (PubChem CID: 1794427); Forsythin (PubChem CID: 12314162); Management; TCM; Treatment; Wogonin (PubChem CID: 5281703); Wogonoside (PubChem CID: 29927693)