title: Inhibitory effects of an aqueous extract from Cortex Phellodendri on the growth and replication of broad-spectrum of viruses in vitro and in vivo.
abstract: BACKGROUND
  Cortex Phellodendri (C. Phellodendri), the dried trunk bark of Phellodendron amurense Ruprecht, has been known as a traditional herbal medicine, showing several bioactivities. However, antiviral activity of C. Phellodendri aqueous extract (CP) not reported in detail, particularly aiming the prophylactic effectiveness.
  
  
  METHODS
  In vitro CP antiviral activity evaluated against Influenza A virus (PR8), Vesicular Stomatitis Virus (VSV), Newcastle Disease Virus (NDV), Herpes Simplex Virus (HSV), Coxsackie Virus (H3-GFP) and Enterovirus-71 (EV-71) infection on immune (RAW264.7) and epithelial (HEK293T/HeLa) cells. Such antiviral effects were explained by the induction of antiviral state which was determined by phosphorylation of signal molecules, secretion of IFNs and cytokines, and cellular antiviral mRNA expression. Furthermore, Compounds present in the aqueous fractions confirmed by HPLC analysis and evaluated their anti-viral activities. Additionally, in vivo protective effect of CP against divergent influenza A subtypes was determined in a BALB/c mouse infection model.
  
  
  RESULTS
  An effective dose of CP significantly reduced the virus replication both in immune and epithelial cells. Mechanically, CP induced mRNA expression of anti-viral genes and cytokine secretion in both RAW264.7 and HEK293T cells. Furthermore, the main compound identified was berberine, and shows promising antiviral properties similar to CP. Finally, BALB/c mice treated with CP displayed higher protection levels against lethal doses of highly pathogenic influenza A subtypes (H1N1, H5N2, H7N3 and H9N2).
  
  
  CONCLUSIONS
  CP including berberine play an immunomodulatory role with broad spectrum antiviral activity, due to induction of antiviral state via type I IFN stimulation mechanism. Consequently, C. Phellodendri could be a potential source for promising natural antivirals or to design other antiviral agents for animal and humans.
authors.affiliation: College of Veterinary Medicine, Chungnam National University, 220 Gung-Dong, Yuseong-Gu, Daejeon, 305-764, Republic of Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Chungnam National University, 220 Gung-Dong, Yuseong-Gu, Daejeon, 305-764, Republic of Korea.
authors.forename: Prasanna
authors.initials: P
authors.lastname: Weeratunga
authors.affiliation: Vitabio, Inc., Daejeon, 305-764, Republic of Korea.
authors.forename: Myun Soo
authors.initials: MS
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Chungnam National University, 220 Gung-Dong, Yuseong-Gu, Daejeon, 305-764, Republic of Korea.
authors.forename: Chamilani
authors.initials: C
authors.lastname: Nikapitiya
authors.affiliation: College of Veterinary Medicine, Chungnam National University, 220 Gung-Dong, Yuseong-Gu, Daejeon, 305-764, Republic of Korea.
authors.forename: Byeong-Hoon
authors.initials: BH
authors.lastname: Lee
authors.affiliation: College of Veterinary Medicine, Chungnam National University, 220 Gung-Dong, Yuseong-Gu, Daejeon, 305-764, Republic of Korea.|Sylhet Agricultural University, Sylhet, Bangladesh.
authors.forename: Md Bashir
authors.initials: MB
authors.lastname: Uddin
authors.affiliation: College of Veterinary Medicine, Chungnam National University, 220 Gung-Dong, Yuseong-Gu, Daejeon, 305-764, Republic of Korea.
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Chungnam National University, 220 Gung-Dong, Yuseong-Gu, Daejeon, 305-764, Republic of Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Yoon
authors.affiliation: LINC Project Group, Daejeon University, 62 Daehak-Ro, Dong-Gu, Daejeon, 300-716, Republic of Korea.
authors.forename: Chung
authors.initials: C
authors.lastname: Park
authors.affiliation: Korean Medicine (KM) Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, Deajeon, 305-764, Republic of Korea.
authors.forename: Jin Yeul
authors.initials: JY
authors.lastname: Ma
authors.affiliation: Vitabio, Inc., Daejeon, 305-764, Republic of Korea. hongiknice@hanmail.net.
authors.forename: Hongik
authors.initials: H
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Chungnam National University, 220 Gung-Dong, Yuseong-Gu, Daejeon, 305-764, Republic of Korea. jongsool@cnu.ac.kr.
authors.forename: Jong-Soo
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D032102:Phellodendron / Q000737:chemistry*; D024301:Plant Bark / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D000067996:RAW 264.7 Cells; D014779:Virus Replication / Q000187:drug effects*; D014780:Viruses / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D010936:Plant Extracts
keywords: Anti-viral effect; Berberine; Cortex Phellodendri; Herbal medicine