title: Antiviral effect of cimicifugin from Cimicifuga foetida against human respiratory syncytial virus.
abstract: Human respiratory syncytial virus (RSV) causes serious infection of the lower respiratory tract in children and an effective antiviral therapy against the viral pathogen remains unavailable. We previously demonstrated that the oriental medicinal plant, Cimicifuga foetida L. (C. foetida), possessed inhibitory activity against RSV. Since cimicifugin is a major constituent of C. foetida, we sought to examine in this study its anti-RSV effect on both the human upper (HEp-2) and lower (A549) respiratory tract cell lines. Results revealed that cimicifugin dose-dependently inhibited RSV-induced plaque formation in both HEp-2 and A549 cells (p < 0.0001), with a superior effect in the latter cell type (p < 0.0001). The antiviral activity of cimicifugin was time-dependent (p < 0.0001) and was most effective when cells were treated with the compound before viral inoculation. Additional experiments demonstrated that cimicifugin could inhibit viral attachment (p < 0.0001) and viral internalization (p < 0.0001). Furthermore, the drug could potentiate heparin's effect against attachment of RSV, particularly in A549 cells. Enzyme-linked immunosorbent assay (ELISA) analysis of antiviral cytokines induction revealed that cimicifugin could also stimulate epithelial cells to secrete IFN-β to counteract viral infection. Taken together, these results indicate that cimicifugin is an efficient antiviral agent against RSV infection. We suggest that cimicifugin might be useful for the management of RSV pathogenesis.
authors.affiliation: Graduate Institute of Natural Products, School of Pharmacy, College of Pharmacy, Kaohsiung Medical University,  Taiwan.
authors.forename: Kuo-Chih
authors.initials: KC
authors.lastname: Wang
authors.forename: Jung-San
authors.initials: JS
authors.lastname: Chang
authors.forename: Liang-Tzung
authors.initials: LT
authors.lastname: Lin
authors.forename: Lien-Chai
authors.initials: LC
authors.lastname: Chiang
authors.forename: Chun-Ching
authors.initials: CC
authors.lastname: Lin
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001572:Benzofurans / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology / Q000627:therapeutic use*; D031885:Cimicifuga / Q000737:chemistry*; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D041743:Herb-Drug Interactions; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000187:drug effects* / Q000472:pathogenicity
chemical_list: D000998:Antiviral Agents; D001572:Benzofurans; D002867:Chromones; D016207:Cytokines; D005343:Fibrinolytic Agents; D010936:Plant Extracts; C577042:cimicifugin; D016899:Interferon-beta; D006493:Heparin