title: Constituents of the anti-asthma herbal formula ASHMI(TM) synergistically inhibit IL-4 and IL-5 secretion by murine Th2 memory cells, and eotaxin by human lung fibroblasts in vitro.
abstract: OBJECTIVE
  Anti-asthma herbal medicine intervention (ASHMI(TM)), a combination of three traditional Chinese medicinal herbs developed in our laboratory, has demonstrated efficacy in both mouse models of allergic asthma, and a double-blind placebo-controlled clinical trial in patients with asthma. This study was designed to determine if the anti-inflammatory effects of individual herbal constituents of ASHMI(TM) exhibited synergy.
  
  
  METHODS
  Effects of ASHMI and its components aqueous extracts of Lingzhi (Ganoderma lucidum), Kushen (Sophora flavescens) and Gancao (Glycyrrhiza uralensis), on Th2 cytokine secretion by murine memory Th2 cells (D10.G4.1) and eotaxin-1 secretion by human lung fibroblast (HLF-1) cells were determined by measuring levels in culture supernatants by enzyme-linked immunosorbent assay. Potential synergistic effects were determined by computing interaction indices from concentration-effect curve parameters.
  
  
  RESULTS
  Individual Lingzhi, Kushen and Gancao extracts and ASHMI (the combination of individual extracts) inhibited production of interleukin (IL)-4 and IL-5 by murine memory Th2 cells and eotaxin-1 production by HLF-1 cells. The mean 25%-inhibitory-concentration (IC25) values (mg/mL) for ASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 30.9, 79.4, 123, and 64.6, respectively; for IL-5 production were 30.2, 263, 123.2 and 100, respectively; for eotaxin-1 were 13.2, 16.2, 30.2, and 25.1, respectively. The IC50 values (mg/mL) for ASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 158.5, 239.9, 446.7, and 281.8, respectively; for eotaxin-1 were 38.1, 33.1, 100, and 158.5, respectively. The interaction indices of ASHMI constituents at IC25 were 0.35 for IL-4, 0.21 for IL-5 and 0.59 for eotaxin-1. The interaction indices at IC50 values were 0.50 for IL-4 and 0.62 for eotaxin-1 inhibition. Inhibition of IL-5 did not reach IC50 values. All interaction indices were below 1 which indicated synergy.
  
  
  CONCLUSIONS
  By comparing the interaction index values, we find that constituents in ASHMI(TM) synergistically inhibited eotaxin-1 production as well as Th2 cytokine production.
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. xiu-min.li@mssm.edu
authors.forename: Bolleddula
authors.initials: B
authors.lastname: Jayaprakasam
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.forename: Ming-Chun
authors.initials: MC
authors.lastname: Wen
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Joseph
authors.initials: J
authors.lastname: Goldfarb
authors.forename: Hugh
authors.initials: H
authors.lastname: Sampson
authors.forename: Xiu-Min
authors.initials: XM
authors.lastname: Li
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism*; D002460:Cell Line; D054413:Chemokine CCL11 / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000032:analysis / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism*; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D010946:Plants, Medicinal / Q000737:chemistry; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism*
chemical_list: D054413:Chemokine CCL11; D004365:Drugs, Chinese Herbal; D015848:Interleukin-5; D015847:Interleukin-4