title: Zingiber cassumunar ROXb. and its active constituent inhibit MMP-9 direct activation by house dust mite allergens and MMP-9 expression in PMA-stimulated human airway epithelial cells.
abstract: BACKGROUND
  House dust mite (HDM) induced matrix metalloproteinase (MMP)-9 plays a role in asthma. Zingiber cassumunar Roxb. (Phlai in Thai) has been used in folk medicine for asthma treatment.
  
  
  OBJECTIVE
  We investigated effects of Phlai and its constituent (E)-4-(3',4'-dimethoxyphenyl)but-3-en-1-ol (compound D) on the cleavage of pro- MMP-9 by HDM. The effects of these compounds on phorbol 12-myristate 13-acetate (PMA)- induced MMP-9 gene and protein expression in airway epithelial cells (NCI-H292) were also investigated.
  
  
  METHODS
  Pro-MMP-9 was directly activated in vitro with HDM in the presence or absence of the ethanolic extracts of Phlai or compound D for 1 hour. The amount of activated MMP-9 was determined using gelatin zymography. To study the cellular response of Phlai, NCI-H292 cells were pretreated with crude Phlai extracts or compound D for 2 hours, and then the cells were stimulated with PMA for 48 hours. The mRNA RT-PCR and Western blotting, respectively. MMP-9 activity was determined by gelatin zymography.
  
  
  RESULTS
  Crude Phlai extracts (0.25 - 2.0 mg/ml) and compound D (0.5 - 4.0 mg/ml) inhibited pro- MMP-9 cleavage by HDM. Furthermore, crude Phlai extracts (100 mg/ml) and compound D, at concentrations of 50 and 100 mg/ml, attenuated the PMA-induced MMP-9 gene and expression in NCI-H292 cells. These compound also suppressed MMP-9 release from PMA-induced NCI-H292 cells.
  
  
  CONCLUSIONS
  The crude ethanolic extract of Z. cassumunar and its active constituent compound D inhibited the cleavage of pro-MMP-9 by HDM. They also inhibited PMA-induced MMP-9 gene and protein synthesis in human airway epithelial cells.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Thammasat University, Paholyothin Road, Klong Luang, Prathumthani 12120, Thailand.
authors.forename: Orapan
authors.initials: O
authors.lastname: Poachanukoon
authors.forename: Ladda
authors.initials: L
authors.lastname: Meesuk
authors.forename: Napaporn
authors.initials: N
authors.lastname: Pattanacharoenchai
authors.forename: Paopanga
authors.initials: P
authors.lastname: Monthanapisut
authors.forename: Thaweephol
authors.initials: T
authors.lastname: Dechatiwongse Na Ayudhya
authors.forename: Sittichai
authors.initials: S
authors.lastname: Koontongkaew
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000302:isolation & purification / Q000494:pharmacology*; D060829:Arthropod Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D000440:Butanols / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000302:isolation & purification / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D028321:Plant Preparations / Q000737:chemistry; D039981:Pyroglyphidae / Q000737:chemistry*; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D030521:Zingiberaceae / Q000737:chemistry*
chemical_list: D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D000440:Butanols; D004792:Enzyme Precursors; D010703:Phorbol Esters; D010936:Plant Extracts; D028321:Plant Preparations; C119222:phorbol-12-myristate; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1; C120487:pro-matrix metalloproteinase 9; D020780:Matrix Metalloproteinase 9