title: A standardized bark extract of Pinus pinaster Aiton (Pycnogenol®) attenuated chronic obstructive pulmonary disease via Erk-sp1 signaling pathway.
abstract: BACKGROUND
  A standardized bark extract of Pinus pinaster Aiton (Pycnogenol®; PYC) used as an herbal medicine to treat various diseases in Europe and North America.
  
  
  OBJECTIVE
  This study evaluates the ability of PYC to inhibit chronic obstructive pulmonary disease (COPD) in the cigarette smoke extract (CSE)-stimulated human airway epithelial cell line NCI-H292 and in a cigarette smoke (CS) and lipopolysaccharide (LPS)-induced mouse model.
  
  
  METHODS
  To induce COPD, the mice intranasally received LPS on day 4 and were exposed to CS for 1h per day (total eight cigarettes per day) from days 1-7. The mice were administered PYC at a dose of 15mg/kg and 30mg/kg 1h before CS exposure.
  
  
  RESULTS
  In the CSE-stimulated NCI-H292 cells, PYC significantly inhibited Erk phosphorylation, sp1 expression, MUC5AC, and pro-inflammatory cytokines in a concentration-dependent manner, as evidenced by a reduction in their mRNA levels. Co-treatment with PYC and Erk inhibitors markedly reduced the levels inflammatory mediators compared to only PYC-treatment. In the COPD mice model, PYC decreased the inflammatory cell count and the levels of pro-inflammatory cytokines in the broncho-alveolar lavage fluid compared with COPD mice. PYC attenuated the recruitment of inflammatory cells in the airways and decreased the expression levels of Erk phosphorylation and sp1. PYC also inhibited the expression of myeloperoxidase and matrix metalloproteinases-9 in lung tissue.
  
  
  CONCLUSIONS
  Our results indicate that PYC inhibited the reduction in the inflammatory response in CSE-stimulated NCI-H292 cells and the COPD mouse model via the Erk-sp1 pathway. Therefore, we suggest that PYC has the potential to treat COPD.
authors.affiliation: College of Veterinary Medicine (BK21 Plus Project Team), Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 500-757, Republic of Korea. Electronic address: tlsskfo870220@gmail.com.
authors.forename: Na-Rae
authors.initials: NR
authors.lastname: Shin
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883, Republic of Korea. Electronic address: ryuhw@kribb.re.kr.
authors.forename: Hyung-Won
authors.initials: HW
authors.lastname: Ryu
authors.affiliation: College of Veterinary Medicine (BK21 Plus Project Team), Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 500-757, Republic of Korea. Electronic address: rheoda@gmail.com.
authors.forename: Je-Won
authors.initials: JW
authors.lastname: Ko
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883, Republic of Korea. Electronic address: youandmecool@naver.com.
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Park
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883, Republic of Korea. Electronic address: dooli@kribb.re.kr.
authors.forename: Ok-Kyoung
authors.initials: OK
authors.lastname: Kwon
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883, Republic of Korea. Electronic address: seiryang@kribb.re.kr.
authors.forename: Sei-Ryang
authors.initials: SR
authors.lastname: Oh
authors.affiliation: College of Veterinary Medicine (BK21 Plus Project Team), Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 500-757, Republic of Korea. Electronic address: toxkim@jnu.ac.kr.
authors.forename: Jong-Choon
authors.initials: JC
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine (BK21 Plus Project Team), Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 500-757, Republic of Korea. Electronic address: dvmmk79@gmail.com.
authors.forename: In-Sik
authors.initials: IS
authors.lastname: Shin
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883, Republic of Korea. Electronic address: ksahn@kribb.re.kr.
authors.forename: Kyung-Seop
authors.initials: KS
authors.lastname: Ahn
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002460:Cell Line; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D010766:Phosphorylation; D028223:Pinus / Q000737:chemistry*; D024301:Plant Bark / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects*; D016329:Sp1 Transcription Factor / Q000378:metabolism*
chemical_list: D018836:Inflammation Mediators; D010936:Plant Extracts; D016329:Sp1 Transcription Factor; D009195:Peroxidase
keywords: Chronic obstructive pulmonary disease; Erk-sp1; MUC5AC; Myeloperoxidase; Pathway; Pycnogenol®