title: Pogostone suppresses proinflammatory mediator production and protects against endotoxic shock in mice.
abstract: BACKGROUND
  Pogostemon cablin (Blanco) Benth is a well-known medicinal herb commonly used in many Asian countries for inflammatory diseases. Pogostone (PO), a natural product isolated from Pogostemon cablin, is known to exert various pharmacological activities. This study aimed to investigate the anti-inflammatory property of PO, to elucidate its mechanism of action, and to evaluate its potential acute toxicity.
  
  
  METHODS
  The in vitro anti-inflammatory activity of PO was assessed using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The protein and mRNA levels of proinflammatory mediators were measured with ELISA and RT-PCR, respectively. Proteins of the NF-κB and MAPK family were determined by Western blot to investigate the underlying molecular mechanisms. The in vivo anti-inflammatory activity of PO was tested using LPS-induced endotoxic shock in mice. In addition, the median lethal dose (LD50) of PO in mice was tested in an acute toxicity test.
  
  
  RESULTS
  In vitro, PO significantly inhibited the protein and mRNA expression of proinflammatory mediators including TNF-α, IL-6, IL-1β, NO, and PGE2. The action mechanism of the anti-inflammatory activity of PO was partly dependent on inhibition of the activation of NF-κB and the phosphorylation of JNK and p38 MAPK. In vivo, PO was able to significantly reduce the mortality induced by LPS in mice. Furthermore, PO could markedly suppress the production of the proinflammatory mediators in serum, and attenuate liver and lung injury. The action mechanisms of PO during endotoxic shock may be attributed to down-regulation of the mRNA expression of inflammatory mediators in multiple organs via inhibition of the activation of NF-κB and the phosphorylation of p38 MAPK. Moreover, the LD50 of PO in mice was about 163mg/kg with intravenous administration, which was about 8-fold higher than the dose used in the animal experiment.
  
  
  CONCLUSIONS
  Our findings regarding the anti-inflammatory effect of PO and the underlying molecular mechanisms help justify the use of Pogostemon cablin in Chinese medicine for the treatment of inflammatory diseases. More importantly, the results also render PO a promising anti-inflammatory agent worthy of further development into a pharmaceutical drug for the treatment of septic shock.
authors.affiliation: College of Chinese Medicines, Guangzhou University of Chinese Medicine, 232 Wai Huan Dong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China.
authors.forename: Yu-Cui
authors.initials: YC
authors.lastname: Li
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, PR China.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Xian
authors.affiliation: College of Chinese Medicines, Guangzhou University of Chinese Medicine, 232 Wai Huan Dong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China; Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan 523808, PR China.
authors.forename: Zi-Ren
authors.initials: ZR
authors.lastname: Su
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, PR China.
authors.forename: Siu-Po
authors.initials: SP
authors.lastname: Ip
authors.affiliation: College of Chinese Medicines, Guangzhou University of Chinese Medicine, 232 Wai Huan Dong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China.
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: Xie
authors.affiliation: College of Chinese Medicines, Guangzhou University of Chinese Medicine, 232 Wai Huan Dong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China.
authors.forename: Jin-Bin
authors.initials: JB
authors.lastname: Liao
authors.affiliation: College of Chinese Medicines, Guangzhou University of Chinese Medicine, 232 Wai Huan Dong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China.
authors.forename: Dian-Wei
authors.initials: DW
authors.lastname: Wu
authors.affiliation: College of Chinese Medicines, Guangzhou University of Chinese Medicine, 232 Wai Huan Dong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China.
authors.forename: Chu-Wen
authors.initials: CW
authors.lastname: Li
authors.affiliation: College of Chinese Medicines, Guangzhou University of Chinese Medicine, 232 Wai Huan Dong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China; Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan 523808, PR China.
authors.forename: Jian-Nan
authors.initials: JN
authors.lastname: Chen
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, PR China. Electronic address: linzx@cuhk.edu.hk.
authors.forename: Zhi-Xiu
authors.initials: ZX
authors.lastname: Lin
authors.affiliation: College of Chinese Medicines, Guangzhou University of Chinese Medicine, 232 Wai Huan Dong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, PR China; Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan 523808, PR China. Electronic address: lxp88@gzhtcm.edu.cn.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Lai
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D018836:Inflammation Mediators / Q000378:metabolism; D019686:Lamiaceae / Q000737:chemistry*; D007928:Lethal Dose 50; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009822:Oils, Volatile / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012772:Shock, Septic / Q000517:prevention & control*
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009822:Oils, Volatile; C483658:Pogostone; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: Anti-inflammatory property; Inflammatory mediators; MAPKs; NF-κB; Pogostone