title: Phillyrin attenuates LPS-induced pulmonary inflammation via suppression of MAPK and NF-κB activation in acute lung injury mice.
abstract: Phillyrin (Phil) is one of the main chemical constituents of Forsythia suspensa (Thunb.), which has shown to be an important traditional Chinese medicine. We tested the hypothesis that Phil modulates pulmonary inflammation in an ALI model induced by LPS. Male BALB/c mice were pretreated with or without Phil before respiratory administration with LPS, and pretreated with dexamethasone as a control. Cytokine release (TNF-α, IL-1β, and IL-6) and amounts of inflammatory cell in bronchoalveolar lavage fluid (BALF) were detected by ELISA and cell counting separately. Pathologic changes, including neutrophil infiltration, interstitial edema, hemorrhage, hyaline membrane formation, necrosis, and congestion during acute lung injury in mice were evaluated via pathological section with HE staining. To further investigate the mechanism of Phil anti-inflammatory effects, activation of MAPK and NF-κB pathways was tested by western blot assay. Phil pretreatment significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. The lung wet-to-dry weight ratios, as the index of pulmonary edema, were markedly decreased by Phil pretreatment. In addition, Phil decreased the production of the proinflammatory cytokines including (TNF-α, IL-1β, and IL-6) and the concentration of myeloperoxidase (MPO) in lung tissues. Phil pretreatment also significantly suppressed LPS-induced activation of MAPK and NF-κB pathways in lung tissues. Taken together, the results suggest that Phil may have a protective effect on LPS-induced ALI, and it potentially contributes to the suppression of the activation of MAPK and NF-κB pathways. Phil may be a new preventive agent of ALI in the clinical setting.
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, PR China.
authors.forename: Wei-ting
authors.initials: WT
authors.lastname: Zhong
authors.forename: Yi-chun
authors.initials: YC
authors.lastname: Wu
authors.forename: Xian-xing
authors.initials: XX
authors.lastname: Xie
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.forename: Miao-miao
authors.initials: MM
authors.lastname: Wei
authors.forename: Lanan-Wassy
authors.initials: LW
authors.lastname: Soromou
authors.forename: Xin-xin
authors.initials: XX
authors.lastname: Ci
authors.forename: Da-cheng
authors.initials: DC
authors.lastname: Wang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D031657:Forsythia / Q000737:chemistry*; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D006470:Hemorrhage / Q000517:prevention & control; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D020556:Neutrophil Infiltration / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D008517:Phytotherapy; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011654:Pulmonary Edema / Q000139:chemically induced; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D004365:Drugs, Chinese Herbal; D005960:Glucosides; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D020928:Mitogen-Activated Protein Kinases; C075528:phillyrin
keywords: ALI; LPS; MAPKs; NF-κB; Phillyrin