title: Platycodin D attenuates acute lung injury by suppressing apoptosis and inflammation in vivo and in vitro.
abstract: Platycodin D (PLD) is the major triterpene saponin in the root of Platycodon grandiflorum (Jacq.) with various pharmacological activities. The purpose of the present study was to evaluate the protective effects and possible mechanisms of PLD on acute lung injury (ALI) both in vivo and in vitro. In vivo, we used two ALI models, lipopolysaccharide (LPS)-induced ALI and bleomycin (BLE)-induced ALI to evaluate the protective effects and possible mechanisms of PLD. Female BALB/c mice were randomly divided into the following groups: control group, LPS group, LPS plus pre-treatment with dexamethasone (2 mg/kg) group, LPS plus pre-treatment with PLD groups (50 mg/kg, 100 mg/kg), LPS plus post-treatment with dexamethasone (2 mg/kg) group, LPS plus post-treatment with PLD groups (50 mg/kg, 100 mg/kg), BLE group, BLE plus pre-treatment with dexamethasone (2 mg/kg) group, BLE plus pre-treatment with PLD groups (50 mg/kg, 100 mg/kg), BLE plus post-treatment with dexamethasone (2 mg/kg) group, and BLE plus post-treatment with PLD groups (50 mg/kg, 100 mg/kg). PLD was orally administered before or after LPS or BLE challenge with mice. Mice were sacrificed, and lung tissues and bronchoalveolar fluid (BALF) were prepared for further analysis. Our results showed that PLD significantly decreased lung wet-to-dry weight ratio (lung W/D weight ratio), total leukocyte number and neutrophil percentage in the BALF, and myeloperoxidase (MPO) activity of lung in a dose-dependent manner. Besides, cytokine levels, including interleukin (IL)-6, tumor neurosis factor (TNF)-α were also found significantly inhibited in BALF. Furthermore, PLD effectively inhibited the expressions of nuclear factor κB (NF-κB), Caspase-3 and Bax in the lung tissues, as well as restored the expression of Bcl-2 in the lungs and improved the superoxide dismutase (SOD) activity in BALF. In vitro, we used LPS-challenged cell model to evaluate the protective effects and possible mechanisms of PLD. MLE-12 cells were stimulated with LPS in the presence and absence of PLD. The levels of TNF-α, IL-6 and the expressions of NF-κB, Caspase-3, and Bax were remarkably down-regulated, while the expression of bcl-2 was significantly up-regulated in PLD treatment groups in MLE-12 cells. These results showed that the administration of PLD improved ALI both in vivo and in vitro, possibly through suppressing apoptosis and inflammation.
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: tw845@163.com.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Tao
authors.affiliation: Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Su
authors.affiliation: College of Pharmacy, Ningxia Medical University, Ningxia 750004, China.
authors.forename: Hanqin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Guo
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: dja@njucm.edu.cn.
authors.forename: Jinao
authors.initials: J
authors.lastname: Duan
authors.affiliation: Changchun University of Chinese Medicine, China.
authors.forename: Shumin
authors.initials: S
authors.lastname: Wang
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001761:Bleomycin / Q000276:immunology; D002460:Cell Line; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D031238:Platycodon / Q000276:immunology; D011014:Pneumonia / Q000188:drug therapy* / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012503:Saponins / Q000008:administration & dosage*; D014315:Triterpenes / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D012503:Saponins; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C023023:lipid-linked oligosaccharides; D001761:Bleomycin; C108953:platycodin D
keywords: Acute lung injury; Apoptosis; Inflammation; Platycodin D