title: A metabolomics approach to studying the effects of Jinxin oral liquid on RSV-infected mice using UPLC/LTQ-Orbitrap mass spectrometry.
abstract: BACKGROUND
  Jinxin oral liquid (JOL) is a traditional Chinese medicine (TCM) formula modified from ma-xing-shi-gan-tang, an ancient formula widely used in the treatment of respiratory diseases such as bronchitis, pneumonia, and asthma. In our previous studies, JOL was shown to safely and effectively treat viral pneumonia, especially that involving respiratory syncytial virus (RSV).
  
  
  OBJECTIVE
  To investigate the mechanism of the effect of JOL in RSV infected mice, using a metabolomics approach based on ultra-performance liquid chromatography coupled with linear ion trap quadrupole-Orbitrap mass spectrometry (UPLC/LTQ-Orbitrap-MS).
  
  
  METHODS
  BALB/c mice were divided into four groups, the control group (saline inoculation/no treatment), RSV group (RSV inoculation/saline treatment), RSV+JOL group (RSV inoculation/JOL treatment), and RSV+Riba group (RSV inoculation/ribavirin treatment). Plasma and lung tissue samples were collected 7 days after the inoculation/treatment protocols, and UPLC/LTQ-Orbitrap-MS method based on metabolomics was developed. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were utilized to identify biomarkers potentially associated with the anti-RSV activity of JOL.
  
  
  RESULTS
  JOL was associated with reduced inflammatory responses in RSV-infected lung tissue. The combination of PCA and OPLS-DA revealed deviations in 11 biomarkers in plasma, and 16 biomarkers in lung tissue induced by RSV that were corrected with JOL treatment. These biomarkers were primarily components of metabolic pathways involving glycerophosphocholines, sphingolipids, and glycerolipids. JOL was able to restore the abnormal levels of these biomarkers detected in the plasma and lung tissue of RSV-infected mice to approximately normal levels.
  
  
  CONCLUSIONS
  This study suggested that JOL can treat RSV pneumonia effectively, partially by ameliorating the associated disturbances to lipid metabolism. The results provided insight into the anti-RSV mechanism of JOL, and also demonstrated that metabolomics is a valuable tool for investigating the efficacy of TCM treatment for RSV pneumonia, and the associated biomarkers involved.
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing 210023, China; Department of Traditional Chinese Medicine, Beijing Children's Hospital Affiliated to Capital Medical University, Beijing 100045, China.
authors.forename: Li-na
authors.initials: LN
authors.lastname: Du
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Xie
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Jian-ya
authors.initials: JY
authors.lastname: Xu
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing 210023, China.
authors.forename: An
authors.initials: A
authors.lastname: Kang
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing 210023, China.
authors.forename: Liu-qing
authors.initials: LQ
authors.lastname: Di
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing 210023, China. Electronic address: jshan@njucm.edu.cn.
authors.forename: Jin-jun
authors.initials: JJ
authors.lastname: Shan
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: wscnj@126.com.
authors.forename: Shou-chuan
authors.initials: SC
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000302:isolation & purification / Q000378:metabolism*; D005260:Female; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D019999:Pharmaceutical Solutions / Q000008:administration & dosage / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000378:metabolism*; D012136:Respiratory Syncytial Viruses; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D004365:Drugs, Chinese Herbal; D019999:Pharmaceutical Solutions; C000591856:ma-xing-shi-gan-tang
keywords: Jinxin oral liquid; Liquid chromatography mass spectrometry; Ma-xing-shi-gan-tang; Metabolomics; Respiratory syncytial virus