title: Metabolomic analysis of anti-hypoxia and anti-anxiety effects of Fu Fang Jin Jing Oral Liquid.
abstract: BACKGROUND
  Herba Rhodiolae is a traditional Chinese medicine used by the Tibetan people for treating hypoxia related diseases such as anxiety. Based on the previous work, we developed and patented an anti-anxiety herbal formula Fu Fang Jin Jing Oral Liquid (FJJOL) with Herba Rhodiolae as a chief ingredient. In this study, the anti-hypoxia and anti-anxiety effects of FJJOL in a high altitude forced-swimming mouse model with anxiety symptoms will be elucidated by NMR-based metabolomics.
  
  
  METHODS
  In our experiments, the mice were divided randomly into four groups as flatland group, high altitude saline-treated group, high altitude FJJOL-treated group, and high altitude diazepam-treated group. To cause anxiety effects and hypoxic defects, a combination use of oxygen level decreasing (hypobaric cabin) and oxygen consumption increasing (exhaustive swimming) were applied to mice. After a three-day experimental handling, aqueous metabolites of mouse brain tissues were extracted and then subjected to NMR analysis. The therapeutic effects of FJJOL on the hypobaric hypoxia mice with anxiety symptoms were verified.
  
  
  RESULTS
  Upon hypoxic exposure, both energy metabolism defects and disorders of functional metabolites in brain tissues of mice were observed. PCA, PLS-DA and OPLS-DA scatter plots revealed a clear group clustering for metabolic profiles in the hypoxia versus normoxia samples. After a three-day treatment with FJJOL, significant rescue effects on energy metabolism were detected, and levels of ATP, fumarate, malate and lactate in brain tissues of hypoxic mice recovered. Meanwhile, FJJOL also up-regulated the neurotransmitter GABA, and the improvement of anxiety symptoms was highly related to this effect.
  
  
  CONCLUSIONS
  FJJOL ameliorated hypobaric hypoxia effects by regulating energy metabolism, choline metabolism, and improving the symptoms of anxiety. The anti-anxiety therapeutic effects of FJJOL were comparable to the conventional anti-anxiety drug diazepam on the hypobaric hypoxia mice. FJJOL might serve as an alternative therapy for the hypoxia and anxiety disorders.
authors.affiliation: Department of Analytical Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Shuhong
authors.initials: S
authors.lastname: Guan
authors.forename: Ruihong
authors.initials: R
authors.lastname: Feng
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Liu
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.forename: Donghai
authors.initials: D
authors.lastname: Lin
authors.forename: Naixia
authors.initials: N
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Shen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects; D029001:Herbal Medicine / Q000379:methods; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008516:Medicine, Chinese Traditional / Q000379:methods; D055432:Metabolomics / Q000379:methods; D051379:Mice; D010100:Oxygen / Q000378:metabolism; D019999:Pharmaceutical Solutions / Q000494:pharmacology*; D028321:Plant Preparations / Q000494:pharmacology*; D013550:Swimming / Q000502:physiology
chemical_list: D014151:Anti-Anxiety Agents; D019999:Pharmaceutical Solutions; D028321:Plant Preparations; D010100:Oxygen