title: NMR-based metabonomics study on the effect of Gancao in the attenuation of toxicity in rats induced by Fuzi.
abstract: BACKGROUND
  Fuzi, the processed lateral root of Aconitum carmichaelii Debeaux, is a traditional Chinese medicine used for its analgesic, antipyretic, anti-rheumatoid arthritis and anti-inflammation effects; however, it is also well known for its toxicity. Gancao, the root of Glycyrrhiza uralensis Fisch., is often used concurrently with Fuzi to alleviate its toxicity. However, the mechanism of detoxication is still not well clear.
  
  
  OBJECTIVE
  In this study, the effect of Gancao on the metabolic changes induced by Fuzi was investigated by NMR-based metabonomic approaches.
  
  
  METHODS
  Fifty male Wistar rats were randomly divided into five groups (group A: control, group B: Fuzi decoction alone, group C: Gancao decoction alone, group D: Fuzi decoction and Gancao decoction simultaneously, group E: Fuzi decoction 5h after Gancao decoction) and urine samples were collected for NMR-based metabolic profiling analysis. Statistical analyses such as unsupervised PCA, t-test, hierarchical cluster, and pathway analysis were used to detect the effects of Gancao on the metabolic changes induced by Fuzi.
  
  
  RESULTS
  The behavioral and biochemical characteristics showed that Fuzi exhibited toxic effects on treated rats (group B) and statistical analyses showed that their metabolic profiles were in contrast to those in groups A and C. However, when Fuzi was administered with Gancao, the metabolic profiles became similar to controls, whereby Gancao reduced the levels of trimethylamine N-oxide, betaine, dimethylglycine, valine, acetoacetate, citrate, fumarate, 2-ketoglutarate and hippurate, and regulated the concentrations of taurine and 3-hydroxybutyrate, resulting in a decrease in toxicity. Furthermore, important pathways that are known to be involved in the effect of Gancao on Fuzi, including phenylalanine, tyrosine and tryptophan biosynthesis, the synthesis and degradation of ketone bodies, and the TCA cycle, were altered in co-treated rats.
  
  
  CONCLUSIONS
  Gancao treatment mitigated the metabolic changes altered by Fuzi administration in rats, demonstrating that dosing with Gancao could reduce the toxicity of Fuzi at the metabolic level. Fuzi and Gancao administered simultaneously resulted in improved toxicity reduction than when Gancao was administrated 5h prior to Fuzi. In summary, co-administration of Gancao with Fuzi reduces toxicity at the metabolic level.
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, PR China. Electronic address: sunbo@proteomics.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, PR China. Electronic address: wangxubin2012@126.com.
authors.forename: Xubin
authors.initials: X
authors.lastname: Wang
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, PR China. Electronic address: crlmail@163.com.
authors.forename: Ruili
authors.initials: R
authors.lastname: Cao
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, PR China. Electronic address: ncba_nmr@126.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, PR China; Chenzhou First People's Hospital, Chenzhou 423000, PR China. Electronic address: liuqiao.707@163.com.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Liu
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, PR China. Electronic address: xumeifeng103@126.com.
authors.forename: Meifeng
authors.initials: M
authors.lastname: Xu
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, PR China; School of Pharmacy, Shengyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: zhangmingln@126.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, PR China. Electronic address: d5194u@163.com.
authors.forename: Xiangbo
authors.initials: X
authors.lastname: Du
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, PR China. Electronic address: dft@proteomics.cn.
authors.forename: Fangting
authors.initials: F
authors.lastname: Dong
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, PR China. Electronic address: yanxz@proteomics.cn.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Yan
mesh_terms: D031841:Aconitum / Q000737:chemistry*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016000:Cluster Analysis; D004224:Diterpenes; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D029882:Glycyrrhiza uralensis / Q000737:chemistry*; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics / Q000379:methods*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010936:Plant Extracts / Q000302:isolation & purification / Q000633:toxicity*; D018517:Plant Roots / Q000737:chemistry; D017208:Rats, Wistar
chemical_list: D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; C575009:fuzi drug herbal
keywords: Aconitum carmichaelii Debeaux; Chinese herbal medicine; Glycyrrhiza uralensis Fisch.; Metabonomics; NMR; Toxicity