title: Urinary metabonomics elucidate the therapeutic mechanism of Orthosiphon stamineus in mouse crystal-induced kidney injury.
abstract: BACKGROUND
  Orthosiphon stamineus (OS), a traditional Chinese herb, is often used for promoting urination and treating nephrolithiasis.
  
  
  OBJECTIVE
  Urolithiasis is a major worldwide public health burden due to its high incidence of recurrence and damage to renal function. However, the etiology for urolithiasis is not well understood. Metabonomics, the systematic study of small molecule metabolites present in biological samples, has become a valid and powerful tool for understanding disease phenotypes. In this study, a urinary metabolic profiling analysis was performed in a mouse model of renal calcium oxalate crystal deposition to identify potential biomarkers for crystal-induced renal damage and the anti-crystal mechanism of OS.
  
  
  METHODS
  Thirty six mice were randomly divided into six groups including Saline, Crystal, Cystone and OS at dosages of 0.5g/kg, 1g/kg, and 2g/kg. A metabonomics approach using ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) was developed to perform the urinary metabolic profiling analysis. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were utilized to identify differences between the metabolic profiles of mice in the saline control group and crystal group.
  
  
  RESULTS
  Using partial least squares-discriminant analysis, 30 metabolites were identified as potential biomarkers of crystal-induced renal damage. Most of them were primarily involved in amino acid metabolism, taurine and hypotaurine metabolism, purine metabolism, and the citrate cycle (TCA). After the treatment with OS, the levels of 20 biomarkers had returned to the levels of the control samples.
  
  
  CONCLUSIONS
  Our results suggest that OS has a protective effect for mice with crystal-induced kidney injury via the regulation of multiple metabolic pathways primarily involving amino acid, energy and choline metabolism.
authors: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors: Songyan
authors: S
authors: Gao
authors: Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Wei
authors: W
authors: Chen
authors: Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Zhongjiang
authors: Z
authors: Peng
authors: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors: Na
authors: N
authors: Li
authors: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors: Li
authors: L
authors: Su
authors: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors: Diya
authors: D
authors: Lv
authors: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors: Ling
authors: L
authors: Li
authors: Proteomics/Mass Spec Facility, Center for Functional Genomics, University at Albany, Rensselaer, NY 12144, USA.
authors: Qishan
authors: Q
authors: Lin
authors: School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: dongxinsmmu@126.com.
authors: Xin
authors: X
authors: Dong
authors: Changhai Hospital, Second Military Medical University, Shanghai 200433, China. Electronic address: drguozhiyong@163.com.
authors: Zhiyong
authors: Z
authors: Guo
authors: School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: ziyanglou@163.com.
authors: Ziyang
authors: Z
authors: Lou
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002129:Calcium Oxalate / Q000494:pharmacology; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D020834:Ethnopharmacology / Q000379:methods; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D008516:Medicine, Chinese Traditional / Q000379:methods; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D031342:Orthosiphon / Q000737:chemistry*; D014556:Urine / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D004365:Drugs, Chinese Herbal; D002129:Calcium Oxalate
keywords: Biomarker discovery; Calcium oxalate crystal; Metabonomics; Orthosiphon stamineus; UHPLC-Q-TOF/MS