Urinary metabonomics elucidate the therapeutic mechanism of Orthosiphon stamineus in mouse crystal-induced kidney injury. (26th May 2015)

• Record Type: Journal Article
• Authors: Gao, Songyan; Chen, Wei; Peng, Zhongjiang; Li, Na; Su, Li; Lv, Diya; Li, Ling; Lin, Qishan; Dong, Xin; Guo, Zhiyong; Lou, Ziyang
• Is Part Of: Journal of ethnopharmacology. Volume 166(2015)
• Page Start: 323
• Page End: 332
• Publication Date: 2015-05-26
• Subjects: OS Orthosiphon stamineus -- UHPLC-Q-TOF/MS ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry -- PCA principal component analysis -- PLS-DA partial least squares discriminant analysis -- TCA Tricarboxylic acid cycle -- CKD chronic kidney disease -- RSD relative standard deviation -- i.p. intraperitoneally -- i.g. intragastrically -- Scr serum creatinine -- BUN blood urea nitrogen -- QC quality control -- ESI electrospray ionization -- ANOVA analysis of variance -- TIC total ion chromatogram -- VIP variable importance value -- EIC extracted ion chromatogram -- AAA aromatic amino acids -- ROS reactive oxygen species; Calcium oxalate crystal -- Biomarker discovery -- Metabonomics -- Orthosiphon stamineus -- UHPLC-Q-TOF/MS; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2015.03.025
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Orthosiphon stamineus (OS), a traditional Chinese herb, is often used for promoting urination and treating nephrolithiasis. Aim of the study: 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. Materials and methods: Thirty six mice were randomly divided into six groups including Saline, Crystal, Cystone and OS at dosages of 0.5 g/kg, 1 g/kg, and 2 g/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. Graphical abstract: