Abstract

The surface layer of Poria cocos (Fu-Ling-Pi, FLP) is commonly used in traditional Chinese medicine and its diuretic effect was confirmed in rat. Ultra performance liquid chromatography/quadrupole time-of-flight high-sensitivity mass spectrometry and a novel mass spectrometryElevated Energy data collection technique was employed to investigate metabonomic characteristics of chronic kidney disease (CKD) induced from adenine excess and the protective effects of FLP. Multiple metabolites are detected in the CKD and are correlated with progressive renal injury. Among these biomarkers, lysoPC(18∶0), tetracosahexaenoic acid, lysoPC(18∶2), creatinine, lysoPC (16∶0) and lysoPE(22∶0/0∶0) in the FLP-treated group were completely reversed to levels in the control group which lacked CKD. Combined with biochemistry and histopathology results, the changes in serum metabolites indicate that the perturbations of phospholipids metabolism, energy metabolism and amino acid metabolism are related to adenine-induced CKD and to the interventions of FLP on all the three metabolic pathways. FLP may regulate the metabolism of these biomarkers, especially their efficient utilization within the context of CKD. Furthermore, these biomarkers might serve as characteristics to explain the mechanisms of FLP.

Highlights

  • Kidney diseases are a serious and prevalent health problem, and manifestation includes changes in renal detoxification capacity, deregulation of salt and water balance and altered endocrine functions -overall, exerting a significant impact on the patient’s short- or long-term survival

  • Urinary volume was markedly increased in the chronic kidney disease (CKD) group compared with that in the control group and arrived at statistical significance (P,0.01), but decrease of urinary volume was revealed in the FLP-treated group

  • blood urea nitrogen (BUN), Scr, cholesterol and triglyceride were all in higher concentrations in CKD group than in control group (P,0.01). These results demonstrate that the rat model exhibited typical pathologic features associated with CKD

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Summary

Introduction

Kidney diseases are a serious and prevalent health problem, and manifestation includes changes in renal detoxification capacity, deregulation of salt and water balance and altered endocrine functions -overall, exerting a significant impact on the patient’s short- or long-term survival. Metabonomics is a part of systems biology which refers to a holistic analytical approach to the low molecular mass organic endogenous metabolites in the tissue or bio-fluids [1]. In the TCM research arena, this strategy has gained broad applications in many aspects, such as symptom subtyping, medicine quality control and therapeutic effect evaluation [3,4,5]. Mass spectrometry (MS) and nuclear magnetic resonance spectroscopy are two analytical tools commonly used in TCM metabonomics study [6]. In the MS-based metabonomics, ultra performance liquid chromatography-mass spectrometry (UPLC-MS) is considered to be suitable for largescale untargeted metabolic profiling study due to its enhanced reproducibility of retention time [7,8]. MSE can provide parallel alternating scans for acquisition at either low collision energy to obtain precursor ion information, or ramping of high collision energy to obtain full-scan accurate mass fragment, precursor ion and neutral loss information [10,11]

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