Abstract
Huangqi–Danshen decoction (HDD) is a commonly used drug pair for clinical treatment of chronic kidney disease (CKD) in traditional Chinese medicine with good efficacy. However, the potential mechanisms of this action have not been well elucidated. The aim of this study was to explore the metabolic profiling variations in response to HDD treatment in a CKD rat model. CKD rat model was induced by adding 0.75% adenine to the diet for 4 weeks. The rats in the treatment group received HDD extract orally at the dose of 4.7 g/kg/day during the experiment. At the end of the experiment, serum and kidney samples were collected for biochemical and pathological examination. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) was used to analyze metabolic profiling variations in the kidney. The results showed that treatment with HDD markedly attenuated kidney injury and improved renal function. A total of 28 metabolites contributing to CKD phenotype were found and identified in the kidney samples. The primary metabolic pathways disordered in the kidney of CKD rats were glycerophospholipid metabolism, glycosylphosphatidylinositol-anchor biosynthesis, and citrate cycle. Partial least squares discriminant analysis (PLS-DA) score plot showed that the three groups of renal samples were obviously divided into three categories, and the metabolic trajectory of the HDD treatment group moved to the control group. (E)-Piperolein A, phosphatidylcholines (PC) (18:1/22:6), phosphatidylinositols (PI) (13:0/18:1), PI (15:0/20:3), phosphatidylserines (PS) (O-20:0/12:0), and triglyceride (TG) (22:4/24:0/O-18:0) represented potential biomarkers of the renoprotective effects of HDD against CKD. In conclusion, HDD has renoprotective effect against adenine-induced CKD, which may be mediated via partially restoration of perturbed metabolism in the kidney.
Highlights
Chronic kidney disease (CKD) arises from many heterogeneous diseases that alter the function and structure of the kidney irreversibly, over months or years (Webster et al, 2017)
In agreement with the improved renal function, massive tubular atrophy in periodic acid–Schiff (PAS) staining and obvious fibrosis in Masson staining in chronic kidney disease (CKD) rats were significantly reversed by Huangqi–Danshen decoction (HDD) treatment (Figures 1E, F)
The potential side effects of HDD were estimated by the levels of aspartate transaminase (AST) and alanine transaminase (ALT)
Summary
Chronic kidney disease (CKD) arises from many heterogeneous diseases that alter the function and structure of the kidney irreversibly, over months or years (Webster et al, 2017). The high prevalence and mortality of CKD makes its treatment an urgent task. Increasing evidence indicates the beneficial effects of TCM on prevention and treatment of CKD in both clinical CKD patients (Wang et al, 2012; Hsieh et al, 2014; Lin et al, 2015; Zheng et al, 2017) and CKD animal models (Zhao et al, 2015a; Wang et al, 2017b; Dou et al, 2018; Liu et al, 2018; Zhang et al, 2018). According to TCM theory, HDD possesses the efficacies of replenishing Qi and activating blood (Yi-Qi-Huo-Xue), which helps delay the progress of CKD. The previous pharmacological study has showed the renoprotective effect of HDD in adenine-induced CKD rats (Liu et al, 2019). The underlying mechanism of HDD on CKD is less known
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