Metabolomics Analysis Reveals the Protection Mechanism of Huangqi–Danshen Decoction on Adenine-Induced Chronic Kidney Disease in Rats

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.

Untargeted Metabolomics Reveals the Protective Effect of a Traditional Chinese Herbal Decoction on Cisplatin‐Induced Acute Kidney Injury

“…TCM formulas are usually composed of many herbs, which makes it difficult to fully understand their therapeutic mechanisms. Metabolomics strategy is beneficial to clarify the connotation of TCM theory [ 19 ] and has been successfully applied in many TCM-related research fields, such as therapeutic mechanisms elucidation [ 20 , 21 ], drug toxicity evaluation [ 22 ], and disease diagnosis [ 23 ]. Hence, metabolomics provides an approach to achieve a comprehensive and systematic understanding of the therapeutic mechanisms of TCM formulas.…”

Identification of differentially expressed genes in diabetic kidney disease by RNA‐Seq analysis of venous blood platelets

“…Although mammalian cells can survive without GPI anchors, a lack of hematopoietic cells can result in hemolytic disease, namely paroxysmal nocturnal hemoglobinuria [ 44 ]. Interestingly, GPI‐anchor biosynthesis was enriched as a pathway with respect to the treatment of CKD in metabonomics studies of rat CKD models [ 45 ]. The most valuable pathway of concern is Hematopoietic cell lineage, which is the most significantly enriched pathway in DKD vs. HC.…”

Involvement of Circulating Exosomal MicroRNAs in Jian-Pi-Yi-Shen Formula Protection Against Adenine-Induced Chronic Kidney Disease

“…After one week of acclimatization, all rats were randomly divided into the following three groups (n = 6 rats per group): (i) control group; (ii) CKD group; and (iii) JPYSF treatment group (CKD + JPYSF). CKD was induced by feeding a diet containing 0.75% w/w adenine (Sangon Biotech, Shanghai, China) for four weeks ( Liu et al, 2019 ). The rats in the CKD + JPYSF group were given 10.89 g/kg JPYSF by gavage every day, starting from the 3rd week of the adenine-containing diet for six weeks.…”