Abstract
Background Chronic kidney disease (CKD) is one of the major causes of renal damage. Shenyan Fangshuai Recipe (SFR), a modified prescription of traditional medicine in China, showed potent effects in alleviating edema, proteinuria, and hematuria of CKD in clinical practices. In this study, we aimed to investigate scientific evidence-based efficacy as well as metabolic regulations of SFR in CKD treatment. Materials and Methods The effect of SFR on CKD was observed in a rat model which is established with oral administration of adenine-ethambutol mixture for 21 days. Further, metabolites in serum were detected and identified with ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). Metabolomics study was performed using Ingenuity Pathway Analysis (IPA) software. Results With H&E staining and Masson's trichrome, the results showed that chronic kidney damage is significantly rescued with SFR treatment and recovered to an approximately normal condition. Along with 44 differential metabolites discovered, the regulation of SFR on CKD was enriched in glycine biosynthesis I, mitochondrial L-carnitine shuttle pathway, phosphatidylethanolamine biosynthesis III, sphingosine-1-phosphate signaling, L-serine degradation, folate transformations I, noradrenaline and adrenaline degradation, salvage pathways of pyrimidine ribonucleotides, cysteine biosynthesis III (Mammalia), glycine betaine degradation, and cysteine biosynthesis/homocysteine degradation. Further, TGFβ-1 and MMP-9 were observed playing roles in this regulatory process by performing immunohistochemical staining. Conclusion SFR exerts potent effects of alleviating glomerular sclerosis and interstitial fibrosis in the kidney, mainly via integrated regulations on metabolism and production of homocysteine, L-carnitine, and epinephrine, as well as the expression of TGFβ-1. This study provides evidence for SFR's protective effects on CKD and reveals the metabolic mechanism behind these benefits for the first time.
Highlights
Chronic kidney disease (CKD), a set of disorders destroying the structure and function of the kidney [1], is becoming a public health problem worldwide along with increasing incidence and prevalence, poor outcomes, and high cost [2]
We aimed to provide more metabolic evidence for the explanation of Shenyan Fangshuai Recipe (SFR)’s protective effect in an experimental way. e metabolic character of CKD was profiled with UPLC-HRMS and Ingenuity Pathway Analysis (IPA) was applied for metabolomic analysis and exploration of SFR’s regulatory mechanism in delaying the development of CKD
SFR Exerted Potent Protective Effects on CKD Model Induced by Hyperuricemia. e content of serum creatinine (SCr) and SUA in blood was kept increasing during the modeling process (Figure 1(a)), indicating the validity of the CKD model
Summary
Chronic kidney disease (CKD), a set of disorders destroying the structure and function of the kidney [1], is becoming a public health problem worldwide along with increasing incidence and prevalence, poor outcomes, and high cost [2]. Hyperuricemia but not serum uric acid levels had been observed to be a risk factor for all-cause mortality and CVD mortality in CKD [4, 5]. Chronic kidney disease (CKD) is one of the major causes of renal damage. We aimed to investigate scientific evidence-based efficacy as well as metabolic regulations of SFR in CKD treatment. With H&E staining and Masson’s trichrome, the results showed that chronic kidney damage is significantly rescued with SFR treatment and recovered to an approximately normal condition. SFR exerts potent effects of alleviating glomerular sclerosis and interstitial fibrosis in the kidney, mainly via integrated regulations on metabolism and production of homocysteine, L-carnitine, and epinephrine, as well as the expression of TGFβ-1. SFR exerts potent effects of alleviating glomerular sclerosis and interstitial fibrosis in the kidney, mainly via integrated regulations on metabolism and production of homocysteine, L-carnitine, and epinephrine, as well as the expression of TGFβ-1. is study provides evidence for SFR’s protective effects on CKD and reveals the metabolic mechanism behind these benefits for the first time
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