Combined systems pharmacology and fecal metabonomics to study the biomarkers and therapeutic mechanism of type 2 diabetic nephropathy treated with <i>Astragalus</i> and Leech

Chen, Ruiqun; Liao, Chengbin; Guo, Qulian; Wu, Lirong; Zhang, Lei; Wang, Xiufeng

doi:10.1039/c8ra04358b

Cited by 18 publications

(12 citation statements)

References 79 publications

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“…The PCA analysis can be used to initially determine the clustering of the overall samples and thereby distinguish whether there are differences among different groups. Besides, the PLS-DA model was validated with a permutation test (200 permutations), and OPLS-DA was validated by both a seven-fold cross-validation and ANOVA of the cross-validated residuals (CV-ANOVA) methods [70,71]. Simultaneously, differential metabolites were extracted from S -plots based on their contribution to the difference.…”

Section: Methodsmentioning

confidence: 99%

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Integrated Systems Pharmacology, Urinary Metabonomics, and Quantitative Real-Time PCR Analysis to Uncover Targets and Metabolic Pathways of the You-Gui Pill in Treating Kidney-Yang Deficiency Syndrome

Chen

Wang

Zhan

et al. 2019

IJMS

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Kidney-yang deficiency syndrome (KYDS) is a metabolic disease caused by a neuro-endocrine disorder. The You-gui pill (YGP) is a classic traditional Chinese medicine (TCM) formula for the treatment of KYDS and has been widely used to warm and recuperate KYDS clinically for hundreds of years in China. However, it is unknown whetherthe corresponding targets and metabolic pathways can also be found via using metabonomics based on one platform (e.g., 1H NMR) to study different biological samples of KYDS. At the same time, relevant reports on further molecular verification (e.g., RT-qPCR analysis) of these targets associated with biomarkers and metabolic pathways have not yet, to our knowledge, been seen in KYDS’s research. In the present study, a comprehensive strategy integrating systems pharmacology and 1H NMR-based urinary metabonomics analysis was proposed to identify the target proteins and metabolic pathways that YGP acts on KYDS. Thereafter, further validation of target proteins in kidney tissue was performed through quantitative real-time PCR analysis (RT-qPCR). Furthermore, biochemical parameters and histopathological analysis were studied. As a result, seven target proteins (L-serine dehydratase; phosphoenolpyruvate carboxykinase; spermidine synthase; tyrosyl-tRNA synthetase, glutamine synthetase; 3-hydroxyacyl-CoA dehydrogenase; glycine amidinotransferase) in YGP were discovered to play a therapeutic role in KYDS via affecting eight metabolic pathways (glycine, serine and threonine metabolism; butanoate metabolism; TCA cycle, etc.). Importantly, three target proteins (i.e., 3-hydroxyacyl-CoA dehydrogenase; glutamine synthetase; and glycine amidinotransferase) and two metabolic pathways (butanoate metabolism and dicarboxylate metabolism) related to KYDS, to our knowledge, had been newly discovered in our study. The mechanism of action mainly involved energy metabolism, oxidative stress, ammonia metabolism, amino acid metabolism, and fatty acid metabolism. In short, our study demonstrated that targets and metabolic pathways for the treatment of KYDS by YGP can be effectively found via combining with systems pharmacology and urinary metabonomics. In addition to this, common and specific targets and metabolic pathways of KYDS treated by YGP can be found effectively by integration with the analysis of different biological samples (e.g., serum, urine, feces, and tissue). It is; therefore, important that this laid the foundation for deeper mechanism research and drug-targeted therapy of KYDS in future.

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Section: Methodsmentioning

confidence: 99%

“…The specify pathway analysis algorithms: Hypergeometric test was used for over representation analysis, and relative-betweenness centrality was used for pathway topology analysis. Besides, metabolic pathways with p < 0.05 were considered to be pathways that significantly affected the development of KYDS, and were further analyzed [7,70].…”

Section: Methodsmentioning

confidence: 99%

Integrated Systems Pharmacology, Urinary Metabonomics, and Quantitative Real-Time PCR Analysis to Uncover Targets and Metabolic Pathways of the You-Gui Pill in Treating Kidney-Yang Deficiency Syndrome

Chen

Wang

Zhan

et al. 2019

IJMS

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“…It has been widely used in metabonomics research [12]. In recent years, network pharmacology has become a powerful tool in clarifying the complex and integral mechanisms of TCM [13]. It can construct related networks from the perspective of biological systems to explore the pathogenesis of diseases and reveal the interactions between the target and the drug in vivo.…”

Section: Introductionmentioning

confidence: 99%

Study on Hypoglycemic Effect of the Drug Pair of Astragalus Radix and Dioscoreae Rhizoma in T2DM Rats by Network Pharmacology and Metabonomics

Guo

Niu

et al. 2019

Molecules

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Type 2 diabetes mellitus (T2DM) is a metabolic disease accompanied by a series of diseases such as diabetic nephropathy. The drug pair (HS) of Astragalus Radix (HQ) and Dioscoreae Rhizoma (SY) was designed by Dr. Shi Jinmo to improve the treatment of T2DM. However, the exact mechanism involved requires further clarification. In this work, 1H-NMR–based metabonomics and network pharmacology were adopted. Metabolic profiling indicated that the metabolic perturbation was reduced after HS treatment. The results found 21 biomarkers. According to the network pharmacology, we found that the regulation of T2DM was primarily associated with 18 active compounds in HS. These active compounds mainly had an effect on 135 targets. Subsequently, combining network pharmacology and metabonomics, we found four target proteins, which indicated that HS has potential hypoglycemic effects through regulating monoamine oxidases B (MAOB), acetyl-CoA carboxylase 1 (ACACA), carbonic anhydrase 2 (CA2), and catalase (CAT). In conclusion, the result showed that these four targets might be the most relevant targets for the treatment of T2DM with HS. This study clarified the mechanism of HS in the treatment of T2DM and also confirmed the feasibility of combining metabonomics and network pharmacology to study the mechanisms of traditional Chinese medicine (TCM). In the future, this approach may be a potentially powerful tool to discovery active components of traditional Chinese medicines and elucidate their mechanisms.

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“…Shuizhi ( Hirudo powder ) is an animal-derived medicine, which has anticoagulant effects [23]. Shuizhi ( Hirudo powder ) combined with Huangqi ( Radix Astragali Mongolici ) is used to treat diabetic nephropathy, as these herbal medicine can protect kidney function, enhance insulin sensitivity, have antioxidant activity, and improve mitochondrial function [24].…”

Section: Discussionmentioning

confidence: 99%

Incipient Diabetes Treated with Long-Term Classical Prescription

Wei

Tian

Wang

et al. 2019

Journal of Diabetes Research

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Background Diabetes mellitus (DM) belongs to the progressive and irreversible disease. With the development of the disease, the function of beta cells declines significantly. Current treatments cannot reverse the course of the disease. The role of traditional Chinese medicine (TCM) in the DM treatment has been recognized widely, while there are few long-term observation reports. In this study, we introduced a case of DM treated by classical prescription alone for 10 years, which would provide the reference for clinical practice. Case Presentation A 64-year-old male complained of a 2-month history of dry mouth, frequent urination, and blurred vision and found increased blood glucose for 3 days. The patient's glycated hemoglobin was 14.2%, fasting plasma glucose fluctuated at 12-15 mmol/L, and urinary albumin excretion rate (UAER) was 32.9 μg/min. The male was treated with 10 years of continuous classical prescription alone. After 3 months of TCM treatment, the patient's blood glucose level decreased significantly and blurred vision symptoms improved. With continued TCM treatment, his UAER normalized. Subsequently, he continued outpatient consultation, and his TCM prescription was adjusted according to clinical symptoms. After 10 years of continuous TCM treatment, his blood glucose remained stable, urinary microalbumin quantitation showed no abnormalities, and blurred vision disappeared. Conclusions This case provides specific treatment plans and effective references for long-term control of blood glucose, prevention and treatment of diabetes complications, delay of disease progression, and protection of impaired islet function in the treatment of diabetes with TCM. TCM may become a meaningful alternative DM treatment in the future.

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Combined systems pharmacology and fecal metabonomics to study the biomarkers and therapeutic mechanism of type 2 diabetic nephropathy treated with Astragalus and Leech

Abstract: In our study, systems pharmacology was used to predict the molecular targets of Astragalus and Leech, and explore the therapeutic mechanism of type 2 diabetic nephropathy (T2DN) treated with Astragalus and Leech.

Cited by 18 publications

References 79 publications

Integrated Systems Pharmacology, Urinary Metabonomics, and Quantitative Real-Time PCR Analysis to Uncover Targets and Metabolic Pathways of the You-Gui Pill in Treating Kidney-Yang Deficiency Syndrome

Integrated Systems Pharmacology, Urinary Metabonomics, and Quantitative Real-Time PCR Analysis to Uncover Targets and Metabolic Pathways of the You-Gui Pill in Treating Kidney-Yang Deficiency Syndrome

Study on Hypoglycemic Effect of the Drug Pair of Astragalus Radix and Dioscoreae Rhizoma in T2DM Rats by Network Pharmacology and Metabonomics

Incipient Diabetes Treated with Long-Term Classical Prescription

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