ABSTRACT
Objective: With the development of the society, the number of people who catch the nephrotic syndrome (NS) is going up roughly. As we all know, traditional Chinese medicine (TCM), especially Fangji Huangqi Decoction (FHD), has a long history with good curative effects on NS. However, the mechanism of FHD treating NS has not been clearly elucidated. Methods: In this study, TCMSP platform was employed to screen active compounds of each herb of Fangji Huangqi Decoction combined with literatures. Furthermore, PharmMapper and SEA were used to predict and screen the active targets of FHD, and the HOME-NCBI-GENE, GeneCards and OMIM database were used to screen the active targets of NS. The GO and KEGG pathways involved in the targets were analyzed by ClueGO. Finally, contribution index was used to screen the active ingredients of FHD in the treatment of NS. Results: After drug-likeness (DL) and bioavailability (OB) filtering, 43 compounds were selected from FHD, interacting with 85 NS-related targets. Systematic analysis of the constructed networks revealed that it was mainly involved in PI3K-Akt signaling pathway, MAPK signaling pathway, T cell receptor signaling pathway and TNF signaling pathway. The contribution index of every active ingredient also indicated five compounds, including astragaloside IV, quercetin, glycyrrhizic acid, glycyrrhizin and fangchinoline. Conclusions: These results have successfully predicted the pharmacodynamic material basis and the mechanism efficiency of FHD in the treatment of NS.
ABSTRACT
We studied the effect of aqueous extract from Huang qi on gene expression profile of doxorubicin induced nephropathy in rats, and explored the molecular mechanism of the intervention. The gene expression profiles of control group, model group and aqueous extract from Huang qi group were detected by using transcriptome sequencing technique. The differentially expressed genes (DEGs) were screened by STEM trend analysis software. GO function enrichment and KEGG pathway analysis were performed for DEGs, and the gene expression level was verified by real-time fluorescence quantitative PCR (RT-qPCR). The results showed that, compared with the control group, 432 DEGs were obtained in doxorubicin nephropathy model group; compared with the model group, 811 DEGs were obtained due to aqueous extract of Huang qi. The results of GO function enrichment and KEGG enrichment analysis indicated that PI3K-AKT pathway (Col6a6, Nr4a1, Sgk1, Gng7) and lipid metabolism-related genes (Cpt1b, Pcsk9, Abca1, Ascm5) were the key pathways and genes in the treatment of doxorubicin induced nephropathy by aqueous extract from Huang qi, which played a protective role in kidney. In conclusion, the molecular mechanism of aqueous extract from Huang qi in protection against doxorubicin induced nephropathy rats is closely related to apoptosis-related genes and lipid metabolism-related genes, suggesting for the need of follow-up study for key gene validation and mechanism of action of aqueous extract from Huang qi for prevention of doxorubicin induced nephropathy.
ABSTRACT
Objective To carry out the quantitative analysis of the injury degree of model rat of doxorubicin-induced nephropathy based on metabolomics. Methods 1H-NMR based metabolomics approach combined with multivariate statistical analysis were used to analyze rat serum samples from different doses and different times of doxorubicin administration and identify the progressive markers reflecting the progress degree of nephropathy. Moreover, the evaluation of injury degree of rat nephropathy model induced by doxorubicin was conducted according to the change degree of related markers. Results Nine potential biomarkers for pathological conditions were obtained such as 2-oxoisocaproate, isoleucine, leucine, valine, pyruvate, 3-hydroxybutyric acid, citric acid, creatinine, and carnitine, among which 2-oxoisocaproate and carnitine were in a dose-dependent manner, that is, the greater the dose of doxorubicin, the greater the variation of the endogenous metabolites, the more severe kidney injury, indicating that 2-oxoisocaproate and carnitine can be used as a progressive markers reflecting the process of kidney disease. Conclusion This study provides the diagnostic marker of nephropathy, and provides research methods and ideas for the study of other progressive diseases and the discovery of early diagnostic markers.
ABSTRACT
Traditional Chinese medicine(TCM) has the characteristics and complexities of multi-component, multi-target and multi-way. The study of TCM compound efficacy material basis is the core part in illuminating the effect and mechanism of TCM. So many methods were involved in the researches on material foundation including the effective part searching, compatibility and its disassembled prescriptions investigating based on pharmacological activity tracking in vivo; the association analysis between chemical fingerprints characterized by a variety of instruments and efficacy; serum pharmacochemistry and Chinmedomics based on metabolic processes in vivo; cell membrane chromatography and bionic technology based on activity discovering in vitro; and network pharmacology based on the computer simulation. The paper summarized the research methods in this field by consulting and concluding some document data of recent years, aiming to provide a theoretical foundation for studying on the effective material foundation of compound prescription of traditional Chinese medicine.
ABSTRACT
This study was designed to explore the mechanism of total flavonoids of Astragali Radix (TFA) in treating nephrotic syndrome through establishing the active components-targets network and protein-protein interaction (PPI) networks and analyzing the functions and pathways involved in the targets. The main active ingredients of TFA were obtained by 1H NMR and LC-MS, TCMSP and TCMID database. PharmMapper, SEA, SIB, HOME-NCBI-GENE, GeneCards and OMIM were used to predict and screen the active components of TFA. The Cytoscape software was used to construct the active components-targets network and protein-protein interactions network. The relation between the main active ingredients and targets were validated by Systems Dock Web Site. The GO and KEGG pathways involved in the targets were analyzed by ClueGO software. The target organ distribution was assigned by the BioGPS database. The results showed that 29 active components and 50 targets of TFA were screened and predicted. The network results showed that the TFA were mainly involved in biological processes such as inflammatory reaction process, oxidative stress process,apoptosis and autophagy, and played a role in the regulation of AGE-RAGE, PI3K/Akt, VEGF, IL-17 and MAPK signaling pathways to treat the nephrotic syndrome. This study reflects the characteristics of multi-components, multi-targets and multi-pathways of TFA, which provides new ideas and clues for further research on the mechanism of anti-nephrotic syndrome effects of TFA.