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Uncovering the mechanism of the effects of Paeoniae Radix Alba on iron-deficiency anaemia through a network pharmacology-based strategy.

ABSTRACT: BACKGROUND:Paeoniae Radix Alba, the root of the plant Paeonia lactiflora Pall, is a common blood-enriching drug in traditional Chinese medicine. Its effectiveness in the clinical treatment of anaemia is remarkable, but its potential pharmacologic mechanism has not been clarified. METHODS:In this study, the potential pharmacologic mechanism of Paeoniae Radix Alba in the treatment of iron-deficiency anaemia was preliminarily elucidated through systematic and comprehensive network pharmacology. RESULTS:Specifically, we obtained 15 candidate active ingredients from among 146 chemical components in Paeoniae Radix Alba. The ingredients were predicted to target 77 genes associated with iron-deficiency anaemia. In-depth analyses of these targets revealed that they were mostly associated with energy metabolism, cell proliferation, and stress responses, suggesting that Paeoniae Radix Alba helps alleviate iron-deficiency anaemia by affecting these processes. In addition, we conducted a core target analysis and a cluster analysis of protein-protein interaction (PPI) networks. The results showed that four pathways, the p53 signalling pathway, the IL-17 signalling pathway, the TNF signalling pathway and the AGE-RAGE signalling pathway in diabetic complications, may be major pathways associated with the ameliorative effects of Paeoniae Radix Alba on iron-deficiency anaemia. Moreover, molecular docking verified the credibility of the network for molecular target prediction. CONCLUSIONS:Overall, this study predicted the functional ingredients in Paeoniae Radix Alba and their targets and uncovered the mechanism of action of this drug, providing new insights for advanced research on Paeoniae Radix Alba and other traditional Chinese medicines.

SUBMITTER: Ye XW

PROVIDER: S-EPMC7189569 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Uncovering the mechanism of the effects of Paeoniae Radix Alba on iron-deficiency anaemia through a network pharmacology-based strategy.

Ye Xian-Wen XW Deng Ya-Ling YL Xia Lan-Ting LT Ren Hong-Min HM Zhang Jin-Lian JL

BMC complementary medicine and therapies 20200428 1

<h4>Background</h4>Paeoniae Radix Alba, the root of the plant Paeonia lactiflora Pall, is a common blood-enriching drug in traditional Chinese medicine. Its effectiveness in the clinical treatment of anaemia is remarkable, but its potential pharmacologic mechanism has not been clarified.<h4>Methods</h4>In this study, the potential pharmacologic mechanism of Paeoniae Radix Alba in the treatment of iron-deficiency anaemia was preliminarily elucidated through systematic and comprehensive network ph ...[more]

PMID: 32345291

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Project description:Combination of Aconiti Lateralis Radix Praeparata (FZ) and Paeoniae Radix Alba (BS) shows a significant effect in rheumatoid arthritis (RA). This study aimed to investigate the efficacy enhancing and toxicity reducing mechanism of combination of them in adjuvant-induced arthritis (AIA) rats by metabolomics. Rats were randomly divided into seven groups, including A (healthy control), B (model control), C1 (therapy group), C2 (efficacy enhancing group), D1 (toxicity group), and D2 (toxicity reducing group), and dexamethasone group was used as positive control. The plasma biochemical indexes showed that therapeutic dose of lipid-soluble alkaloids of FZ could significantly inhibit the concentrations of IL-1β, TNF-α, and IFN-γ in AIA rats, and combination with total glucosides of peony could further reduce the concentration of IL-1β. Then, UPLC-LTQ/Orbitrap MS with untargeted metabolomics was performed to identify the possible metabolites and pathways. Through multivariate data analysis of therapeutic dose groups (A vs. B vs. C1 vs. C2) and multivariate data analysis of toxic dose groups (A vs. B vs. D1 vs. D2), 10 and 7 biomarkers were identified based on biomarker analysis, respectively. After inducing AIA model, the plasma contents of spermidine, vanillylmandelic acid, catechol, and linoleate were increased significantly, and the contents of citric acid, L-tyrosine, L-phenylalanine, leucine, L-tryptophan, and uridine 5'-monophosphate (UMP) were decreased significantly. High dose of lipid-soluble alkaloids of FZ could increase the plasma contents of L-lysine, L-arginine, and deoxycholic acid, while the plasma contents of UMP, carnitine, N-formylanthranilic acid, and adenosine were decreased significantly. The pathway analysis indicated that therapeutic dose of lipid-soluble alkaloids of FZ could regulate energy and amino acid metabolic disorders in AIA rats. However, toxic dose could cause bile acid, fat, amino acid, and energy metabolic disorders. And combination with total glucosides of peony could enhance the therapeutic effects and attenuate the toxicity induced by lipid-soluble alkaloids of FZ.

Project description:Background:Radix Paeoniae Alba (RPA) and other natural medicines have remarkable curative effects and are widely used in traditional Chinese Medicine (TCM). However, due to their multi-component and multi-target characteristics, it is difficult to study the detailed pharmacological mechanisms for those natural medicines in vivo. Therefore, their real effects on organisms is still uncertain. Methods:RPA was selected as research object, the present study was designed to study the complex mechanisms of RPA in vivo by integrating and interpreting the transcriptomic based RNA-seq and metabolomic based NMR spectrum after RPA administration in mice. A variety of dimension-reduction algorithms and classifier models were applied to the processing of high-throughput data. Results:Among serum metabolites, the contents of PC and glucose were significantly increased, while the contents of various amino acids, lipids and their metabolites were significantly decreased in mice after RPA administration. Based on the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, differential analysis showed that the liver was the site where RPA exerted a significant effect, which confirmed the rationality of "meridian tropism" in the theory in TCM. In addition, RPA played a role in lipid metabolism by regulating genes encoding enzymes of the glycerolipid metabolism pathway, such as 1-acyl-sn-glycerol-3-phosphate acyltransferase (Agpat), phosphatidate phosphatase (Lpin), phospholipid phosphatase (Plpp) and endothelial lipase (Lipg). We also found that RPA regulates several substance addiction pathways in the brain, such as the cocaine addiction pathway, and the related targets were predicted based on the sequencing data from pathological model in the GEO database. The overall effective pattern of RPA was intuitively presented with a multidimensional radar map through a self-designed model which found that liver and brain were mainly regulated by RPA compared with the traditional meridian tropism theory. Conclusions:Overall this study expanded the potential application of RPA and provided possible targets and directions for further mechanism study, meanwhile, it also established a multi-dimensional evaluation model to represent the overall effective pattern of TCM for the first time. In the future, such study based on the high-throughput data sets can be used to interpret the theory of TCM and to provide a valuable research model and clinical medication reference for the TCM researchers and doctors.

Dataset Information

Uncovering the mechanism of the effects of Paeoniae Radix Alba on iron-deficiency anaemia through a network pharmacology-based strategy.

Publications

Uncovering the mechanism of the effects of Paeoniae Radix Alba on iron-deficiency anaemia through a network pharmacology-based strategy.

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