A Systems Biology-Based Investigation into the Pharmacological Mechanisms of Wu Tou Tang Acting on Rheumatoid Arthritis by Integrating Network Analysis

Zhang, Yanqiong; Wang, Danhua; Tan, Siew‐Ann; Xu, Haiyu; Lin, Na

doi:10.1155/2013/548498

Cited by 26 publications

(33 citation statements)

References 59 publications

(58 reference statements)

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“…It indicates that calcium signaling pathway is target pathway of RA treatment. 33 The other five pathways are not reported as RA-risk pathways in the literature at present. However, we found some possible correlations between them and RA through literature reviews.…”

Section: Same Results From Gaw16 and Wtccc Data Setmentioning

confidence: 86%

“…Lu et al 32 also pointed out calcium signaling pathway may be related to heat pattern of RA. Zhang et al 33 investigated into the pharmacological mechanisms of traditional Chinese medicine acting on RA by integrating network analysis and found that the predicted effector molecules of traditional Chinese medicine were significantly enriched in calcium signaling pathway. It indicates that calcium signaling pathway is target pathway of RA treatment.…”

Section: Same Results From Gaw16 and Wtccc Data Setmentioning

confidence: 99%

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Pathway-based association analysis of two genome-wide screening data identifies rheumatoid arthritis-related pathways

Jiang

et al. 2014

Genes Immun

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The pathways can explain molecular mechanisms of complex diseases from the perspective of biology function. We carried out a genome-wide pathway-based association analysis to identify the risk pathways of rheumatoid arthritis (RA). First, we performed two genome-wide association studies using two RA data sets from GAW16 (Genetic Analysis Workshop 16) and the Wellcome Trust Case Control Consortium, and obtained risk P-value for each single-nucleotide polymorphism (SNP). Next, we mapped all the SNPs to genome-wide autosomal genes and calculated gene-wise risk values by minimum P-value method. We calculated the KEGG (Kyoto Encyclopedia of Gene and Genomes) pathway risk scores according to Fisher combination method and identified the significant pathways by permutation test. At last, we merged the results from the two pathway-based genome-wide association analyses to identify the high-risk pathways, which were found in both the data sets. The results showed that there were nine pathways, focal adhesion pathway, extracellular matrix-receptor interaction pathway, calcium signaling pathway, dopaminergic synapse pathway, long-term potentiation pathway, retrograde endocannabinoid signaling pathway, glutamatergic synapse pathway, cholinergic synapse pathway and morphine addiction pathway, associated with susceptibility to RA. Among these pathways, four pathways were reported as RA-risk pathways in the previous literatures. We also inferred that other five pathways may be related to RA. Further researches of these pathways will help us to understand the molecular mechanisms of RA.

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Section: Same Results From Gaw16 and Wtccc Data Setmentioning

confidence: 86%

Section: Same Results From Gaw16 and Wtccc Data Setmentioning

confidence: 99%

Pathway-based association analysis of two genome-wide screening data identifies rheumatoid arthritis-related pathways

Jiang

et al. 2014

Genes Immun

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“…Based on our previous developed target prediction system [25], a total of 142 genes were predicted as putative targets of HYD. As shown in Supplementary Table S6, the amount of putative targets hit by HZ, KB, FBX, ZBM, QP, CP, DG, CX, DH, LQ and GC were 11, 3, 1, 5, 48, 25, 30, 25, 30, 53, 37, 30 and 28, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…This prediction method achieves good prediction performance according to the evaluation in our previous study [25]. Detailed description on this drug target prediction method is provided in Supplementary File Section 1.…”

Section: Methodsmentioning

confidence: 91%

Thyroid hormone synthesis: a potential target of a Chinese herbal formula Haizao Yuhu Decoction acting on iodine-deficient goiter

Zhang

Mao

et al. 2016

Oncotarget

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Haizao Yuhu Decoction (HYD), a famous multi-component herbal formula, has been widely used to treat various thyroid-related diseases, including iodine-deficient goiter. Herb pair Thallus Sargassi Pallidi (HZ) and Radix Glycyrrhizae (GC), one of the so-called “eighteen antagonistic medicaments”, contains in HYD. To explore pharmacological mechanisms of HYD acting on iodine-deficient goiter and to provide evidence for potential roles of herb pair HZ and GC in HYD, our genome-wide microarray detection and network analysis identified a list of goiter-related genes, mainly involved into the alterations in hypothalamus-pituitary-thyroid/gonad/growth axes. Then, the disease genes-drug genes interaction network illustrated the links between HYD regulating genes and goiter-related genes, and identified the candidate targets of HYD acting on goiter. Functionally, these candidate targets were closely correlated with thyroid hormone synthesis. Moreover, the potential regulating genes of herb pair HZ and GC were revealed to be crucial components in the pathway of thyroid hormone synthesis. The prediction results were all verified by following experiments based on goiter rats. Collectively, this integrative study combining microarray gene expression profiling, network analysis and experimental validations offers the convincing evidence that HYD may alleviate iodine-deficient goiter via regulating thyroid hormone synthesis, and explains the necessity of herb pair HZ and GC in HYD. Our work provides a novel and powerful means to clarify the mechanisms of action for multi-component drugs such as herbal formulae in a holistic way, which may improve drug development and applications.

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“…According to our previous studies [32][33][34] , node degree was calculated to select hubs in the above network, and the hub network was constructed using the interactions among the hubs. Then, four network topological features, including 'Degree,' 'Betweenness,' 'Closeness' and 'K value,' were calculated to evaluate the importance of hubs in the hub network.…”

Section: Network Construction and Analysismentioning

confidence: 99%

Main active constituent identification in Guanxinjing capsule, a traditional Chinese medicine, for the treatment of coronary heart disease complicated with depression

Zhang

Guo

et al. 2017

Acta Pharmacol Sin

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Guanxinjing capsules (GXJCs) are used in traditional Chinese medicine as a common therapy for coronary heart disease (CHD) complicated with depression. In this study, we aimed to identify the main active constituents in GXJCs and to investigate the mechanisms of GXJC action on CHD complicated with depression. The chemical constituent profile of the GXJC was identified by UHPLC-LTQ-Orbitrap assay, and oral bioavailability was evaluated to screen the GXJC drug-like chemical constituents. A total of 16 GXJC drug-like chemical constituents were identified. Then, putative targets of the GXJC drug-like chemical constituents were predicted using MedChem Studio, with 870 genes found to be the putative targets of these molecules. After that, a GXJC putative target-known CHD/depression therapeutic target network was constructed, and four topological features, including degree, betweenness, closeness and K-coreness, were calculated. According to the topological feature values of the GXJC putative targets, 14 main active constituents were identified because their corresponding putative targets had topological importance in the GXJC putative target-known CHD/depression therapeutic target network, which were defined as the candidate targets of GXJC against CHD complicated with depression. Functionally, these candidate targets were significantly involved in several CHD/depression-related pathways, including repairing pathological vascular changes, reducing platelet aggregation and inflammation, and affecting patient depression. This study identified a list of main active constituents of GXJC acting on CHD complicated with depression using an integrative pharmacology-based approach that combined active chemical constituent identification, drug target prediction and network analysis. This method may offer an efficient way to understand the pharmacological mechanisms of traditional Chinese medicine prescriptions.

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A Systems Biology-Based Investigation into the Pharmacological Mechanisms of Wu Tou Tang Acting on Rheumatoid Arthritis by Integrating Network Analysis

Cited by 26 publications

References 59 publications

Pathway-based association analysis of two genome-wide screening data identifies rheumatoid arthritis-related pathways

Pathway-based association analysis of two genome-wide screening data identifies rheumatoid arthritis-related pathways

Thyroid hormone synthesis: a potential target of a Chinese herbal formula Haizao Yuhu Decoction acting on iodine-deficient goiter

Main active constituent identification in Guanxinjing capsule, a traditional Chinese medicine, for the treatment of coronary heart disease complicated with depression

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