Exploring the Potential Mechanism of Guchang Zhixie Wan for Treating Ulcerative Colitis by Comprehensive Network Pharmacological Approaches and Molecular Docking Validation as Well as Cell Experiments

Zhang, Wei; Xu, Chao; Wu, Jieqiong; Ma, Xiao-Bing; Yang, Yin-Li; Wu, Yang; Lin, Jia

doi:10.1002/cbdv.202000810

Cited by 15 publications

(16 citation statements)

References 59 publications

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“…The GeneCards, OMIM, DrugBank, and PharmGKB databases were searched for relevant gene targets using the keyword “ulcerative colitis,” as shown in previous studies [ 4 ]. These potential XJD target genes were then linked to UC target genes to identify candidate targets.…”

Section: Methodsmentioning

confidence: 99%

“…Aminosalicylic acid preparations, commonly used in the treatment of UC, exert anti-inflammatory effects mainly by affecting the metabolism of arachidonic acid and inhibiting prostaglandin synthesis, but their adverse effects are more frequent and their therapeutic effects are less satisfactory. Traditional Chinese medicine (TCM) has been shown to have potential advantages in UC treatment [ 1 , 4 , 5 ]. Hu et al recently found that XJD was effective in treating UC by effectively regulating neuroendocrine factors, improving the intestinal immune response, and reducing patient symptoms [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Exploring the Potential Mechanism of Xiaokui Jiedu Decoction for Ulcerative Colitis Based on Network Pharmacology and Molecular Docking

Wang¹,

Liu²,

Sun³

et al. 2021

Journal of Healthcare Engineering

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Introduction. Network pharmacology is in line with the holistic characteristics of TCM and can be used to elucidate the complex network of interactions between disease-specific genes and compounds in TCM herbal medicines. Here, we investigate the pharmacological mechanism of Xiaokui Jiedu decoction (XJD) for the treatment of ulcerative colitis (UC). Methods. The Computational Systems Biology Laboratory Platform (TCMSP) database was searched and screened for the active ingredients of all drugs in XJD. The Uniport database was used to retrieve possible gene targets for the therapeutic effects of XJD. GeneCards, PharmGKB, TTD, and OMIM databases were used to retrieve XJD-related gene targets. A herb-compound-protein network and a protein-protein interaction (PPI) network were constructed, and hub genes were screened for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, molecular docking was performed to validate the interrelationship between disease target proteins and active drug components. Results. A total of 135 XJD potential action targets, 5097 UC-related gene targets, and 103 XJD-UC intersection gene targets were screened. The hub gene targets of XJD that exert therapeutic effects on UC are RB1, MAPK1, TP53, JUN, NR3C1, MAPK3, and ESR1. GO enrichment analysis showed 741 biofunctional enrichments, and KEGG enrichment analysis showed 124 related pathway enrichments. Molecular docking showed that the active components of XJD (β-sitosterol, kaempferol, formononetin, quercetin, and luteolin) showed good binding activities to five of the six hub gene targets. Discussion. The active ingredients of XJD (β-sitosterol, kaempferol, formononetin, quercetin, and luteolin) may regulate the inflammatory and oxidative stress-related pathways of colon cells during the course of UC by binding to the hub gene targets. This may be a potential mechanism of XJD in the treatment of UC.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Exploring the Potential Mechanism of Xiaokui Jiedu Decoction for Ulcerative Colitis Based on Network Pharmacology and Molecular Docking

Wang¹,

Liu²,

Sun³

et al. 2021

Journal of Healthcare Engineering

View full text Add to dashboard Cite

show abstract

“…As described in previous studies, we molecularly docked the screened core active ingredient to the core protein to verify the interaction strength ( 43 ). The active ingredient structures were obtained from the PubChem database and the protein structures were obtained from the Protein Data Bank (PDB) ( 44 , 45 ).…”

Section: Methodsmentioning

confidence: 99%

Eucommia ulmoides Oliver-Tribulus terrestris L. Drug Pair Regulates Ferroptosis by Mediating the Neurovascular-Related Ligand-Receptor Interaction Pathway- A Potential Drug Pair for Treatment Hypertension and Prevention Ischemic Stroke

Zhang

Yang

et al. 2022

Front. Neurol.

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BackgroundIn this study, we used the network pharmacology approach to explore the potential disease targets of the Eucommia ulmoides Oliver (EUO)-Tribulus terrestris L. (TT) drug pair in the treatment of hypertension-associated neurovascular lesions and IS via the ferroptosis pathway.MethodsWe used the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform to search for the key active compounds and targets of the drug pair. Based on the GeneCards database, the relevant targets for the drug pair were obtained. Then, we performed the molecular docking of the screened core active ingredients and proteins using the DAVID database and the R AutoDock Vina software. Based on the GSE22255 dataset, these screened target proteins were used to build random forest (RF) and support vector machine (SVM) models. Finally, a new IS nomogram prediction model was constructed and evaluated.ResultsThere were 36 active compounds in the EUO-TT drug pair. CHRM1, NR3C1, ADRB2, and OPRD1 proteins of the neuroactive ligand-receptor interaction pathway interacted with the proteins related to the ferroptosis pathway. Molecular docking experiments identified 12 active ingredients of the drug pair that may tightly bind to those target proteins. We constructed a visual IS nomogram prediction model using four genes (CHRM1, NR3C1, ADRB2, and OPRD1). The calibration curve, DCA, and clinical impact curves all indicated that the nomogram model is clinically applicable and diagnostically capable. CHRM1, NR3C1, ADRB2, and OPRD1, the target genes of the four effective components of the EUO-TT drug pair, were considered as risk markers for IS.ConclusionsThe active ingredients of EUO-TT drug pair may act on proteins associated with the neuroactive ligand-receptor interaction pathway to regulate ferroptosis in vascular neurons cells, ultimately affecting the onset and progression of hypertension.

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“…(3) The pathway enrichment analysis of single cells was performed using the Single-Cell Signature Explorer, and the expression abundance of the target pathway is calculated. (4) GO and KEGG enrichment analyses are widely used research methods; they are conducted using the clusterProfiler package (version 3.14.3), and the org.Mm.eg.db package (version 3.10.0) was used for ID transformation [ 59 , 62 , 63 ].…”

Section: Methodsmentioning

confidence: 99%

Single‐Cell Integration Analysis of Heterotopic Ossification and Fibrocartilage Developmental Lineage: Endoplasmic Reticulum Stress Effector Xbp1 Transcriptionally Regulates the Notch Signaling Pathway to Mediate Fibrocartilage Differentiation

Chen

Sun

et al. 2021

Oxidative Medicine and Cellular Longevity

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Introduction. Regeneration of fibrochondrocytes is essential for the healing of the tendon-bone interface (TBI), which is similar to the formation of neurogenic heterotopic ossification (HO). Through single-cell integrative analysis, this study explored the homogeneity of HO cells and fibrochondrocytes. Methods. This study integrated six datasets, namely, GSE94683, GSE144306, GSE168153, GSE138515, GSE102929, and GSE110993. The differentiation trajectory and key transcription factors (TFs) for HO occurrence were systematically analyzed by integrating single-cell RNA (scRNA) sequencing, bulk RNA sequencing, and assay of transposase accessible chromatin seq. The differential expression and enrichment pathways of TFs in heterotopically ossified tissues were identified. Results. HO that mimicked pathological cells was classified into HO1 and HO2 cell subsets. Results of the pseudo-temporal sequence analysis suggested that HO2 is a differentiated precursor cell of HO1. The analysis of integrated scRNA data revealed that ectopically ossified cells have similar transcriptional characteristics to cells in the fibrocartilaginous zone of tendons. The modified SCENIC method was used to identify specific transcriptional regulators associated with ectopic ossification. Xbp1 was defined as a common key transcriptional regulator of ectopically ossified tissues and the fibrocartilaginous zone of tendons. Subsequently, the CellPhoneDB database was completed for the cellular ligand-receptor analysis. With further pathway screening, this study is the first to propose that Xbp1 may upregulate the Notch signaling pathway through Jag1 transcription. Twenty-four microRNAs were screened and were found to be potentially associated with upregulation of XBP1 expression after acute ischemic stroke. Conclusion. A systematic analysis of the differentiation landscape and cellular homogeneity facilitated a molecular understanding of the phenotypic similarities between cells in the fibrocartilaginous region of tendon and HO cells. Furthermore, by identifying Xbp1 as a hub regulator and by conducting a ligand–receptor analysis, we propose a potential Xbp1/Jag1/Notch signaling pathway.

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Exploring the Potential Mechanism of Guchang Zhixie Wan for Treating Ulcerative Colitis by Comprehensive Network Pharmacological Approaches and Molecular Docking Validation as Well as Cell Experiments

Cited by 15 publications

References 59 publications

Exploring the Potential Mechanism of Xiaokui Jiedu Decoction for Ulcerative Colitis Based on Network Pharmacology and Molecular Docking

Exploring the Potential Mechanism of Xiaokui Jiedu Decoction for Ulcerative Colitis Based on Network Pharmacology and Molecular Docking

Eucommia ulmoides Oliver-Tribulus terrestris L. Drug Pair Regulates Ferroptosis by Mediating the Neurovascular-Related Ligand-Receptor Interaction Pathway- A Potential Drug Pair for Treatment Hypertension and Prevention Ischemic Stroke

Single‐Cell Integration Analysis of Heterotopic Ossification and Fibrocartilage Developmental Lineage: Endoplasmic Reticulum Stress Effector Xbp1 Transcriptionally Regulates the Notch Signaling Pathway to Mediate Fibrocartilage Differentiation

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