Dataset Information

Network Pharmacology and Metabolomics Studies on Antimigraine Mechanisms of Da Chuan Xiong Fang (DCXF).

ABSTRACT:

Background

Da Chuan Xiong Fang (DCXF) is a traditional Chinese medicine (TCM) formula used to treat migraines. Previously, we uncovered partial mechanisms involved in the therapeutic actions of DCXF on migraines.

Methods

In this study, we further elucidated its antimigraine mechanisms in vivo by using an integrated strategy coupling with network pharmacology and metabolomics techniques.

Results

Network pharmacology identified 33 genes linked with both migraine and DCXF, most of which were 5-hydroxytryptamine receptors, dopamine, and peptide receptors. The results of GO and KEGG enrichment analysis showed that DCXF significantly regulated tyrosine metabolism, tryptophan metabolism, dopamine metabolic process, glucose transmembrane transport, lipid metabolism, and fatty acid transport. The results of metabolomics analysis found that the metabolism of tryptophan and tyrosine in the brain tissue and energy and lipid metabolism of rats tended towards normal and reached normal levels after administering DCXF. The metabolomics and network pharmacology approaches demonstrated similar antimigraine effects of DCXF on endogenous neurotransmitters and overall trends in serum and brain tissue. Using both approaches, 62 hub genes were identified from the protein-protein interaction (PPI) network of DCXF and gene-metabolite interaction network, with hub genes and different metabolites in serum and brain tissue. The hub genes of DCXF, which were mostly linked with inflammation, might affect mainly neurotransmitters in serum and brain tissue metabolisms.

Conclusion

Network pharmacology and metabolomics study may help identify hub genes, metabolites, and possible pathways of disease and treatment. Additionally, two parts of the results were integrated to confirm each other. Their combination may help elucidate the relationship between hub genes and metabolites and provide the further understanding of TCM mechanisms.

SUBMITTER: Ma S

PROVIDER: S-EPMC8081595 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Network Pharmacology and Metabolomics Studies on Antimigraine Mechanisms of Da Chuan Xiong Fang (DCXF).

Ma Shiyu S Zheng Lin L Lin Xiao X Feng Yi Y Yang Ming M Shen Lan L

Evidence-based complementary and alternative medicine : eCAM 20210420

<h4>Background</h4>Da Chuan Xiong Fang (DCXF) is a traditional Chinese medicine (TCM) formula used to treat migraines. Previously, we uncovered partial mechanisms involved in the therapeutic actions of DCXF on migraines.<h4>Methods</h4>In this study, we further elucidated its antimigraine mechanisms in vivo by using an integrated strategy coupling with network pharmacology and metabolomics techniques.<h4>Results</h4>Network pharmacology identified 33 genes linked with both migraine and DCXF, mos ...[more]

PMID: 33995549

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Project description:BackgroundDa-Chuan-Xiong Decoction (DCXD) is an aqueous extract from a classic Chinese herbal formula composed of dried rhizomes of Ligusticum chuanxiong Hort and Gastrodia elata Bl. in the mass ratio of 4 : 1. It has been long used to treat chronic cardiovascular disease caused by blood stasis and wind pathogen in the clinic. This experimental study aimed to investigate the blood pressure (BP)-lowering effect of DCXD treatment on hypertension and underlying mechanisms.MethodsMale Sprague-Dawley rats were used in the experiment, and the hypertensive models were created by administering deoxycorticosterone acetate (DOCA) in conjunction with a high salt intake in uninephrectomized rats. DCXD was administered to hypertensive rats by oral gavage daily at a dose of 5 g/kg or 2.5 g/kg bodyweight for 28 days. The brain sodium sensitivity, ENaC function, superoxide anion level, NADPH oxidase activity, and expression of ENaC, p67phox, p47phox, and Rac1 in the paraventricular nucleus were assessed by using the appropriate methods.ResultsThe 28 days of DCXD (5 g/kg) treatment significantly reduced the increased BP effectively, inhibited the enhanced heart index, kidney index, and 24 h urinary protein, and improved the progressive pathological changes of heart and kidney, which was comparable to that of the positive control amlodipine. DCXD treatment also caused a marked reduction in plasma norepinephrine and induced a significant improvement in brain sodium sensitivity and ENaC function in DOCA-salt hypertensive rats. Rats in DCXD-treated groups also exhibited decreased superoxide anion levels and NADPH oxidase activity in the paraventricular nucleus. The level of ENaC, p67phox, and Rac1 protein expression in the paraventricular nucleus was significantly downregulated by DCXD treatment in DOCA-salt hypertensive rats.ConclusionsThese findings indicate that the depressor action and sympathetic inhibition of DCXD on salt-sensitive hypertension may be by ameliorating brain sodium sensitivity, modulating ENaC function, and inhibiting the expression of ENaC and NADPH oxidase in the hypothalamic paraventricular nucleus.

Project description:Objectives: This study aimed to explore the mechanism of Xiong-Pi-Fang (XPF) in the treatment of coronary heart disease (CHD) with depression by an integrative strategy combining serum pharmacochemistry, network pharmacology analysis, and experimental validation. Methods: An ultrahigh performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) method was constructed to identify compounds in rat serum after oral administration of XPF, and a component-target network was established using Cytoscape, between the targets of XPF ingredients and CHD with depression. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to deduce the mechanism of XPF in treating CHD with depression. Finally, in a chronic unpredictable mild stress (CUMS)-and isoproterenol (ISO)-induced rat model, TUNEL was used to detect the apoptosis index of the myocardium and hippocampus, ELISA and western blot were used to detect the predicted hub targets, namely AngII, 5-HT, cAMP, PKA, CREB, BDNF, Bcl-2, Bax, Cyt-c, and caspase-3. Results: We identified 51 compounds in rat serum after oral administration of XPF, which mainly included phenolic acids, saponins, and flavonoids. Network pharmacology analysis revealed that XPF may regulate targets, such as ACE2, HTR1A, HTR2A, AKT1, PKIA, CREB1, BDNF, BCL2, BAX, CASP3, cAMP signaling pathway, and cell apoptosis process in the treatment of CHD with depression. ELISA analysis showed that XPF decreased Ang-II content in the circulation and central nervous system, inhibited 5-HT levels in peripheral circulation, and increased 5-HT content in the central nervous system and cAMP content in the myocardia and hippocampus. Meanwhile, western blot analysis indicated that XPF could upregulate the expression levels of PKA, CREB, and BDNF both in the myocardia and hippocampus. TUNEL staining indicated that the apoptosis index of myocardial and hippocampal cells increased in CUMS-and ISO-induced CHD in rats under depression, and XPF could increase the expression of Bcl-2, inhibit the expression of Bax, Cyt-c, and caspase-3, and rectify the injury of the hippocampus and myocardium, which exerted antidepressant and antimyocardial ischemia effects. Conclusion: Our study proposed an integrated strategy, combining serum pharmacochemistry and network pharmacology to investigate the mechanisms of XPF in treating CHD with depression. The mechanism of XPF in treating CHD with depression may be related to the activation of the cAMP signaling pathway and the inhibition of the apoptosis.

Project description:Migraine is a common neurological disorder that manifests as recurrent attacks of unilateral and throbbing headache. Conioselinum anthriscoides "Chuanxiong" (Apiaceae; Chuanxiong rhizoma) and Cyperus rotundus L. (Cyperaceae; Cyperi rhizoma) (CRCR), is a classic prescription for treating migraine. This study aimed to reveal the potential mechanisms of CRCR extract against migraine using integrated analysis of metabolomics and network pharmacology. Behavioral changes in the nitroglycerin rat migraine model were determined from von Frey withdrawal response. Untargeted serum metabolomics was used to identify the differentially expressed metabolites and metabolic pathways. The differentially expressed metabolites were analyzed to obtain the corresponding targets by a compound-reaction-enzyme-gene network. Network pharmacology was used to construct a compound-target-pathway network. The common targets of metabolomics and network pharmacology were further analyzed. Metabolomics analysis identified 96 differentially expressed metabolites and 77 corresponding targets. Network pharmacology analysis identified 201 potential targets for CRCR against migraine. By intersecting 77 targets with 201 targets, monoamine oxidase A (MAO-A), monoamine oxidase B (MAO-B), and catechol-O-methyltransferase (COMT) were identified as the common targets, and MAO-A, MAO-B, and COMT were involved in the tyrosine metabolism pathway. Further experiments demonstrated that the contents of MAO-A and COMT were significantly increased in serum and brainstem tissue of the migraine rats. CRCR extract significantly decreased the contents of MAO-A and COMT, while no significant difference was found in MAO-B. Metabolomics analysis indicated that the contents of 3,4-dihydroxyphenylacetate (DOPAC) and 3-(4-hydroxyphenyl)pyruvate (HPP) were significantly increased in the migraine rats, and CRCR extract caused significant decreases in DOPAC and HPP. Interestingly, DOPAC and HPP were two differentially expressed metabolites involved in the tyrosine metabolism pathway. Correlation analysis showed that DOPAC and HPP were highly positively correlated with MAO-A and COMT. Taken together, two key differentially expressed metabolites (DOPAC and HPP), two key targets (MAO-A and COMT), and one relevant metabolic pathway (tyrosine metabolism) showed great importance in the treatment of migraine. This research could provide a new understanding of the potential mechanism of CRCR against migraine. More attentions should be paid into the tyrosine metabolism pathway in future studies.

Project description:BackgroundCondyloma acuminatum (CA) is a sexually transmitted disease characterized by the anomalous proliferation of keratinocytes caused by human papillomavirus (HPV) infection. Fu Fang Gang Liu liquid (FFGL) is an effective externally administered prescription used to treat CA; however, its molecular mechanism remains unclear. This study aimed to identify and experimentally validate the major active ingredients and prospective targets of FFGL.MethodsNetwork pharmacology, transcriptomics, and enrichment analysis were used to identify the active ingredients and prospective targets of FFGL, which were confirmed through subsequent experimental validation using mass spectrometry, molecular docking, western blotting, and in vitro assays.ResultsThe network pharmacology analysis revealed that FFGL contains a total of 78 active compounds, which led to the screening of 610 compound-related targets. Among them, 59 overlapped with CA targets and were considered to be targets with potential therapeutic effects. The protein-protein interaction network analysis revealed that protein kinase B (Akt) serine/threonine kinase 1 was a potential therapeutic target. To further confirm this result, we performed ribonucleic acid sequencing (RNA-seq) assays on HPV 18+ cells after FFGL exposure and conducted enrichment analyses on the differentially expressed genes that were screened. The enrichment analysis results indicated that the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway may be a key pathway through which FFGL exerts its effects. Further in vitro experiments revealed that FFGL significantly inhibited the activity of HPV 18+ cells and reduced PI3K and Akt protein levels. A rescue experiment indicated that the reduction in cell viability induced by FFGL was partially restored after the administration of activators of the PI3K/Akt pathway. We further screened two active components of FFCL that may be efficacious in the treatment of CA: periplogenin and periplocymarin. The molecular docking experiments showed that these two compounds exhibited good binding activity to Akt1.ConclusionFFGL reduced HPV 18+ cell viability by inhibiting key proteins in the PI3K/Akt pathway; this pathway may represent an essential mechanism through which FFGL treats CA. Periplogenin and periplocymarin may play a significant role in this process.

Dataset Information

Network Pharmacology and Metabolomics Studies on Antimigraine Mechanisms of Da Chuan Xiong Fang (DCXF).

Background

Methods

Results

Conclusion

Publications

Network Pharmacology and Metabolomics Studies on Antimigraine Mechanisms of Da Chuan Xiong Fang (DCXF).

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