Dataset Information

Network Pharmacology-Based Approach to Investigate the Analgesic Efficacy and Molecular Targets of Xuangui Dropping Pill for Treating Primary Dysmenorrhea.

ABSTRACT: This study aimed to evaluate the clinical analgesic efficacy and identify the molecular targets of XGDP for treating primary dysmenorrhea (PD) by a network pharmacology approach. Analysis of pain disappearance rate of XGDP in PD treatment was conducted based on data from phase II and III randomized, double-blind, double-simulation, and positive parallel controlled clinical trials. The bioactive compounds were obtained by the absorption, distribution, metabolism, and excretion processes with oral bioavailability (OB) and drug-likeness (DL) evaluation. Subsequently, target prediction, pathway identification, and network construction were employed to clarify the mechanisms of the analgesic effect of XGDP on PD. The pain disappearance rates in phase II and III clinical trials of XGDP in PD treatment were 62.5% and 55.8%, respectively, yielding a significant difference (P < 0.05) when compared with the control group using Tongjingbao granules (TJBG). Among 331 compounds, 53 compounds in XGDP were identified as the active compounds related to PD through OB, DL, and target prediction. The active compounds and molecular targets of XGDP were identified, and our study showed that XGDP may exert its therapeutic effects on PD through the regulation of the targets related to anti-inflammation analgesia and central analgesia and relieving smooth muscle contraction.

SUBMITTER: Huang J

PROVIDER: S-EPMC5651156 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Network Pharmacology-Based Approach to Investigate the Analgesic Efficacy and Molecular Targets of Xuangui Dropping Pill for Treating Primary Dysmenorrhea.

Huang Jihan J Li Lei L Cheung Fan F Wang Ning N Li Yunfei Y Fan Zhenyu Z Yin Fang F Yang Juan J Gao Rui R He Yingchun Y Feng Yibin Y

Evidence-based complementary and alternative medicine : eCAM 20171008

This study aimed to evaluate the clinical analgesic efficacy and identify the molecular targets of XGDP for treating primary dysmenorrhea (PD) by a network pharmacology approach. Analysis of pain disappearance rate of XGDP in PD treatment was conducted based on data from phase II and III randomized, double-blind, double-simulation, and positive parallel controlled clinical trials. The bioactive compounds were obtained by the absorption, distribution, metabolism, and excretion processes with oral ...[more]

PMID: 29234428

Similar Datasets

Project description:PurposeSinomenine has been known to inhibit the proliferation of breast cancer cells. However, its targets have not been found yet. This study aimed to search for molecular targets of sinomenine for treating breast cancer via network pharmacology.MethodsPotential targets of sinomenine or breast cancer were separately screened from indicated databases. The common targets of both sinomenine and breast cancer were considered as the targets of sinomenine for treating breast cancer. A sinomenine-target-pathway network was constructed based on the obtained results from Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The putative targets of sinomenine were further determined by using protein-protein interaction (PPI) analysis and molecular docking. Finally, the putative targets were verified in vitro and in vivo.ResultsTwenty predicted targets were identified through network pharmacological analysis. Gene Ontology (GO) and KEGG pathway enrichment indicated that these predicted targets enriched in the process of MAP kinase activity, VEGF signaling pathway, Relaxin signaling pathway, Growth hormone synthesis, secretion and action. MAPK1, NOS3, NR3C1, NOS1 and NOS2 were further identified as the putative targets by using PPI and molecular docking analysis. Expression of MAPK1, NR3C1, NOS1, NOS2 and NOS3 genes were significantly regulated by sinomenine in both MCF-7 cells and MDA-MB-231 cells. Furthermore, the expression of NR3C1 in human breast cancer specimens was lower than that in para-tumor normal tissues. Meanwhile, the expression of NR3C1 in xenograft tumors was up-regulated after sinomenine treatment.ConclusionMAPK1, NR3C1, NOS1, NOS2 and NOS3 were identified as the putative targets of sinomenine for treating breast cancer. NR3C1 was preliminarily confirmed as a target of sinomenine in two breast cancer cell lines, xenograft tumor models and human breast cancer specimens. These data indicated that the network pharmacology-based prediction of sinomenine targets for treating breast cancer could be reliable.

Project description:BackgroundMicrovascular angina (MVA) is a group of clinical manifestations of angina pectoris or angina-like chest pain, positive exercise test, and exclusion of epicardial coronary artery spasm, wherein coronary angiography (CAG) does not present obvious epicardial vascular stenosis. Shexiang Tongxin dropping pill (STDP) has the effect of benefiting the Qi and opening the blood vessels, activating blood circulation, and resolving blood stasis. We explored the mechanism of STDP against MVA by network pharmacology and molecular docking.MethodsTraditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), literature search, SwissTargetPrediction database, and high-throughput experiment- and reference-guided database of traditional Chinese medicine (HERB) were applied to identify the active ingredients and targets of STDP. The MVA targets were searched in the databases of GeneCards, Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB), DisGeNET, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD). The common targets of STDP and MVA were screened. The software RStudio 4.1.3 was used to analyze the enrichment of these targets using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Protein-protein interaction (PPI) network analysis of the common targets was performed using the Search Tool for the Retrieval of Interacting Genes/Genomes (STRING) database. The cytoHubba plug-in of Cytoscape 3.9.1 software was employed to analyze the PPI network and obtain the core targets. Molecular docking was performed to verify the relationship between the core compounds and proteins with AutoDock Tools 1.5.7 and Pymol 2.4.0.ResultsWe identified 93 effective components of STDP, 310 potential targets, 981 MVA targets, and 138 intersectional targets. The potential anti-MVA mechanism of STDP may involve the advanced glycation end products/receptor for advanced glycation end products (AGE-RAGE) signaling pathway in diabetic complications; lipids and atherosclerosis; fluid shear stress; atherosclerosis; the tumor necrosis factor (TNF), interleukin (IL)-17, hypoxia-inducible factor (HIF)-1, and C-type lectin receptor signaling pathways. Further, STDP mainly acts on its targets IL-6, AKT1, STAT3, JUN, and IL-1β to against MVA.ConclusionsThe STDP may exert its therapeutic effects through processes, such as anti-inflammation, promotion of smooth muscle cell proliferation and differentiation, lipid metabolism, immunomodulation, and regulation of cellular autophagy.

Project description:BackgroundThere are scanty data to apply radial extracorporeal shock wave therapy (rESWT) on the acupuncture points in the lower abdomen to reduce the menstrual pain. This trial aimed to test the rESWT safety and efficacy for treating primary dysmenorrhea (PD).MethodsForty-four young-women with PD were randomly assigned to one of the three groups: to receive rESWT on the acupuncture points during the follicular phase (Group A, n = 15) or during the luteal phase (Group B, n = 14), or to apply heat patch to the acupuncture points during the follicular phase as the control (Group C, n = 15) over three menstrual cycles. The pain severity (using 0-to-10 visual analog scale), the pain duration (hours), plasma PGF2α prostaglandin F2alpha and prostaglandin E2 (PGE2), self-rating anxiety scale and menstrual blood loss were assessed before and after interventions.ResultsThe pain severity and duration significantly decreased in all groups after interventions. Although the reduced pain duration was not different among the groups, the reduced pain severity was more significant (P = .003) in Groups A (-53.8 ± 33.7%) and B (-59.3 ± 36.7%) than in Group C (-18.7 ± 27.1%). The rESWT intervention did not change plasma prostaglandins in Group A, although there was a decreased prostaglandin F2alpha (-20.5 ± 32.9%) in Group B or a decreased PGE2 (-18.9 ± 17.8%) in Group C. The anxiety level showed no change after intervention. The menstrual blood volume reduced slightly after intervention and the change of menstrual blood loss in Group B was significant (P = .038).ConclusionThe rESWT applications on the abdominal acupuncture points safely and effectively reduced the menstrual pain, which was not associated with the prostaglandin changes. The rESWT-reduced pain seemed equally effective with the intervention applied during the follicular phase or luteal phase of the menstrual cycle. Heat patch placed on the abdominal acupuncture points also reduced the pain severity and duration, indicating that the improved blood flow could effectively alleviate the menstrual pain with PD. The changes in anxiety level and menstrual blood loss were slight after intervention.

Project description:Postmenopausal osteoporosis (PMOP) has became 1 of most prevalent bone disorders with aging population. Liuwei Dihuang (LWDH) Pill, a classical kidney-tonifying prescription, is extensively used to treat PMOP in China. The aim of this study is to explore the pharmacological mechanisms of LWDH Pill against PMOP via network pharmacological strategy. The active ingredients of LWDH Pill were screened out from the Traditional Chinese Medicine System Pharmacology, Encyclopedia of Traditional Chinese Medicine and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine Databases, and their related target genes were fished in the UniProt database. Simultaneously, the GeneCards and DisGeNET databases were used to identify the target genes of PMOP. Through establishing a protein-protein interaction network, the overlapping genes between LWDH Pill and PMOP were identified to analyze their interactions and the hub target genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to predict the underlying biological processes (BP) and signaling pathways, respectively. A total of 64 active ingredients and 653 related target genes were identified in LWDH Pill, and 292 target genes were closely associated with PMOP. After matching the target genes between LWDH Pill and PMOP, 84 overlapping targets were obtained and considered as therapeutically relevant. Through construction of a protein-protein interaction network, we identified 20 hub target genes including IL6, INS, tumor necrosis factor, AKT1, vascular endothelial growth factor A, IGF1, TP53, IL1B, MMP9, JUN, LEP, CTNNB1, EGF, PTGS2, PPARG, CXCL8, IL10, CCL2, FOS and ESR1. Gene Ontology enrichment analysis suggested that LWDH Pill exerted anti-PMOP effects via regulating multiple BP including cell proliferation and apoptosis, oxidative stress, inflammation and angiogenesis. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed several pathways, such as PI3K-AKT pathway, mitogen-activated protein kinase pathway, hypoxia-inducible factors-1 pathway, tumor necrosis factor pathway, interleukin-17 (IL-17) pathway and FoxO pathway that might be involved in modulating the above BP. Through network pharmacological approach, we investigated the potential therapeutic mechanism of LWDH Pill against postmenopausal osteoporosis in a systemic perspective. These identified multi-targets and multi-pathways provide promising directions for further revealing more exact mechanisms.

Project description:BackgroundAstragalus Radix (AR)-Panax notoginseng (PN), a classical herb pair, has shown significant effects in treating diabetic nephropathy (DN). However, the intrinsic mechanism of AR-PN treating DN is still unclear. This study aims to illustrate the mechanism and molecular targets of AR-PN treating DN based on network pharmacology combined with bioinformatics.Materials and methodsThe Traditional Chinese Medicine Systems Pharmacology database was used to screen bioactive ingredients of AR-PN. Subsequently, putative targets of bioactive ingredients were predicted utilizing the DrugBank database and converted into genes on UniProtKB database. DN-related targets were retrieved via analyzing published microarray data (GSE30528) from the Gene Expression Omnibus database. Protein-protein interaction networks of AR-PN putative targets and DN-related targets were established to identify candidate targets using Cytoscape 3.8.0. GO and KEGG enrichment analyses of candidate targets were reflected using a plugin ClueGO of Cytoscape. Molecular docking was performed using AutoDock Vina software, and the results were visualized by Pymol software. The diagnostic capacity of hub genes was verified by receiver operating characteristic (ROC) curves.ResultsTwenty-two bioactive ingredients and 189 putative targets of AR-PN were obtained. Eight hundred and fifty differently expressed genes related to DN were screened. The PPI network showed that 115 candidate targets of AR-PN against DN were identified. GO and KEGG analyses revealed that candidate targets of AR-PN against DN were mainly involved in the apoptosis, oxidative stress, cell cycle, and inflammation response, regulating the PI3K-Akt signaling pathway, cell cycle, and MAPK signaling pathway. Moreover, MAPK1, AKT1, GSK3B, CDKN1A, TP53, RELA, MYC, GRB2, JUN, and EGFR were considered as the core potential therapeutic targets. Molecular docking demonstrated that these core targets had a great binding affinity with quercetin, kaempferol, isorhamnetin, and formononetin components. ROC curve analysis showed that AKT1, TP53, RELA, JUN, CDKN1A, and EGFR are effective in discriminating DN from controls.ConclusionsAR-PN against DN may exert its renoprotective effects via various bioactive chemicals and the related pharmacological pathways, involving multiple molecular targets, which may be a promising herb pair treating DN. Nevertheless, these results should be further validated by experimental evidence.

Dataset Information

Network Pharmacology-Based Approach to Investigate the Analgesic Efficacy and Molecular Targets of Xuangui Dropping Pill for Treating Primary Dysmenorrhea.

Publications

Network Pharmacology-Based Approach to Investigate the Analgesic Efficacy and Molecular Targets of Xuangui Dropping Pill for Treating Primary Dysmenorrhea.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets