Integrated network pharmacology and proteomics to reveal the cognitive improvement effect of Wuzang Wenyang Huayu decoction on vascular dementia.
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ABSTRACT:
SUBMITTER: Sun Y
PROVIDER: S-EPMC9771300 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
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Integrated network pharmacology and proteomics to reveal the cognitive improvement effect of Wuzang Wenyang Huayu decoction on vascular dementia.
Sun Yuhao Y Wen Xiaoyu X Li Zhuoxian Z Xu Lijing L Xia Meng M Xia Meng M
Chinese medical journal 20221005 19
Similar Datasets
Project description:To investigate the Wuzang Wenyang Huayu Decoction Regulates Differentially Expressed Proteins in the Rat, Hippocampus after Cerebral Hypoperfusion.
2023-03-11 | PXD028968 | Pride
Project description:The modified Wenyang Huayu decoction has been widely used to treat vascular dementia in China for thousands of years. We have previously proved that a modified version, Wuzang Wenyang Huayu decoction has the potential to be a more effective clinical treatment that can attenuate cerebral ischaemic injury. However, the global transcript profile and signalling conduction pathways regulated by this recipe remains unclear. This study established a two-vessel occlusion rat model by bilateral common carotid artery occlusion. Two groups of rats were intragastrically treated Wuzang Wenyang Huayu 2.5 g/kg vs or Piracetam 0.15 g/kg for 2 weeks. Learning and memory abilities were measured with Morris water maze. Neuronal plasticity was observed by HE staining. Differentially expressed transcripts of rat hippocampus were analysed by transcriptomics with Illumina HiSeq2500 platform. Results showed that Wuzang Wenyang Huayu decoction significantly alleviated learning, memory deficits, coordination dysfunction and prevented hippocampus cellular injury; Results further revealed the increased gene expression in KEGG metabolic pathways (MT-ND2. MT-ND3, MT-ND4, MT-ND4L, MT-ND5 and MT-ATP8) and genes involved in signal transduction, carcinogenesis, immune system, endocrine system, nervous system etc (Results further revealed differential expression of genes involved in various systems, including MT-ND2) Our discovery is likely to provide new insights to molecular mechanisms of Wuzang Wenyang Huayu regarding hippocampal transcripts in a murine vascular dementia model.
| S-EPMC6933406 | biostudies-literature
Project description:Background Vascular dementia (VD), associated with cerebrovascular injury, is characterized by severe cognitive impairment. Jianpi Tianjing Decoction (JTD) has been widely used to treat VD. However, its molecular targets and mechanisms of action in this treatment remain unclear. This study integrated network pharmacology and proteomics to identify targets and mechanisms of JTD in the treatment of VD and to provide new insights and goals for clinical treatments. Methods Systematic network pharmacology was used to identify active chemical compositions, potential targets, and mechanisms of JTD in VD treatment. Then, a mouse model of VD was induced via transient bilateral common carotid artery occlusion to verify the identified targets and mechanisms of JTD against VD using 4D label-free quantitative proteomics. Results By screening active chemical compositions and potential targets in relevant databases, 187 active chemical compositions and 416 disease-related compound targets were identified. In vivo experiments showed that JTD improved learning and memory in mice. Proteomics also identified 112 differentially expressed proteins in the model and sham groups and the JTD and model groups. Integrating the network pharmacology and proteomics results revealed that JTD may regulate expressions of cytochrome c oxidase subunit 7C, metabotropic glutamate receptor 2, Slc30a1 zinc transporter 1, and apolipoprotein A-IV in VD mice and that their mechanisms involve biological processes like oxidative phosphorylation, regulation of neuron death, glutamate secretion, cellular ion homeostasis, and lipoprotein metabolism. Conclusions JTD may suppress VD development via multiple components, targets, and pathways. It may thus serve as a complementary treatment option for patients with VD.
| S-EPMC9876684 | biostudies-literature
Project description:ObjectiveTo explore the biological mechanism of Fugui Wenyang Decoction (FGWYD) in treating vascular dementia (VD) rats based on systems pharmacology, proteomics, and a multidirectional pharmacology integration strategy.MethodsChemoinformatics was utilized to construct and analyze the FGWYD-VD protein-protein interaction (PPI) network. Then, the total protein in the brain tissue of the infarcted side of the rat was extracted for protein identification, pattern identification, and protein quantitative analysis. The differentially expressed proteins are analyzed by bioinformatics. Finally, the important proteins in the oxidative stress-related biological process proteins and indicators were detected through experimental pharmacology to verify the findings of systems biology and chemoinformatics.ResultsThere were a total of 73 FGWYD components with 245 FGWYD and 145 VD genes. The results of GO enrichment analysis and pathway enrichment analysis showed that MBHD may regulate the inflammation module, oxidative stress, the synaptic plasticity regulation module, and the neuronal apoptosis section module. Compared with the sham operation group, there were 23 upregulated proteins and 17 downregulated proteins in the model group (P < 0.05). Compared with the model group, there were 16 upregulated proteins and 10 downregulated proteins in the FGWYD group (P < 0.05). Bioinformatics analysis shows that those proteins were closely related to processes such as inflammation, oxidative stress, neuronal apoptosis, neuronal growth and differentiation, signaling pathways, and transcriptional regulation. Multidirectional pharmacology further verified the neuroprotective mechanism of the Nrf2/HO-1 pathway in FGWYD treatment of VD.ConclusionThe mechanism of FGWYD in the treatment of VD may be related to inflammation, oxidative stress, angiogenesis, and neuronal apoptosis.
| S-EPMC8517630 | biostudies-literature
Project description:BackgroundYiqi Huayu Jiedu (YQHYJD) is a traditional Chinese medicine decoction made up of eight traditional Chinese medicines. Although YQHYJD is effectively used to prevent and treat ARDS/acute lung injury (ALI) in rats, the molecular mechanisms supporting its clinical application remain elusive. The purpose of the current study was to understand its lung protective effects at the molecular level using network pharmacology approach.MethodsIn an ARDS animal model, the beneficial pharmacological activities of YQHYJD were confirmed by reduced lung tissue damage levels observed on drug treated rats versus control group. We then proposed a network analysis to discover the key nodes based on drugs and disease network. Subsequently, we analyzed interaction networks and screened key targets. Using Western blot to detect the expression level of key targets, the intervention effect of changes in expression level of key targets on ARDS was evaluated.ResultsPathway enrichment analysis of highly ranked genes showed that ErbB pathways were highly related to ARDS. Finally, western blot results showed decreased level of the AKT1 and KRAS/NRAS/HRAS protein in the lung after treatment which confirmed the hypothesis.ConclusionIn conclusion, our results suggest that YQHYJD can exert lung tissue protective effect against the severe injury through multiple pathways, including the endothelial cells permeability improvement, inflammatory reaction inhibition, edema, and lung tissue hemorrhage reduction.
| S-EPMC7439204 | biostudies-literature
Project description:ObjectiveThis study aimed to identify the mechanism of Yiqi Huayu Decoction (YQHY) induced ferroptosis in gastric cancer (GC) by using network pharmacology and experimental validation.MethodsThe targets of YQHY, ferroptosis-related targets, and targets related to GC were derived from databases. Following the protein-protein interaction (PPI) network, the hub targets for YQHY induced ferroptosis in GC were identified. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to analyze the hub targets from a macro perspective. We verified the hub targets by molecular docking, GEPIA, HPA, and the cBioPortal database. Finally, we performed cell viability assays, quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, lipid peroxidation, and GSH assays to explore the mechanism of YQHY induced ferroptosis in GC.ResultsWe identified the main active compounds and hub targets: Quercetin, DIBP, DBP, Mipax, Phaseol and TP53, ATM, SMAD4, PTGS2, and ACSL4. KEGG enrichment analyses indicated that the JAK2-STAT3 signaling pathway may be a significant pathway. Molecular docking results showed that the main active compounds had a good binding activity with the hub targets. The experimental results proved that YQHY could induce ferroptosis in AGS by increasing the MDA content and reducing the GSH content. qRT-PCR and Western blot results showed that YQHY can induce ferroptosis in GC by affecting the JAK2-STAT3 pathway and the expression of ACSL4.ConclusionsThis study indicated that YQHY can induce ferroptosis in GC by affecting the JAK2-STAT3 pathway and the expression of ACSL4, and induction of ferroptosis may be one of the possible mechanisms of YQHY's anti-recurrence and metastasis of GC.
| S-EPMC8883049 | biostudies-literature
Project description:ObjectivesChronic pain, the main symptom of knee osteoarthritis (OA), remains the primary reason for decreased functional capacity. Quzhi decoction, a TCM prescription, is effective in treating chronic pain in OA, but the potential mechanisms require further exploration.MethodsAn anterior cruciate ligament transection (ACLT) rat model was established, and pain-like behavior was evaluated. Metabolomics analysis of serum samples was performed to identify differential metabolites, and network pharmacology was used to identify potential targets of Quzhi decoction for the treatment of OA. Finally, we constructed a comprehensive network of serum metabolomics and network pharmacology. At the same time, the obtained key targets were verified by molecular docking.ResultsQuzhi decoction was shown to attenuate pain-like behavior and joint inflammation in OA rats. Through serum metabolomics, thirty potentially significant metabolites were found to be involved in the therapeutic effects of Quzhi decoction against OA pain. According to network pharmacology, 107 active drug components were matched with 115 disease targets, which was partly consistent with the metabolomics findings. Further analysis focused on 6 key targets, including CYP3A4, PLA2G4A, PTGS1, PTGS2, TYR, and ALOX5, and their associated core metabolites and pathways. Molecular docking results showed that the related targets had high affinity with the active pharmaceutical ingredients in Quzhi decoction.ConclusionThe effect of Quzhi decoction on OA pain may be related to the inhibition of joint inflammation, mainly through disturbing arachidonic acid metabolism, tyrosine metabolism, and leukotriene metabolism. Further systematic molecular biology experiments are needed to verify the accurate mechanism.
| S-EPMC9391123 | biostudies-literature
Project description:BackgroundTraditional Chinese medicine (TCM) has the advantage of multi-component and multi-target, which becomes a hot spot in the treatment of numerous diseases. Shaoyao decoction (SYD) is a TCM prescription, which is mainly used to treat damp-heat dysentery clinically, with small side effects and low cost. However, its mechanism remains elusive. The purpose of this study is to explore the mechanism of SYD in the treatment of mice with ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) through metabolomics and network pharmacology, and verify through molecular docking and immunohistochemistry, so as to provide a scientific basis for the role of SYD in the treatment of UC.Materials and methodsFirstly, DSS-induced UC models were established and then untargeted metabolomics analysis of feces, livers, serum and urine was performed to determine biomarkers and metabolic pathways closely related to the role of SYD. Besides, network pharmacology was applied to screen the active components and UC-related targets, which was verified by molecular docking. Finally, metabonomics and network pharmacology were combined to draw the metabolite-pathway-target network and verified by immunohistochemistry.ResultsMetabolomics results showed that a total of 61 differential metabolites were discovered in SYD-treated UC with 3 main metabolic pathways containing glycerophospholipid metabolism, sphingolipid metabolism and biosynthesis of unsaturated fatty acids, as well as 8 core targets involving STAT3, IL1B, IL6, IL2, AKT1, IL4, ICAM1 and CCND1. Molecular docking demonstrated that the first five targets had strong affinity with quercetin, wogonin, kaempferol and baicalein. Combined with metabolomics and network pharmacology, sphingolipid signaling pathway, PI3K/AKT-mTOR signaling pathway and S1P3 pathway were identified as the main pathways.ConclusionSYD can effectively ameliorate various symptoms and alleviate intestinal mucosal damage and metabolic disorder in DSS induced UC mice. Its effect is mainly related to sphingolipid metabolism, PI3K/AKT-mTOR signaling pathway and S1P3 pathway.
| S-EPMC9620839 | biostudies-literature
Project description:BackgroundVascular dementia (VaD) is a degenerative cerebrovascular disease that leads to progressive decline of patients' cognitive ability and memory. Yizhi Tongmai (YZTM) decoction is an empirical prescription first formulated by Professor Guomin Si. Our previous experiments proved the effectiveness of this prescription in the treatment of VaD. In this study, we aimed to use network pharmacology and molecular docking technology to systematically explain the potential anti-VaD mechanism of YZTM.MethodsWe identified the core compounds of YZTM and their potential targets through the TCMSP, BATMAN, and SwissTargetPrediction databases. Then, we identified the molecular targets of YZTM in VaD using the Online Mendelian Inheritance in Man and GeneCards databases. The common targets of YZTM and VaD were screened out, and then the pathways of these target genes were analyzed using the Database for Annotation, Visualization and Integrated Discovery v6.8. Molecular docking was used to verify the relationship between the core compounds and proteins.ResultsThrough network pharmacology analysis, we discovered that the 5 core compounds in YZTM exert an anti-VaD effect. The potential mechanism of YZTM anti-VaD may be through inhibiting the NLRP3 inflammasome, TNF signaling pathway, and toll-like receptor signaling pathways. Subsequently, key compounds were docked with related proteins in the NLRP3 inflammasome (NLRP3, ASC, caspase-1, interleukin-18, and interleukin-1 β) using molecular docking technology. The compounds were found to spontaneously bind to the proteins.ConclusionsYZTM may exert an anti-VaD effect through inhibition of the NLRP3 inflammasome. In addition, TNF signaling pathway and toll-like receptor signaling pathway may also be its underlying mechanism. The application of network pharmacology and molecular docking technology may provide a novel method for research of Chinese herbal medicine. YZTM may also provide a complementary treatment option for patients with VaD.
| S-EPMC7867933 | biostudies-literature
Project description:BackgroundAlthough a common disease, astriction is difficult to treat and severely affects quality of life. Wenyang Yiqi Decoction (WYD) is a kind of traditional Chinese medicine (TCM) that is used to treat astriction; however, the mechanism remains unclear. Therefore, this work assessed the laxative effect of WYD on loperamide-induced astriction (LIA) model mice.MethodsWe replicated a constipation model in mice and detected changes in fecal parameters such as feces quantity and water content, intestinal transit function, and histopathological changes in the constipated mice. After five days of WYD intervention, mouse tissues were taken out for detection. We also measured the levels of gastrin (Gas), substance P (SP), acetylcholinesterase (AChE), and vasoactive intestinal peptide (VIP) in the mice's serum. Additionally, we used quantitative real-time polymerase chain reaction (qRT-PCR) and Western Blot to detect c-Kit and stem cell factor (SCF), and examined the effects of WYD on the tight junction (TJ) proteins occludin (Ocln), zonula occludens-1 (ZO-1), and claudin-1 (Cldn-1) in the mice's intestines.ResultsThrough histopathological changes, we observed less destruction of epithelial cells and greater integrity of goblet and epithelial cells in WYD-treated mice than in mice in the loperamide group. qRT-PCR and western blot analysis of c-Kit and SCF showed that WYD could boost the levels of c-Kit and SCF. The qRT-PCR and immunohistochemical (IHC) analyses of enteral tight occludin (Ocln), occludenas-1 (ZO-1), and cldin-1 (Cldn-1) showed that WYD could boost the level of ZO-1 and decrease the level of Cldn-1. The study also investigated the effect of WYD treatment on the enteral barrier function of astriction model mice and found that the TJ proteins (ZO-1, Cldn-1) in the colon of the astriction model mice had significant changes compared to the normal group, and WYD intervention was found to increase the expression of ZO-1, and decrease the expression of Cldn-1.ConclusionsWYD alleviates LIA by regulating enteral hormones, boosting the number of interstitial cells of Cajal (ICCs), or adjusting enteral block action.
| S-EPMC10009577 | biostudies-literature