Proteins in cord blood as a new target for prevention and treatment of bronchopulmonary dysplasia: a proteomic analysis

Abstract This study aimed to explore the proteins in cord blood that could regulate the development of neonatal bronchi and lungs, and to find a new target for the prevention and treatment of bronchopulmonary dysplasia (BPD). In this study, proteomic analysis was used to analyze the proteins in cord blood of preterm and term infants. A total of 100 differentially expressed (57 up-regulated and 43 down-regulated) proteins were identified from preterm with BPD and term infants cord blood (fold change ≥ 1.5, P value < 0.05). GO analysis revealed that the major enrichment functions of these differential proteins were multi-organism process, stimulus, immune system process growth, reproductive process, development process and antioxidant activity. The signaling pathways involved included insulin resistance, insulin signaling pathway, IL−17 signaling pathway, PI3K−Akt signaling pathway, NF−kappa B signaling pathway, glucagon signaling pathway, apoptosis, MAPK signaling pathway, as well as glycolysis/gluconeogenesis. Further protein and protein interact (PPI) analysis revealed that the interacting proteins involved were PGAM1, CNN2, HSP90AA and DAG1, which were all crucial in the development of BPD. We found that these differential proteins in cord blood might regulate bronchopulmonary development through the abovementioned signaling pathways or their interaction proteins, which may provide a new research direction for the intervention of BPD.

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MAPK: A Key Player in the Development and Progression of Stroke

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527319666200613223018 ◽

2020 ◽

Vol 19 (4) ◽

pp. 248-256

Author(s):

Yangmin Zheng ◽

Ziping Han ◽

Haiping Zhao ◽

Yumin Luo

Keyword(s):

Ischemic Stroke ◽

Signaling Pathway ◽

Complex Disease ◽

Therapeutic Targets ◽

Cell Types ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Effective Prevention ◽

Prevention And Treatment ◽

Different Cell Types

Conclusion: Stroke is a complex disease caused by genetic and environmental factors, and its etiological mechanism has not been fully clarified yet, which brings great challenges to its effective prevention and treatment. MAPK signaling pathway regulates gene expression of eukaryotic cells and basic cellular processes such as cell proliferation, differentiation, migration, metabolism and apoptosis, which are considered as therapeutic targets for many diseases. Up to now, mounting evidence has shown that MAPK signaling pathway is involved in the pathogenesis and development of ischemic stroke. However, the upstream kinase and downstream kinase of MAPK signaling pathway are complex and the influencing factors are numerous, the exact role of MAPK signaling pathway in the pathogenesis of ischemic stroke has not been fully elucidated. MAPK signaling molecules in different cell types in the brain respond variously after stroke injury, therefore, the present review article is committed to summarizing the pathological process of different cell types participating in stroke, discussed the mechanism of MAPK participating in stroke. We further elucidated that MAPK signaling pathway molecules can be used as therapeutic targets for stroke, thus promoting the prevention and treatment of stroke.

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Targeting ERK-Hippo Interplay in Cancer Therapy

International Journal of Molecular Sciences ◽

10.3390/ijms21093236 ◽

2020 ◽

Vol 21 (9) ◽

pp. 3236 ◽

Cited By ~ 2

Author(s):

Karel Vališ ◽

Petr Novák

Keyword(s):

Cancer Therapy ◽

Signaling Pathways ◽

Signaling Pathway ◽

Cross Talk ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Mitogen Activated Protein Kinase ◽

Cancer Therapies ◽

Anti Cancer ◽

Targeted Inhibition

Extracellular signal-regulated kinase (ERK) is a part of the mitogen-activated protein kinase (MAPK) signaling pathway which allows the transduction of various cellular signals to final effectors and regulation of elementary cellular processes. Deregulation of the MAPK signaling occurs under many pathological conditions including neurodegenerative disorders, metabolic syndromes and cancers. Targeted inhibition of individual kinases of the MAPK signaling pathway using synthetic compounds represents a promising way to effective anti-cancer therapy. Cross-talk of the MAPK signaling pathway with other proteins and signaling pathways have a crucial impact on clinical outcomes of targeted therapies and plays important role during development of drug resistance in cancers. We discuss cross-talk of the MAPK/ERK signaling pathway with other signaling pathways, in particular interplay with the Hippo/MST pathway. We demonstrate the mechanism of cell death induction shared between MAPK/ERK and Hippo/MST signaling pathways and discuss the potential of combination targeting of these pathways in the development of more effective anti-cancer therapies.

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Identification of the Crucial Gene in Overflow Arteriovenous Fistula by Bioinformatics Analysis

Frontiers in Physiology ◽

10.3389/fphys.2021.621830 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zhengde Zhao ◽

Qining Fu ◽

Liangzhu Hu ◽

Yangdong Liu

Keyword(s):

Signaling Pathways ◽

Signaling Pathway ◽

Intimal Hyperplasia ◽

Enrichment Analysis ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Biological Processes ◽

Hub Genes ◽

Av Fistula ◽

Core Genes

Objective: The aim was to study the preliminary screening of the crucial genes in intimal hyperplasia in the venous segment of arteriovenous (AV) fistula and the underlying potential molecular mechanisms of intimal hyperplasia with bioinformatics analysis.Methods: The gene expression profile data (GSE39488) was analyzed to identify differentially expressed genes (DEGs). We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of DEGs. Gene set enrichment analysis (GSEA) was used to understand the potential activated signaling pathway. The protein–protein interaction (PPI) network was constructed with the STRING database and Cytoscape software. The Venn diagram between 10 hub genes and gene sets of 4 crucial signaling pathways was used to obtain core genes and relevant potential pathways. Furthermore, GSEAs were performed to understand their biological functions.Results: A total of 185 DEGs were screened in this study. The main biological function of the 111 upregulated genes in AV fistula primarily concentrated on cell proliferation and vascular remodeling, and the 74 downregulated genes in AV fistula were enriched in the biological function mainly relevant to inflammation. GSEA found four signaling pathways crucial for intimal hyperplasia, namely, MAPK, NOD-like, Cell Cycle, and TGF-beta signaling pathway. A total of 10 hub genes were identified, namely, EGR1, EGR2, EGR3, NR4A1, NR4A2, DUSP1, CXCR4, ATF3, CCL4, and CYR61. Particularly, DUSP1 and NR4A1 were identified as core genes that potentially participate in the MAPK signaling pathway. In AV fistula, the biological processes and pathways were primarily involved with MAPK signaling pathway and MAPK-mediated pathway with the high expression of DUSP1 and were highly relevant to cell proliferation and inflammation with the low expression of DUSP1. Besides, the biological processes and pathways in AV fistula with the high expression of NR4A1 similarly included the MAPK signaling pathway and the pathway mediated by MAPK signaling, and it was mainly involved with inflammation in AV fistula with the low expression of NR4A1.Conclusion: We screened four potential signaling pathways relevant to intimal hyperplasia and identified 10 hub genes, including two core genes (i.e., DUSP1 and NR4A1). Two core genes potentially participate in the MAPK signaling pathway and might serve as the therapeutic targets of intimal hyperplasia to prevent stenosis after AV fistula creation.

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Cross-talk of Signaling Pathways in the Pathogenesis of Allergic Asthma and Cataract

Protein and Peptide Letters ◽

10.2174/0929866527666200207113439 ◽

2020 ◽

Vol 27 (9) ◽

pp. 810-822

Author(s):

Yang Zhao ◽

Sumei Liu ◽

Xiangsheng Li ◽

Zhenzhen Xu ◽

Lifang Hao ◽

...

Keyword(s):

Signaling Pathways ◽

Allergic Asthma ◽

Signaling Pathway ◽

Academic Research ◽

Notch Signaling Pathway ◽

Mapk Signaling ◽

Chronic Inflammatory Disease ◽

Smad Signaling Pathway ◽

Immune Imbalance ◽

Cellular Components

: Allergic asthma is a chronic inflammatory disease, which involves many cellular and cellular components. Cataract is a condition that affects the transparency of the lens, which the opacity of the lens caused by any innate or acquired factor degrades its transparency or changes in color. Both of them belong to diseases induced by immune disorders or inflammation. We want to confirm the signaling pathways involved in the regulation of asthma and cataract simultaneously, and provide reference for the later related experiments. So we conducted a scoping review of many databases and searched for studies (Academic research published in Wiley, Springer and Bentham from 2000 to 2019) about the possible relationship between asthma and cataract. It was found that during the onset of asthma and cataract, Rho/Rock signaling pathway, Notch signaling pathway, Wnt/β-catenin signaling pathway, PI3K/AKT signaling pathway, JAK/STAT signaling pathway, MAPK signaling pathway, TGF-β1/Smad signaling pathway and NF-κB signaling pathway are all active, so they may have a certain correlation in pathogenesis. Asthma may be associated with cataract through the eight signaling pathways, causing inflammation or immune imbalance based on allergy that can lead to cataract. According to these studies, we speculated that the three most likely signaling pathways are PI3K/AKT, MAPK and NF-κB signaling pathway.

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Comparison of Signaling Pathways Gene Expression in CD34−Umbilical Cord Blood and Bone Marrow Stem Cells

Stem Cells International ◽

10.1155/2016/5395261 ◽

2016 ◽

Vol 2016 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Rafał Stojko ◽

Monika Bojdys-Szyndlar ◽

Agnieszka Drosdzol-Cop ◽

Andrzej Madej ◽

Krzysztof Wilk

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Cord Blood ◽

Signaling Pathways ◽

Signaling Pathway ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Biological Processes ◽

Blood Stem Cells ◽

Cord Blood Stem Cells

The aim of the study was to compare the biological activity of the total pool of genes in CD34−umbilical cord blood and bone marrow stem cells and to search for the differences in signaling pathway gene expression responsible for the biological processes. The introductory analysis revealed a big similarity of gene expression among stem cells. When analyzing GO terms for biological processes, we observed an increased activity of JAK-STAT signaling pathway, calcium-mediated, cytokine-mediated, integrin-mediated signaling pathway, and MAPK in a cluster of upregulating genes in CD34−umbilical cord blood stem cells. At the same time, we observed a decreased activity of BMP signaling pathways, TGF-beta pathway, and VEGF receptor signaling pathway in a cluster of downregulating genes in CD34−umbilical cord blood stem cells. In accordance with KEGG classification, the cytokine-cytokine receptor interaction, toll-like receptor signaling pathway, and JAK-STAT signaling pathway are overrepresented in CD34−umbilical cord blood stem cells. A similar gene expression in both CD34−UCB and BM stem cells was characteristic for such biological processes as cell division, cell cycle gene expression, mitosis, telomere maintenance with telomerase, RNA and DNA treatment processes during cell division, and similar genes activity of Notch and Wnt signaling pathways.

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Selenoproteins and their emerging roles in signaling pathways

Regulatory Mechanisms in Biosystems ◽

10.15421/022028 ◽

2020 ◽

Vol 11 (2) ◽

pp. 186-199

Author(s):

N. V. Stanishevska

Keyword(s):

Endoplasmic Reticulum ◽

Signaling Pathways ◽

Signaling Pathway ◽

Thioredoxin Reductase ◽

Methionine Sulfoxide ◽

Mapk Signaling ◽

Methionine Sulfoxide Reductase ◽

Selenoprotein S ◽

Selenoprotein K ◽

Er Membrane

The functional activity of selenoproteins has a wide range of effects on complex pathogenetic processes, including teratogenesis, immuno-inflammatory, neurodegenerative. Being active participants and promoters of many signaling pathways, selenoproteins support the lively interest of a wide scientific community. This review is devoted to the analysis of recent data describing the participation of selenoproteins in various molecular interactions mediating important signaling pathways. Data processing was carried out by the method of complex analysis. For convenience, all selenoproteins were divided into groups depending on their location and function. Among the group of selenoproteins of the ER membrane, selenoprotein N affects the absorption of Ca2+ by the endoplasmic reticulum mediated by oxidoreductin (ERO1), a key player in the CHOP/ERO1 branch, a pathogenic mechanism that causes myopathy. Another selenoprotein of the ER membrane selenoprotein K binding to the DHHC6 protein affects the IP3R receptor that regulates Ca2+ flux. Selenoprotein K is able to affect another protein of the endoplasmic reticulum CHERP, also appearing in Ca2+ transport. Selenoprotein S, associated with the lumen of ER, is able to influence the VCP protein, which ensures the incorporation of selenoprotein K into the ER membrane. Selenoprotein M, as an ER lumen protein, affects the phosphorylation of STAT3 by leptin, which confirms that Sel M is a positive regulator of leptin signaling. Selenoprotein S also related to luminal selenoproteins ER is a modulator of the IRE1α-sXBP1 signaling pathway. Nuclear selenoprotein H will directly affect the suppressor of malignant tumours, p53 protein, the activation of which increases with Sel H deficiency. The same selenoprotein is involved in redox regulation. Among the cytoplasmic selenoproteins, abundant investigations are devoted to SelP, which affects the PI3K/Akt/Erk signaling pathway during ischemia/reperfusion, is transported into the myoblasts through the plasmalemma after binding to the apoER2 receptor, and into the neurons to the megaline receptor and in general, selenoprotein P plays the role of a pool that stores the necessary trace element and releases it, if necessary, for vital selenoproteins. The thioredoxin reductase family plays a key role in the invasion and metastasis of salivary adenoid cystic carcinoma through the influence on the TGF-β-Akt/GSK-3β pathway during epithelial-mesenchymal transition. The deletion of thioredoxin reductase 1 affects the levels of messengers of the Wnt/β-catenin signaling pathway. No less studied is the glutathione peroxidase group, of which GPX3 is able to inhibit signaling in the Wnt/β-catenin pathway and thereby inhibit thyroid metastasis, as well as suppress protein levels in the PI3K/Akt/c-fos pathway. A key observation is that in cases of carcinogenesis, a decrease in GPX3 and its hypermethylation are almost always found. Among deiodinases, deiodinase 3 acts as a promoter of the oncogenes BRAF, MEK or p38, while stimulating a decrease in the expression of cyclin D1. The dependence of the level of deiodinase 3 on the Hedgehog (SHH) signaling pathway is also noted. Methionine sulfoxide reductase A can compete for the uptake of ubiquitin, reduce p38, JNK and ERK promoters of the MAPK signaling pathway; methionine sulfoxide reductase B1 suppresses MAPK signaling messengers, and also increases PARP and caspase 3.

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Therapeutic mechanism of Toujie Quwen granules in COVID-19 based on network pharmacology

BioData Mining ◽

10.1186/s13040-020-00225-8 ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Ying Huang ◽

Wen-jiang Zheng ◽

Yong-shi Ni ◽

Mian-sha Li ◽

Jian-kun Chen ◽

...

Keyword(s):

Chinese Medicine ◽

Signaling Pathways ◽

Signaling Pathway ◽

Mapk Signaling ◽

Venn Diagram ◽

Network Pharmacology ◽

Active Ingredients ◽

Integrated Network ◽

Therapeutic Mechanism ◽

The World

Abstract Background Chinese medicine Toujie Quwen granule (TJQW) has proven to be effective in the treatment of mild coronavirus disease 2019 (COVID-19) cases by relieving symptoms, slowing the progression of the disease, and boosting the recovery of patients. But the bioactive compounds and potential mechanisms of TJQW for COVID-19 prevention and treatment are unclear. This study aimed to explore the potential therapeutic mechanism of TJQW in coronavirus disease 2019 (COVID-19) based on an integrated network pharmacology approach. Methods TCMSP were used to search and screen the active ingredients in TJQW. The Swiss TargetPrediction was used to predict the potential targets of active ingredients. Genes co-expressed with ACE2 were considered potential therapeutic targets on COVID-19. Venn diagram was created to show correlative targets of TJQW against COVID-19. Cytoscape was used to construct a “drug-active ingredient-potential target” network, STRING were used to construct protein-protein interaction network, and cytoHubba performed network topology analysis. Enrichment of biological functions and signaling pathways of core targets was performed by using the clusterProfiler package in R software and ClueGO with CluePedia plugins in Cytoscape. Results A total of 156 active ingredients were obtained through oral bioavailability and drug-likeness screenings. Two hundred twenty-seven potential targets of TJQW were related to COVID-19. The top ten core targets are EGFR, CASP3, STAT3, ESR1, FPR2, F2, BCL2L1, BDKRB2, MPO, and ACE. Based on that, we obtained 19 key active ingredients: umbelliprenin, quercetin, kaempferol, luteolin, praeruptorin E, stigmasterol, and oroxylin A. And the enrichment analysis obtained multiple related gene ontology functions and signaling pathways. Lastly, we constructed a key network of “drug-component-target-biological process-signaling pathway”. Our findings suggested that TJQW treatment for COVID-19 was associated with elevation of immunity and suppression of inflammatory stress, including regulation of inflammatory response, viral process, neutrophil mediated immunity, PI3K-Akt signaling pathway, MAPK signaling pathway, Jak-STAT signaling pathway, Complement and coagulation cascades, and HIF-1 signaling pathway. Conclusions Our study uncovered the pharmacological mechanism underlying TJQW treatment for COVID-19. These results should benefit efforts for people around the world to gain more knowledge about Chinese medicine TJQW in the treatment of this vicious epidemic COVID-19, and help to address this pressing problem currently facing the world.

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107 FVIIa Prevents the Progressive Hemorrhaging of a Brain Contusion by Protecting Microvessels Via Formation of the TF-FVIIa-FXa Complex

Neurosurgery ◽

10.1093/neuros/nyx417.107 ◽

2017 ◽

Vol 64 (CN_suppl_1) ◽

pp. 221-222

Author(s):

Qiang Yuan

Keyword(s):

Endothelial Cells ◽

Signaling Pathways ◽

Signaling Pathway ◽

Vascular Endothelial Cells ◽

Mapk Signaling ◽

Coagulation Cascade ◽

Cell Protein ◽

Vascular Endothelial ◽

Brain Contusion ◽

Microvessel Endothelial Cells

Abstract INTRODUCTION Factor VII (FVII) plays a key role in the initiation of the coagulation cascade and, in clinical situations, recombinant human activated FVII (rFVIIa) effectively prevents progressive hemorrhaging after a brain contusion. However, it remains unclear whether decreases in FVII activity directly lead to progressive hemorrhaging and, moreover, the precise mechanisms underlying this process are not yet known. METHODS Controlled cortical impact model of mouse brain contusion was used to examine whether decreased FVII activity would directly lead to the occurrence of progressive hemorrhaging in mice and whether administration of FVIIa would prevent the delayed catastrophic structural failure of microvessels and the progressive hemorrhaging of brain contusions by protecting vascular endothelial cells via formation of the ternary TF FVIIa FXa complex. Activations of p44/42 MAPK, p38 MAPK, and p65 NF-kB signaling pathways by ternary TF FVIIa FXa complex were tested by WB in HUVECs. RESULTS >The present study demonstrated that decreased FVII activity directly led to progressive hemorrhaging of the cerebral contusions. Administration of FVII prevented the progression of hemorrhaging from cerebral contusions by protecting microvessel endothelial cells in the penumbra of the contusion. The present study also showed that the ternary TF FVIIa FXa complex cleaved endogenous protease-activated receptor 2 (PAR2) on endothelial cells, activated the p44/42 mitogen-activated protein kinase (MAPK) signaling cascade, and inhibited p65 nuclear factor-kB (NF-kB) signaling. Furthermore, exposure to ternary TF FVIIa FXa protected endothelial cells from thrombin- or inflammatory cytokine-induced apoptosis. Although activation of the p44/42 MAPK signaling pathway is endothelial cell protein C receptor (EPCR)-dependent, inhibition of the p65 NF-kB signaling pathway is EPCR independent; thus, the regulation mechanism underlying the effects of TF FVIIa FXa in vascular endothelial cells appears to be multiple signaling pathways. CONCLUSION In summary, the present findings demonstrated that FVIIa prevented the progressive hemorrhaging of brain contusions by protecting microvessel endothelial cells via the formation of the ternary TF FVIIa FXa complex. These findings are novel and of great clinical significance because FVIIa is used to prevent the progressive hemorrhaging of brain contusions in humans.

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A network pharmacology analysis on drug-like compounds from Ganoderma lucidum for alleviation of Atherosclerosis

10.21203/rs.3.rs-236410/v1 ◽

2021 ◽

Author(s):

Ki Kwang Oh ◽

Md. Adnan ◽

Dong Ha Cho

Keyword(s):

Signaling Pathways ◽

Signaling Pathway ◽

Ganoderma Lucidum ◽

Mapk Signaling ◽

Mendelian Inheritance ◽

Chronic Inflammatory Disease ◽

Mapk Signaling Pathway ◽

Venn Diagram ◽

Network Pharmacology ◽

Overlapping Genes

Abstract Background: Ganoderma lucidum (GL) is known as a potent alleviator against chronic inflammatory disease like atherosclerosis (AS), but its critical bioactive compounds and their mechanisms against AS have not been unveiled. This research aimed to identify the key compounds(s) and mechanism(s) of GL against AS through network pharmacology.Methods: The compounds from GL were identified by gas chromatography-mass spectrum (GC-MS), and SwissADME screened their physicochemical properties. Then, the gene(s) associated with the screened compound(s) or AS related genes were identified by public databases, and we selected the overlapping genes using a Venn diagram. The networks between overlapping genes and compounds were visualized, constructed, and analyzed by RStudio. Finally, we performed molecular docking test (MDT) to identify key gene(s), compound(s) on AutoDockVina.Results: A total of 35 compounds in GL was detected via GC-MS, and 34 compounds (accepted by the Lipinski's rule) were selected as drug-like compounds (DLCs). A total of 34 compounds were connected to the number of 785 genes and 2,606 AS-related genes were identified by DisGeNET and Online Mendelian Inheritance in Man (OMIM). The final 98 overlapping genes were extracted between the compounds-genes network and AS-related genes. On Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, the number of 27 signaling pathways were sorted out, and a hub signaling pathway (MAPK signaling pathway), a core gene (PRKCA), and a key compound (Benzamide, 4-acetyl-N-(2,6-dimethylphenyl)) were selected among the 27 signaling pathways via MDT. Conclusion: Overall, we found that the identified 3 DLCs from GL have potent anti-inflammatory efficacy, improving AS by inactivating the MAPK signaling pathway.

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Exploring the mechanism of (-)-Epicatechin on premature ovarian insufficiency based on network pharmacology and experimental evaluation

Bioscience Reports ◽

10.1042/bsr20203955 ◽

2021 ◽

Vol 41 (2) ◽

Author(s):

Fei Yan ◽

Qi Zhao ◽

Huanpeng Gao ◽

Xiaomei Wang ◽

Ke Xu ◽

...

Keyword(s):

Gene Ontology ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Signaling Pathways ◽

Signaling Pathway ◽

Mapk Signaling ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Related Factor ◽

Nrf2 Signaling Pathway

Abstract Methods: Relevant potential targets for EC were obtained based on Traditional Chinese Medicine System Pharmacology Database (TCMSP), a bioinformatics analysis tool for molecular mechanism of Traditional Chinese Medicine (BATMAN-TCM) and STITCH databases. The Online Mendelian Inheritance in Man (OMIM) and GeneCards databases were utilized to screen the known POI-related targets, while Cytoscape software was used for network construction and visualization. Then, the Gene Ontology (GO) and pathway enrichment analysis were carried out by the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. Furthermore, KGN cells were performed to validate the predicted results in oxidative stress (OS) model, and antioxidant effect was examined. Results: A total of 70 potential common targets for EC in the treatment of POI were obtained through network pharmacology. Metabolic process, response to stimulus and antioxidant activity occupied a leading position of Gene Ontology (GO) enrichment. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that PI3K/protein kinase B (AKT), TNF, estrogen, VEGF and MAPK signaling pathways were significantly enriched. In addition, cell experiments showed that EC exhibited antioxidant effects in an H2O2-mediated OS model in ovarian granulosa cells by regulating the expression of PI3K/AKT/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and multiple downstream antioxidant enzymes. Conclusion: EC could regulate multiple signaling pathways and several biological processes (BPs). EC had the ability to down-regulate elevated OS level through the PI3K/AKT/Nrf2 signaling pathway and represented a potential novel treatment for POI.

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