AB0066 MECHANISMS OF TOTAL SAPONINS OF PANAX JAPONICUS MITIGATES COLLAGEN-INDUCED ARTHRITIS

Background:Total saponins of Panax japonicus (TSPJ) are extracted from Panax japonicus (T.Nees) C.A.Mey and have achieved a good therapeutic effect in the treatment of rheumatoid arthritis (RA). Unfortunately, the mechanism of TSPJ acting on RA is not clear.Objectives:To investigate the potential mechanisms and key targets of TSPJ on RA.Methods:The raw data were downloaded from the Gene Expression Omnibus (GEO) database, and the RStudio3.6.1 software was used to identify differentially expressed genes (DEGs). The potential targets of active compounds from TSPJ were predicted by the Pharmmapper and SwissTargetPrediction databases. Based on the overlapping genes, we used Cytoscape 3.7.2 software to construct a protein-protein interactions (PPI) network and to determine the mechanisms of the treatment by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Collagen-induced arthritis (CIA) model was established and treated with different doses of TSPJ. Arthritis index (AI) and histology score were used to evaluate the symptoms of CIA. The levels of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1 (HIF-1), IL-1β, and IL-17A tested by enzyme linked immunosorbent assay and real time-quantitative Polymerase Chain Reaction.Results:A total of 2670 DEGs and 371 TSPJ targets were obtained, including 52 overlapping genes. 41 genes had protein interactions that are used to build the PPI network. The results of the KEGG enrichment analysis included VEGF and HIF-1 signaling pathway. Seven negative correlation genes and 16 positive correlation genes were obtained by correlational analysis of DEGs in VEGF and HIF-1 signaling pathway. SRC proto-oncogene, nonreceptor tyrosine kinase (SRC), and the signal transducer and the activator of transcription 3 (STAT 3) had a higher value of degree in PPI and showed a significant correlation in the pathways; they were regarded as key targets. Compared with the CIA model group, TSPJ significantly decreased the AI and histology scores. Moreover, the expression of VEGF-A, HIF-1α, IL-1β, and IL-17A in serum or spleens significantly reduced in a dose-dependent.Conclusion:Present study show that SRC and STAT 3 may be the key targets of TSPJ acting on the VEGF and HIF-1 signaling pathways, thus inhibiting angiogenesis and improving RA.Disclosure of Interests:None declared

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Computational Prediction of Antiangiogenesis Synergistic Mechanisms of Total Saponins of Panax japonicus Against Rheumatoid Arthritis

Frontiers in Pharmacology ◽

10.3389/fphar.2020.566129 ◽

2020 ◽

Vol 11 ◽

Author(s):

Xiang Guo ◽

Jinyu Ji ◽

Goutham Sanker Jose Kumar Sreena ◽

Xiaoqiang Hou ◽

Yanan Luo ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Signaling Pathways ◽

Protein Interactions ◽

Drug Targets ◽

Mrna Levels ◽

Overlapping Genes ◽

Differential Analysis ◽

Ppi Network ◽

Kegg Analysis ◽

Panax Japonicus

Objective: To investigate the anti-angiogenesis mechanisms and key targets of total saponins of Panax japonicus (TSPJ) in the treatment of rheumatoid arthritis (RA).Methods: RStudio3.6.1 software was used to obtain differentially expressed genes (DEGs) by analyzing the differences in gene expression in the synovial tissue of RA and to predict the potential targets of active compounds from TSPJ by the PharmMapper and SwissTargetPrediction databases. We evaluated the overlapping genes by intersectional analysis of DEGs and drug targets. Based on the overlapping genes, we used Cytoscape 3.7.2 software to construct a protein–protein interactions (PPI) network and applied Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to determine the mechanisms of the treatment. Finally, the correlations with angiogenesis-related genes were explored. Collagen-induced arthritis (CIA) model was established and treated with different doses of TSPJ. The manifestations of CIA were determined by evaluation of arthritis index and histology score. Serum levels of vascular endothelial growth factor (VEGF) and the hypoxia-inducible factor 1 (HIF-1) were tested by ELISA. The mRNA levels of IL-1β and IL-17A were detected by real time-quantitative PCR.Results: Altogether, 2670 DEGs were obtained by differential analysis, and 371 drug targets were predicted for four active components (Araloside A, Chikusetsusaponin IVa, Ginsenoside Rg2, and Ginsenoside Ro). A total of 52 overlapping genes were included in the PPI network and the KEGG analysis. However, only 41 genes in the PPI network had protein interactions. The results of the KEGG enrichment analysis were all related to angiogenesis, including VEGF and HIF-1 signaling pathways. Seven genes with negative correlations and 16 genes with positive correlations were obtained by correlational analysis of DEGs in the VEGF and HIF-1 signaling pathways. SRC proto-oncogene, nonreceptor tyrosine kinase (SRC), and the signal transducer and activator of transcription 3 (STAT 3) had a higher value of degree and showed a significant correlation in the pathways; they were regarded as key targets. Compared with the model group, TSPJ significantly relieved the symptoms and decreased the expression of VEGFA, HIF-1α, IL-1β, and IL-17A in serum or spleens of CIA mice.Conclusion: In the current study, we found that antiangiogenesis is one of the effective strategies of TSPJ against RA; SRC and STAT 3 may be the key targets of TSPJ acting on the VEGF and HIF-1 signaling pathways, which will provide new insight into the treatment of RA by inhibiting inflammation and angiogenesis.

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The Absence of TLR4 Prevents Fetal Brain Injury in the Setting of Intrauterine Inflammation

Reproductive Sciences ◽

10.1177/1933719118805859 ◽

2018 ◽

Vol 26 (8) ◽

pp. 1082-1093 ◽

Cited By ~ 1

Author(s):

Natalia M. Tulina ◽

Amy G. Brown ◽

Guillermo O. Barila ◽

Michal A. Elovitz

Keyword(s):

Brain Injury ◽

Notch Signaling ◽

Signaling Pathway ◽

Quantitative Polymerase Chain Reaction ◽

Fetal Brain ◽

Notch Signaling Pathway ◽

Mouse Strains ◽

Enzyme Linked Immunosorbent Assay ◽

Tlr4 Signaling ◽

Tlr4 Signaling Pathway

Background: Exposure to intrauterine inflammation during pregnancy is linked to brain injury and neurobehavioral disorders in affected children. Innate immunity, specifically Toll-like receptor (TLR) signaling pathways are present throughout the reproductive tract as well as in the placenta, fetal membranes, and fetus. The TLR pathways are mechanistically involved in host responses to foreign pathogens and may lead to brain injury associated with prenatal inflammation. Objective: We aimed to determine whether the activation of the TLR4 signaling pathway, in the mother and fetus, is critical to fetal brain injury in the setting of intrauterine inflammation. Methods: A mini-laparotomy was performed on time pregnant C57B6 mice and 2 knockout mouse strains lacking the function of the Tlr4 and Myd88 genes on embryonic day 15. Intrauterine injections of Escherichia coli lipopolysaccharide or saline were administered as described previously. Dams were killed 6 hours postsurgery, and placental, amniotic fluid, and fetal brain tissue were collected. To assess brain injury, quantitative polymerase chain reaction (qPCR) analysis was performed on multiple components of the NOTCH signaling pathway, including Hes genes. Interleukin (IL) IL6, IL1β, and CCL5 expression was assessed using qPCR and enzyme-linked immunosorbent assay. Results: Using an established mouse model of intrauterine inflammation, we demonstrate that the abrogation of TLR4 signaling eliminates the cytokine response in mother and fetus and prevents brain injury associated with increased expression of transcriptional effectors of the NOTCH signaling pathway, Hes1 and Hes5. Conclusions: These data show that the activation of the TLR4 signaling pathway is necessary for the development of fetal brain injury in response to intrauterine inflammation.

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Integrated Transcriptional Profiling Analysis and Immune-Related Risk Model Construction for Intracranial Aneurysm Rupture

Frontiers in Neuroscience ◽

10.3389/fnins.2021.613329 ◽

2021 ◽

Vol 15 ◽

Author(s):

Dezhi Shan ◽

Xing Guo ◽

Guozheng Yang ◽

Zheng He ◽

Rongrong Zhao ◽

...

Keyword(s):

Immune Response ◽

Inflammatory Response ◽

Signaling Pathway ◽

Immune Cell ◽

Risk Model ◽

Enrichment Analysis ◽

Cell Infiltration ◽

Enzyme Linked Immunosorbent Assay ◽

Immune Cell Infiltration ◽

Related Risk

Intracranial aneurysms (IAs) may cause lethal subarachnoid hemorrhage upon rupture, but the molecular mechanisms are poorly understood. The aims of this study were to analyze the transcriptional profiles to explore the functions and regulatory networks of differentially expressed genes (DEGs) in IA rupture by bioinformatics methods and to identify the underlying mechanisms. In this study, 1,471 DEGs were obtained, of which 619 were upregulated and 852 were downregulated. Gene enrichment analysis showed that the DEGs were mainly enriched in the inflammatory response, immune response, neutrophil chemotaxis, and macrophage differentiation. Related pathways include the regulation of actin cytoskeleton, leukocyte transendothelial migration, nuclear factor κB signaling pathway, Toll-like receptor signaling pathway, tumor necrosis factor signaling pathway, and chemokine signaling pathway. The enrichment analysis of 20 hub genes, subnetworks, and significant enrichment modules of weighted gene coexpression network analysis showed that the inflammatory response and immune response had a causal relationship with the rupture of unruptured IAs (UIAs). Next, the CIBERSORT method was used to analyze immune cell infiltration into ruptured IAs (RIAs) and UIAs. Macrophage infiltration into RIAs increased significantly compared with that into UIAs. The result of principal component analysis revealed that there was a difference between RIAs and UIAs in immune cell infiltration. A 4-gene immune-related risk model for IA rupture (IRMIR), containing CXCR4, CXCL3, CX3CL1, and CXCL16, was established using the glmnet package in R software. The receiver operating characteristic value revealed that the model represented an excellent clinical situation for potential application. Enzyme-linked immunosorbent assay was performed and showed that the concentrations of CXCR4 and CXCL3 in serum from RIA patients were significantly higher than those in serum from UIA patients. Finally, a competing endogenous RNA network was constructed to provide a potential explanation for the mechanism of immune cell infiltration into IAs. Our findings highlighted the importance of immune cell infiltration into RIAs, providing a direction for further research.

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Network Pharmacology-Based Strategy to Investigate Pharmacological Mechanisms of the Drug Pair Astragalus-Angelica for Treatment of Male Infertility

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/8281506 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Feng Zhao ◽

Yingjun Deng ◽

Guanchao Du ◽

Shengjing Liu ◽

Jun Guo ◽

...

Keyword(s):

Male Infertility ◽

Signaling Pathway ◽

Mechanism Of Action ◽

Protein Interactions ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Protein Protein Interactions ◽

Drug Pair ◽

Effective Components ◽

New Ideas

Background. The traditional Chinese medicines Astragalus and Angelica are often combined to treat male infertility, but the specific therapeutic mechanism is not clear. Therefore, this study applies a network pharmacology approach to investigate the possible mechanism of action of the drug pair Astragalus-Angelica (PAA) in the treatment of male infertility. Methods. Relevant targets for PAA treatment of male infertility are obtained through databases. Protein-protein interactions (PPIs) are constructed through STRING database and screen core targets, and an enrichment analysis is conducted through the Metascape platform. Finally, molecular docking experiments were carried out to evaluate the affinity between the target protein and the ligand of PAA. Results. The active ingredients of 112 PAA, 980 corresponding targets, and 374 effective targets of PAA for the treatment of male infertility were obtained, which are related to PI3K-Akt signaling pathway, HIF-1 signaling pathway, AGE-RAGE signaling pathway, IL-17 signaling pathway, and thyroid hormone signaling pathway. Conclusion. In this study, using a network pharmacology method, we preliminarily analyzed the effective components and action targets of the PAA. We also explored the possible mechanism of action of PAA in treating male infertility. They also lay a foundation for expanding the clinical application of PAA and provide new ideas and directions for further research on the mechanisms of action of the PAA and its components for male infertility treatment.

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RiPerC Attenuates Cerebral Ischemia Injury through Regulation of miR-98/PIK3IP1/PI3K/AKT Signaling Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/6454281 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Dengwen Zhang ◽

Li Mei ◽

Ruichun Long ◽

Can Cui ◽

Yi Sun ◽

...

Keyword(s):

Cerebral Ischemia ◽

Signaling Pathway ◽

Regulatory Mechanism ◽

Ischemia Reperfusion ◽

Quantitative Polymerase Chain Reaction ◽

Akt Signaling ◽

Enzyme Linked Immunosorbent Assay ◽

Akt Signaling Pathway ◽

Remote Ischemic Perconditioning ◽

Cerebral Ischemic

Background. Cerebral ischemic stroke is a refractory disease which seriously endangers human health. Remote ischemic perconditioning (RiPerC) by which the sublethal ischemic stimulus is administered during the ischemic event is beneficial after an acute stroke. However, the regulatory mechanism of RiPerC that relieves cerebral ischemic injury is still not completely clear. Methods. In the present study, we investigated the regulatory mechanism of RiPerC in a rat model of ischemia induced by the middle cerebral artery occlusion (MCAO). Forty-eight adult male Sprague-Dawley (SD) rats were injected intracerebroventricularly with miR-98 agomir, miR-98 antagomir, or their negative controls (agomir-NC, antagomir-NC) 2 h before MCAO or MCAO+RiPerC followed by animal behavior tests and infraction volume measurement at 24 h after MCAO. The expression of miR-98, PIK3IP1, and tight junction proteins in rat hippocampus and cerebral cortex tissues was detected by quantitative polymerase chain reaction (qPCR) and Western blot (WB). Enzyme-linked immunosorbent assay (ELISA) was used to assess the IL-1β, IL-6, and TNF-α levels in the rat serum. Results. The results showed that in MCAO group, the expression of PIK3IP1 was upregulated, but decreased after RiPerC treatment. Then, we found that PIK3IP1 was a potential target of miR-98. Treatment with miR-98 agomir decreased the infraction volume, reduced brain edema, and improved neurological functions compared to control rats. But treating with miR-98 antagomir in RiPerC group, the protective effect on cerebral ischemia injury was canceled. Conclusion. Our finding indicated that RiPerC inhibited the MCAO-induced expression of PIK3IP1 through upregulated miR-98, thereby reducing the apoptosis induced by PIK3IP1 through the PI3K/AKT signaling pathway, thus reducing the cerebral ischemia-reperfusion injury.

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Impaired trophoblast Toll-Like Receptor 3 signaling pathway involves in hepatitis B vaccine non- or hypo-response of infants born to HBsAg-positive mothers

10.21203/rs.3.rs-20386/v1 ◽

2020 ◽

Author(s):

Lina Wu ◽

Ruijun Zhang ◽

Yongliang Feng ◽

Tian Yao ◽

Linzhu Yi ◽

...

Keyword(s):

Hepatitis B ◽

Signaling Pathway ◽

Hepatitis B Surface Antigen ◽

Quantitative Polymerase Chain Reaction ◽

Hbv Dna ◽

Enzyme Linked Immunosorbent Assay ◽

Toll Like Receptor ◽

Insufficient Response ◽

Hb Vaccine ◽

Tlr3 Signaling

Abstract Background: Babies born to hepatitis B surface antigen (HBsAg) positive mothers bear a high risk of being non- or hypo-responsive to hepatitis B (HB) vaccine with unilluminated mechanisms. Placental immunity is closely related to the development of baby immune system, however, the roles of the placental immunity in the insufficient response of these babies are unclear. This study was aimed to investigate the role of placental trophoblast Toll-Like Receptor 3（TLR3）signaling pathway in HB vaccine non- or hypo-response of these special babies. Methods: A total of 399 pairs of HBsAg-positive mothers and their neonates were recruited to perform a nested case-control study. The maternal and children’s HBV DNA and the HBV serological markers were detected by Fluorescence Quantitative Polymerase Chain Reaction (FQ-PCR) and Electrochemiluminescence Immunoassay (ECLIA). The trophoblast TLR3 signaling pathway proteins and infant cytokines IL-6, IL-12, TNF-α, IFN-α and IFN-γ were tested by immunohistochemistry (IHC) and Enzyme–Linked Immunosorbent Assay (ELISA). Results: The expression of TLR3 and NF-κB, a TLR3 downstream protein, were significantly decreased in the non- or hypo-responders ( Z= -3.00 and -2.46, P <0.01 and =0.01). Furthermore, the trophoblast TLR3 expression negatively correlated with maternal HBV DNA ( r = -0.29, P = 0.003), HBeAg ( r = -0.28, P = 0.01) and HBV DNA+HBeAg ( r = -0.24, P = 0.02). Besides, NF-κB positively correlated with infant IL-6 ( r = 0.24, P = 0.026). By comprehensive analysis of maternal, placental and infant information, a Bayesian network model showed that the trophoblast TLR3 signaling pathway contacted with the non- or hypo-responsiveness. onclusions: Maternal HBV infection affected the trophoblast TLR3 signaling pathway protein expression, and consequently the impaired TLR3 signaling pathway involved in the HB vaccine non- or hypo-responsiveness mainly by influencing infant IL-6.

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Network Pharmacology-Based Strategy for Predicting Therapy Targets of Tripterygium wilfordii on Acute Myeloid Leukemia

10.21203/rs.3.rs-29959/v1 ◽

2020 ◽

Author(s):

Tingting Fang ◽

Lanqin Liu ◽

wenjun liu

Keyword(s):

Acute Myeloid Leukemia ◽

Chinese Medicine ◽

Signaling Pathway ◽

Myeloid Leukemia ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Overlapping Genes ◽

Tripterygium Wilfordii ◽

Active Ingredients ◽

Acute Myeloid

Abstract Background. Acute myeloid leukemia (AML) is a common malignant tumor of the hematopoietic system. How to extend the survival time of AML patients and improve their prognosis is still a major medical problem. Chinese medicine has a long history in treating AML. Tripterygium wilfordii (TW) is a traditional Chinese medicine. With the deepening of pharmacological research of traditional Chinese medicine, triptolide, one of its active ingredients, has been proven to have a positive effect on the treatment of AML. Therefore，this study aimed on studying the potential therapeutic targets and pharmacological mechanism of TW in Acute myeloid leukemia (AML) based on network pharmacology.Methods. The active components of TW were obtained by network pharmacology through oral bioavailability, drug-likeness filtration. Comparative analysis was used to study the overlapping genes between active ingredient’s targets and AML treatment-related targets. Using STRING database to analyze interactions between overlapping genes. KEGG pathway analysis and Gene Ontology enrichment analysis were conducted in DAVID. These genes were analyzed for survival in OncoLnc database.Key findings. We screened 53 active ingredients, the results of comparative analysis showed that 8 active ingredients had an effect on AML treatment. Based on the active ingredients and overlapping genes, we constructed the Drug-Compounds-Genes-Disease Network. Survival analysis of overlapping genes indicated that some targets possess a significant influence on patients’ survival and prognosis. The enrichment analysis showed that the main pathways of targets are Toll-like receptor signaling pathway, NF-kappa B signaling pathway and HIF-1 signaling pathway.Conclusion. This study, using a network pharmacologic approach, provides another strategy that can help us to understand the mechanisms by which TW treats AML comprehensively.

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Longitudinal Analysis of Gene Expression Changes During Cervical Carcinogenesis Reveals Potential Therapeutic Targets

Evolutionary Bioinformatics ◽

10.1177/1176934320920574 ◽

2020 ◽

Vol 16 ◽

pp. 117693432092057

Author(s):

Lijun Yu ◽

Meiyan Wei ◽

Fengyan Li

Keyword(s):

Gene Expression ◽

Western Blotting ◽

Protein Interactions ◽

Target Genes ◽

Quantitative Polymerase Chain Reaction ◽

Enrichment Analysis ◽

Gene Interaction ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Gene Expressions

Despite advances in the treatment of cervical cancer (CC), the prognosis of patients with CC remains to be improved. This study aimed to explore candidate gene targets for CC. CC datasets were downloaded from the Gene Expression Omnibus database. Genes with similar expression trends in varying steps of CC development were clustered using Short Time-series Expression Miner (STEM) software. Gene functions were then analyzed using the Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Protein interactions among genes of interest were predicted, followed by drug-target genes and prognosis-associated genes. The expressions of the predicted genes were determined using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Red and green profiles with upward and downward gene expressions, respectively, were screened using STEM software. Genes with increased expression were significantly enriched in DNA replication, cell-cycle-related biological processes, and the p53 signaling pathway. Based on the predicted results of the Drug-Gene Interaction database, 17 drug-gene interaction pairs, including 3 red profile genes (TOP2A, RRM2, and POLA1) and 16 drugs, were obtained. The Cancer Genome Atlas data analysis showed that high POLA1 expression was significantly correlated with prolonged survival, indicating that POLA1 is protective against CC. RT-qPCR and Western blotting showed that the expressions of TOP2A, RRM2, and POLA1 gradually increased in the multistep process of CC. TOP2A, RRM2, and POLA1 may be targets for the treatment of CC. However, many studies are needed to validate our findings.

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Silencing XIST mitigated lipopolysaccharide (LPS)-induced inflammatory injury in human lung fibroblast WI-38 cells through modulating miR-30b-5p/CCL16 axis and TLR4/NF-κB signaling pathway

Open Life Sciences ◽

10.1515/biol-2021-0005 ◽

2021 ◽

Vol 16 (1) ◽

pp. 108-127

Author(s):

Jiahui Xu ◽

Honggui Li ◽

Ying Lv ◽

Chang Zhang ◽

Yiting Chen ◽

...

Keyword(s):

Signaling Pathway ◽

Western Blotting ◽

Human Lung ◽

Quantitative Polymerase Chain Reaction ◽

B Cell Lymphoma ◽

Lung Fibroblast ◽

Luciferase Reporter ◽

Enzyme Linked Immunosorbent Assay ◽

Human Lung Fibroblast ◽

Inflammatory Injury

Abstract Background Emerging evidence shows that long noncoding RNA (lncRNA) has been a novel insight in various diseases, including pneumonia. Even though lncRNA X-inactive-specific transcript (XIST) is well studied, its role in pneumonia remains to be largely unrevealed. Methods Expression of XIST, miRNA-30b-5p (miR-30b-5p), and CC chemokine ligand 16 (CCL16) was detected using reverse transcriptase quantitative polymerase chain reaction and western blotting; their interaction was confirmed by dual-luciferase reporter assay. Apoptosis, inflammation, and toll-like receptor 4 (TLR4)/NF-κB signaling pathway were measured using methyl thiazolyl tetrazolium assay, flow cytometry, western blotting, and enzyme-linked immunosorbent assay. Results Lipopolysaccharide (LPS) stimulation decreased cell viability and B cell lymphoma (Bcl)-2 expression, and increased cell apoptosis rate and expression of Bcl-2-associated X protein (Bax), cleaved-caspase-3, interleukin (IL)-6, IL-1β, and tumor necrosis factor α (TNF-α) in WI-38 cells. Expression of XIST and CCL16 was upregulated in the serum of patients with pneumonia and LPS-induced WI-38 cells, respectively; silencing XIST and CCL16 could suppress LPS-induced apoptosis and inflammation in WI-38 cells, and this protection was abolished by miR-30b-5p downregulation. Moreover, XIST and CCL16 could physically bind to miR-30b-5p, and XIST regulated CCL16 expression via sponging miR-30b-5p. TLR4 and phosphorylated P65 (p-P65) and p-IκB-α were highly induced by LPS treatment, and this upregulation was diminished by blocking XIST, accompanied with CCL16 downregulation and miR-30b-5p upregulation. Conclusions Silencing XIST could alleviate LPS-induced inflammatory injury in human lung fibroblast WI-38 cells through modulating miR-30b-5p/CCL16 axis and inhibiting TLR4/NF-κB signaling pathway.

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Network Pharmacological Analysis of Huanglian Jiedu Decoction for Anti- Atherosclerosis

10.21203/rs.3.rs-44241/v1 ◽

2020 ◽

Author(s):

Kerui Wu ◽

Lu Jiang ◽

Lanlin Huang ◽

Yaxing He ◽

Xia Yan ◽

...

Keyword(s):

Signaling Pathways ◽

Signaling Pathway ◽

Fluid Shear Stress ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Ppi Network ◽

Active Ingredients ◽

Active Components ◽

Protein Protein Interaction ◽

Target Regulation

Abstract Objective: We aimed to predict the possible active components,key targets and pathways of Huanglian Jiedu Decoction(HLJDD) for anti-atherosclerosis. Methods: The TCMSP database was searched to obtain the active components and targets of HLJDD, the GeneCards and OMIM databases were searched to obtain related targets of atherosclerosis, and we obtain the intersection targets of them, which are the potential targets of HLJDD for anti-atherosclerosis.Application of Cytoscape 3.6.0 software to build a herbal-active ingredient-potential target regulation network.We perform protein-protein interaction(PPI) network analysis of potential targets through STRING 11.0 database and obtain the key targets,and the results of PPI network of key targets were visualized by Cytoscape3.6.0 software. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the key targets were performed using STRING11.0 database, and we finally constructed the possible pharmacological network of HLJDD for anti-atherosclerosis .Results: We finally obtained 14 key active ingredients of HLJDD, 65 key targets of anti-atherosclerosis, and 14 key active ingredients corresponded to 52 of these targets. These targets are mainly involved in biological processes such as reaction to organic substance, reaction to chemical stimulation,etc.They mainly involved in biological signaling pathways such as pathways in cancer,IL-17 signaling pathway,etc. Conclusion: HLJDD may act on 52 key targets such as PTGS2, HSP90AA1 and RELA through 14 key active ingredients, and influence the signaling pathways including fluid shear stress and atherosclerosis,PI3K-Akt signaling pathway,IL-17 signaling pathway,AGE-RAGE signaling pathway in diabetic complications,TNF signaling pathway,etc.Thus, it may play an anti-atherosclerosis role by inhibiting inflammatory reaction, oxidative stress and improving hemodynamics,etc.

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