scholarly journals A System Bioinformatics Approach Predicts the Molecular Mechanism Underlying the Course of Action of Radix Salviae Reverses GBM Effects

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Sun Jiaojiao ◽  
He Yuping ◽  
Li Yajuan ◽  
Liu Guangyi ◽  
Li Qiuhong ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanism ◽  
Enrichment Analysis ◽  
The Body ◽  
Inflammatory Factor ◽  
Active Components ◽  
Human Glioblastoma ◽  
In Vitro Techniques ◽  
Course Of Action

Objective. This study used in vitro techniques to investigate the therapeutic effect of Radix Salviae on human glioblastoma and decode its underlying molecular mechanism. Methods. The active components and targets of the Radix Salviae were identified from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP). The targets of human glioblastoma were obtained from the GeneCards Database. The Radix Salviae-mediated antiglioblastoma was evaluated by Gene Ontology (GO) analyses and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Finally, mechanism of action of Radix Salviae against human glioblastoma was deduced by molecular docking and experiments. Results. We screened 66 active ingredients and 45 targets of the Radix Salviae. The enrichment analysis based on the targets mentioned above suggested a possible role in protein phosphorylation, cell transcription, apoptosis, and inflammatory factor signaling pathways. Further study demonstrated that cryptotanshinone, an essential component of Radix Salviae, played a significant role in killing human glioblastoma cells and protecting the body by inhibiting the AKT, IKB, and STAT3 signaling pathways. Conclusions. Radix Salviae could inhibit the proliferation and invasion of human glioblastoma by regulating STAT3, Akt, and IKB signaling pathways. Radix Salviae has potential therapeutic value in the future for human glioblastoma.

scholarly journals Study on the Mechanism of Prunella Vulgaris L on Diabetes Mellitus Complicated with Hypertension Based on Network Pharmacology and Molecular Docking Analyses

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Xinyi Jiao ◽  
Haiying Liu ◽  
Qinan Lu ◽  
Yu Wang ◽  
Yue Zhao ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Enrichment Analysis ◽  
Prunella Vulgaris ◽  
Active Components ◽  
Analysis Platform

The role of traditional Chinese medicine Prunella vulagaris L in the treatment of tumors and inflammation has been widely confirmed. We found that some signaling pathways of Prunella vulgaris L action can also regulate diabetes and hypertension, so we decided to study the active ingredients, potential targets and signaling pathway of Prunrlla vulgaris L, and explore the “multi-target, multi-pathway” molecular mechanism of Prunella vulgaris L on diabetes mellitus complicated with hypertension(DH). Methods. Based on TCMSP(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and CNKI(China National Knowledge Infrastructure), the components and action targets related to Prunella vulgaris L were screened. The OMIM(Online Mendelian Inheritance in Man) and GeneCards (The human gene database) were used to search for targets related to DH. The “gene - drug - disease” relationship map was drawn by Cytoscape_v3.7.2 plug-in. The target was amplified by the STRING platform, and the “protein - protein” interaction relationship (PPI) network of the interacting target was obtained by the STRING online analysis platform and the Cytoscape_v3.7.2 plug-in. Finally, GO enrichment analysis and KEGG pathway enrichment analysis were conducted on David and Metascape platform to study the co-acting targets. Results. 11 active components, 41 key targets and 16 significant signaling pathways were identified from Prunella vulgaris L. The main active components of Prunella vulgaris L against DH were quercetin and kaumferol, etc, and potential action targets were IL-6 and INS, etc and signaling pathways were AGE-RAGE signaling pathway, TNF signaling pathway, MAPK signaling pathway, PI3K-AKT signaling pathway, etc. It involves in biological processes such as cell proliferation, apoptosis and inflammatory response. Conclusions. The main molecular mechanism of Prunella vulgaris L against DH is that sterols and flavonoids play an active role by affecting TNF signaling pathway, AGE-RAGE signaling pathway, MAPK pathway, PI3K-Akt pathway related targets such as IL-6 and INS.

scholarly journals Active Substances from Callicarpa nudiflora Exert Anti-Cervicitis Effects and Regulate NLRP3-Associated Inflammation

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6217
Author(s):  
Tianchi Liu ◽  
Ruiqi Wang ◽  
Chenpeng Liu ◽  
Jiahong Lu ◽  
Yitao Wang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Ethanol Extract ◽  
Inflammatory Factor ◽  
Potential Mechanism ◽  
Active Components ◽  
New Agents ◽  
Scientific Support ◽  
Active Substances

Luohuazizhu suppository is a Traditional Chinese Medicine used in clinic to treat cervicitis, which is prepared from Callicarpa nudiflora Hook. et Arn (C. nudiflora), an herbal Chinese medicine named Luohuazizhu. This study aimed to figure out the active constituents of C. nudiflora and the potential mechanism for its anti-cervicitis effect. The ethanol extract in C. nudiflora (CNE) and the different fractions of CNE extracted by petroleum ether (CNE-p), dichloromethane (CNE-d), and n-butanol (CNE-b) were tested in vivo for their anti-cervicitis effects. Then the isolated compounds from the CNE-p were tested in vitro for their anti-inflammatory activities. The results displayed that CNE-p, CNE-d, and CNE-b exhibited adequate anti-cervicitis effects, with CNE-p showing the highest efficacy. Further experiment demonstrated that CNE-p could significantly inhibit the expression of NLRP3 in vitro. Six diterpenoids obtained from the CNE-p showed the ability to regulate inflammatory factor levels in vitro. Among these compounds, compounds 1 (callicarpic acid A) and 2 (syn-3,4-seco-12S-hydroxy-15,16-epoxy-4(18),8(17),3(16),14(15)-labdatetraen-3-oic acid) were the most effective agents, and they also inhibited the expression level of NLRP3 in vitro. The results confirmed that C. nudiflora has significant anti-cervicitis effects and the diterpenoids were most likely to be its active components. These data provide scientific support for the clinic usage of Luohuazizhu suppository and the development of new agents in treating cervicitis.

Gene Expression Analysis to Investigate Biological Networks Underlying Nasal Inflammatory Dysfunctions Induced by Diesel Exhaust Particles Using an In Vivo System

2019 ◽  
Vol 129 (3) ◽  
pp. 245-255 ◽  
Author(s):  
Hyun Soo Kim ◽  
Byeong-Gon Kim ◽  
Sohyeon Park ◽  
Nahyun Kim ◽  
An-Soo Jang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Diesel Exhaust ◽  
Expression Profiles ◽  
Complex Mixture ◽  
Diesel Exhaust Particles ◽  
The Body ◽  
Exhaust Particles

Objectives: Diesel exhaust particles (DEP)s are notorious ambient pollutants composed of a complex mixture of a carbon core and diverse chemical irritants. Several studies have demonstrated significant relationships between DEP exposure and serious nasal inflammatory response in vitro, but available information regarding underlying networks in terms of gene expression changes has not sufficiently explained potential mechanisms of DEP-induced nasal damage, especially in vivo. Methods: In the present study, we identified DEP-induced gene expression profiles under short-term and long-term exposure, and identified signaling pathways based on microarray data for understanding effects of DEP exposure in the mouse nasal cavity. Results: Alteration in gene expression due to DEP exposure provokes an imbalance of the immune system via dysregulated inflammatory markers, predicted to disrupt protective responses against harmful exogenous substances in the body. Several candidate markers were identified after validation using qRT-PCR, including S100A9, CAMP, IL20, and S100A8. Conclusions: Although further mechanistic studies are required for verifying the utility of the potential biomarkers suggested by the present study, our in vivo results may provide meaningful suggestions for understanding the complex cellular signaling pathways involved in DEP-induced nasal damages.

Rat endogenous pyrogen and fever

1986 ◽  
Vol 250 (5) ◽  
pp. R776-R782
Author(s):  
A. Morimoto ◽  
T. Watanabe ◽  
T. Ono ◽  
Y. Sakata ◽  
N. Murakami
Keyword(s):  
White Blood Cells ◽  
The Body ◽  
Endogenous Pyrogen ◽  
Physiological Mechanisms ◽  
In Vitro Techniques ◽  
Time To Peak ◽  
Fever Onset ◽  
Maximum Elevation ◽  
Fever Response

Rat endogenous pyrogen (EP), prepared from the white blood cells of lipopolysaccharide-pretreated rats, produced a fever in both rabbits and rats. The effects of human, rabbit, and rat EP on the body temperatures of rabbits and rats were investigated to clarify differences in the febrile response to each kind of EP. The latency to fever onset and the time to peak fever induced by rat EP in rabbits and rats were significantly greater than those induced by human and rabbit EP. The maximum elevation of the body temperature induced by rat EP in both animals was almost identical to that induced by human and rabbit EP. In a comparison of the febrile responses to various EPs between rabbits and rats, the latency to fever onset, the time to peak, and the maximum elevation of fever in rats were approximately half those observed for rabbits. Furthermore, the threshold dosage to induce a fever response in rats was greater than that necessary for rabbits. It is concluded that rat EP could be obtained by in vitro techniques and that rats have the physiological mechanisms to develop a fever through production of EP.

scholarly journals Network pharmacology, molecular docking, and experimental study for the mechanisms of Qishen Yiqi Pills against Cardiovascular Diseases

2021 ◽  
Author(s):  
Jie-wen Zhao ◽  
Hai-dong Liu ◽  
Ming-yin Man ◽  
Lv-ya Wang ◽  
Ning Li ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cardiovascular Diseases ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Literature Mining ◽  
Therapeutic Effects ◽  
Active Components

Abstract Background Qishen Yiqi Pills (QSYQP) is a traditional Chinese compound recipe. However, our understanding of its mechanism has been hindered due to the complexity of its components and targets. In this work, the network pharmacology-based approaches were used to explore QSYQP’s pharmacological mechanism on treating cardiovascular diseases (CVD). Results From ETCM and TCM MESH databases we collected QSYQP’s 333 active components and their 674 putative targets. We constructed the sub-network influence by CVD genes and found that 40% QSYQP targets appeared in 20 modules, in which QSYQP’s targets and CVD genes co-existed as hub nodes in the sub-network. Functional enrichment analysis suggested that the 42 key targets were mainly expressed in platelets, blood vessels, cardiomyocytes, and other tissues. The main signaling pathways regulated and controlled by the key targets were inflammation, immunity, blood coagulation and energy metabolism. Network and pathway analysis identified 7 key targets, which were regulated by 7 compounds of QSYQP. 26 of the 42 important targets, including the 7 key targets were verified by literature mining. Twelve pairs of interactions between key targets and QSYQP’s compounds were validated by molecular docking. Further validation experiments suggested that QSYQP suppressed H/R induced apoptosis and cytoskeleton disruption of cardiomyocytes. Western blotting showed that the expression of cardiovascular diseases-related genes including ACTC1, FoxO1 and DIAPH1 was significantly decreased by establishing the hypoxia-reoxygenation model in vitro, while the protein expression of experimental group was significantly increased by adding QSYQP or its ingredients. Conclusion These results indicated the correlation of QSYQP treatment to the therapeutic effects of CVD. At the molecular level, this study revealed the multicomponent and multitargeting mechanisms of QSYQP in the regulation and treatment of cardiovascular diseases, potentially providing a reference for the further utilization of QSYQP.

scholarly journals Network Pharmacology/Metabolomics-Based Validation of AMPK and PI3K/AKT Signaling Pathway as a Central Role of Shengqi Fuzheng Injection Regulation of Mitochondrial Dysfunction in Cancer-Related Fatigue

2021 ◽  
Vol 2021 ◽  
pp. 1-23
Author(s):  
Wei Guo ◽  
Shan Liu ◽  
Xinting Zheng ◽  
Zhiwei Xiao ◽  
Hanrui Chen ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Muscle Cell ◽  
Herbal Medicines ◽  
Enrichment Analysis ◽  
Akt Signaling ◽  
Network Pharmacology ◽  
Cancer Therapies ◽  
Cancer Related Fatigue ◽  
Associated Proteins

Chinese herbal medicines have multiple targets and properties, and their use in multidisciplinary cancer therapies has consequently received increasing attention. Here, we have investigated the possible active ingredients associated with cancer-related fatigue (CRF) in the Shengqi Fuzheng Injection (SFI). In vitro cell models were used to measure the regulation effects of SFI on CRF. Metabolomic analysis was used to identify the potential genes and pathways in C2C12 mouse myoblasts treated with SFI, and the interaction of compounds and CRF targets was predicted using network pharmacology and molecular docking analyses. The putative pathways were further verified using immuno-blotting assays. The results showed that SFI significantly inhibited muscle cell apoptosis and increased the mitochondrial membrane potential of muscle cells. The network pharmacology analysis results identified 36 candidate compounds, and 244 potential targets were yielded by SFI, and they shared 10 key targets associated with cancer-related fatigue. According to the enrichment analysis and experimental validation, SFI might ameliorate muscle cell mitochondrial function by activating AMPK and inhibiting the PI3K/Akt signaling pathways, and the expression changes of mitochondrial metabolic enzymes MnSOD and apoptosis-associated proteins Bax and Bcl-2 were also triggered. The functions and mechanisms of SFI in anticancer-related fatigue were found here to be at least partly due to the targeting of the AMPK and PI3K/Akt signaling pathways, and this has highlighted new potential applications for network pharmacology when researching Chinese Medicines.

scholarly journals Identification on the potential mechanism of Radix pueraria on colon cancer based on network pharmacology

2021 ◽  
Author(s):  
Yi Li ◽  
Chunli Zhang ◽  
Xiaohan Ma ◽  
Liuqing Yang ◽  
Huijun Ren
Keyword(s):  
Colon Cancer ◽  
Chinese Medicine ◽  
Target Genes ◽  
Enrichment Analysis ◽  
In Vivo Studies ◽  
Network Pharmacology ◽  
Biological Mechanism ◽  
Active Components

Abstract Radix Puerariae (RP), a dry root of the Pueraria lobata (Willd.) Ohwi, is used to treat a variety of diseases, including cancer. Several in vitro and in vivo studies have demonstrated the efficacy of RP in the treatment of colon cancer (CC). However, the biological mechanism of RP in the treatment of colon cancer remains unclear. In this study, the active component of RP and its potential molecular mechanism against CC were studied by network pharmacology and enrichment analysis. The methods adopted included screening of active ingredients of Chinese medicine, prediction of target genes of Chinese medicine and disease, construction of protein interaction network, and GO and KEGG Enrichment Analysis. Finally, the results of network pharmacology were further validated by molecular docking experiments and cell experiments. 8 active constituents and 14 potential protein targets were screened from RP, including EGFR, JAK2 and SRC. The biological mechanism of RP against CC was analyzed by studying the relationship between active components, targets, and enrichment pathway. This provides a basis for understanding the clinical application of RP in CC.

scholarly journals Potential function and molecular mechanism of circRNAs involved in idiopathic pulmonary fibrosis

2020 ◽  
Author(s):  
Fangwei Li ◽  
Hong Wang ◽  
Hongyan Tao ◽  
Fanqi Wu ◽  
Dan Wang ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Molecular Mechanism ◽  
Target Genes ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Circular Rnas

Abstract Background: Recent studies have found a regulatory role of circular RNAs (circRNAs) in the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, the function and underlying molecular mechanism of circRNAs involved in IPF are uncertain and incomplete. This study aimed to further provide some critical information for the circRNA function in IPF using bioinformatic analysis. Methods: We searched in the NCBI (National Center for Biotechnology Information) Gene Expression Omnibus (GEO) database to find the circRNA expression profiles of human IPF. The microarray data GSE102660 was obtained and differentially expressed circRNAs were identified through R software. Results: 6 significantly up-regulated and 13 significantly down-regulated circRNAs were identified involved in the pathogenesis of IPF. The binding sites of miRNAs for each differentially expressed circRNA were also predicted and circRNA-miRNA-mRNA networks were constructed for the most up-regulated hsa_circ_0004099 and down-regulated hsa_circ_0029633. In addition, GO and KEGG enrichment analysis revealed the molecular function and enriched pathways of the target genes of circRNAs in IPF.Conclusion: These findings suggest that candidate circRNAs might serve an important role in the pathogenesis of IPF. Therefore, these circRNAs might be potential biomarkers for diagnosis and promising targets for treatment of IPF, which still need further verification in vivo and in vitro.

scholarly journals NOD-like receptors mediate inflammatory lung injury during plateau hypoxia exposure

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Haiyan Wang ◽  
Xue Lin ◽  
Xiaoyan Pu
Keyword(s):  
Lung Injury ◽  
Signaling Pathways ◽  
P38 Mapk ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
The Body ◽  
Inflammatory Factors ◽  
Hypoxia Exposure ◽  
Tnf Α ◽  
Mapk Signaling Pathways

Abstract Background The lung is an important target organ for hypoxia treatment, and hypoxia can induce several diseases in the body. Methods We performed transcriptome sequencing for the lungs of rats exposed to plateau hypoxia at 0 day and 28 days. Sequencing libraries were constructed, and enrichment analysis of the differentially expressed genes (DEGs) was implemented using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, experimental validation was executed by quantitative real-time PCR (qRT-PCR) and western blot. Results The results showed that the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) signaling pathway that was involved in immunity may play a crucial function in lung injury caused by plateau hypoxia. And the expressions of NOD1, NOD2, IL-1β, TNF-α, IL-6, and IL-18 were higher at 28 days of exposure to plateau hypoxia than that at 0 day. Similarly, CARD9, MYD88, p38 MAPK, and NF-κB p65, which are related to the NF-κB and MAPK signaling pathways, also demonstrated increased expression at 28 days exposure to plateau hypoxia than at 0 day. Conclusions Our study suggested that the NF­κBp65 and p38 MAPK signaling pathways may be activated in the lungs of rats during plateau hypoxia. Upregulated expression of NF­κBp65 and p38 MAPK can promote the transcription of downstream inflammatory factors, thereby aggravating the occurrence and development of lung tissue remodeling.

scholarly journals Berbamine Exerts Anti-Inflammatory Effects via Inhibition of NF-κB and MAPK Signaling Pathways

2017 ◽  
Vol 41 (6) ◽  
pp. 2307-2318 ◽  
Author(s):  
Xiao-Jian Jia ◽  
Xi Li ◽  
Feng Wang ◽  
Han-Qing Liu ◽  
Da-Jun Zhang
Keyword(s):  
Signaling Pathways ◽  
Mapk Signaling ◽  
Inflammatory Factor ◽  
Anti Inflammatory ◽  
Underlying Mechanisms ◽  
Peritonitis Model ◽  
Mapk Signaling Pathways ◽  
Superoxide Release

Background/Aims: This study aimed to investigate the anti-inflammatory activity of Berbamine (BER), a bisbenzylisoquinoline alkaloid extracted from Berberis amurensis (Xiao Bo An), and the underlying mechanisms. Methods: Macrophages and neutrophils were treated with BER in vitro and stimulated with LPS and fMLP. The effects of BER on the expression of pro-inflammatory mediators in macrophages were evaluated with quantitative RT-PCR and ELISA. The effects of BER on the activation and superoxide release of neutrophils were determined with flow cytometry and WST-1 reduction test. The inhibitory effects of BER on the activation of signaling pathways related to inflammatory response in macrophages were evaluated by western blot analysis. In addition, a mouse peritonitis model was made by peritoneal injection of thioglycollate medium and anti-inflammatory effects of BER were investigated in vivo by quantitative analysis of pro-inflammatory factor production and leukocyte exudation. Results: BER significantly inhibited inflammatory factor expression by LPS-stimulated macrophages and suppressed activation and superoxide release of fMLP-stimulated neutrophils. In the mouse peritonitis model, BER significantly inhibited the activation of macrophages and exudation of neutrophils. According to analysis, BER significantly suppressed phosphorylation of NF-κB and MAPK (JNK and ERK1/2) signaling pathways in LPS-stimulated macrophages. Conclusions: Collectively, data from this study suggest that BER has anti-inflammatory potential, which is effected via inhibition of NF-κB and MAPK signaling pathways, and thus holds promise for treatment of inflammatory disease.

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