scholarly journals Network Pharmacology for Analyzing the Key Targets and Potential Mechanism of Wogonin in Gliomas

2021 ◽  
Vol 12 ◽  
Author(s):  
Zaizhong Wang ◽  
Lulu Cheng ◽  
Zhigang Shang ◽  
Zhihui Li ◽  
Yuping Zhao ◽  
...  
Keyword(s):  
Target Genes ◽  
Network Pharmacology ◽  
Control Group ◽  
Volatile Components ◽  
Active Components ◽  
Necrosis Factor Alpha ◽  
Regulatory Pathways ◽  
Factor Alpha ◽  
Dose Dependent ◽  
Necrosis Factor

Objective: To analyze the key targets and potential mechanisms underlying the volatile components of Scutellaria baicalensis Georgi acting on gliomas through network pharmacology combined with biological experiments.Methods: We have extracted the volatile components of Scutellaria baicalensis by gas chromatography-mass spectrometry (GC-MS) and determined the active components related to the onset and development of gliomas by combining the results with the data from the Traditional Chinese Medicine Systems Pharmacology database. We screened the same targets for the extracted active components and gliomas through network pharmacology and then constructed a protein-protein interaction network. Using a Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we analyzed the protein effects and regulatory pathways of the common targets. Lastly, we employed ELISA and Western blot in verifying the key targets in the regulatory pathway.Results: We ultimately determined that the active component in S. baicalensis Georgi related to the onset and development of gliomas was Wogonin. The results of the network pharmacology revealed 85 targets for glioma and Wogonin. We used gene ontology to analyze these target genes and found that they involved 30 functions, such as phosphatidylinositol phosphokinase activation, while the KEGG analysis showed that there were 10 regulatory pathways involved. Through the following analysis, we found that most of the key target genes are distributed in the PI3K-Akt and interleukin 17 signaling pathways. We then cultured U251 glioma cells for the experiments. Compared with the control group, no significant change was noted in the caspase-3 expression; however, cleaved caspase-3 expression increased significantly and was dose-dependent on Wogonin. The expression of Bad and Bcl-2 with 25 μM of Wogonin has remained unchanged, but when the Wogonin dose was increased to 100 μM, the expression of Bad and Bcl-2 was noted to change significantly (Bad was significantly upregulated, while Bcl-2 was significantly downregulated) and was dose-dependent on Wogonin. The ELISA results showed that, compared with the control group, the secretion of tumor necrosis factor alpha, IL-1β, and IL-6 decreased as the Wogonin concentration increased. Tumor necrosis factor alpha downregulation had no significant dose-dependent effect on Wogonin, the inhibitory effect of 25 μM of Wogonin on IL-6 was not significant, and IL-1β downregulation had a significant dose-dependent effect on Wogonin.Conclusion: Wogonin might promote the apoptosis of glioma cells by upregulating proapoptotic factors, downregulating antiapoptotic factors, and inhibiting the inflammatory response, thereby inhibiting glioma progression.

scholarly journals Identification of Tumor Necrosis Factor-Alpha (TNF-α) Inhibitor in Rheumatoid Arthritis Using Network Pharmacology and Molecular Docking

2021 ◽  
Vol 12 ◽  
Author(s):  
Liang Liang Bai ◽  
Hao Chen ◽  
Peng Zhou ◽  
Jun Yu
Keyword(s):  
Molecular Docking ◽  
Signaling Pathway ◽  
Target Genes ◽  
Network Pharmacology ◽  
Active Ingredients ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Receptor Signaling Pathway ◽  
Factor Alpha ◽  
Necrosis Factor

Background: This study aimed to investigate the molecular mechanism of Radix Paeoniae Alba (white peony, WP) in treating immune inflammatory diseases of rheumatoid arthritis (RA) and tumor necrosis factor-alpha (TNF-α) inhibitors (TNFis) by using network pharmacology and molecular docking.Methods: In this study, the ingredient of WP and the potential inflammatory targets of RA were obtained from the Traditional Chinese Medicine Systematic Pharmacology Database, GeneCard, and OMIM databases, respectively. The establishment of the RA–WP-potential inflammatory target gene interaction network was accomplished using the STRING database. Network maps of the WP–RA-potential inflammatory target gene network were constructed using Cytoscape software. Gene ontology (GO) and the biological pathway (KEGG) enrichment analyses were used to further explore the RA mechanism and therapeutic effects of WP. Molecular docking technology was used to analyze the optimal effective components from WP for docking with TNF-α.Results: Thirteen active ingredients and 71 target genes were screened from WP, and 49 of the target genes intersected with RA target inflammatory genes and were considered potential therapeutic targets. Network pharmacological analysis showed that the WP active ingredients such as mairin, DPHCD, (+)-catechin, beta-sitosterol, paeoniflorin, sitosterol, and kaempferol showed better correlation with RA inflammatory target genes such as PGR, PTGS1, PTGS2, NR3C2, TNFSF15, and CHRM2, respectively. The immune-inflammatory signaling pathways of the active ingredients for the treatment of RA are the TNF-α signaling pathway, Toll-like receptor signaling pathway, cell apoptosis, interleukin-17 signaling pathway, C-type lectin receptor signaling pathway, mitogen-associated protein kinase, etc. Molecular docking results suggested that mairin was the most appropriate natural TNFis.Conclusion: Our findings provide an essential role and basis for further immune-inflammatory studies into the molecular mechanisms of WP and TNFis development in RA.

scholarly journals Identification of Tumor Necrosis Factor-Alpha (Tnf-α) Inhibitor in Rheumatoid Arthritis Using Network Pharmacology and Molecular Docking

2021 ◽  
Author(s):  
Jun Yu ◽  
Peng Zhou
Keyword(s):  
Molecular Docking ◽  
Signaling Pathway ◽  
Target Genes ◽  
Network Pharmacology ◽  
Active Ingredients ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Receptor Signaling Pathway ◽  
Factor Alpha ◽  
Necrosis Factor

Abstract Background: This study aimed to investigate the molecular mechanism of Radix Paeoniae Alba (White peony, WP) in treating rheumatoid arthritis (RA) and tumor necrosis factor-alpha (TNF-α) inhibitor (TNFi) by using network pharmacology and molecular docking. Methods: In this study, the ingredient of WP and the potential targets of RA were obtained from the Traditional Chinese Medicine Systematic Pharmacology Database, GeneCard and OMIM databases, respectively. Establishment of RA-WP potential target genes interaction network using STRING database. Network maps of WP-RA-potential target genes network was constructed using Cytoscape software. gene ontology (GO), and biological pathway (KEGG) pathway enrichment analysis were used to further explore the RA mechanism and therapeutic effects of WP. Using molecular docking technology to analyze the optimal effective components from WP to docking with TNF-α. Results: 13 active ingredients and 71 target genes were screened from WP, 49 of which intersect with RA target genes and are considered as potential therapeutic targets.Network pharmacological analysis showed that the WP active ingredients of mairin, DPHCD, (+)-catechin, beta-sitosterol, paeoniflorin, sitosterol, and kaempferol showed better correlation with RA target genes such as PGR, PTGS1, PTGS2, NR3C2, TNFSF15, CHRM2. The signaling pathways of the active ingredients for the treatment of RA are TNF-α signaling pathway, toll-like receptor signaling pathway, cell apoptosis, interleukin-17 signaling pathway, C-type lectin receptor signaling pathway, mitogen-associated-protein kinase, etc. Molecular docking results suggest that mairin was the most appropriate natural TNFi.Conclusions: Our findings provide the essential role and basis, for further studies into the molecular mechanisms of WP and TNFi development in RA.

Leukogram and cortisol parameters in Swiss mice experimentally infected with Angiostrongylus costaricensis

2021 ◽  
Vol 95 ◽  
Author(s):  
E. Benvegnú ◽  
C.C. Hermes ◽  
J.A. Guizzo ◽  
S.M. Soares ◽  
M.M. Costa ◽  
...  
Keyword(s):  
Cytokine Profile ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Swiss Mice ◽  
Hypochromic Anaemia ◽  
Third Stage ◽  
Factor Alpha ◽  
Cortisol Levels ◽  
Necrosis Factor

Abstract This study describes changes in haematological parameters, cytokine profile, histopathology and cortisol levels in Swiss mice experimentally infected with Angiostrongylus costaricensis. Twenty-eight Swiss mice were divided into two groups (G1 and G2) of 14 animals each. In each group, eight animals were infected orally with ten third-stage larvae of A. costaricensis and six were used as a control group. The mice of groups G1 and G2 were sacrificed 14 and 24 days after infection, respectively. Samples were collected for histopathological and haematological analyses and determination of the cytokine profile and cortisol levels. Granulomatous reaction, eosinophilic infiltrate and vasculitis in the intestinal tract, pancreas, liver and spleen were observed with varying intensity in infected animals. Our results showed that the mice developed normocytic and hypochromic anaemia, and that the histopathological lesions caused by the experimental infection influenced increases in cortisol, neutrophil and monocyte levels. In addition to this, we detected increased interleukin-6 and tumour necrosis factor alpha levels in the infected animals.

scholarly journals EKSPRESI Tumor Necrosis Factor alpha (TNF-α) DAN Transforming growth factors beta (TGF-β) PADA PERIODONTITIS APIKALIS KRONIS AKIBAT INDUKSI Enterococcus faecalis PADA TIKUS WISTAR

2019 ◽  
Vol 7 (2) ◽  
pp. 66
Author(s):  
Richard Fritzgerald ◽  
Cecilia Lunardhi ◽  
Ruslan Effendy ◽  
Tamara Yuanita
Keyword(s):  
Tissue Damage ◽  
Treated Group ◽  
Positive Control ◽  
Negative Control ◽  
Control Group ◽  
Transforming Growth Factors ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

Background. Root canal treatment is a main role in decreasing infection from root canal and pulp. The main cause of periapical damage mostly are bacteries. E.faecalis is a bactery that is found as an etiology of endodontic treatment failure. Cell wall of this bacteria is containing Lipoteichoic acid (LTA). LTA can penetrate into the periradicular tissue, act as endotoxin in host and cause periradicular inflammation then lead to bone destruction. LTA stimulates immunology reaction that produce Tumor Necrosis Factor alpha (TNF-α) and Transforming growth factors beta (TGF-ß). TNF-α is a main mediator and also have an important role in inflamation response otherwise TGF-ß is working as a multifunction  regulator of cell growth and differentiation during reforming and remodelling.  Purpose. The aim of this study is to know about the expression of TNF-α and TGF-ß during the periapical tissue damage due to induction of E.faecalis. Method. This study used laboratory experimental with the post test only control group design. A total of 30 male rats were randomly divided into 3 main groups, Group A (control negative) : normal tooth. Group B (control positive) : every tooth was induced only by sterile BHI-b. Group C (treated group) : every tooth  was induced by 10 μl BHI-b E.faecalis ATCC212(106 CFU). The animals were sacrificed 21 days later and prepared for histological examination of tissue damage, then we did the immunohistochemistry  followed by calculation on the light microscope. Result. The analysis revealed that the expression of TNF-α at treated group are higher than negative control and positive control but the expression of  TGF-ß at treated group are higher than the negative control group but lower than positive control. Conclusion. From this study we know that the expression of TNF-α and TGF-ß are changing during the periapical tissue damage that induced by E.faecalis.

scholarly journals Assessment Of Tumour Necrosis Factor-Alpha (Tnf- Α) And Creatinine Levels In Echis Ocellatus Bite Victims In Jos Metropolis, Nigeria

2016 ◽  
Vol 12 (21) ◽  
pp. 70
Author(s):  
Manafa P.O. ◽  
Osmond E.O. ◽  
Onyenekwe C.C. ◽  
Okeke C.O. ◽  
Chukwuma G.O. ◽  
...  
Keyword(s):  
Serum Level ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Alpha ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Significant Difference ◽  
Factor Alpha ◽  
The Mean ◽  
Necrosis Factor

This study was designed to assess tumour necrosis factor-alpha and creatinine levels in Echis ocellatus bite victims. A total of 50 subjects were recruited. Out of this number, 40 were victims of E. ocellatus bite and the remaining 10 were non-victims of snake bite who served as the control group. Blood samples were collected from the victims within 24 hours of the snake bite and EchiTAb-G antivenom administered within the same period. Another batch of blood sample was collected 48 hours post-administration of the anti-venom. Tumour necrosis factor-alpha (TNF-alpha) levels were estimated by the Enzyme Linked Immunosorbent Assay technique while creatinine levels were determined using kinetic-spectrophotometric procedure. The mean serum levels of tumour necrosis factor-alpha and creatinine were significantly increased in E. ocellatus bite victims compared with the control group (P<0.05). Furthermore, the mean serum level of TNFalpha was significantly lower in E. ocellatus bite victims, post-administration of anti-venom, compared with the pre-administration of anti-venom (P<0.05). In contrast, no significant difference was observed in the mean serum level of creatinine in E. ocellatus bite victims, post-administration of anti-venom, compared with the pre-administration of anti-venom (P>0.05). Moreover, the mean serum level of creatinine was found to be significantly increased in E. ocellatus bite victims, post-administration of anti-venom, compared with the control group (P<0.05), while no significant difference was observed in the mean serum level of tumour necrosis factor-alpha in E. ocellatus bite victims, post-administration of anti-venom, compared with the control group(P>0.05). A positive correlation existed between tumour necrosis factor-alpha and creatinine levels in E. ocellatus bite subjects (r= 0.782). Echis ocellatus bite is a risk factor for renal damage indicated by an elevated serum creatinine, thus health authorities should make EchiTAb-G anti-venom freely available in health facilities and administered as quickly as possible to reduce the risk of renal damage in Echis ocellatus bite-prone areas.

scholarly journals Temperature regulates NF-κB dynamics and function through timing of A20 transcription

2018 ◽  
Vol 115 (22) ◽  
pp. E5243-E5249 ◽  
Author(s):  
C. V. Harper ◽  
D. J. Woodcock ◽  
C. Lam ◽  
M. Garcia-Albornoz ◽  
A. Adamson ◽  
...  
Keyword(s):  
Cell Fate ◽  
Target Genes ◽  
Early Response ◽  
Strong Temperature Dependence ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Multidimensional Information ◽  
Dynamics And Function ◽  
And Function ◽  
Necrosis Factor

NF-κB signaling plays a pivotal role in control of the inflammatory response. We investigated how the dynamics and function of NF-κB were affected by temperature within the mammalian physiological range (34 °C to 40 °C). An increase in temperature led to an increase in NF-κB nuclear/cytoplasmic oscillation frequency following Tumor Necrosis Factor alpha (TNFα) stimulation. Mathematical modeling suggested that this temperature sensitivity might be due to an A20-dependent mechanism, and A20 silencing removed the sensitivity to increased temperature. The timing of the early response of a key set of NF-κB target genes showed strong temperature dependence. The cytokine-induced expression of many (but not all) later genes was insensitive to temperature change (suggesting that they might be functionally temperature-compensated). Moreover, a set of temperature- and TNFα-regulated genes were implicated in NF-κB cross-talk with key cell-fate–controlling pathways. In conclusion, NF-κB dynamics and target gene expression are modulated by temperature and can accurately transmit multidimensional information to control inflammation.

Serum tumor necrosis factor-alpha does not mediate endotoxin-induced myocardial depression in rabbits

1996 ◽  
Vol 270 (2) ◽  
pp. H485-H491 ◽  
Author(s):  
Y. Nishikawa ◽  
J. Mathison ◽  
W. Y. Lew
Keyword(s):  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Control Group ◽  
Lv Function ◽  
Necrosis Factor Alpha ◽  
Systolic Volume ◽  
End Diastolic Volume ◽  
End Systolic Volume ◽  
Factor Alpha ◽  
Necrosis Factor

Tumor necrosis factor-alpha (TNF-alpha) is an endogenous mediator for several effects of endotoxin. To evaluate whether TNF-alpha mediates endotoxin-induced left ventricular (LV) dysfunction, we measured LV function (sonomicrometers) and serum TNF-alpha (cytolytic assay) in anesthetized rabbits given endotoxin (100 micrograms/kg iv). In the control group (n = 8), systolic depression (defined by a > 10% increase in end-systolic volume at a matched end-systolic pressure) developed in four rabbits and diastolic dilation (> 10% increase in end-diastolic volume at a matched end-diastolic pressure) developed in three rabbits. Neither the increase in end-systolic volume nor the increase in end-diastolic volume correlated with the increase in TNF-alpha, which reached a peak of 2,875 +/- 762 U/ml. In a second group of rabbits (n = 7), a goat polyclonal anti-rabbit antibody to TNF-alpha was given 30-60 min before endotoxin. Anti-TNF-alpha antibody alone did not alter LV function. Although the TNF-alpha response to endotoxin was effectively blunted (peak TNF-alpha remained < 100 U/ml), all seven rabbits developed systolic depression (P = 0.08 compared with control group) and diastolic dilation (P = 0.03). We conclude that serum TNF-alpha does not mediate endotoxin-induced LV systolic depression or diastolic dilation in this model.

scholarly journals Bikunin Inhibits Lipopolysaccharide-Induced Tumor Necrosis Factor Alpha Induction in Macrophages

2004 ◽  
Vol 11 (6) ◽  
pp. 1140-1147 ◽  
Author(s):  
Hidenori Matsuzaki ◽  
Hiroshi Kobayashi ◽  
Tatsuo Yagyu ◽  
Kiyoshi Wakahara ◽  
Toshiharu Kondo ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Dose Dependent ◽  
Necrosis Factor

ABSTRACT Bikunin, a Kunitz-type protease inhibitor, exhibits anti-inflammatory activity in protection against cancer and inflammation. To investigate the molecular mechanism of this inhibition, we analyzed the effect of bikunin on tumor necrosis factor alpha (TNF-α) production in human peripheral mononuclear cells stimulated by lipopolysaccharide (LPS), an inflammatory inducer. Here, we show the following results. (i) LPS induced TNF-α expression in time- and dose-dependent manners through phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase pathways. (ii) Bikunin inhibits LPS-induced up-regulation of TNF-α protein expression in a dose-dependent manner, reaching 60% inhibition at the highest doses of bikunin tested (5.0 μM). (iii) Inhibition by bikunin of TNF-α induction correlates with the suppressive capacity of ERK1/2, JNK, and p38 signaling pathways, implicating repressions of at least three different signals in the inhibition. (iv) Bikunin blocks the induction of TNF-α target molecules interleukin-1β (IL-1β) and IL-6 proteins. (v) Bikunin is functional in vivo, and this glycoprotein blocks systemic TNF-α release in mice challenged with LPS. (vi) Finally, bikunin can prevent LPS-induced lethality. In conclusion, bikunin significantly inhibits LPS-induced TNF-α production, suggesting a mechanism of anti-inflammation by bikunin through control of cytokine induction during inflammation. Bikunin might be a candidate for the treatment of inflammation, including septic shock.

scholarly journals Tumor Necrosis Factor-Alpha in Peripical Tissue Exudates of Teeth with Apical Periodontitis

2007 ◽  
Vol 2007 ◽  
pp. 1-4 ◽  
Author(s):  
Sonja Pezelj-Ribaric ◽  
Karolina Magašic ◽  
Jelena Prpic ◽  
Ivana Miletic ◽  
Zoran Karlovic
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Control Group ◽  
Radiological Findings ◽  
Necrosis Factor Alpha ◽  
Root Canals ◽  
Factor Alpha ◽  
Radiological Changes ◽  
Necrosis Factor

Aim.The aim of this study was to determine tumor necrosis factor-alpha (TNF-α) levels in periapical exudates and to evaluate their relationship with radiological findings.Methodology.Periapical exudates were collected from root canals of 60 single-rooted teeth using absorbent paper points. TNF-αlevels were determined by enzyme-linked immunosorbent assays. The samples were divided into three groups according to the periapical radiolucent area.Results.Nonparametric Kruskal-Wallis test revealed significant differences between TNF-αconcentrations in control group (40,57±28, 15 pg/mL) and group with larger radiolucent areas (2365,79±582, 95 pg/mL), as well as between control and canals with small radiolucent areas (507,66±278, 97) (P<.05).Conclusions.The levels of TNF-αincrease significantly in teeth with periapical pathosis, from smaller to bigger lesions. This research and its results have shown that objective analysis of the TNF-αlevels enables establishment of a relationship between different concentrations of TNF-αand different radiological changes.

scholarly journals Depletion of Complement Enhances the Clearance of Brucella abortus in Mice

2018 ◽  
Vol 86 (10) ◽  
Author(s):  
Gabriela González-Espinoza ◽  
Elías Barquero-Calvo ◽  
Esteban Lizano-González ◽  
Alejandro Alfaro-Alarcón ◽  
Berny Arias-Gómez ◽  
...  
Keyword(s):  
Immune System ◽  
Brucella Abortus ◽  
Innate Immune ◽  
Control Group ◽  
Bacterial Disease ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Brucellosis is a bacterial disease of animals and humans. Brucella abortus barely activates the innate immune system at the onset of infection, and this bacterium is resistant to the microbicidal action of complement. Since complement stands as the first line of defense during bacterial invasions, we explored the role of complement in B. abortus infections. Brucella abortus-infected mice depleted of complement with cobra venom factor (CVF) showed the same survival rate as mice in the control group. The complement-depleted mice readily eliminated B. abortus from the spleen and did so more efficiently than the infected controls after 7 days of infection. The levels of the proinflammatory cytokines tumor necrosis factor alpha and interleukin-6 (IL-6) remained within background levels in complement-depleted B. abortus-infected mice. In contrast, the levels of the immune activator cytokine gamma interferon and the regulatory cytokine IL-10 were significantly increased. No significant histopathological changes in the liver and spleen were observed between the complement-depleted B. abortus-infected mice and the corresponding controls. The action exerted by Brucella on the immune system in the absence of complement may correspond to a broader phenomenon that involves several components of innate immunity.

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