Ginsenoside Rb1 Mitigates Escherichia coli Lipopolysaccharide-Induced Endometritis through TLR4-Mediated NF-κB Pathway

Endometritis is the inflammatory response of the endometrial lining of the uterus and is associated with low conception rates, early embryonic mortality, and prolonged inter-calving intervals, and thus poses huge economic losses to the dairy industry worldwide. Ginsenoside Rb1 (GnRb1) is a natural compound obtained from the roots of Panax ginseng, having several pharmacological and biological properties. However, the anti-inflammatory properties of GnRb1 in lipopolysaccharide (LPS)-challenged endometritis through the TLR4-mediated NF-κB signaling pathway has not yet been researched. This study was planned to evaluate the mechanisms of how GnRb1 rescues LPS-induced endometritis. In the present research, histopathological findings revealed that GnRb1 ameliorated LPS-triggered uterine injury. The ELISA and RT-qPCR assay findings indicated that GnRb1 suppressed the expression level of pro-inflammatory molecules (TNF-α, IL-1β and IL-6) and boosted the level of anti-inflammatory (IL-10) cytokine. Furthermore, the molecular study suggested that GnRb1 attenuated TLR4-mediated NF-κB signaling. The results demonstrated the therapeutic efficacy of GnRb1 in the mouse model of LPS-triggered endometritis via the inhibition of the TLR4-associated NF-κB pathway. Taken together, this study provides a baseline for the protective effect of GnRb1 to treat endometritis in both humans and animals.

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Angelica Polysaccharide Attenuates LPS-Induced Inflammation Response of Primary Dairy Cow Claw Dermal Cells Via NF-κB and MAPK Signaling Pathways

10.21203/rs.3.rs-152594/v1 ◽

2021 ◽

Author(s):

Mengyue Tian ◽

Ke Li ◽

Ruonan Liu ◽

Jinliang Du ◽

Dongmin Zou ◽

...

Keyword(s):

Signaling Pathways ◽

Dairy Cow ◽

Colorimetric Method ◽

Mapk Signaling ◽

Economic Losses ◽

Tnf Α ◽

Inflammatory Chemokines ◽

Anti Inflammatory ◽

Dermal Cells ◽

Mapk Signaling Pathways

Abstract Background: Laminitis, an inflammation of the claw laminae, is one of the major causes of bovine lameness, which can lead to enormous economic losses and animal welfare problems in dairy farms. Angelica polysaccharide (AP) is proved to possess anti-inflammatory properties. But the role of AP on inflammatory response of the claw dermal cells has not been reported. The aim of this study was to investigate the anti-inflammatory effects of AP on lipopolysaccharide (LPS)-induced primary claw dermal cells of dairy cow and clarify the potential mechanisms. In the current research, the primary claw dermal cells were exposed to gradient concentrations of AP (10, 50, 100 µg/mL) in the presence of 10 µg/mL LPS. The levels of cytokines and nitric oxide (NO) were detected with ELISA and Griess colorimetric method. The mRNA expressions of TLR4, MyD88 and chemokines were measured with qPCR. The activation of NF-κB and MAPK signaling pathways was detected with western blotting.Results: The results indicated that AP reduced the production of inflammatory mediators (TNF-α, IL-1β, IL-6 and NO), downregulated the mRNA expression of TLR4, MyD88 and some pro-inflammatory chemokines (CCL2, CCL20, CXCL2, CXCL8, CXCL10), and suppressed the NF-κB and MAPK signaling pathways evidenced by inhibition of the phosphorylation of IκBα, p65 and ERK, JNK, p38.Conclusions: Our results demonstrated that AP may exert its anti-inflammatory effects on claw dermal cells of dairy cow by regulating the NF-κB and MAPK signaling pathways.

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Angelica polysaccharide attenuates LPS-induced inflammation response of primary dairy cow claw dermal cells via NF-κB and MAPK signaling pathways

BMC Veterinary Research ◽

10.1186/s12917-021-02952-4 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Mengyue Tian ◽

Ke Li ◽

Ruonan Liu ◽

Jinliang Du ◽

Dongmin Zou ◽

...

Keyword(s):

Signaling Pathways ◽

Dairy Cow ◽

Colorimetric Method ◽

Mapk Signaling ◽

Economic Losses ◽

Tnf Α ◽

Inflammatory Chemokines ◽

Anti Inflammatory ◽

Dermal Cells ◽

Mapk Signaling Pathways

Abstract Background Laminitis, an inflammation of the claw laminae, is one of the major causes of bovine lameness, which can lead to enormous economic losses and animal welfare problems in dairy farms. Angelica polysaccharide (AP) is proved to possess anti-inflammatory properties. But the role of AP on inflammatory response of the claw dermal cells has not been reported. The aim of this study was to investigate the anti-inflammatory effects of AP on lipopolysaccharide (LPS)-induced primary claw dermal cells of dairy cow and clarify the potential mechanisms. In the current research, the primary claw dermal cells were exposed to gradient concentrations of AP (10, 50, 100 µg/mL) in the presence of 10 µg/mL LPS. The levels of cytokines and nitric oxide (NO) were detected with ELISA and Griess colorimetric method. The mRNA expressions of TLR4, MyD88 and chemokines were measured with qPCR. The activation of NF-κB and MAPK signaling pathways was detected with western blotting. Results The results indicated that AP reduced the production of inflammatory mediators (TNF-α, IL-1β, IL-6 and NO), downregulated the mRNA expression of TLR4, MyD88 and some pro-inflammatory chemokines (CCL2, CCL20, CXCL2, CXCL8, CXCL10), and suppressed the NF-κB and MAPK signaling pathways evidenced by inhibition of the phosphorylation of IκBα, p65 and ERK, JNK, p38. Conclusions Our results demonstrated that AP may exert its anti-inflammatory effects on claw dermal cells of dairy cow by regulating the NF-κB and MAPK signaling pathways.

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Anti-Inflammatory Effects of the Fraction from the Leaves of Pyrus pyrifolia on LPS-Stimulated THP-1 Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/4946241 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Gilhye Lee ◽

Jung-Hee Kim ◽

Hyun-Jae Jang ◽

Ji-Won Park ◽

Jae-Won Lee ◽

...

Keyword(s):

East Asia ◽

Biological Activities ◽

Pyrus Pyrifolia ◽

Rna Expression ◽

Inflammatory Drug ◽

Pyrus Pyrifolia Nakai ◽

Tnf Α ◽

Bioactive Fraction ◽

Anti Inflammatory ◽

Inflammatory Molecules

Pyrus pyrifolia Nakai (P. pyrifolia) has been traditionally used in East Asia to treat diseases such as phlegm, cough, hangover, and fever. However, there is no investigation that evaluates the biological activities of the leaves of P. pyrifolia. This study aims at describing the anti-inflammatory effects of PP, a bioactive fraction from the leaves of P. pyrifolia, in lipopolysaccharide (LPS)-stimulated THP-1 cells. Initially, PP decreased the protein and RNA expression of TNF-α, MCP-1, IL-8, and IL-6 induced by LPS. Moreover, PP attenuated the phosphorylation of p38, JNK, and ERK. In addition, after stimulation with LPS, the degradation of IκB-α was suppressed by PP, and the phosphorylation of IκB-α and p65 was suppressed by PP. Additionally, PP increased HO-1, which controls the production of inflammatory molecules, by activating Nrf2. These results indicated that PP could be used as an anti-inflammatory drug to promote wellness.

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The Role of TNF-α induced MSCs on Suppressive Inflammation by Increasing TGF-β and IL-10

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2018.404 ◽

2018 ◽

Vol 6 (10) ◽

pp. 1779-1783 ◽

Cited By ~ 18

Author(s):

Agung Putra ◽

Fatkhan Baitul Ridwan ◽

Allisha Irwaniyanti Putridewi ◽

Azizah Retno Kustiyah ◽

Ken Wirastuti ◽

...

Keyword(s):

Study Groups ◽

Significant Negative Correlation ◽

Control Group ◽

Control Group Design ◽

Tnf Α ◽

Post Test ◽

Anti Inflammatory ◽

Suppressive Phenotype ◽

Inflammatory Milieu ◽

Inflammatory Molecules

BACKGROUND: Mesenchymal stem cells (MSCs) may serve as immunoregulators by producing various anti-inflammatory molecules. Under sufficient level of TNF-α, MSCs become activated and adopt immune-suppressive phenotype (MSCs type-2) by releasing various anti-inflammatory molecule including TGF-β and IL-10. However, the ability of MSC itself to produce IL-10 under TNF-α stimulation and the correlation of TGF-β production of MSCs to IL-10 level remains to be elucidated. AIM: In this study, MSCs were activated with various TNF-α doses to determine the increase of IL-10 and TGF-β level as well as its correlation. MATERIAL AND METHODS: This study used post-test only control group design, by using 3 study groups, consist of 1 control (C) and 2 treatments (T) (TNF-α = 5 and 10 ng/mL) with triplicate induced in MSC for 24 hours, then the levels of IL-10 and TGF-β were measured by using ELISA assay. RESULTS: The results of this study showed a significant increase of TGF-β and IL-10 levels (p < 0.05) at TNF-α 5 and 10 ng/mL dose of TNF-α. Moreover, there was a significant negative correlation between TGF-β and IL-10 level on 5 and 10 ng/mL dose TNF-α treatment. CONCLUSION: Based on our study, we conclude that the 5 ng/mL dose of TNF-α is a sufficient dose for MSCs to suppress the inflammatory milieu. The higher increase of TGF beta is due to the controlled inflammation by IL-10.

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Tangeretin Inhibits Oxidative Stress and Inflammation via Upregulating Nrf-2 Signaling Pathway in Collagen-Induced Arthritic Rats

Pharmacology ◽

10.1159/000501163 ◽

2019 ◽

Vol 104 (3-4) ◽

pp. 187-195 ◽

Cited By ~ 7

Author(s):

Xing Li ◽

Peigen Xie ◽

Yu Hou ◽

Shudong Chen ◽

Peiheng He ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

Chinese Herb ◽

Biological Properties ◽

Therapeutic Effects ◽

Protective Effects ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Ifn Γ ◽

Anti Inflammatory

Background/Aims: Tangeretin (TAN), a major phytochemical in tangerine peels and an important Chinese herb, has multiple biological properties, especially antioxidative and anti-inflammatory effects. However, the mechanisms remain unclear. Based on these findings, the aim of the present study was to assess the antioxidant and anti-inflammatory properties of TAN in bovine type II collagen-induced arthritis rats. Methods: TAN (50 mg/kg) was given orally once daily for 14 days. The effects of treatment were evaluated by biochemical assay (articular elastase, myeloperoxidase, end products of lipid peroxidation [MDA], antioxidant enzyme, such as superoxide dismutase, catalase, glutathione), nitric oxide, and inflammatory cytokines (interleukin-1β [IL-1β], IL-10, tumor necrosis factor-alpha [TNF-α], interferon-γ [IFN-γ], and prostaglandin E2 [PGE2]). The protective effects of TAN against rheumatoid arthritis (RA) were evident from the decrease in arthritis scoring. Furthermore, the Nrf-2 signaling pathway was assessed to illustrate the molecular mechanism. Results: TAN had therapeutic effects on RA by decreasing the oxidative stress damage and regulating inflammatory cytokine expression, including suppression of the accumulation of MDA products, decreasing the IL-1β, TNF-α, IFN-γ, and PGE2 levels, enhancing the IL-10 and the activity of antioxidant enzymes, which was through upregulating Nrf-2 signaling pathway. Conclusion: TAN might have potential as a therapeutic agent for the treatment of RA.

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Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation

Pharmaceuticals ◽

10.3390/ph14060588 ◽

2021 ◽

Vol 14 (6) ◽

pp. 588

Author(s):

Chi-Han Huang ◽

Shu-Chi Wang ◽

I-Chen Chen ◽

Yi-Ting Chen ◽

Po-Len Liu ◽

...

Keyword(s):

Nlrp3 Inflammasome ◽

Ex Vivo ◽

Biological Properties ◽

Inflammasome Activation ◽

Activated Macrophages ◽

Nlrp3 Inflammasome Activation ◽

Tnf Α ◽

Anti Inflammatory

Piplartine (or Piperlongumine) is a natural alkaloid isolated from Piper longum L., which has been proposed to exhibit various biological properties such as anti-inflammatory effects; however, the effect of piplartine on sepsis has not been examined. This study was performed to examine the anti-inflammatory activities of piplartine in vitro, ex vivo and in vivo using murine J774A.1 macrophage cell line, peritoneal macrophages, bone marrow-derived macrophages and an animal sepsis model. The results demonstrated that piplartine suppresses iNOS and COX-2 expression, reduces PGE2, TNF-α and IL-6 production, decreases the phosphorylation of MAPKs and NF-κB and attenuates NF-κB activity by LPS-activated macrophages. Piplartine also inhibits IL-1β production and suppresses NLRP3 inflammasome activation by LPS/ATP- and LPS/nigericin-activated macrophages. Moreover, piplartine reduces the production of nitric oxide (NO) and TNF-α, IL-6 and IL-1β, decreases LPS-induced tissue damage, attenuates infiltration of inflammatory cells and enhances the survival rate. Collectively, these results demonstrate piplartine exhibits anti-inflammatory activities in LPS-induced inflammation and sepsis and suggest that piplartine might have benefits for sepsis treatment.

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Protective Effects of Lentinan Against Lipopolysaccharide-Induced Mastitis in Mice

Frontiers in Pharmacology ◽

10.3389/fphar.2021.755768 ◽

2021 ◽

Vol 12 ◽

Author(s):

Huifang Yin ◽

Guanhong Xue ◽

Ailing Dai ◽

Haichong Wu

Keyword(s):

Mammary Epithelial ◽

Economic Losses ◽

Dependent Manner ◽

Protective Effects ◽

Dairy Farmers ◽

Worldwide Production ◽

Tnf Α ◽

Anti Inflammatory

Mastitis is a worldwide production disease in dairy cows, which mainly affects milk yield, causing huge economic losses to dairy farmers. Lentinan is a kind of polysaccharide extracted from Lentinus edodes, which has no toxicity and possesses various pharmacological activities including antibacterial and immunomodulatory effects. Therefore, the anti-inflammatory function of lentinan on LPS-stimulated mastitis was carried out, and the mechanism involved was explored. In vivo, lentinan greatly reduced LPS-stimulated pathological injury, myeloperoxidase (MPO) activity, and the proinflammatory factor production (TNF-α and IL-1β) in mice. Further study was performed to determine the activation of the Wnt/β-catenin pathway during LPS stimulation. These results suggested that LPS-induced activation of the Wnt/β-catenin pathway was suppressed by lentinan administration. In vitro, we observed that the mouse mammary epithelial cell (mMEC) viability was not affected by lentinan treatment. As expected, LPS increased the TNF-α and IL-1β protein secretion and the activation of the Wnt/β-catenin pathway that was inhibited by lentinan administration in a dose-dependent manner in mMECs. Conclusively, lentinan exerts the anti-inflammatory function in LPS-stimulated mastitis via inhibiting the activation of the Wnt/β-catenin pathway. Thus, the results of our study also gave an insight that lentinan may serve as a potential treatment for mastitis.

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Lysozyme-Induced Transcriptional Regulation of TNF-α Pathway Genes in Cells of the Monocyte Lineage

International Journal of Molecular Sciences ◽

10.3390/ijms20215502 ◽

2019 ◽

Vol 20 (21) ◽

pp. 5502 ◽

Cited By ~ 1

Author(s):

Alberta Bergamo ◽

Marco Gerdol ◽

Alberto Pallavicini ◽

Samuele Greco ◽

Isabelle Schepens ◽

...

Keyword(s):

Expression Profiles ◽

Gene Expression Profiles ◽

Transcriptome Profiling ◽

Biological Properties ◽

Broad Perspective ◽

Tnf Α ◽

Transcriptional Modulation ◽

Anti Inflammatory ◽

Whole Transcriptome

Lysozyme is one of the most important anti-bacterial effectors in the innate immune system of animals. Besides its direct antibacterial enzymatic activity, lysozyme displays other biological properties, pointing toward a significant anti-inflammatory effect, many aspects of which are still elusive. Here we investigate the perturbation of gene expression profiles induced by lysozyme in a monocyte cell line in vitro considering a perspective as broad as the whole transcriptome profiling. The results of the RNA-seq experiment show that lysozyme induces transcriptional modulation of the TNF-α/IL-1β pathway genes in U937 monocytes. The analysis of transcriptomic profiles with IPA® identified a simple but robust molecular network of genes, in which the regulation trends are fully consistent with the anti-inflammatory activity of lysozyme. This study provides the first evidence in support of the anti-inflammatory action of lysozyme on the basis of transcriptomic regulation data resulting from the broad perspective of a whole-transcriptome profiling. Such important effects can be achieved with the supplementation of relatively low concentrations of lysozyme, for a short time of exposure. These new insights allow the potential of lysozyme in pharmacological applications to be better exploited.

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Diverse chemical and biological potentials of various pyridazine and pyridazinone derivatives

10.31221/osf.io/n5xvt ◽

2019 ◽

Author(s):

Chem Int

Keyword(s):

Heterocyclic Compounds ◽

Biological Activities ◽

Wide Spectrum ◽

Biological Properties ◽

Industrial Chemical ◽

Anti Inflammatory ◽

Pyridazinone Derivatives

A series of heterocyclic compounds incorporating pyridazine moiety were for diverse biological activities. Pyridazines and pyridazinones derivatives showed wide spectrum of biological activities such as vasodialator, cardiotonic, anticonvulsant, antihypertensive, antimicrobial, anti-inflammatory, analgesic, anti-feedant, herbicidal, and various other biological, agrochemical and industrial chemical activities. The results illustrated that the synthesized pyridazine/pyridazine compounds have diverse and significant biological activities. Mechanistic insights into the biological properties of pyridazinone derivatives and various synthetic techniques used for their synthesis are also described.

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Pentoxifylline and Oxypurinol: Potential Drugs to Prevent the “Cytokine Release (Storm) Syndrome” Caused by SARS-CoV-2?

Current Pharmaceutical Design ◽

10.2174/1381612826666200811180232 ◽

2020 ◽

Vol 26 (35) ◽

pp. 4515-4521

Author(s):

Francisco J. López-Iranzo ◽

Ana M. López-Rodas ◽

Luis Franco ◽

Gerardo López-Rodas

Keyword(s):

Lung Parenchyma ◽

Interstitial Tissue ◽

Cytokine Release ◽

Phase I Clinical Trials ◽

Infected People ◽

Tnf Α ◽

Transient Loss ◽

Anti Inflammatory ◽

And Control ◽

Inflammatory Action

Background: COVID-19, caused by SARS-CoV-2, is a potentially lethal, rapidly-expanding pandemic and many efforts are being carried out worldwide to understand and control the disease. COVID-19 patients may display a cytokine release syndrome, which causes severe lung inflammation, leading, in many instances, to death. Objective: This paper is intended to explore the possibilities of controlling the COVID-19-associated hyperinflammation by using licensed drugs with anti-inflammatory effects. Hypothesis: We have previously described that pentoxifylline alone, or in combination with oxypurinol, reduces the systemic inflammation caused by experimentally-induced pancreatitis in rats. Pentoxifylline is an inhibitor of TNF-α production and oxypurinol inhibits xanthine oxidase. TNF-α, in turn, activates other inflammatory genes such as Nos2, Icam or IL-6, which regulate migration and infiltration of neutrophils into the pulmonary interstitial tissue, causing injury to the lung parenchyma. In acute pancreatitis, the anti-inflammatory action of pentoxifylline seems to be mediated by the prevention of the rapid and presumably transient loss of PP2A activity. This may also occur in the hyperinflammatory -cytokine releasing phase- of SARS-CoV-2 infection. Therefore, it may be hypothesized that early treatment of COVID-19 patients with pentoxifylline, alone or in combination with oxypurinol, would prevent the potentially lethal acute respiratory distress syndrome. Conclusion: Pentoxifylline and oxypurinol are licensed drugs used for diseases other than COVID-19 and, therefore, phase I clinical trials would not be necessary for the administration to SARS-CoV-2- infected people. It would be worth investigating their potential effects against the hyperinflammatory response to SARS-CoV-2 infection.

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