scholarly journals Anemoside B4 protects against Klebsiella pneumoniae- and influenza virus FM1-induced pneumonia via the TLR4/Myd88 signaling pathway in mice

2020 ◽  
Author(s):  
Jia He ◽  
Renyikun Yuan ◽  
Xiaolan Cui ◽  
Yushun Cui ◽  
Shan Han ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Molecular Docking ◽  
Signaling Pathway ◽  
Therapeutic Effect ◽  
Inflammatory Cytokines ◽  
Inflammatory Activity ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Myd88 Signaling ◽  
Pro Inflammatory Cytokines

Abstract Background Pneumonia refers to the inflammation of the terminal airway, alveoli and pulmonary interstitium, which can be caused by pathogenic microorganisms, physical and chemical factors, immune damage, and drugs. Anemoside B4, the major ingredient of Pulsatilla chinensis (Bunge) Regel, exhibited anti-inflammatory activity. However, the therapeutic effect of anemoside B4 on pneumonia has not been unraveled. This study aims to investigate that anemoside B4 attenuates the inflammatory responses in Klebsiella pneumonia (KP)- and influenza virus FM1 (FM1)-induced pneumonia mice model.Methods The network pharmacology and molecular docking assays were employed to predict the targets of anemoside B4’s treatment of pneumonia. Two models (bacterial KP-infected mice and virus FM1-infected mice) were employed in our study. BALB/c mice were divided into six groups: control, model group (KP- induced pneumonia or FM1-induced pneumonia), anemoside B4 (B4)-treated group (2.5, 5, 10 mg/kg), and positive drug group (Ribavirin or Ceftriaxone Sodium Injection). Blood samples were collected for hematology analysis. The effects of B4 on inflammation-associated mediators were investigated by Enzyme-linked immunosorbent assay (ELISA). Proteins expression was quantified by western blotting.Results The network results indicated that many pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) participated in anemoside B4’s anti-inflammatory activity. The counts of neutrophil (NEU) and white blood cell (WBC), the level of myeloperoxidase (MPO), and the release of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 increased by KP or FM1 infection, which were reversed by anemoside B4. In addition, anemoside B4 significantly suppressed the FM1-induced expression of Toll-like receptor 4 (TLR4), myeloid differential protein-88 (MyD88), and myeloid differentiation protein-2 (MD-2), which were further validated by molecular docking data that anemoside B4 bound to bioactive sites of TLR4. Therefore, anemoside B4 exhibited a significant therapeutic effect on pneumonia via the TLR4/MyD88 pathway.Conclusion Our findings demonstrated that anemoside B4 attenuates pneumonia via the TLR4/Myd88 signaling pathway, suggesting that anemoside B4 is a promising therapeutic candidate for bacterial-infected or viral-infected pneumonia.

scholarly journals Anemoside B4 protects against Klebsiella pneumoniae- and influenza virus FM1-induced pneumonia via the TLR4/Myd88 signaling pathway in mice

2020 ◽  
Author(s):  
Jia He ◽  
Renyikun Yuan ◽  
Xiaolan Cui ◽  
Yushun Cui ◽  
Shan Han ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Molecular Docking ◽  
Signaling Pathway ◽  
Therapeutic Effect ◽  
Inflammatory Cytokines ◽  
Inflammatory Activity ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Myd88 Signaling ◽  
Pro Inflammatory Cytokines

Abstract Background: Pneumonia refers to the inflammation of the terminal airway, alveoli and pulmonary interstitium, which can be caused by pathogenic microorganisms, physical and chemical factors, immune damage, and drugs. Anemoside B4, the major ingredient of Pulsatilla chinensis (Bunge) Regel, exhibited anti-inflammatory activity. However, the therapeutic effect of anemoside B4 on pneumonia has not been unraveled. This study aims to investigate that anemoside B4 attenuates the inflammatory responses in Klebsiella pneumonia (KP)- and influenza virus FM1 (FM1)-induced pneumonia mice model.Methods: The network pharmacology and molecular docking assays were employed to predict the targets of anemoside B4’s treatment of pneumonia. Two models (bacterial KP-infected mice and virus FM1-infected mice) were employed in our study. BALB/c mice were divided into six groups: control, model group (KP- induced pneumonia or FM1-induced pneumonia), anemoside B4 (B4)-treated group (2.5, 5, 10 mg/kg), and positive drug group (Ribavirin or Ceftriaxone Sodium Injection). Blood samples were collected for hematology analysis. The effects of B4 on inflammation-associated mediators were investigated by Enzyme-linked immunosorbent assay (ELISA) and hematoxylin and eosin staining (HE) staining. Proteins expression was quantified by western blotting.Results: The network results indicated that many pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) participated in anemoside B4’s anti-inflammatory activity. The counts of neutrophil (NEU) and white blood cell (WBC), the level of myeloperoxidase (MPO), and the release of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 increased by KP or FM1 infection, which were reversed by anemoside B4. In addition, anemoside B4 significantly suppressed the FM1-induced expression of Toll-like receptor 4 (TLR4), myeloid differential protein-88 (MyD88), and myeloid differentiation protein-2 (MD-2), which were further validated by molecular docking data that anemoside B4 bound to bioactive sites of TLR4. Therefore, anemoside B4 exhibited a significant therapeutic effect on pneumonia via the TLR4/MyD88 pathway.Conclusion: Our findings demonstrated that anemoside B4 attenuates pneumonia via the TLR4/Myd88 signaling pathway, suggesting that anemoside B4 is a promising therapeutic candidate for bacterial-infected or viral-infected pneumonia.

scholarly journals Isoimperatorin exerts anti-inflammatory activity by targeting the LPS-TLR4/MD-2-NF-κB pathway

2021 ◽  
Vol 19 ◽  
pp. 205873922110005
Author(s):  
Guirong Chen ◽  
Yunong Liu ◽  
Yubin Xu ◽  
Mingbo Zhang ◽  
Song Guo ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Real Time ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Inflammatory Cytokines ◽  
Real Time Pcr ◽  
Inflammatory Responses ◽  
Inflammatory Activity ◽  
Tnf Α ◽  
Anti Inflammatory

Isoimperatorin (QHS) is a phytoconstituent found in the methanolic extracts obtained from the roots of Angelica dahurica, which contains anti-inflammatory, anti-bacterial, analgesic, anti-tumor, and vasodilatory activities. QHS possesses potent antagonistic activity against lipopolysaccharide (LPS)-induced inflammation; however, the mechanism of action remains unclear. In this study, we investigated the anti-inflammatory effect of QHS and explored the underlying mechanisms. The QHS was purchased from Jiangsu Yongjian Pharmaceutical Co., Ltd. (Jiangsu, China). We performed MTT assay, real-time PCR, ELISA, and western blotting experiments to assess the anti-inflammatory activity and the possible mechanism of QHS in vitro. Molecular docking was performed to study the binding of QHS and myeloid differentiation protein-2 (MD-2) and elucidate the possible anti-inflammatory mechanism. QHS had no significant effect on cell viability. Moreover, pre-treatment with QHS significantly decreased the release of inflammatory cytokines and mediators including NO, TNF-α, IL-6, and IL-1β. In addition, real-time PCR showed that QHS decreased the mRNA expressions of iNOS, COX-2 TNF-α, IL-6, and IL-1β. Western blotting indicated that QHS could inhibit the expression of the proteins associated with the LPS-TLR4/MD-2-NF-κB signaling pathway. Lastly, molecular docking revealed a possible binding mechanism between QHS and MD-2. QHS exhibited anti-inflammatory activity when combined with MD-2, regulating the LPS-TLR4/MD-2-NF-κB signaling pathway, and inhibiting the release and expression of inflammatory cytokines and mediators. Furthermore, QHS can be used as a potential TLR4 antagonist, which blocks MD-2 binding, for treating inflammatory responses induced by LPS.

scholarly journals Computational Identification of Potential Anti-Inflammatory Natural Compounds Targeting the p38 Mitogen-Activated Protein Kinase (MAPK): Implications for COVID-19-Induced Cytokine Storm

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 653
Author(s):  
Seth O. Asiedu ◽  
Samuel K. Kwofie ◽  
Emmanuel Broni ◽  
Michael D. Wilson
Keyword(s):  
Molecular Docking ◽  
P38 Mapk ◽  
Inflammatory Cytokines ◽  
Binding Energies ◽  
Mitogen Activated Protein Kinase ◽  
Inflammatory Activity ◽  
Computational Techniques ◽  
Cytokine Storm ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Severely ill coronavirus disease 2019 (COVID-19) patients show elevated concentrations of pro-inflammatory cytokines, a situation commonly known as a cytokine storm. The p38 MAPK receptor is considered a plausible therapeutic target because of its involvement in the platelet activation processes leading to inflammation. This study aimed to identify potential natural product-derived inhibitory molecules against the p38α MAPK receptor to mitigate the eliciting of pro-inflammatory cytokines using computational techniques. The 3D X-ray structure of the receptor with PDB ID 3ZS5 was energy minimized using GROMACS and used for molecular docking via AutoDock Vina. The molecular docking was validated with an acceptable area under the curve (AUC) of 0.704, which was computed from the receiver operating characteristic (ROC) curve. A compendium of 38,271 natural products originating from Africa and China together with eleven known p38 MAPK inhibitors were screened against the receptor. Four potential lead compounds ZINC1691180, ZINC5519433, ZINC4520996 and ZINC5733756 were identified. The compounds formed strong intermolecular bonds with critical residues Val38, Ala51, Lys53, Thr106, Leu108, Met109 and Phe169. Additionally, they exhibited appreciably low binding energies which were corroborated via molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) calculations. The compounds were also predicted to have plausible pharmacological profiles with insignificant toxicity. The molecules were also predicted to be anti-inflammatory, kinase inhibitors, antiviral, platelet aggregation inhibitors, and immunosuppressive, with probable activity (Pa) greater than probable inactivity (Pi). ZINC5733756 is structurally similar to estradiol with a Tanimoto coefficient value of 0.73, which exhibits anti-inflammatory activity by targeting the activation of Nrf2. Similarly, ZINC1691180 has been reported to elicit anti-inflammatory activity in vitro. The compounds may serve as scaffolds for the design of potential biotherapeutic molecules against the cytokine storm associated with COVID-19.

scholarly journals Small molecule therapeutics for COVID-19: repurposing of inhaled furosemide

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9533 ◽  
Author(s):  
Zhiyu Wang ◽  
Yanfei Wang ◽  
Prachi Vilekar ◽  
Seung-Pil Yang ◽  
Mayuri Gupta ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Small Molecule ◽  
Inflammatory Activity ◽  
Health Concern ◽  
Docking Simulations ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Novel Coronavirus ◽  
Pro Inflammatory Cytokines

The novel coronavirus SARS-CoV-2 has become a global health concern. The morbidity and mortality of the potentially lethal infection caused by this virus arise from the initial viral infection and the subsequent host inflammatory response. The latter may lead to excessive release of pro-inflammatory cytokines, IL-6 and IL-8, as well as TNF-α ultimately culminating in hypercytokinemia (“cytokine storm”). To address this immuno-inflammatory pathogenesis, multiple clinical trials have been proposed to evaluate anti-inflammatory biologic therapies targeting specific cytokines. However, despite the obvious clinical utility of such biologics, their specific applicability to COVID-19 has multiple drawbacks, including they target only one of the multiple cytokines involved in COVID-19’s immunopathy. Therefore, we set out to identify a small molecule with broad-spectrum anti-inflammatory mechanism of action targeting multiple cytokines of innate immunity. In this study, a library of small molecules endogenous to the human body was assembled, subjected to in silico molecular docking simulations and a focused in vitro screen to identify anti-pro-inflammatory activity via interleukin inhibition. This has enabled us to identify the loop diuretic furosemide as a candidate molecule. To pre-clinically evaluate furosemide as a putative COVID-19 therapeutic, we studied its anti-inflammatory activity on RAW264.7, THP-1 and SIM-A9 cell lines stimulated by lipopolysaccharide (LPS). Upon treatment with furosemide, LPS-induced production of pro-inflammatory cytokines was reduced, indicating that furosemide suppresses the M1 polarization, including IL-6 and TNF-α release. In addition, we found that furosemide promotes the production of anti-inflammatory cytokine products (IL-1RA, arginase), indicating M2 polarization. Accordingly, we conclude that furosemide is a reasonably potent inhibitor of IL-6 and TNF-α that is also safe, inexpensive and well-studied. Our pre-clinical data suggest that it may be a candidate for repurposing as an inhaled therapy against COVID-19.

SYSTEM INFLAMMATORY RESPONSE AT THE EXACERBATION OF CHRONIC SIMPLE BRONCHITIS CAUSED BY INFLUENZA VIRUS B IN WOMEN IN THE FIRST TRIMESTER OF PREGNANCY

2016 ◽  
Vol 1 (60) ◽  
pp. 67-69
Author(s):  
Смирнова ◽  
Tatyana Smirnova ◽  
Резник ◽  
Vadim Reznik ◽  
Одиреев ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Inflammatory Cytokines ◽  
First Trimester ◽  
Fourth Group ◽  
The Third ◽  
Early Stages ◽  
Tnf Α ◽  
Antibody Titers ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

The contents of anti-inflammatory and pro-inflammatory cytokines in 95 women in the first trimester of gestation were studied. The first (control) group included 25 women with physiologic course of pregnancy; the second group consisted of 25 patients with exacerbation of chronic simple bronchitis caused by influenza virus B (antibody titers were 1:16-1:64); the third group consisted of 24 pregnant women with exacerbation of chronic simple bronchitis under influenza virus В (antibody titers were 1:32-1:128); the fourth group consisted of 21 women with exacerbation of chronic simple bronchitis induced by influenza virus B (antibody titers were 1:64-1:256) at early stages of gestation. In the patients of the second group in comparison with the patients of the first group there was an increase of IL-4 till 19.7±2.17 pg/ml, of TNF-α till 33.4±3.09 pg/ml and of INF-γ till 30.9±2.64 pg/ml (in the control it was 12.9±1.16 pg/ml, р<0.01; 24.7±2.27 pg/ml, р<0.05 and 22.3±2.08 pg/ml, р<0.05, respectively). In the third group in comparison with the second group there was no growth of anti-inflammatory and pro-inflammatory cytokines. In the fourth group in comparison with the second group there was the biggest increase of IL-4 till 27.7±2.42 pg/ml (р<0.05), of TNF-α till 43.6±2.79 pg/ml (p<0.05) and of INF-γ till 40.7±2.96 pg/ml (p<0.05). This suggest the paramount importance of the growth of anti-virus antibodies titers in the pathogenesis of exacerbation of chronic simple bronchitis under influenza virus B in women at early stages of gestation.

scholarly journals Anti-inflammatory activity of methanolic extract of Ficus hispida dried fruit

2021 ◽  
Vol 10 (8) ◽  
pp. 997
Author(s):  
Asif Choudhury ◽  
Deepak Kumar Jha ◽  
U. Rajashekhar
Keyword(s):  
Inflammatory Cytokines ◽  
Methanolic Extract ◽  
Inflammatory Activity ◽  
Bioactive Metabolites ◽  
Paw Oedema ◽  
Tnf Α ◽  
Ficus Hispida ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Background: Natural products are a valuable resource of novel bioactive metabolites and these products exist in which the anti-inflammatory activity. The present investigation studies the in vivo and in vitro anti-inflammatory activity of methanolic extract of Ficus hispida in rat’s model.Methods: Plant material was extracted with methanol in a Soxhlet extraction apparatus. Indomethacin was used as a standard drug here, which is a known potent inhibitor of PG synthesis. The carrageenin and histamine induced paw oedema were selected to represent models of acute inflammations. The test compounds and standard drugs were administered orally. After 60 minutes paw oedema was induced by giving 0.1 ml of 1% Carrageenan and 0.1 % histamine by sub-plantar administration. Paw volume-Plethysmometer by mercury displacement method, before and after 1 hr to 4 hours of carrageenan and histamine administration. Performed MTT-based cytotoxicity assay of the Ficus hispida on the RAW264.7 cell line to determine the IC50 and calculate the pro-inflammatory cytokines viz, IL-6, IL-1β and TNF-α and compared to the LPS control.Results: The result obtained from the in-vivo study shows that the Ficus hispida has significant anti- inflammatory activity in a dose dependent manner. This effect is similar to that produced by NSAIDS such as Indomethacin. The concentrations of IL-6, IL-1β and TNF-α, secreted by the cells after challenging with bacterial LPS (2 µg/ml) and subsequent treatment with 50 µg Ficus hispida has been found to reduce the production of all the three pro-inflammatory cytokines viz, IL-6, IL-1β and TNF-α as compared to the LPS control. The activity, in fact, is comparable to the standard NSAID Indomethacin.Conclusions: All these findings and phytoconstituents present in the extract could be the possible chemicals involved in the prevention of inflammations.

Anti-inflammatory activity of emu oil-based nanofibrous scaffold through downregulation of IL-1, IL-6, and TNF-α pro-inflammatory cytokines

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Vahid Vahedian ◽  
Amirhooman Asadi ◽  
Parisa Esmaeili ◽  
Shahbaz Zamani ◽  
Reza Zamani ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
The Body ◽  
Nanofibrous Scaffold ◽  
Inflammatory Activity ◽  
Fibroblast Cells ◽  
Loss Of Function ◽  
Emu Oil ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

AbstractBackgroundInflammation is one of the most important responses of the body against infection or disease, and it protects tissues from injury; however, it causes redness, swelling, pain, fever and loss of function. The aim of this present study was to evaluate the anti-inflammatory activity of emu oil (Eu) formulated nanofibrous scaffold in HFFF2 fibroblast cells.Materials and methodsEu was formulated successfully in nanofibers through the electrospinning method. Besides, the morphological and structural properties of Eu nanofibres were evaluated using Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) was performed to evaluate the HFFF2 fibroblast cells’ viability. Also, real-time polymerase chain reaction (PCR) was used to evaluate the anti-inflammatory signaling pathway in treated HFFF2 cells with Eu nanofiber.ResultsOur study showed that the Eu nanofiber increased the viability of fibroblast HFFF2 cells (p < 0.05). Also, the expression of interleukin1 (IL1), IL6 and tumor necrosis factor- alpha (TNF-α) pro-inflammatory cytokines genes were significantly decreased in treated HFFF2 cells with Eu nanofiber (p < 0.05).ConclusionsIn conclusion, Eu nanofiber scaffold potentially can reduce the inflammation process through downregulation of IL-1, IL-6 and TNF-α cytokines.

scholarly journals Punicalagin Prevents Inflammation in LPS-Induced RAW264.7 Macrophages by Inhibiting FoxO3a/Autophagy Signaling Pathway

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2794 ◽  
Author(s):  
Cao ◽  
Chen ◽  
Ren ◽  
Zhang ◽  
Tan ◽  
...  
Keyword(s):  
Western Blot ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Inflammatory Responses ◽  
Raw264.7 Macrophages ◽  
Tnf Α ◽  
Autophagy Inhibition ◽  
Pro Inflammatory Cytokines

Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In this study, we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide (LPS) induced RAW264.7 macrophages and uncovered the underlying mechanisms. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration. We found that punicalagin inhibited NF-κB and MAPK activation in LPS-induced RAW264.7 macrophages. Western blot analysis revealed that punicalagin pre-treatment enhanced LC3II, p62 expression, and decreased Beclin1 expression in LPS-induced macrophages. MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis. In addition, our observations indicated that LPS-induced releases of NO, TNF-α, and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine, suggesting that autophagy inhibition participated in anti-inflammatory effect. We also found that punicalagin downregulated FoxO3a expression, resulting in autophagy inhibition. Overall these results suggested that punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway.

scholarly journals P0527AROLE OF PROMOTING INFLAMMATION OF KLF6 IN ACUTE KIDNEY INURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dan Li ◽  
Chenyu Li ◽  
Yan Xu
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tnf Α ◽  
Public Dataset ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine ◽  
Pro Inflammatory Cytokines

Abstract Background and Aims Acute kidney injury (AKI), commonly appeared in cardiac arrest, surgery and kidney transplantation which involved in ischemia-reperfusion (IR) injury of kidney. However, the mechanisms underlying inflammatory response in IR AKI is still unclear. Method Public dataset showed kruppel-like factor 6 (KLF6) was significantly highly expressed (P&lt;0.05) in AKI, implies KLF6 might be associated with AKI. To evaluate the mechanism of KLF6 on IR AKI, 30 rats were randomly divided into sham and IR group, and were sacrificed at 0 h, 3 h, 6 h, 12 h or 24 h after IR. Results The results showed KLF6 expression was peaking at 6 h after IR, and the expression of pro-inflammatory cytokines MCP-1 and TNF-α were increased both in serum and kidney tissues after IR, while anti-inflammatory cytokine IL-10 was decreased after IR. Furthermore, in vitro results showed KLF6 knock-down reduced the pro-inflammatory cytokines expression and increased the anti-inflammatory cytokines expression. Conclusion These results suggest that (1) KLF6 might be a novel biomarker for early diagnosis of AKI and (2) targeting KLF6 expression may offer novel strategies to protect kidneys from IR AKI Figure KLF6, AKI, Control Inflammation

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