A new mixed-ligand Ni(II) complex: crystal structure, protective and anti-inflammatory activity of its nanoparticles on acute viral myocarditis by reducing the release of inflammatory cytokines TNF-α and IL‐1β

Concentrations of eight different cytokines and the level of expression of CD86 and CD163 macrophages were studied in peritoneal fluid in women with endometriosis. It was found that the concentration of both inflammatory (IL-6, IL-8, TNF-α) and anti-inflammatory cytokines (IL-4) as well as the level of macrophage expression of the proinflammatory marker CD86 and anti-inflammatory marker CD163 increased in women with mild external genital endometriosis (1-2 stage), and did not differ from the control group in women with severe endometriosis (3-4 stage). The content of IL-2, IL-10, CM-CSF and IFN-γ in the peritoneal fluid of women with endometriosis did not differ significantly from the control group. The results of the study indicate that the development of external genital endometriosis may be based on insufficient both inflammatory and anti-inflammatory activity of macrophages in the peritoneal fluid.

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

PeerJ ◽

10.7717/peerj.9533 ◽

2020 ◽

Vol 8 ◽

pp. e9533 ◽

Cited By ~ 1

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.

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

European Journal of Inflammation ◽

10.1177/20587392211000573 ◽

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.

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

10.21203/rs.3.rs-27002/v2 ◽

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.

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Mixed-ligand CuII complexes with Me5dien and heterocyclic acids. Synthesis, antioxidant and anti-inflammatory activity. Crystal structure of [Cu(Me5dien)(tpaa)(H2O)](ClO4)

Journal of Molecular Structure ◽

10.1016/j.molstruc.2007.02.021 ◽

2008 ◽

Vol 872 (2-3) ◽

pp. 73-80 ◽

Cited By ~ 24

Author(s):

Panayiotis C. Christidis ◽

Zacharias D. Georgousis ◽

Dimitra Hadjipavlou-Litina ◽

Christos A. Bolos

Keyword(s):

Crystal Structure ◽

Mixed Ligand ◽

Inflammatory Activity ◽

Anti Inflammatory

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Capsaicin affects macrophage anti-inflammatory activity via the MAPK and NF-κB signaling pathways

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000721 ◽

2021 ◽

Author(s):

Jingshuang Li ◽

Hui Wang ◽

Lili Zhang ◽

Ni An ◽

Wan Ni ◽

...

Keyword(s):

Signaling Pathways ◽

Inflammatory Cytokines ◽

Inflammatory Diseases ◽

Underlying Mechanism ◽

Peritoneal Macrophages ◽

The Body ◽

Inflammatory Activity ◽

Inflammatory Factors ◽

Tnf Α ◽

Anti Inflammatory

Abstract. Capsaicin, the main constituent in chili, is an extremely spicy vanillin alkaloid and is found in several Capsicum species in China. Traditionally, it has been used to treat inflammatory diseases such as allergic rhinitis, neuralgia after shingles, refractory female urethral syndrome, spontaneous recalcitrant anal pruritus, and solid tumors. Constant stimulation of the body by inflammatory factors can lead to chronic inflammation. Capsaicin possesses anti-inflammatory activity; however, the underlying mechanism is unknown. We investigated the effect of capsaicin on the secretion of macrophage inflammatory factors in a lipopolysaccharide-induced inflammation model using 56 healthy, SPF grade, BALB/c mice. To this end, mice peritoneal macrophages were isolated and stimulated with lipopolysaccharide (1 μg/mL) and capsaicin (25, 50, 75, or 100 μg/mL) for 24 h. At all concentrations tested, capsaicin significantly promoted the phagocytosis of neutral red dye by macrophages. Furthermore, the gene expression and secretion of inflammatory cytokines significantly increased after induction with lipopolysaccharide (P<0.01); the interleukin (IL)-6 level was 204 μg/mL, tumor necrosis factor (TNF)-α level was 860 μg/mL, and nitric oxide (NO) level was 19.8 μg/mL. However, the treatment with capsaicin reduced their levels (P<0.01) and protein expression of lipopolysaccharide-induced extracellular signal-related kinase 1/2 and p65 (P<0.05). Overall, capsaicin reduced the secretion of inflammatory cytokines (P<0.01), interleukins, TNF-α (P<0.01), and NO by inhibiting the nuclear factor-kappa B and microtubule-associated protein kinase signaling pathways, and thereby reduced lipopolysaccharide-induced inflammatory response in macrophages.

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Mixed-Ligand Mononuclear Copper(II) Complex: Crystal Structure and Anticancer Activity

ChemMedChem ◽

10.1002/cmdc.201402060 ◽

2014 ◽

pp. n/a-n/a ◽

Cited By ~ 2

Author(s):

Xiu-Ying Qin ◽

Ya-Nan Liu ◽

Qian-Qian Yu ◽

Li-Cong Yang ◽

Ying Liu ◽

...

Keyword(s):

Crystal Structure ◽

Anticancer Activity ◽

Mixed Ligand ◽

Complex Crystal Structure ◽

Complex Crystal

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

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20212930 ◽

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.

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

10.21203/rs.3.rs-27002/v1 ◽

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.

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