Design of a 3D BMP-2-Delivering Tannylated PCL Scaffold and Its Anti-Oxidant, Anti-Inflammatory, and Osteogenic Effects In Vitro

In this study, a novel three-dimensional (3D) bone morphogenic protein-2 (BMP-2)-delivering tannylated polycaprolactone (PCL) (BMP-2/tannic acid (TA)/PCL) scaffold with anti-oxidant, anti-inflammatory, and osteogenic activities was fabricated via simple surface coating with TA, followed by the immobilization of BMP-2 on the TA-coated PCL scaffold. The BMP-2/TA/PCL scaffold showed controlled and sustained BMP-2 release. It effectively scavenged reactive oxygen species (ROS) in cells, and increased the proliferation of MC3T3-E1 cells pre-treated with hydrogen peroxide (H2O2). Additionally, the BMP-2/TA/PCL scaffold significantly suppressed the mRNA levels of pro-inflammatory cytokines, including matrix metalloproteinases-3 (MMP-3), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in lipopolysaccharide (LPS)-induced MC3T3-E1 cells. Furthermore, it showed outstanding enhancement of the osteogenic activity of MC3T3-E1 cells through increased alkaline phosphatase (ALP) activity and calcium deposition. Our findings demonstrated that the BMP-2/TA/PCL scaffold plays an important role in scavenging ROS, suppressing inflammatory response, and enhancing the osteogenic differentiation of cells.

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Accelerated Osteogenic Differentiation of MC3T3-E1 Cells by Lactoferrin-Conjugated Nanodiamonds through Enhanced Anti-Oxidant and Anti-Inflammatory Effects

Nanomaterials ◽

10.3390/nano10010050 ◽

2019 ◽

Vol 10 (1) ◽

pp. 50 ◽

Cited By ~ 2

Author(s):

Sung Eun Kim ◽

Somang Choi ◽

Jae-Young Hong ◽

Kyu-Sik Shim ◽

Tae-Hoon Kim ◽

...

Keyword(s):

Osteogenic Differentiation ◽

Calcium Deposition ◽

H2o2 Treatment ◽

Tnf Α ◽

Dichlorofluorescin Diacetate ◽

Anti Oxidant ◽

Factor Α ◽

Anti Inflammation ◽

Necrosis Factor

The purpose of this study was to investigate the effects of lactoferrin (LF)-conjugated nanodiamonds (NDs) in vitro on both anti-oxidant and anti-inflammation activity as well as osteogenic promotion. The application of LF-NDs resulted in sustained release of LF for up to 7 days. In vitro anti-oxidant analyses performed using Dichlorofluorescin diacetate (DCF-DA) assay and cell proliferation studies showed that LF (50 μg)-NDs effectively scavenged the reactive oxygen species (ROS) in MC3T3-E1 cells (osteoblast-like cells) after H2O2 treatment and increased proliferation of cells after H2O2 treatment. Treatment of lipopolysaccharide (LPS)-induced MC3T3-E1 cells with LF-NDs suppressed levels of pro-inflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). In addition, LF-NDs were associated with outstanding enhancement of osteogenic activity of MC3T3-E1 cells due to increased alkaline phosphatase (ALP) and calcium deposition. Our findings suggest that LF-NDs are an important substrate for alleviating ROS effects and inflammation, as well as promoting osteogenic differentiation of cells.

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Acyclic Triterpenoid Isolated from Alpinia katsumadai Alleviates Formalin-Induced Chronic Mouse Paw Inflammation by Inhibiting the Phosphorylation of ERK and NF-κB

Molecules ◽

10.3390/molecules25153345 ◽

2020 ◽

Vol 25 (15) ◽

pp. 3345 ◽

Cited By ~ 1

Author(s):

Hyung Jin Lim ◽

Seon Gyeong Bak ◽

Hee Ju Lim ◽

Seung Woong Lee ◽

Soyoung Lee ◽

...

Keyword(s):

Mouse Model ◽

Inflammatory Diseases ◽

Extracellular Signal ◽

Tnf Α ◽

J774 Cells ◽

Inflammatory Bowel ◽

Anti Inflammatory ◽

Factor Α ◽

Necrosis Factor

Chronic and excessive inflammation can destroy host organs and cause inflammatory diseases such as inflammatory bowel disease, asthma, and rheumatoid arthritis. In this study, we investigated the anti-inflammatory effects of Alpinia katsumadai seed-derived 2,3,5,22,23-pentahydroxy-2,6,10,15,19,23-hexamethyl-tetracosa-6,10,14,18-tetraene (PHT) using lipopolysaccharide (LPS)-stimulated J774 cells and a formalin-induced chronic paw inflammation mouse model. The in vitro results showed that PHT exhibited no cytotoxicity and decreased LPS-induced NO secretion. Additionally, PHT inhibited LPS-induced inducible NO synthase (iNOS) and cyclooxygenase 2 (COX2) protein expression. The quantitative real-time PCR results showed that PHT downregulated the gene expression of the proinflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6) but not tumor necrosis factor α (TNF-α). PHT inhibited the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB). In a mouse model, oral administration of 50 mg/kg PHT significantly alleviated both mouse paw thickness and volume. These results indicate that PHT has potential anti-inflammatory effects and should be considered a possible functional material.

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Fatsia polycarpa Triterpenoids and Acetylated Derivatives Thereof Inhibit Tumor Necrosis Factor-α-Induced Inflammation

Natural Product Communications ◽

10.1177/1934578x1701200907 ◽

2017 ◽

Vol 12 (9) ◽

pp. 1934578X1701200

Author(s):

Chang-Hung Chou ◽

Yan-Ting Lu ◽

Shi-Yie Cheng ◽

Hsueh-Ling Cheng

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Raw 264.7 Cells ◽

Induced Expression ◽

Tnf Α ◽

Anti Inflammatory ◽

Factor Α ◽

Necrosis Factor

Fatsia polycarpa Hayata is an evergreen shrub endemic to Taiwan and used locally to treat several inflammatory disorders. The crude extract of F. polycarpa has been proven to exhibit an anti-inflammatory effect in vitro and in vivo; however, which constituents of the extract confer the anti-inflammatory function remains unclear. Fatsicarpain D (Fat D) and fatsicarpain F (Fat F) are oleanane-type triterpenoids and two of the feature constituents of the F polycarpa extract. Ester substitution on C-3 has been proposed to enhance the activities of triterpenoids. Thus, this study compared and characterized the anti-inflammatory activities of Fat D, Fat F, and the C-3-acetylated derivatives thereof. These compounds were toxic to RAW 264.7 cells, but not to FL83B cells. The compounds dose-dependently inhibited tumor necrosis factor-α (TNF-α)-induced expression of inducible nitric oxide synthase in FL83B cells, with the IC50 values being Fat D 8.5 μM, acetylated Fat D 10.4 μM, acetylated Fat F 10.7 μM, and Fat F 27.4 μM, respectively. Thus, acetylation of C-3 improved the activity of Fat F. Moreover, the compounds suppressed TNF-α-induced expression of nuclear factor-κB (NF-κB) p65 subunit and protein tyrosine phosphatase-1B. Furthermore, they inhibited TNF-α-mediated activation of the inhibitor kappa B kinase (IKK), and that of the mitogen-activated protein kinases (MAPKs) extracellular-signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK), but promoted the activation of MAPK p38, which was found to be anti-inflammatory in certain cell types. Thus, Fat D and Fat F exhibited obvious anti-inflammatory activities in vitro and inhibited ERK, JNK, and the IKK/NF-κB pathway.

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Terpene Glycosides from Sanguisorba officinalis and Their Anti-Inflammatory Effects

Molecules ◽

10.3390/molecules24162906 ◽

2019 ◽

Vol 24 (16) ◽

pp. 2906 ◽

Cited By ~ 5

Author(s):

Da-Le Guo ◽

Jin-Feng Chen ◽

Lu Tan ◽

Meng-Ying Jin ◽

Feng Ju ◽

...

Keyword(s):

Tumor Necrosis ◽

High Resolution Mass Spectrometry ◽

Experimental Platform ◽

Tnf Α ◽

Anti Inflammatory ◽

Sanguisorba Officinalis ◽

Factor Α ◽

Necrosis Factor

Two new terpene glycosides (1–2) along with two known analogs (3–4) were obtained from the root of Sanguisorba officinalis, which is a common traditional Chinese medicine (TCM). Their structures were elucidated by nuclear magnetic resonance (NMR), electrospray ionization high resolution mass spectrometry (HRESIMS), and a hydrolysis reaction, as well as comparison of these data with the literature data. Compounds 1–4 exhibited anti-inflammatory properties in vitro by attenuating the production of inflammatory mediators, such as nitric oxide (NO) as well as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). An anti-inflammatory assay based on the zebrafish experimental platform indicated that compound 1 had good anti-inflammatory activity in vivo by not only regulating the distribution, but also by reducing the amount of the macrophages of the zebrafish exposed to copper sulfate.

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Anti-Inflammatory Effect of Simonsinol on Lipopolysaccharide Stimulated RAW264.7 Cells through Inactivation of NF-κB Signaling Pathway

Molecules ◽

10.3390/molecules25163573 ◽

2020 ◽

Vol 25 (16) ◽

pp. 3573

Author(s):

Lian-Chun Li ◽

Zheng-Hong Pan ◽

De-Sheng Ning ◽

Yu-Xia Fu

Keyword(s):

Nitric Oxide ◽

Signaling Pathway ◽

Morphological Changes ◽

Raw264.7 Cells ◽

Enzyme Linked Immunosorbent Assay ◽

Tnf Α ◽

Anti Inflammatory ◽

Factor Α ◽

Oxide Synthase ◽

Necrosis Factor

Simonsinol is a natural sesqui-neolignan firstly isolated from the bark of Illicium simonsii. In this study, the anti-inflammatory activity of simonsinol was investigated with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW264.7 cells model. The results demonstrated that simonsinol could antagonize the effect of LPS on morphological changes of RAW264.7 cells, and decrease the production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 cells, as determined by Griess assay and enzyme-linked immunosorbent assay (ELISA). Furthermore, simonsinol could downregulate transcription of inducible nitric oxide synthase (iNOS), TNF-α, and IL-6 as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibit phosphorylation of the alpha inhibitor of NF-κB (IκBα) as assayed by Western blot. In conclusion, these data demonstrate that simonsinol could inhibit inflammation response in LPS-stimulated RAW264.7 cells through the inactivation of the nuclear transcription factor kappa-B (NF-κB) signaling pathway.

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Epinephrine inhibits endotoxin-induced IL-1β production: roles of tumor necrosis factor-α and IL-10

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1997.273.6.r1885 ◽

1997 ◽

Vol 273 (6) ◽

pp. R1885-R1890 ◽

Cited By ~ 3

Author(s):

Tom Van Der Poll ◽

Stephen F. Lowry

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Ex Vivo ◽

Systemic Infection ◽

Tnf Α ◽

Cytokine Tumor Necrosis Factor ◽

Dose Dependent Decrease ◽

Factor Α ◽

Necrosis Factor

Epinephrine has been found to inhibit the production of the proinflammatory cytokine tumor necrosis factor (TNF)-α and to enhance the production of anti-inflammatory cytokine interleukin (IL)-10. To determine the effect of epinephrine on IL-1β production, the following experiments were performed: 1) blood obtained from subjects at 4–21 h after the start of a continuous infusion of epinephrine (30 ng ⋅ kg−1⋅ min−1) produced less IL-1β after ex vivo stimulation with lipopolysaccharide (LPS), compared with blood drawn from subjects infused with saline; 2) in whole blood in vitro, epinephrine caused a dose-dependent decrease in LPS-induced IL-1β production, which was likely mediated via adrenergic receptors; and 3) inhibition of TNF and enhancement of IL-10 both contributed to epinephrine-induced inhibition of IL-1β production. Epinephrine, either endogenously produced or administered as a component of sepsis treatment, may attenuate excessive activity of proinflammatory cytokines early in the course of systemic infection.

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Ectopic HOXB4 overcomes the inhibitory effect of tumor necrosis factor-α on Fanconi anemia hematopoietic stem and progenitor cells

Blood ◽

10.1182/blood-2008-09-180224 ◽

2009 ◽

Vol 113 (21) ◽

pp. 5111-5120 ◽

Cited By ~ 16

Author(s):

Michael D. Milsom ◽

Bernhard Schiedlmeier ◽

Jeff Bailey ◽

Mi-Ok Kim ◽

Dandan Li ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Fanconi Anemia ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Ectopic Expression ◽

Hematopoietic Stem ◽

Tnf Α ◽

Factor Α ◽

Necrosis Factor

AbstractEctopic delivery of HOXB4 elicits the expansion of engrafting hematopoietic stem cells (HSCs). We hypothesized that inhibition of tumor necrosis factor-α (TNF-α) signaling may be central to the self-renewal signature of HOXB4. Because HSCs derived from Fanconi anemia (FA) knockout mice are hypersensitive to TNF-α, we studied Fancc−/− HSCs to determine the physiologic effects of HOXB4 on TNF-α sensitivity and the relationship of these effects to the engraftment defect of FA HSCs. Overexpression of HOXB4 reversed the in vitro hypersensitivity to TNF-α of Fancc−/− HSCs and progenitors (P) and partially rescued the engraftment defect of these cells. Coexpression of HOXB4 and the correcting FA-C protein resulted in full correction compared with wild-type (WT) HSCs. Ectopic expression of HOXB4 resulted in a reduction in both apoptosis and reactive oxygen species in Fancc−/− but not WT HSC/P. HOXB4 overexpression was also associated with a significant reduction in surface expression of TNF-α receptors on Fancc−/− HSC/P. Finally, enhanced engraftment was seen even when HOXB4 was expressed in a time-limited fashion during in vivo reconstitution. Thus, the HOXB4 engraftment signature may be related to its effects on TNF-α signaling, and this pathway may be a molecular target for timed pharmacologic manipulation of HSC during reconstitution.

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Suppression of tumor necrosis factor-alpha-induced neutrophil adherence responses by essential oils

Mediators of Inflammation ◽

10.1080/09629350310001633342 ◽

2003 ◽

Vol 12 (6) ◽

pp. 323-328 ◽

Cited By ~ 39

Author(s):

Shigeru Abe ◽

Naho Maruyama ◽

Kazumi Hayama ◽

Hiroko Ishibashi ◽

Shigeharu Inoue ◽

...

Keyword(s):

Essential Oils ◽

Tumor Necrosis ◽

Neutrophil Activation ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Neutrophil Adherence ◽

Factor Alpha ◽

Anti Inflammatory ◽

Necrosis Factor

Background:In aromatherapy, essential oils are used as anti-inflammatory remedies, but experimental studies on their action mechanisms are very limited.Aims:To assess their anti-inflammatory activities, effects of essential oils on neutrophil activation were examinedin vitro.Methods:Neutrophil activation was measured by tumor necrosis factor-alpha (TNF-α)-induced adherence reaction of human peripheral neutrophils.Results:All essential oils tested at 0.1% concentration suppressed TNF-α-induced neutrophil adherence, and, in particular, lemongrass, geranium and spearmint oils clearly lowered the reaction even at 0.0125%. Similar inhibitory activities for the neutrophil adherence were obtained by their major constituent terpenoids: citral, geraniol, citronellol and carvone. In contrast, very popular essential oils, tea tree oil and lavender oil, did not display the inhibitory activity at the concentration.Conclusion:Thus, some essential oils used as anti-inflammatory remedies suppress neutrophil activation by TNF-α at a low concentration (0.0125-0.025%)in vitro.

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Effect of the proinflammatory cytokine TNF-α on intestinal riboflavin uptake: inhibition mediated via transcriptional mechanism(s)

AJP Cell Physiology ◽

10.1152/ajpcell.00295.2018 ◽

2018 ◽

Vol 315 (5) ◽

pp. C653-C663 ◽

Cited By ~ 5

Author(s):

Kasin Yadunandam Anandam ◽

Omar A. Alwan ◽

Veedamali S. Subramanian ◽

Padmanabhan Srinivasan ◽

Rubina Kapadia ◽

...

Keyword(s):

Ex Vivo ◽

Significant Inhibition ◽

Mrna Levels ◽

In Vivo Models ◽

Uptake Inhibition ◽

Tnf Α ◽

Vitro Model ◽

Factor Α

Riboflavin (RF), is essential for normal cellular metabolism/function. Intestinal RF absorption occurs via a specific carrier-mediated process that involves the apical transporter RFVT-3 ( SLC52A3) and the basolateral RFVT-1 (SLC52A1). Previously, we characterized different cellular/molecular aspects of the intestinal RF uptake process, but nothing is known about the effect of proinflammatory cytokines on the uptake event. We addressed this issue using in vitro, ex vivo, and in vivo models. First, we determined the level of mRNA expression of the human (h)RFVT-3 and hRFVT-1 in intestinal tissue of patients with inflammatory bowel disease (IBD) and observed a markedly lower level compared with controls. In the in vitro model, exposing Caco-2 cells to tumor necrosis factor-α (TNF-α) led to a significant inhibition in RF uptake, an effect that was abrogated upon knocking down TNF receptor 1 (TNFR1). The inhibition in RF uptake was associated with a significant reduction in the expression of hRFVT-3 and -1 protein and mRNA levels, as well as in the activity of the SLC52A3 and SLC52A1 promoters. The latter effects appear to involve Sp1 and NF-κB sites in these promoters. Similarly, exposure of mouse small intestinal enteroids and wild-type mice to TNF-α led to a significant inhibition in physiological and molecular parameters of intestinal RF uptake. Collectively, these findings demonstrate that exposure of intestinal epithelial cells to TNF-α leads to inhibition in RF uptake and that this effect is mediated, at least in part, via transcriptional mechanism(s). These findings may explain the significantly low RF levels observed in patients with IBD.

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Essential Oil of Myrtus communis Inhibits Inflammation in Rats by Reducing Serum IL-6 and TNF-α

Natural Product Communications ◽

10.1177/1934578x1100601034 ◽

2011 ◽

Vol 6 (10) ◽

pp. 1934578X1100601 ◽

Cited By ~ 8

Author(s):

Andrea Maxia ◽

Maria Assunta Frau ◽

Danilo Falconieri ◽

Manvendra Singh Karchuli ◽

Sanjay Kasture

Keyword(s):

Essential Oil ◽

Inflammatory Activity ◽

Myrtus Communis ◽

Ear Edema ◽

Tnf Α ◽

Cotton Pellet ◽

Anti Inflammatory ◽

Factor Α ◽

Necrosis Factor ◽

Serum Tumor Necrosis

The topical anti-inflammatory activity of the essential oil of Myrtus communis L. was studied using croton oil induced ear edema and myeloperoxidase (MPO) activity in mice, and cotton pellet induced granuloma, and serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in rats. On topical application, the oil exhibited a significant decrease in the ear edema as well as MPO activity. The oil also inhibited cotton pellet-induced granuloma and serum TNF-α and IL-6. It can be concluded that the essential oil of Myrtus communis reduces leukocyte migration to the damaged tissue and exhibits anti-inflammatory activity.

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