Anti-inflammatory Activity of Herbal Medicines: Inhibition of Nitric Oxide Production and Tumor Necrosis Factor-α Secretion in an Activated Macrophage-like Cell Line

2005 ◽  
Vol 33 (03) ◽  
pp. 415-424 ◽  
Author(s):  
Eunkyue Park ◽  
Susan Kum ◽  
Chuanhua Wang ◽  
Seung Yong Park ◽  
Bo Sook Kim ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Tumor Necrosis ◽  
No Production ◽  
Dependent Manner ◽  
Aqueous Extracts ◽  
Tnf Α ◽  
Activated Macrophage ◽  
Anti Inflammatory ◽  
Dose Dependent ◽  
Necrosis Factor

Houttuynia cordata Thunb. (HC), Glycyrrhiza uralensis Fischer (GU), Forsythia suspense (Thunb.) Vahl (FS), and Lonicera japonica Thunb. (LJ) are Chinese herbs known to possess anti-inflammatory properties. The effects of aqueous extracts of these herbs on the production of the pro-inflammatory mediators, nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) were examined in an activated macrophage-like cell line, RAW 264.7 cells. Aqueous extracts from FS at 0.0625–2.0 mg/ml inhibited in vitro production of NO and secretion of TNF-α in a dose-dependent manner. FS at 1.0–2.0 mg/ml and 0.125–2.0 mg/ml significantly inhibited NO production and TNF-α, respectively. An extract of LJ demonstrated potent inhibition of both NO production and TNF-α secretion in a dose-dependent manner. An aqueous extract from HC inhibited NO production in a dose-dependent manner, but minimally (approximately 30%) inhibited TNF-α secretion at 0.0625 and 0.125 mg/ml. In contrast, an aqueous extract of GU had a minimal effect on both the production of NO and the secretion of TNF-α. Viability of cells at all concentrations studied was unaffected as determined by MTT cytotoxicity assay and trypan blue dye exclusion. These results suggest that aqueous extracts from FS, LJ and HC have anti-inflammatory actions as measured by inhibition of NO production and/or TNF-α secretion.

scholarly journals Nitric Oxide and Tumor Necrosis Factor-Alpha Inhibitory Substances from the Rhizomes of Kaempferia Marginata

2013 ◽  
Vol 8 (9) ◽  
pp. 1934578X1300800 ◽  
Author(s):  
Kanidta Kaewkroek ◽  
Chatchai Wattanapiromsakul ◽  
Palangpon Kongsaeree ◽  
Supinya Tewtrakul
Keyword(s):  
Nitric Oxide ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
No Production ◽  
Significant Activity ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

The ethanol extract of the rhizomes of Kaempferia marginata showed a potent inhibitory effect against lipopolysaccharide (LPS)-induced nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) release in RAW264.7 cells. Moreover, the partition with various organic solvents also inhibited NO production. One new pimarane-type diterpene, 1α-acetoxysandaracopimaradien-2α-ol (5), along with four known diterpenes (1–4), were isolated from the n-hexane and chloroform layers, respectively. Among these metabolites, compounds 1 and 4 were isolated for the first time from K. marginata. Compounds 1–5 showed significant inhibitory effects on NO production, with IC50 values ranging from 38.6 to 51.9 μM. Furthermore, compound 2 also exhibited significant activity against TNF-α release (IC50 = 48.3 μM). These findings may support the use of K. marginata by traditional doctors for treatment of inflammatory-related diseases.

Epigallocatechin Gallate Modulates Cytokine Production by Bone Marrow-Derived Dendritic Cells Stimulated with Lipopolysaccharide or Muramyldipeptide, or Infected with Legionella pneumophila

2005 ◽  
Vol 230 (9) ◽  
pp. 645-651 ◽  
Author(s):  
James Rogers ◽  
Izabella Perkins ◽  
Alberto van Olphen ◽  
Nicholas Burdash ◽  
Thomas W. Klein ◽  
...  
Keyword(s):  
Legionella Pneumophila ◽  
Tumor Necrosis ◽  
Epigallocatechin Gallate ◽  
Dependent Manner ◽  
Enhanced Production ◽  
Tnf Α ◽  
Factor Α ◽  
Dose Dependent ◽  
Antimicrobial Immunity ◽  
Necrosis Factor

The primary polyphenol in green tea extract is the catechin epigallocatechin gallate (EGCG). Various studies have shown significant suppressive effects of catechin on mammalian cells, either tumor or normal cells, including lymphoid cells. Previous studies from this laboratory reported that EGCG has marked suppressive activity on murine macrophages infected with the intracellular bacterium Legionella pneumophila (Lp), an effect mediated by enhanced production of both tumor necrosis factor-α (TNF-α) and γ-interferon (IFN-γ). In the present study, primary murine bone marrow (BM)-derived dendritic cells (DCs), a phagocytic monocytic cell essential for innate immunity to intracellular microorganisms, such as Lp, were stimulated in vitro with the microbial stimulant lipopolysaccharide (LPS) from gram-negative bacteria, the cell wall component from gram-positive bacteria muramyldipeptide (MDP) or infected with Lp. Production of the T helper cell (Th1)-activating cytokine, interleukin-12 (IL-12) and the proinflammatory cytokine, tumor necrosis factor-α (TNF-α), produced mainly by phagocytic cells and important for antimicrobial immunity, was determined in cell culture supernatants by enzyme-linked immunosorbent assay (ELISA). Treatment of the cells with EGCG inhibited, in a dose-dependent manner, production of IL-12. In contrast, enhanced production of TNF-α occurred in a dose-dependent manner in the DC cultures stimulated with either soluble bacterial product or infected with Lp. Thus, the results of this study show that the EGCG catechin has a marked effect in modulating production of these immunoregulatory cytokines in stimulated DCs, which are important for antimicrobial immunity, especially innate immunity. Further studies are necessary to characterize the physiologic function of the effect of EGCG on TNF-α and IL-12 during Lp infection, and the mechanisms involved.

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.

Moringa Fruit Inhibits LPS-Induced NO/iNOS Expression through Suppressing the NF-κB Activation in RAW264.7 Cells

2013 ◽  
Vol 41 (05) ◽  
pp. 1109-1123 ◽  
Author(s):  
Hyo-Jin Lee ◽  
Yun-Jeong Jeong ◽  
Tae-Sung Lee ◽  
Yoon-Yub Park ◽  
Whi-Gun Chae ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Mediators ◽  
Nuclear Translocation ◽  
Biologically Active ◽  
Raw264.7 Cells ◽  
No Production ◽  
Dependent Manner ◽  
Fruit Extract ◽  
Tnf Α ◽  
Anti Inflammatory

In this study, we evaluated the anti-inflammatory effects of moringa (Moringa oleifera Lam.), a natural biologically active substance, by determining its inhibitory effects on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophage RAW264.7 cells. Extracts from different parts of moringa (root, leaf, and fruit) reduced LPS-induced nitric oxide (NO) release in a dose-dependent manner. The moringa fruit extract most effectively inhibited LPS-induced NO production and levels of inducible nitric oxide synthase (iNOS). The moringa fruit extract also was shown to suppress the production of inflammatory cytokines including IL-1β, TNF-α, and IL-6. Furthermore, moringa fruit extract inhibited the cytoplasmic degradation of I κ B -α and the nuclear translocation of p65 proteins, resulting in lower levels of NF -κ B transactivation. Collectively, the results of this study demonstrate that moringa fruit extract reduces the levels of pro-inflammatory mediators including NO , IL-1β, TNF-α, and IL-6 via the inhibition of NF -κ B activation in RAW264.7 cells. These findings reveal, in part, the molecular basis underlying the anti-inflammatory properties of moringa fruit extract.

Leonurus sibiricus induces nitric oxide and tumor necrosis factor-α in mouse peritoneal macrophages

2008 ◽  
Vol 86 (10) ◽  
pp. 682-690 ◽  
Author(s):  
Hyo-Jin An ◽  
Hong-Kun Rim ◽  
Jong-Hyun Lee ◽  
Se-Eun Suh ◽  
Ji-Hyun Lee ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Host Defense ◽  
Tumor Necrosis ◽  
Peritoneal Macrophages ◽  
No Production ◽  
Tnf Α ◽  
Leonurus Sibiricus ◽  
Factor Α ◽  
Mouse Peritoneal Macrophages ◽  
Necrosis Factor

Using mouse peritoneal macrophages, we have examined the mechanism by which Leonurus sibiricus (LS) regulates nitric oxide (NO) production. When LS was used in combination with recombinant interferon-γ (rIFN-γ), there was a marked cooperative induction of NO production; however, LS by itself had no effect on NO production. The increased production of NO from rIFN-γ plus LS-stimulated cells was almost completely inhibited by pretreatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor κB. Furthermore, treatment of peritoneal macrophages with rIFN-γ plus LS caused a significant increase in tumor necrosis factor-α (TNF-α) production. PDTC also decreased the effect of LS on TNF-α production significantly. Because NO and TNF-α play an important role in immune function and host defense, LS treatment could modulate several aspects of host defense mechanisms as a result of stimulation of the inducible nitric oxide synthase.

scholarly journals Hypericum triquetrifolium—Derived Factors Downregulate the Production Levels of LPS-Induced Nitric Oxide and Tumor Necrosis Factor-αin THP-1 Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Bashar Saad ◽  
Bernadette Soudah AbouAtta ◽  
Walid Basha ◽  
Alaa Hmade ◽  
Abdalsalam Kmail ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Experimental Period ◽  
Secretory Proteins ◽  
Dependent Manner ◽  
Aerial Parts ◽  
Anti Inflammatory ◽  
Necrosis Factor

Based on knowledge from traditional Arab herbal medicine, thisin vitrostudy aims to examine the anti-inflammatory mechanism ofHypericum triquetrifoliumby measuring the expression and release of pro-inflammatory cytokines, tumor necrosis factor-α(TNF-α) and interleukine-6 (IL-6), and inducible nitric oxide synthase (iNOS) in human monocytic cells, THP-1. The effects were assessed by measuring the levels of secretory proteins and mRNA of TNF-αand IL-6, the levels of nitric oxide (NO) secretion and the expression of iNOS in THP-1 cells. Cells were treated with 5 μg lipopolysaccharide/ml (LPS) in the presence and absence of increasing concentrations of extracts from the aerial parts ofH. triquetrifolium. During the entire experimental period, we used extract concentrations (up to 250 μg mL−1) that had no cytotoxic effects, as measured with MTT and LDH assays.Hypericum triquetrifoliumextracts remarkably suppressed the LPS-induced NO release, significantly attenuated the LPS-induced transcription of iNOS and inhibited in a dose-dependent manner the expression and release of TNF-α. No significant effects were observed on the release of IL-6. Taken together, these results suggest thatH. triquetrifoliumprobably exerts anti-inflammatory effects through the suppression of TNF-αand iNOS expressions.

scholarly journals Mechanisms of TQ-6, a Novel Ruthenium-Derivative Compound, against Lipopolysaccharide-Induced In Vitro Macrophage Activation and Liver Injury in Experimental Mice: The Crucial Role of p38 MAPK and NF-κB Signaling

Cells ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 217 ◽  
Author(s):  
Chih-Hsuan Hsia ◽  
Marappan Velusamy ◽  
Thanasekaran Jayakumar ◽  
Yen-Jen Chen ◽  
Chih-Wei Hsia ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Liver Injury ◽  
P38 Mapk ◽  
Macrophage Activation ◽  
Molecular Mechanisms ◽  
No Production ◽  
Dependent Manner ◽  
Tnf Α ◽  
Anti Inflammatory

Several studies have reported that metal complexes exhibit anti-inflammatory activities; however, the molecular mechanism is not well understood. In this study, we used a potent ruthenium (II)-derived compound, [Ru(η6-cymene)2-(1H-benzoimidazol-2-yl)-quinoline Cl]BF4 (TQ-6), to investigate the molecular mechanisms underlying the anti-inflammatory effects against lipopolysaccharide (LPS)-induced macrophage activation and liver injury in mice. Treating LPS-stimulated RAW 264.7 cells with TQ-6 suppressed nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in a concentration-dependent manner. The LPS-induced expression of tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) were reduced in TQ-6-treated cells. TQ-6 suppressed, LPS-stimulated p38 MAPK phosphorylation, IκBα degradation, and p65 nuclear translocation in cells. Consistent with the in vitro studies, TQ-6 also suppressed the expression of iNOS, TNF-α, and p65 in the mouse model with acute liver injury induced by LPS. The present study showed that TQ-6 could protect against LPS-induced in vitro inflammation in macrophage and in vivo liver injury in mice, and suggested that NF-κB could be a promising target for protecting against LPS-induced inflammation and liver injury by TQ-6. Therefore, TQ-6 can be a potential therapeutic agent for treating inflammatory diseases.

scholarly journals Uncommon Bis-Amide Matrine-type Alkaloids From Sophora alopecuroides With Anti-inflammatory Effects

2021 ◽  
Vol 9 ◽  
Author(s):  
Ding Luo ◽  
Zhenchao Tu ◽  
Wenjing Yin ◽  
Chunlin Fan ◽  
Nenghua Chen ◽  
...  
Keyword(s):  
Dependent Manner ◽  
X Ray Diffraction ◽  
Sophora Alopecuroides ◽  
Tnf Α ◽  
Ic50 Values ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Dose Dependent ◽  
Necrosis Factor ◽  
Pro Inflammatory Cytokines

Four new alkaloids (1–4) belonging to rare examples of bis-amide matrine-type were isolated from the seeds of sophora alopecuroides. Their structures including absolute configuration were determined by extensive spectroscopic analysis, electronic circular dichroism (ECD) interpretation, and X-ray diffraction crystallography. Chemically, bis-amide matrine-type alkaloids can provide new molecular template for structural modification. Compounds 3–4 displayed obvious anti-inflammatory effects based on the inhibition of two key pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in a dose-dependent manner, with IC50 values from 35.6 to 45.8 μm.

scholarly journals Augmentation of Nitric Oxide Production by Gamma Interferon in a Mouse Vascular Endothelial Cell Line and Its Modulation by Tumor Necrosis Factor Alpha and Lipopolysaccharide

2000 ◽  
Vol 68 (11) ◽  
pp. 6209-6214 ◽  
Author(s):  
Akiko Morikawa ◽  
Naoki Koide ◽  
Yutaka Kato ◽  
Tsuyoshi Sugiyama ◽  
Dipshikha Chakravortty ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Tumor Necrosis ◽  
No Production ◽  
High Concentration ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
D Cells ◽  
Necrosis Factor

ABSTRACT The effect of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and lipopolysaccharide (LPS) on nitric oxide (NO) production in the mouse vascular aortic endothelial cell line END-D was examined. LPS, TNF-α, and a low concentration of IFN-γ inhibited NO production in END-D cells, while a high concentration of IFN-γ definitely enhanced it. The NO production induced by a high concentration of IFN-γ was further augmented by using IFN-γ in combination with LPS or TNF-α. In sequential incubations of LPS and IFN-γ, the enhancement of NO production required prior treatment with IFN-γ. Stimulation of END-D cells with a high concentration of IFN-γ led to the expression of inducible NO synthase (iNOS). The augmentation of NO production by IFN-γ alone or in combination with LPS or TNF-α was completely blocked by several inhibitors of iNOS. It was strongly suggested that a high concentration of IFN-γ itself enhanced NO production in END-D cells through inducing the expression of iNOS. LPS and TNF-α exclusively modulated the activity of iNOS once its expression was triggered by IFN-γ. On the other hand, a low concentration of IFN-γ, LPS, and TNF-α reduced NO production through down-regulating constitutive NOS (cNOS). The differential regulation of cNOS- and iNOS-mediated NO production by IFN-γ, TNF-α, and LPS is discussed.

Effect of recombinant tumor necrosis factor-α on three-dimensional growth, morphology, and invasiveness of human glioblastoma cells in vitro

1993 ◽  
Vol 78 (6) ◽  
pp. 952-958 ◽  
Author(s):  
Koichi Iwasaki ◽  
Lisa R. Rogers ◽  
Gene H. Barnett ◽  
Melinda L. Estes ◽  
Barbara P. Barna
Keyword(s):  
Tumor Necrosis ◽  
Three Dimensional ◽  
Dependent Manner ◽  
Glioblastoma Cells ◽  
Human Glioblastoma ◽  
Tnf Α ◽  
Human Glioblastoma Cells ◽  
Dose Dependent ◽  
Necrosis Factor

✓ In order to investigate the antiproliferative and anti-invasive effects of tumor necrosis factor (TNF)-α on human glioblastoma cells, an in vitro three-dimensional (anchorage-independent) assay was performed using Matrigel, a mixture of extracellular matrix proteins. Four glioblastoma-derived cell lines, including one cloned line, were cultured in Matrigel with or without TNF-α. In the Matrigel containing TNF-α, three of the four cell lines, including the cloned line, showed significant growth inhibition in a dose-dependent manner. Dramatic three-dimensional morphological differences were observed between TNF-treated and untreated glioblastoma cells cultured in Matrigel. Untreated cells formed large and highly branched colonies throughout the gel. In contrast, the majority of TNF-treated cells demonstrated truncated branching processes and, at a high TNF-α dose, an increasing number of cells remained in relatively small spherical aggregates, their cell processes being significantly reduced. Quantitative invasion assay using a micro-Boyden chamber system confirmed that TNF-treated cells lost invasiveness in a dose-dependent manner. These results suggest that TNF-α exerts not only antiproliferative but also anti-invasive effects on human glioblastoma cells in vitro. It is believed that this is the first report showing the anti-invasive effect of TNF-α on tumor cells.

Sign in / Sign up

Export Citation Format

Share Document