Lotus Leaf (Nelumbo nucifera) and its Active Constituents Prevent Inflammatory Responses in Macrophages via JNK/NF-κB Signaling Pathway

2014 ◽  
Vol 42 (04) ◽  
pp. 869-889 ◽  
Author(s):  
Shing-Hwa Liu ◽  
Tien-Hui Lu ◽  
Chin-Chuan Su ◽  
Ing-Shiow Lay ◽  
Hui-Yi Lin ◽  
...  
Keyword(s):  
Protein Expression ◽  
Inflammatory Responses ◽  
Specific Inhibitor ◽  
Nelumbo Nucifera ◽  
Perennial Plant ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Oxide Synthase

Inflammation is a serious health issue worldwide that induces many diseases, such as inflammatory bowel disease (IBD), sepsis, acute pancreatitis and lung injury. Thus, there is a great deal of interest in new methods of limiting inflammation. In this study, we investigated the leaves of Nelumbo nucifera Gaertn, an aquatic perennial plant cultivated in eastern Asia and India, in anti-inflammatory pharmacological effects in the murine macrophage cell line RAW264.7. Results showed that lipopolysaccharide (LPS) increased the protein expression of inducible nitric oxide synthase (iNOS) and COX-2, as well as the mRNA expression and level of IL-6 and TNF-α, while NNE significantly reduced these effects of LPS. LPS also induced phospho-JNK protein expression. The JNK-specific inhibitor SP600125 decreased the proteins expression of phospho-JNK, iNOS, COX-2, and the mRNAs expression and levels of IL-6 and TNF-α. Further, NNE reduced the protein expression of phospho-JNK. LPS was also found to promote the translocation of NF-κB from the cytosol to the nucleus and to decrease the expression of cytosolic IκB. NNE and SP600125 treatment recovered the LPS-induced expression of NF-κB and IκB. While phospho-ERK and phospho-p38 induced by LPS, could not be reversed by NNE. To further investigate the major components of NNE in anti-inflammatory effects, we determined the quercetin and catechin in inflammatory signals. Results showed that quercetin and catechin significantly decreased the proteins expression of iNOS, COX-2 and phospho-JNK. Besides, the mRNAs and levels of IL-6 and TNF-α also decreased by quercetin and catechin treatment in LPS-induced RAW264.7 cells. These results showed that NNE and its major components quercetin and catechin exhibit anti-inflammatory activities by inhibiting the JNK- and NF-κB-regulated pathways and could therefore be an useful anti-inflammatory agent.

scholarly journals Phytosterols Suppress Phagocytosis and Inhibit Inflammatory Mediators via ERK Pathway on LPS-Triggered Inflammatory Responses in RAW264.7 Macrophages and the Correlation with Their Structure

Foods ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 582 ◽  
Author(s):  
Yuan ◽  
Zhang ◽  
Shen ◽  
Jia ◽  
Xie
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Responses ◽  
Ester Group ◽  
No Production ◽  
Raw264.7 Macrophages ◽  
Extracellular Signal ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Oxide Synthase

Phytosterols, found in many commonly consumed foods, exhibit a broad range of physiological activities including anti-inflammatory effects. In this study, the anti-inflammatory effects of ergosterol, β-sitosterol, stigmasterol, campesterol, and ergosterol acetate were investigated in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Results showed that all phytosterol compounds alleviated the inflammatory reaction in LPS-induced macrophage models; cell phagocytosis, nitric oxide (NO) production, release of tumor necrosis factor-α (TNF-α), and expression and activity of pro-inflammatory mediator cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and phosphorylated extracellular signal-regulated protein kinase (p-ERK) were all inhibited. The anti-inflammatory activity of β-sitosterol was higher than stigmasterol and campesterol, which suggests that phytosterols without a double bond on C-22 and with ethyl on C-24 were more effective. However, inconsistent results were observed upon comparison of ergosterol and ergosterol acetate (hydroxy or ester group on C-3), which suggest that additional research is still needed to ascertain the contribution of structure to their anti-inflammatory effects.

scholarly journals TNF-α potentiates lysophosphatidic acid-induced COX-2 expression via PKD in human colonic myofibroblasts

2011 ◽  
Vol 300 (4) ◽  
pp. G637-G646 ◽  
Author(s):  
Citlali Ekaterina Rodriguez Perez ◽  
Wenxian Nie ◽  
James Sinnett-Smith ◽  
Enrique Rozengurt ◽  
James Yoo
Keyword(s):  
Protein Expression ◽  
Pertussis Toxin ◽  
Lysophosphatidic Acid ◽  
Critical Role ◽  
Specific Inhibitor ◽  
Detectable Effect ◽  
Inflammatory Microenvironment ◽  
Downstream Target ◽  
Tnf Α ◽  
Cox 2

The myofibroblast (MFB) has recently been identified as an important mediator of tumor necrosis factor-α (TNF-α)-associated colitis and cancer, but the mechanism(s) involved remains incompletely understood. Here, we show that treatment of 18Co cells, a model of human colonic MFBs, with TNF-α and lysophosphatidic acid (LPA) induced striking synergistic cyclooxygenase-2 (COX-2) protein expression and production of PGE2. This effect was prevented by the LPA1 receptor antagonist Ki16425, the Giα-specific inhibitor pertussis toxin, and by the preferential protein kinase (PK) C inhibitors GF109203X and Go6983. As a known downstream target of LPA and PKC, we tested whether PKD, recently implicated in the regulation of COX-2 expression in MFB, was involved in this response. TNF-α, while having no detectable effect on the activation of PKD when added alone, augmented PKD activation stimulated by LPA, as measured by PKD autophosphorylation at Ser910. LPA-induced PKD activation was also inhibited by Ki16425, pertussis toxin, GF109203X, and Go6983. Transfection of 18Co cells with short interfering RNA targeting PKD completely inhibited the synergistic increase in COX-2 protein, demonstrating a critical role of PKD in this response. Our results imply that cross talk between TNF-α and LPA results in the amplification of COX-2 protein expression via a conserved PKD-dependent signaling pathway that appears to involve the LPA1 receptor and the G protein Giα. PKD plays a critical role in the expression of COX-2 in human colonic MFBs and may contribute to an inflammatory microenvironment that promotes tumor growth.

Anti-Inflammatory Activity ofSchizonepeta tenuifoliathrough the Inhibition of MAPK Phosphorylation in Mouse Peritoneal Macrophages

2008 ◽  
Vol 36 (06) ◽  
pp. 1145-1158 ◽  
Author(s):  
Su-Jin Kim ◽  
Jung-Sun Kim ◽  
In-Young Choi ◽  
Dong-Hyun Kim ◽  
Min-Cheol Kim ◽  
...  
Keyword(s):  
Peritoneal Macrophages ◽  
Mapk Phosphorylation ◽  
Inflammatory Reactions ◽  
Inflammatory Mechanism ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Oxide Synthase ◽  
Mouse Peritoneal Macrophages ◽  
Necrosis Factor

Schizonepeta tenuifolia (ST) is a well-known herb to treat the cold and its associated headache. However, the anti-inflammatory mechanism of ST in mouse peritoneal macrophages is not clear. In this study, we demonstrated that ST inhibited lipopolysaccaride (LPS)-induced tumor necrosis factor (TNF)-α and interleukin (IL)-6 production. The maximal inhibition rate of TNF-α and IL-6 production by ST (2 mg/ml) was 48.01 ± 2.8% and 56.45 ± 2.8%, respectively. During the inflammatory process, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) were increased in mouse peritoneal macrophages. However, treated with ST decreased the protein level of COX-2 and iNOS, as well as the production of PGE2and NO in LPS-stimulated mouse peritoneal macrophages. In addition, ST inhibited the phosphorylation of MAPK. Taken together, the results of this study suggest an important molecular mechanism by which ST reduces inflammation, which may explain its beneficial effect in the regulation of inflammatory reactions.

scholarly journals Anti-Inflammatory Effects of Aurantio-Obtusin from Seed of Cassia obtusifolia L. through Modulation of the NF-κB Pathway

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3093 ◽  
Author(s):  
Jingyi Hou ◽  
Yu Gu ◽  
Shuai Zhao ◽  
Mengqi Huo ◽  
Shifeng Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Protein Expression ◽  
Therapeutic Agent ◽  
Raw264.7 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cassia Obtusifolia ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory

Aurantio-obtusin, an anthraquinone compound, isolated from dried seeds of Cassia obtusifolia L. (syn. Senna obtusifolia; Fabaceae) and Cassia tora L. (syn. Senna tora). Although the biological activities of Semen Cassiae have been reported, the anti-inflammatory mechanism of aurantio-obtusin, its main compound, on RAW264.7 cells, remained unknown. We investigated the anti-inflammatory effect of aurantio-obtusin on lipopolysaccharide- (LPS)-induced RAW264.7 cells in vitro and elucidated the possible underlying molecular mechanisms. Nitric oxide production (NO) and prostaglandin E2 (PGE2) were measured by the Griess colorimetric method and enzyme-linked immunosorbent assay (ELISA), respectively. Protein expression levels of cyclooxygenase 2 (COX-2) were monitored by cell-based ELISA. Interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) synthesis were analyzed using ELISA. The mRNA expression of nitric oxide synthase (iNOS), COX-2, and the critical pro-inflammatory cytokines (IL-6 and TNF-α) were detected by quantitative real-time PCR. Aurantio-obtusin significantly decreased the production of NO, PGE2, and inhibited the protein expression of COX-2, TNF-α and IL-6, which were similar to those gene expression of iNOS, COX-2, TNF-α and IL-6 (p < 0.01). Consistent with the pro-inflammatory gene expression, the Aurantio-obtusin efficiently reduced the LPS-induced activation of nuclear factor-κB in RAW264.7 cells. These results suggested that aurantio-obtusin may function as a therapeutic agent and can be considered in the further development of treatments for a variety of inflammatory diseases. Further studies may provide scientific evidence for the use of aurantio-obstusin as a new therapeutic agent for inflammation-related diseases.

scholarly journals Anti-Inflammatory Activity and ROS Regulation Effect of Sinapaldehyde in LPS-Stimulated RAW 264.7 Macrophages

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4089
Author(s):  
Seung-Hwa Baek ◽  
Tamina Park ◽  
Myung-Gyun Kang ◽  
Daeui Park
Keyword(s):  
Nitric Oxide ◽  
Polymerase Chain Reaction Analysis ◽  
Inos Mrna ◽  
Raw 264.7 ◽  
Raw 264.7 Macrophages ◽  
Docking Simulations ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Oxide Synthase

We evaluated the anti-inflammatory effects of SNAH in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages by performing nitric oxide (NO) assays, cytokine enzyme-linked immunosorbent assays, Western blotting, and real-time reverse transcription-polymerase chain reaction analysis. SNAH inhibited the production of NO (nitric oxide), reactive oxygen species (ROS), tumor necrosis factor (TNF)-α, and interleukin (IL)-6. Additionally, 100 μM SNAH significantly inhibited total NO and ROS inhibitory activity by 93% (p < 0.001) and 34% (p < 0.05), respectively. Protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) stimulated by LPS were also decreased by SNAH. Moreover, SNAH significantly (p < 0.001) downregulated the TNF-α, IL-6, and iNOS mRNA expression upon LPS stimulation. In addition, 3–100 µM SNAH was not cytotoxic. Docking simulations and enzyme inhibitory assays with COX-2 revealed binding scores of −6.4 kcal/mol (IC50 = 47.8 μM) with SNAH compared to −11.1 kcal/mol (IC50 = 0.45 μM) with celecoxib, a known selective COX-2 inhibitor. Our results demonstrate that SNAH exerts anti-inflammatory effects via suppression of ROS and NO by COX-2 inhibition. Thus, SNAH may be useful as a pharmacological agent for treating inflammation-related diseases.

scholarly journals Semisynthesis and Inhibitory Effects of Solidagenone Derivatives on TLR-Mediated Inflammatory Responses

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3197 ◽  
Author(s):  
Irene Cuadrado ◽  
Ángel Amesty ◽  
Juan Cedrón ◽  
Juan Oberti ◽  
Ana Estévez-Braun ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Spectroscopic Studies ◽  
Peritoneal Macrophages ◽  
Transcriptional Level ◽  
Inhibitory Effects ◽  
Structure Activity ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Oxide Synthase

A series of nine derivatives (2–10) were prepared from the diterpene solidagenone (1) and their structures were elucidated by means of spectroscopic studies. Their ability to inhibit inflammatory responses elicited in peritoneal macrophages by TLR ligands was investigated. Compounds 5 and 6 showed significant anti-inflammatory effects, as they inhibited the protein expression of nitric oxide synthase (NOS-2), cyclooxygenase-2 (COX-2), and cytokine production (TNF-α, IL-6, and IL-12) induced by the ligand of TLR4, lipopolysaccharide (LPS), acting at the transcriptional level. Some structure–activity relationships were outlined. Compound 5 was selected as a representative compound and molecular mechanisms involved in its biological activity were investigated. Inhibition of NF-κB and p38 signaling seems to be involved in the mechanism of action of compound 5. In addition, this compound also inhibited inflammatory responses mediated by ligands of TLR2 and TLR3 receptors. To rationalize the obtained results, molecular docking and molecular dynamic studies were carried out on TLR4. All these data indicate that solidagenone derivative 5 might be used for the design of new anti-inflammatory agents.

scholarly journals Attenuation of Inflammatory Symptoms by Icariside B2 in Carrageenan and LPS-Induced Inflammation Models via Regulation of MAPK/NF-κB Signaling Cascades

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1037
Author(s):  
Md Badrul Alam ◽  
Yoon-Gyung Kwon ◽  
Shakina Yesmin Simu ◽  
Sk Abrar Shahriyar ◽  
Sang Han Lee
Keyword(s):  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Binding Energies ◽  
Inhibitory Protein ◽  
Expression Levels ◽  
Bv2 Cells ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory

Prolonged inflammatory responses can lead to the development of several chronic diseases, such as autoimmune disorders and the development of natural therapeutic agents is required. A murine model was used to assess the anti-inflammatory effects of the megastigmane glucoside, icariside B2 (ICSB), and the assessment was carried out in vitro, and in vivo. The in vitro anti-inflammatory effects of ICSB were tested using LPS-stimulated BV2 cells, and the protein expression levels of inflammatory genes and cytokines were assessed. Mice were subcutaneously injected with 1% carrageenan (CA) to induce acute phase inflammation in the paw. Inflammation was assessed by measuring paw volumes hourly; subsequently, the mice were euthanized and the right hind paw skin was expunged and processed for reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. ICSB inhibits LPS-stimulated nitric oxide (NO) and prostaglandin E2 (PGE2) generation by reducing the expression of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2). ICSB also inhibits the COX-2 enzyme with an IC50 value of 7.80 ± 0.26 µM. Molecular docking analysis revealed that ICSB had a strong binding affinity with both murine and human COX-2 proteins with binding energies of −8 kcal/mol and −7.4 kcal/mol, respectively. ICSB also reduces the manifestation of pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1β, at their transcriptional and translational level. ICSB hinders inhibitory protein κBα (IκBα) phosphorylation, thereby terminating the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) nuclear translocation. ICSB also represses the mitogen-activated protein kinases (MAPKs) signaling pathways. ICSB (50 mg/kg) showed an anti-edema effect in CA-induced mice and suppressed the CA-induced increases in iNOS and COX-2 protein levels. ICSB attenuated inflammatory responses by downregulating NF-κB expression through interference with extracellular signal-regulated kinase (ERK) and p38 phosphorylation, and by modulating the expression levels of iNOS, COX-2, TNF-α, IL-1β, and IL-6.

Piper sarmentosum extract alleviates inflammatory responses and improves barrier function in porcine intestinal epithelial (IPEC-J2) cells induced by lipopolysaccharide (LPS)

2020 ◽  
Author(s):  
Dingfa Wang ◽  
Luli Zhou ◽  
zhou Hanlin ◽  
Guanyu Hou
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Inflammatory Activity ◽  
Complete Medium ◽  
Metabolic Pathway Analysis ◽  
Metabolic Pattern ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Lps Treatment

Abstract Background: In this study, we investigated the anti-inflammatory effect of Piper sarmentosum extract (PSE) in the IPEC-J2 cells induced by lipopolysaccharide (LPS). Meanwhile, we also tested the metabolomics profile of cells treated by LPS and PSE. Method: IPEC-J2 cells (6×105 cell/well) were seeded on 6-well plates, and cells were divided into three treatments (control, LPS treatment and LPS + PSE-NB treatment). Each treatment was conducted in five replicates. After incubation for 24 h, cells in LPS + PSE-NB treatment were treated by media containing PSE-NB at 10 ug/ml (cells in control and LPS treatments were treated by complete medium). Cells were culture for 24 h, and cells in LPS treatment and LPS + PSE-NB treatment then were treated by media contain 1 μg/ml of LPS (cells in control was treated by complete medium) for another 24 h. After treatment, cells were used for gene expression assays, protein expression assays and metabolomics analysis.Results: We demonstrated that LPS stimulation significantly up-regulated the mRNA expression of IL-1, IL-6 and TNF-α (P < 0.05) compared with the control in the IPEC-J2 cells. Piper sarmentosum extract with n-butanol (PSE-NB) pre-treatment with 10 ug/mL before LPS stimulation significantly decreased the expression of IL-1, IL-6 and TNF-α compared with LPS treatment (P < 0.05). We found that PSE-NB improved the expression of intestinal tight junction proteins (ZO1 and Occludin) and NHE3 that were reduced by LPS stimulation (P < 0.05). Moreover, PSE-NB alleviated LPS-induced protein expression of p65 and p-p65 (P < 0.05) and inhibited the NF-κB signaling pathway. Metabolic pathway analysis indicated that PSE-NB exert anti-inflammatory activity mainly through affecting tryptophan metabolism. Its metabolic product, melatonin, has anti-inflammatory properties by inhibition of NF-κB activation, which consistent with our results regarding to anti-inflammatory activity of PSE-NB on inflammatory signaling pathway. Conclusion: These results suggested that PSE-NB might attenuate LPS-induced inflammatory responses in the IPEC-J2 cells by regulating inflammatory NF-κB signaling pathway and intracellular metabolic pattern.

scholarly journals Nootkatone Inhibits Acute and Chronic Inflammatory Responses in Mice

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2181 ◽  
Author(s):  
Lindaiane Bezerra Rodrigues Dantas ◽  
Ana Letícia Moreira Silva ◽  
Cícero Pedro da Silva Júnior ◽  
Isabel Sousa Alcântara ◽  
Maria Rayane Correia de Oliveira ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Acute Inflammation ◽  
Inflammatory Responses ◽  
In Silico Analysis ◽  
Histamine Receptor ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Acute And Chronic Inflammation ◽  
The Impact

Nootkatone (NTK) is a sesquiterpenoid found in essential oils of many species of Citrus (Rutaceae). Considering previous reports demonstrating that NTK inhibited inflammatory signaling pathways, this study aimed to investigate the effects of this compound in mice models of acute and chronic inflammation. Murine models of paw edema induced by carrageenan, dextran, histamine, and arachidonic acid, as well as carrageenan-induced peritonitis and pleurisy, were used to evaluate the effects of NTK on acute inflammation. A murine model of granuloma induced by cotton pellets was used to access the impact of NTK treatment on chronic inflammation. In the acute inflammation models, NTK demonstrated antiedematogenic effects and inhibited leukocyte recruitment, which was associated with decreased vascular permeability, inhibition of myeloperoxidase (MPO), interleukin (IL)1-β, and tumor necrosis factor (TNF)-α production. In silico analysis suggest that NTZ anti-inflammatory effects may also occur due to inhibition of cyclooxygenase (COX)-2 activity and antagonism of the histamine receptor type 1 (H1). These mechanisms might have contributed to the reduction of granuloma weight and protein concentration in the homogenates, observed in the chronic inflammation model. In conclusion, NTK exerted anti-inflammatory effects that are associated with inhibition of IL1-β and TNF-α production, possibly due to inhibition of COX-2 activity and antagonism of the H1 receptor. However, further studies are required to characterize the effects of this compound on chronic inflammation.

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

Molecules ◽  
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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