scholarly journals Anti-Inflammatory Activity of Quercetogetin Isolated from Citrus Unshiu Peel Involves Suppression of NF-κB and MAPK Signaling Pathways in LPS-induced RAW264.7 Macrophages

2018 ◽  
Author(s):  
Eun Suk Son ◽  
Jeong-Wooung Park ◽  
Hye Ran Park ◽  
Woorijarang Han ◽  
Dae Eun Yun ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Raw264.7 Cells ◽  
Raw 264.7 Cells ◽  
Citrus Peel ◽  
Raw264.7 Macrophages ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Citrus peel has been used in Asian traditional medicine for the treatment of cough, asthma, and bronchial disorders. However, the anti-inflammatory effect of quercetogetin (QUE), a polymethoxylated flavone isolated from the peel of citrus unshui is poorly understood. We investigated the anti-inflammatory effect and the molecular mechanisms of QUE in lipopolysaccharide (LPS)-induced RAW264.7 cells. QUE inhibited the production of NO and prostaglandin E2 by suppressing the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 at both the mRNA and protein levels. QUE suppressed the production of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. QUE also inhibited the translocation of the nuclear factor kappa B subunit, p65, into the nucleus by interrupting the phosphorylation of IκB-α in LPS-induced RAW 264.7 cells. Based on the finding that QUE significantly decreased p-ERK protein expression in LPS-induced RAW264.7 cells, we confirmed that suppression of the inflammatory process by QUE was mediated through the MAPK pathway. This is the first report on the strong anti-inflammatory effects of QUE, which is a compound that can potentially be used as a therapeutic agent for inflammatory diseases.

scholarly journals Impressic Acid Attenuates the Lipopolysaccharide-Induced Inflammatory Response by Activating the AMPK/GSK3β/Nrf2 Axis in RAW264.7 Macrophages

2021 ◽  
Vol 22 (2) ◽  
pp. 762
Author(s):  
Gi Ho Lee ◽  
Ji Yeon Kim ◽  
Sun Woo Jin ◽  
Thi Hoa Pham ◽  
Jin Song Park ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Raw264.7 Cells ◽  
Raw264.7 Macrophages ◽  
Nrf2 Signaling Pathway ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines ◽  
Inflammatory Effect

Inflammatory diseases are caused by excessive inflammation from pro-inflammatory mediators and cytokines produced by macrophages. The Nrf2 signaling pathway protects against inflammatory diseases by inhibiting excessive inflammation via the regulation of antioxidant enzymes, including HO-1 and NQO1. We investigated the anti-inflammatory effect of impressic acid (IPA) isolated from Acanthopanax koreanum on the lipopolysaccharide (LPS)-induced inflammation and the underlying molecular mechanisms in RAW264.7 cells. IPA attenuated the LPS-induced production of pro-inflammatory cytokines and reactive oxygen species, and the activation of the NF-κB signaling pathway. IPA also increased the protein levels of Nrf2, HO-1, and NQO1 by phosphorylating CaMKKβ, AMPK, and GSK3β. Furthermore, ML385, an Nrf2 inhibitor, reversed the inhibitory effect of IPA on LPS-induced production of pro-inflammatory cytokines in RAW264.7 cells. Therefore, IPA exerts an anti-inflammatory effect via the AMPK/GSK3β/Nrf2 signaling pathway in macrophages. Taken together, the findings suggest that IPA has preventive potential for inflammation-related diseases.

scholarly journals Anti-inflammatory effects of Morus alba Linne bark on the activation of toll-like receptors and imiquimod-induced ear edema in mice

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lin Umeyama ◽  
Besse Hardianti ◽  
Shiori Kasahara ◽  
Dya Fita Dibwe ◽  
Suresh Awale ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Morus Alba ◽  
Raw264.7 Cells ◽  
Luciferase Reporter ◽  
Γδt Cells ◽  
Ear Edema ◽  
Raw264.7 Macrophages ◽  
Anti Inflammatory

Abstract Background Morus alba L. bark has been widely used in traditional medicine for treating several inflammatory diseases, such as hypertension, diabetes mellitus and coughing; however, the molecular mechanisms underlying its anti-inflammatory effects are not well understood. Methods We examined the effects of an extract of Morus alba L. bark (MabE) on Toll-like receptor (TLR) ligand-induced activation of RAW264.7 macrophages using a luciferase reporter assay and immunoassays. For the in vivo experiment, we used an imiquimod-induced ear edema model to examine the anti-inflammatory effects of MabE. Results MabE inhibited the TLR ligand-induced activation of NF-κB in RAW264.7 cells without affecting their viability. Consistent with the inhibition of NF-κB activation, MabE also inhibited the production of IL-6 and IL-1β from TLR ligand-treated RAW264.7 cells. In vivo MabE treatment inhibited the ear swelling of IMQ-treated mice, in addition to the mRNA expression of IL-17A, IL-1β and COX-2. The increases in splenic γδT cells in IMQ-treated mice and the production of IL-17A from splenocytes were significantly inhibited by MabE treatment. Conclusion Our study suggests that the anti-inflammatory effects of MabE on the activation of the macrophage cell line RAW246.7 by TLRs and IMQ-induced ear edema are through the inhibition of NF-κB activation and IL-17A-producing γδT cells, respectively.

scholarly journals Gancaonin N from Glycyrrhiza uralensis Attenuates the Inflammatory Response by Downregulating the NF-κB/MAPK Pathway on an Acute Pneumonia In Vitro Model

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1028
Author(s):  
Hyun Min Ko ◽  
Seung-Hyeon Lee ◽  
Wona Jee ◽  
Ji Hoon Jung ◽  
Kwan-Il Kim ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Molecular Mechanisms ◽  
Mapk Pathway ◽  
A549 Cells ◽  
Mapk Signaling ◽  
Glycyrrhiza Uralensis ◽  
Raw264.7 Cells ◽  
Acute Pneumonia ◽  
Cox 2 ◽  
Anti Inflammatory

Acute pneumonia is an inflammatory disease caused by several pathogens, with symptoms such as fever and chest pain, to which children are particularly vulnerable. Gancaonin N is a prenylated isoflavone of Glycyrrhiza uralensis that has been used in the treatment of various diseases in oriental medicine. There are little data on the anti-inflammatory efficacy of Gancaonin N, and its effects and mechanisms on acute pneumonia are unknown. Therefore, this study was conducted as a preliminary analysis of the anti-inflammatory effect of Gancaonin N in lipopolysaccharide (LPS)-induced RAW264.7 cells, and to identify its preventive effect on the lung inflammatory response and the molecular mechanisms underlying it. In this study, Gancaonin N inhibited the production of NO and PGE2 in LPS-induced RAW264.7 cells and significantly reduced the expression of iNOS and COX-2 proteins at non-cytotoxic concentrations. In addition, in LPS-induced A549 cells, Gancaonin N significantly reduced the expression of COX-2 and pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6. Moreover, Gancaonin N reduced MAPK signaling pathway phosphorylation and NF-κB nuclear translocation. Therefore, Gancaonin N relieved the inflammatory response by inactivating the MAPK and NF-κB signaling pathways; thus, it is a potential natural anti-inflammatory agent that can be used in the treatment of acute pneumonia.

scholarly journals Frutescone O from Baeckea frutescens Blocked TLR4-Mediated Myd88/NF-κB and MAPK Signaling Pathways in LPS Induced RAW264.7 Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaobing Lin ◽  
Junhan Zhang ◽  
Decai Fan ◽  
Jiqin Hou ◽  
Hao Wang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Raw264.7 Cells ◽  
Raw264.7 Macrophages ◽  
Anti Inflammatory ◽  
Baeckea Frutescens ◽  
Myd88 Signaling ◽  
Myeloid Differentiation Factor ◽  
Mapk Signaling Pathways

Frutescone O was isolated from the aerial parts of Baeckea frutescens L., which was commonly used as a folk medicinal material for treating anti-inflammatory disease in South East Asia. This study aimed to investigate the anti-inflammatory activity and related signaling cascade of Frutescone O (Fru) in LPS induced RAW264.7 cells. The anti-inflammation activity of Frutescone O was determined according to the inhibitory effects on the secretion of nitric oxide (NO), expression of inducible NO synthase, and pro-inflammatory cytokines. The regulation of Myeloid differentiation factor 88 (Myd88), inhibition of NF-κB, and MAPK pathways were further investigated for molecular mechanisms. Fru significantly decreased the expression of iNOS and the production of NO in LPS-stimulated RAW264.7 cells. It also dose-dependently suppressed LPS induced expression of IL-1β, IL-6, and TNF-α. Furthermore, Fru remarkably inhibited the upregulation of NF-κB (p50) expression in the nucleus and the phosphorylation ratio of p38, JNK, ERK, and Myd88 signaling protein. The molecular docking and cellular thermal shift assay (CETSA) results indicated that Fru participated in a robust and stable interaction with the active site of TLR4-MD2. Thus, Fru suppressed the LPS induced inflammation in RAW264.7 cells by blocking the TLR4 mediated signal transduction through the NF-κB and MAPK signaling pathways and inhibiting the Myd88 and iNOS expression.

scholarly journals Benzoylaconine Modulates LPS-Induced Responses through Inhibition of Toll-Like Receptor-Mediated NF-κB and MAPK Signaling in RAW264.7 Cells

2021 ◽  
Author(s):  
Changkai Zhou ◽  
Jing Gao ◽  
Hongyan Ji ◽  
Wenjing Li ◽  
Xiaomin Xing ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Toll Like Receptor ◽  
Protein Levels ◽  
Raw264.7 Macrophages ◽  
Elevated Protein ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Abstract Previous studies have shown that benzoylaconine (BAC), a representative monoester alkaloid, has a potential anti-inflammatory effect. This study investigated the underlying molecular mechanisms using the mode of LPS-activated RAW264.7 macrophage cells. Our findings showed that BAC significantly suppressed the release of pro-inflammatory cytokines and mediators, including IL-6, TNF-α, IL-1β, ROS, NO, and PGE2. BAC treatment also effectively downregulated the elevated protein levels of iNOS and COX-2 induced by LPS in a dose-dependent manner. In this study, we found that BAC inhibited LPS-induced NF-κB activation by reducing the phosphorylation and degradation of IκBα by Western blotting and blocking the nuclear translocation of p65 using an immunofluorescence assay. The elevated protein levels of JNK, p38, and ERK phosphorylation after LPS stimulation were restored effectively by BAC treatment. Moreover, LPS-induced phosphorylation of TAK1, which is a crucial upstream regulatory factor of Toll-like receptor-induced MAPK and NF-κB signaling, was inhibited by BAC in activated RAW264.7 macrophages. These findings demonstrated that BAC exhibited an anti-inflammatory effect by inhibition of Toll-like receptor-induced MAPK and NF-κB pathways, indicating that it could potentially be used for treating inflammatory diseases.

scholarly journals Asperuloside and Asperulosidic Acid Exert an Anti-Inflammatory Effect via Suppression of the NF-κB and MAPK Signaling Pathways in LPS-Induced RAW 264.7 Macrophages

2018 ◽  
Vol 19 (7) ◽  
pp. 2027 ◽  
Author(s):  
Jingyu He ◽  
Xianyuan Lu ◽  
Ting Wei ◽  
Yaqian Dong ◽  
Zheng Cai ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Signaling Pathways ◽  
Mapk Signaling ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Mapk Signaling Pathways ◽  
Inflammatory Effect

Hedyotis diffusa is a folk herb that is used for treating inflammation-related diseases in Asia. Previous studies have found that iridoids in H. diffusa play an important role in its anti-inflammatory activity. This study aimed to investigate the anti-inflammatory effect and potential mechanism of five iridoids (asperuloside (ASP), asperulosidic acid (ASPA), desacetyl asperulosidic acid (DAA), scandoside methyl ester (SME), and E-6-O-p-coumaroyl scandoside methyl ester (CSME)) that are presented in H. diffusa using lipopolysaccharide (LPS)—induced RAW 264.7 cells. ASP and ASPA significantly decreased the production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in parallel with the inhibition of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and IL-6 mRNA expression in LPS-induced RAW 264.7 cells. ASP treatment suppressed the phosphorylation of the inhibitors of nuclear factor-kappaB alpha (IκB-α), p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). The inhibitory effect of ASPA was similar to that of ASP, except for p38 phosphorylation. In summary, the anti-inflammatory effects of ASP and ASPA are related to the inhibition of inflammatory cytokines and mediators via suppression of the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways, which provides scientific evidence for the potential application of H. diffusa.

scholarly journals Anti-inflammatory Effect of Pratol in LPS-stimulated RAW 264.7 Cells via NF-κB Signaling Pathways

2018 ◽  
Vol 13 (5) ◽  
pp. 1934578X1801300
Author(s):  
You Chul Chung ◽  
Sung-Min Park ◽  
Jin Hwa Kim ◽  
Geun Soo Lee ◽  
Jung No Lee ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Trifolium Pratense ◽  
Skin Diseases ◽  
Inflammatory Diseases ◽  
Red Clover ◽  
Raw 264.7 Cells ◽  
Prostaglandin E ◽  
Raw 264.7 ◽  
Anti Inflammatory ◽  
Inflammatory Effect

The Trifolium pratense L. (red clover), which blossoms, leaves and stems can be used as medicines for treatment of burns, skin diseases, diabetes and other diseases. Recently study shown that pratol (7-hydroxy-4-methoxyflavone), an O-methylated flavone in T. pratense has been evaluated to induce melanogenesis in B16F10 melanoma cells. However, the anti-inflammatory effect of pratol has not been reported. In this study, we investigated the effects of pratol on anti-inflammation. We also studied the mechanism of action of pratol in LPS-stimulated RAW 264.7 cells. The cells were treated with various concentration of pratol (25, 50, or 100 μM) and 25 μM ammonium pyrrolidinedithiocarbamate (APDC) was used as control. The results in LPS-stimulated RAW 264.7 cells showed that pratol significantly reduced nitric oxide (NO) and prostaglandin E2 (PGE2) production without any cytotoxic. In addition, pratol strongly decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooygenase (COX-2). Furthermore, pratol reduced proinflammatory cytokines such as tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6. We also found that pratol strongly inhibited activation of nuclear factor kappa B (NF-κB) by reducing the p65 phosphorylation and protecting inhibitory factor kappa B alpha (IκBα) degradation. The results suggest that, pratol may be used to treat or prevent inflammatory diseases such as dermatitis, arthritis, cardiovascular and cancer.

scholarly journals Flavonoids Identified from KoreanScutellaria baicalensisGeorgi Inhibit Inflammatory Signaling by Suppressing Activation of NF-κB and MAPK in RAW 264.7 Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Gyeong-Eun Hong ◽  
Jin-A. Kim ◽  
Arulkumar Nagappan ◽  
Silvia Yumnam ◽  
Ho-Jeong Lee ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Mediators ◽  
Inflammatory Diseases ◽  
Mapk Signaling ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Two Dimensional Gel Electrophoresis ◽  
Necrosis Factor Alpha ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Scutellaria baicalensisGeorgi has been used as traditional medicine for treating inflammatory diseases, hepatitis, tumors, and diarrhea in Asia. Hence, we investigated the anti-inflammatory effect and determined the molecular mechanism of action of flavonoids isolated from KoreanS. baicalensisG. in lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to examine cytotoxicity of the flavonoids at various concentrations of 10, 40, 70, and 100 µg/mL. No cytotoxicity was observed in RAW 264.7 cells at these concentrations. Furthermore, the flavonoids decreased production of inflammatory mediators such as inducible nitric oxide synthase, cyclooxygenase-2, interleukin-6, and tumor necrosis factor-alpha and inhibited phosphorylation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) in LPS-induced RAW 264.7 cells. Moreover, to identify the differentially expressed proteins in RAW 264.7 cells of the control, LPS-treated, and flavonoid-treated groups, two-dimensional gel electrophoresis and mass spectrometry were conducted. The identified proteins were involved in the inflammatory response and included PRKA anchor protein and heat shock protein 70 kD. These findings suggest that the flavonoids isolated fromS. baicalensisG. might have anti-inflammatory effects that regulate the expression of inflammatory mediators by inhibiting the NF-κB signaling pathway via the MAPK signaling pathway in RAW 264.7 cells.

scholarly journals 4-Hydroxy-7-Methoxycoumarin Inhibits Inflammation in LPS-activated RAW264.7 Macrophages by Suppressing NF-κB and MAPK Activation

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4424
Author(s):  
Jin Kyu Kang ◽  
Chang-Gu Hyun
Keyword(s):  
Nitric Oxide ◽  
Nuclear Factor Kappa B ◽  
Inflammatory Diseases ◽  
Raw264.7 Cells ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Alternative Medicines ◽  
Raw264.7 Macrophages ◽  
Extracellular Signal ◽  
Anti Inflammatory

Coumarins are natural products with promising pharmacological activities owing to their anti-inflammatory, antioxidant, antiviral, anti-diabetic, and antimicrobial effects. Coumarins are present in many plants and microorganisms and have been widely used as complementary and alternative medicines. To date, the pharmacological efficacy of 4-hydroxy-7-methoxycoumarin (4H-7MTC) has not been reported yet. Therefore, in this study, we investigated the anti-inflammatory effects of 4H-7MTC in LPS-stimulated RAW264.7 cells as well as its mechanisms of action. Cells were treated with various concentrations of 4H-7MTC (0.3, 0.6, 0.9, and 1.2 mM) and 40 μM L-N6-(1-iminoethyl)-L-lysine (L-NIL) were used as controls. LPS-stimulated RAW264.7 cells showed that 4H-7MTC significantly reduced nitric oxide (NO) and prostaglandin E2 (PGE2) production without cytotoxic effects. In addition, 4H-7MTC strongly decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2). Furthermore, 4H-7MTC reduced the production of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. We also found that 4H-7MTC strongly exerted its anti-inflammatory actions by downregulating nuclear factor kappa B (NF-κB) activation by suppressing inhibitor of nuclear factor kappa B alpha (IκBα) degradation in macrophages. Moreover, 4H-7MTC decreased phosphorylation of extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase/stress-activated protein kinase (JNK), but not that of p38 MAPK. These results suggest that 4H-7MTC may be a good candidate for the treatment or prevention of inflammatory diseases such as dermatitis, psoriasis, and arthritis. Ultimately, this is the first report describing the effective anti-inflammatory activity of 4H-7MTC.

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