scholarly journals Anti-Inflammatory Effects of 6-Methylcoumarin in LPS-Stimulated RAW 264.7 Macrophages via Regulation of MAPK and NF-κB Signaling Pathways

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5351
Author(s):  
Jin-Kyu Kang ◽  
You-Chul Chung ◽  
Chang-Gu Hyun
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Cytokines ◽  
Mitogen Activated Protein Kinase ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Persistent inflammatory reactions promote mucosal damage and cause dysfunction, such as pain, swelling, seizures, and fever. Therefore, in this study, in order to explore the anti-inflammatory effect of 6-methylcoumarin (6-MC) and suggest its availability, macrophages were stimulated with lipopolysaccharide (LPS) to conduct an in vitro experiment. The effects of 6-MC on the production and levels of pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α) and inflammatory mediators (nitric oxide (NO), prostaglandin E2 (PGE2)) in LPS-stimulated RAW 264.7 cells were examined. The results showed that 6-MC reduced the levels of NO and PGE2 without being cytotoxic. In addition, it was demonstrated that the increase in the expression of pro-inflammatory cytokines caused by LPS stimulation, was decreased in a concentration-dependent manner with 6-MC treatment. Moreover, Western blot results showed that the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), which increased with LPS treatment, were decreased by 6-MC treatment. Mechanistic studies revealed that 6-MC reduced the phosphorylation of the mitogen-activated protein kinase (MAPK) family and IκBα in the MAPK and nuclear factor-kappa B (NF-κB) pathways, respectively. These results suggest that 6-MC is a potential therapeutic agent for inflammatory diseases that inhibits inflammation via the MAPK and NF-κB pathways.

scholarly journals 7-Acetoxycoumarin Inhibits LPS-Induced Inflammatory Cytokine Synthesis by IκBα Degradation and MAPK Activation in Macrophage Cells

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3124 ◽  
Author(s):  
Taejin Park ◽  
Jin-Soo Park ◽  
Ji Han Sim ◽  
Seung-Young Kim
Keyword(s):  
Inflammatory Cytokines ◽  
Mitogen Activated Protein Kinase ◽  
In Vitro Assays ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Macrophage Cells ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Acetylation involves the chemical introduction of an acetyl group in place of an active hydrogen group into a compound. In this study, we synthesized 7-acetoxycoumarin (7AC) from acetylation of umbelliferone (UMB). We examined the anti-inflammatory properties of 7AC in lipopolysaccharide (LPS)-treated RAW 264.7 macrophage cells. The anti-inflammatory activity of 7AC on viability of treated cells was assessed by measuring the level of expression of NO, PGE2 and pro-inflammatory cytokines, namely interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in 7AC-treated RAW 264.7 macrophages. The 7AC was nontoxic to cells and inhibited the production of cytokines in a concentration-dependent manner. In addition, its treatment suppressed the production of pro-inflammatory cytokines in a dose-dependent manner and concomitantly decreased the protein and mRNA expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, the levels of the phosphorylation of mitogen-activated protein kinase (MAPK) family proteins such as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 and nuclear factor kappa B (NF-κB) were reduced by 7AC. In conclusion, we generated an anti-inflammatory compound through acetylation and demonstrated its efficacy in cell-based in vitro assays.

scholarly journals 5-Hydroxymethylfurfural Mitigates Lipopolysaccharide-Stimulated Inflammation via Suppression of MAPK, NF-κB and mTOR Activation in RAW 264.7 Cells

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 275 ◽  
Author(s):  
Fanhui Kong ◽  
Bae Lee ◽  
Kun Wei
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Cytokines ◽  
Mammalian Target Of Rapamycin ◽  
Inflammatory Activity ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

5-Hydroxymethylfurfural (5-HMF) is found in many food products including honey, dried fruits, coffee and black garlic extracts. Here, we investigated the anti-inflammatory activity of 5-HMF and its underlying mechanisms in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. 5-HMF pretreatment ranging from 31.5 to 126.0 μg/mL reduced the production of nitric oxide (NO), prostaglandin E2 (PGE2) and pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in a concentration-dependent manner in LPS-stimulated cells. Moreover, 5-HMF-pretreated cells significantly down-regulated the mRNA expression of two major inflammatory mediators, nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and suppressed the production of pro-inflammatory cytokines, as compared with the only LPS-stimulated cells. 5-HMF suppressed the phosphorylation of extracellular regulated protein kinases (ERK1/2), c-Jun N-terminal kinase (JNK), IκBα, NF-κB p65, the mammalian target of rapamycin (mTOR) and protein kinase B (Akt). Besides, 5-HMF was proved to inhibit NF-κB p65 translocation into nucleus to activate inflammatory gene transcription. These results suggest that 5-HMF could exert the anti-inflammatory activity in the LPS-induced inflammatory response by inhibiting the MAPK, NF-κB and Akt/mTOR pathways. Thus, 5-HMF could be considered as a therapeutic ingredient in functional foods.

scholarly journals New 12,23-Epoxydammarane Type Saponins Obtained from Panax notoginseng Leaves and Their Anti-Inflammatory Activity

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3784
Author(s):  
Jingya Ruan ◽  
Ying Zhang ◽  
Wei Zhao ◽  
Fan Sun ◽  
Lifeng Han ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Panax Notoginseng ◽  
Inflammatory Activity ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Anti Inflammatory

Two new 12,23-epoxydammarane-type saponins, notoginsenosides NL-I (1) and NL-J (2), were isolated and identified from Panax notoginseng leaves through the combination of various chromatographies and extensive spectroscopic methods, as well as chemical reactions. Among them, notoginsenoside NL-J (2) had a new skeleton. Furthermore, the lipopolysaccharide (LPS)-induced RAW 264.7 macrophage model was used to identify the in vitro anti-inflammatory activity and mechanisms of compounds 1 and 2. Both of them exerted strong inhibition on nitric oxide (NO) productions in a concentration-dependent manner at 1, 10, and 25 μM. Moreover, these two compounds significantly decreased the secretion of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), cyclooxygenase-2 (COX-2), nuclear factor kappa-B (NF-κB/p65), and nitric-oxide synthase (iNOS) in LPS-activated RAW 264.7 cells.

scholarly journals ANTI-INFLAMMATORY ACTIVITY OF TINOCRISPOSIDE BY INHIBITING NITRIC OXIDE PRODUCTION IN LIPOPOLYSACCHARIDES-STIMULATED RAW 264.7 CELLS

2018 ◽  
Vol 11 (4) ◽  
pp. 149 ◽  
Author(s):  
Adek Zamrud Adnan ◽  
Muhammad Taher ◽  
Tika Afriani ◽  
Annisa Fauzana ◽  
Dewi Imelda Roesma ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Diseases ◽  
Positive Control ◽  
Inflammatory Activity ◽  
Raw 264.7 Cells ◽  
No Production ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Anti Inflammatory

 Objective: The aim of this study was to investigate in vitro anti-inflammatory activity of tinocrisposide using lipopolysaccharides (LPS)-stimulated RAW 264.7 macrophage cells. Tinocrisposide is a furano diterpene glycoside that was isolated in our previous study from Tinospora crispa.Methods: Anti-inflammatory effect was quantified spectrometrically using Griess method by measuring nitric oxide (NO) production after the addition of Griess reagent.Results: The sample concentrations of 1, 5, 25, 50, and 100 μM and 100 μM of dexamethasone (positive control) have been tested against the LPS-stimulated RAW 264.7 cells, and the results showed NO level production of 39.23, 34.00, 28.9, 20.25, 16.3, and 13.68 μM, respectively, and the inhibition level of 22.67, 33.00, 43.03, 60.10, 68.00, and 73%, respectively.Conclusions: From the study, it could be concluded that tinocrisposide was able to inhibit the formation of NO in the LPS-stimulated RAW 264.7 cells in concentration activity-dependent manner, with half-maximal inhibition concentration 46.92 μM. It can be developed as anti-inflammatory candidate drug because NO is a reactive nitrogen species which is produced by NO synthase. The production of NO has been established as a mediator in inflammatory diseases.

scholarly journals IN VITRO ANTI-INFLAMMATORY ACTIVITY OF THE COMPONENTS OF AMOMUM TSAO-KO IN MURINE MACROPHAGE RAW 264.7 CELLS

2018 ◽  
Vol 15 (2) ◽  
pp. 26
Author(s):  
Chun Whan Choi ◽  
Ju Young Shin ◽  
Changon Seo ◽  
Seong Su Hong ◽  
Eun-Kyung Ahn ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Benzoic Acid ◽  
Inflammatory Activity ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Murine Macrophage ◽  
Etoh Extract ◽  
Anti Inflammatory

Background: Plants still remain the prime source of drugs for the treatment of inflammation and can provide leads for the development of novel anti-inflammatory agents. Material and methods: An in vitro bioassay guide revealed that the 80% ethanol (EtOH) extract of the whole plant, Amomum tsao-ko (Zingiberaceae), displayed anti-inflammatory activity after assessing its effects on murine macrophage RAW 264.7 cells. Result: Phytochemical study of the 80% EtOH extract of Amomum tsao-ko led to the isolation of eight compounds: 4-hydroxy-3-methoxy-benzoic acid (1), meso-hannokinol (2), (+)-hannokinol (3), coumaric acid (4), 4-hydroxy-benzoic acid (5), (+)-epicatechin (6), (-)-catechin (7), and myrciaphenone A (8). The results indicated that two of the isolated components, (+)-epicatechin (6) and (-)-catechin (7), inhibited the production of nitric oxide (NO) significantly in lipopolysaccharide treated RAW 264.7 cells. Conclusion: LPS-induced interleukin tumor necrosis factor-alpha (TNF-), IL-1β and IL-10 production was also decreased in a dose-dependent manner. In addition, western blot analysis revealed that (+)-epicatechin (6) and (-)-catechin (7) reduced the expression of inducible nitric oxide synthase and inhibited nuclear localization of nuclear factor kappa-B (NF-κB).

scholarly journals Anti-Inflammatory Effects of 6,7-Dihydroxy-4-Methylcoumarin on LPS-Stimulated Macrophage Phosphorylation in MAPK Signaling Pathways

2021 ◽  
Vol 16 (5) ◽  
pp. 1934578X2110209
Author(s):  
Yun Sil Kang ◽  
You Chul Chung ◽  
Jung No Lee ◽  
Bong Seok Kim ◽  
Chang-Gu Hyun
Keyword(s):  
Signaling Pathways ◽  
Inflammatory Cytokines ◽  
Inflammatory Diseases ◽  
Mapk Signaling ◽  
Raw 264.7 Cells ◽  
Inflammatory Factors ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Coumarin derivatives, such as esculetin, have various physiological functions, including antioxidant, anti-inflammatory, antibacterial, antiviral, and anti-cancer. 6,7-Dihydroxy-4-methylcoumarin (6,7-DH-4MC) is a derivative of esculetin, and its anti-inflammatory effect and mechanism in macrophages have not been studied. In this study, the anti-inflammatory activity of 6,7-DH-4MC was evaluated by measuring the expression of inflammatory factors (NO and PGE2) and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in LPS-stimulated RAW 264.7 macrophages. The results revealed that 6,7-DH-4MC significantly reduced NO levels and PGE2 expression without inducing cytotoxicity; it was confirmed that the inhibition of NO and PGE2 expression was related to iNOS and COX-2 downregulation in response to 6,7-DH-4MC treatment. Moreover, 6,7-DH-4MC decreased the levels of pro-inflammatory cytokines, such as IL-1β and IL-6, in a dose-dependent manner. Mechanistic studies revealed reduced phosphorylation of ERK and p38-MAPK upon 6,7-DH-4MC treatment. Furthermore, the degradation of IκB-α and phosphorylation of NF-κB in cells treated with LPS were interrupted by 6,7-DH-4MC treatment. These results suggest that 6,7-DH-4MC is a potential therapeutic agent for inflammatory diseases. To the best of our knowledge, this is the first report demonstrating the anti-inflammatory effects of 6,7-DH-4MC in RAW 264.7 cells via MAPK and NF-κB signaling pathways.

scholarly journals In vitro and In vivo Anti-inflammatory Activities of Mesua ferrea Linn

2018 ◽  
Vol 10 (03) ◽  
Author(s):  
Krishna Chaithanya K ◽  
Gopalakrishnan V K ◽  
ZenebeHagos . ◽  
Nagaraju B ◽  
Kamalakararao K ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Wistar Rats ◽  
Inflammatory Activity ◽  
Raw 264.7 Cells ◽  
Bark Extract ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Anti Inflammatory

Objective: Mesuaferrea L is a medicinal plant belongs to the family Clusiace, it is extensively used in folk medicine for treatment of chronic inflammatory diseases.The present study was aimed to evaluate in vitro and in vivo anti-inflammatory activity of M. ferrea L. Methods: The in vitro anti-inflammatory activities such as nitric oxide, PGE2, pro-inflammatory cytokines (TNF-α and IL-1β) were studied in RAW 264.7 cells and in vivo studies were carried out on carrageenan -induced inflammation in Wistar rats. The sequentially extracted M. ferreaL bark extracts (MFBHE, MFBEE, and MFBME) exhibited inhibitory effects on pro-inflammatory mediators such as nitric oxide, prostaglandin E2, tumour necrosis factorαandinterleukin-1βproduction in concentration dependent manner in LPS induced RAW 264.7 cells andCarrageenan induced paw oedema in Wistar rats. Conclusion: The result of the present study indicated that M. ferrea L ethyl acetate bark extract exhibited significant in vitroand in vivoanti-inflammatory activity.

scholarly journals Designing Single-Molecule Magnets as Drugs with Dual Anti-Inflammatory and Anti-Diabetic Effects

2020 ◽  
Vol 21 (9) ◽  
pp. 3146
Author(s):  
Arturo Navas ◽  
Fatin Jannus ◽  
Belén Fernández ◽  
Javier Cepeda ◽  
Marta Medina O’Donnell ◽  
...  
Keyword(s):  
Metal Complexes ◽  
Single Molecule ◽  
Raw 264.7 Cells ◽  
Cobalt Metal ◽  
No Production ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Anti Inflammatory

We have designed and synthesized two novel cobalt coordination compounds using bumetanide (bum) and indomethacin (ind) therapeutic agents. The anti-inflammatory effects of cobalt metal complexes with ind and bum were assayed in lipopolysaccharide stimulated RAW 264.7 macrophages by inhibition of nitric oxide production. Firstly, we determined the cytotoxicity and the anti-inflammatory potential of the cobalt compounds and ind and bum ligands in RAW 264.7 cells. Indomethacin-based metal complex was able to inhibit the NO production up to 35% in a concentration-dependent manner without showing cytotoxicity, showing around 6–37 times more effective than indomethacin. Cell cycle analysis showed that the inhibition of NO production was accompanied by a reversion of the differentiation processes in LPS-stimulated RAW 264.7 cells, due to a decreased of cell percentage in G0/G1 phase, with the corresponding increase in the number of cells in S phase. These two materials have mononuclear structures and show slow relaxation of magnetization. Moreover, both compounds show anti-diabetic activity with low in vitro cell toxicities. The formation of metal complexes with bioactive ligands is a new and promising strategy to find new compounds with high and enhanced biochemical properties and promises to be a field of great interest.

scholarly journals Two methoxy derivatives of resveratrol, 3,3′,4,5′-tetramethoxy-trans-stilbene and 3,4′,5-trimethoxy-trans-stilbene, suppress lipopolysaccharide-induced inflammation through inactivation of MAPK and NF-κB pathways in RAW 264.7 cells

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Chunxiu Zhou ◽  
Xutao Zhang ◽  
Cheng-Chao Ruan ◽  
Wai San Cheang
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathways ◽  
Inflammatory Cytokines ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Trans Stilbene ◽  
No Release ◽  
Derivatives Of ◽  
Pro Inflammatory Cytokines

Abstract Background 3,3′,4,5′-tetramethoxy-trans-stilbene (3,3′,4,5′-TMS) and 3,4′,5-trimethoxy-trans-stilbene (3,4′,5-TMS) are two methoxy derivatives of resveratrol. Previous researches have proved that resveratrol and its analogues have anti-inflammatory effect through suppressing mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. This study aims to study whether 3,3′,4,5′-TMS and 3,4′,5-TMS alleviate inflammation and the underlying mechanism. Methods RAW 264.7 macrophage cells were treated with lipopolysaccharide (LPS) to induce inflammation and pretreated with 3,3′,4,5′-TMS or 3,4′,5-TMS. Cell viability was measured with the 3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Nitric oxide (NO) release was detected by Griess reagent. The secretions of pro-inflammatory cytokines were assessed by ELISA kits. Protein expressions of signaling molecules were determined by Western blotting. Reactive oxygen species (ROS) production was detected by fluorescence staining and malondialdehyde (MDA) assay. Results 3,3′,4,5′-TMS and 3,4′,5-TMS suppressed LPS-induced NO release and pro-inflammatory cytokines (IL-6 and TNF-α) secretions in a dose-dependent manner in RAW 264.7 cells. 3,3′,4,5′-TMS and 3,4′,5-TMS significantly down-regulated the LPS-induced expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), and partially suppressed the activation of MAPK (phosphorylation of p38, JNK, ERK), and NF-κB (phosphorylation of IKKα/β, p65 and IκBα) signaling pathways; where phosphorylation of ERK and p65 was mildly but not significantly decreased by 3,3′,4,5′-TMS. LPS-induced NF-κB/p65 nuclear translocation was inhibited by both 3,3′,4,5′-TMS and 3,4′,5-TMS. Moreover, both resveratrol derivatives decreased the ROS levels. Conclusions 3,3′,4,5′-TMS and 3,4′,5-TMS significantly suppress LPS-induced inflammation in RAW 264.7 cells through inhibition of MAPK and NF-κB signaling pathways and also provide anti-oxidative effect. This study reveals potential therapeutic applications of 3,3′,4,5′-TMS and 3,4′,5-TMS for inflammatory diseases.

scholarly journals Phaseolin Attenuates Lipopolysaccharide-Induced Inflammation in RAW 264.7 Cells and Zebrafish

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 420
Author(s):  
Su-Jung Hwang ◽  
Ye-Seul Song ◽  
Hyo-Jong Lee
Keyword(s):  
Nitric Oxide ◽  
Nuclear Translocation ◽  
Raw 264.7 Cells ◽  
Network Pharmacology ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Bioactive Constituents

Kushen (Radix Sophorae flavescentis) is used to treat ulcerative colitis, tumors, and pruritus. Recently, phaseolin, formononetin, matrine, luteolin, and quercetin, through a network pharmacology approach, were tentatively identified as five bioactive constituents responsible for the anti-inflammatory effects of S. flavescentis. However, the role of phaseolin (one of the primary components of S. flavescentis) in the direct regulation of inflammation and inflammatory processes is not well known. In this study, the beneficial role of phaseolin against inflammation was explored in lipopolysaccharide (LPS)-induced inflammation models of RAW 264.7 macrophages and zebrafish larvae. Phaseolin inhibited LPS-mediated production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS), without affecting cell viability. In addition, phaseolin suppressed pro-inflammatory mediators such as cyclooxygenase 2 (COX-2), interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6) in a dose-dependent manner. Furthermore, phaseolin reduced matrix metalloproteinase (MMP) activity as well as macrophage adhesion in vitro and the recruitment of leukocytes in vivo by downregulating Ninjurin 1 (Ninj1), an adhesion molecule. Finally, phaseolin inhibited the nuclear translocation of nuclear factor-kappa B (NF-κB). In view of the above, our results suggest that phaseolin could be a potential therapeutic candidate for the management of inflammation.

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