scholarly journals Discovery of Novel Pterostilbene Derivatives That Might Treat Sepsis by Attenuating Oxidative Stress and Inflammation through Modulation of MAPKs/NF-κB Signaling Pathways

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1333
Author(s):  
Mengyuan Fang ◽  
Tingfeng Zou ◽  
Xiaoxiao Yang ◽  
Zhen Zhang ◽  
Peichang Cao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Responses ◽  
Nuclear Factor Κb ◽  
Severe Trauma ◽  
Mrna Levels ◽  
Raw264.7 Macrophages ◽  
Life Threatening ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Oxide Synthase

Sepsis remains one of the most common life-threatening illnesses that is characterized by a systemic inflammatory response syndrome (SIRS) and usually arises following severe trauma and various septic infections. It is still in urgent need of new effective therapeutic agents, and chances are great that some candidates can be identified that can attenuate oxidative stress and inflammatory responses. Pterostilbene, which exerts attractive anti-oxidative and anti-inflammatory activities, is a homologue of natural polyphenolic derivative of resveratrol. Starting from it, we have made several rounds of rational optimizations. Firstly, based on the strategy of pharmacophore combination, indanone moiety was introduced onto the pterostilbene skeleton to generate a novel series of pterostilbene derivatives (PIF_1–PIF_16) which could possess both anti-oxidative and anti-inflammatory activities for sepsis treatment. Then, all target compounds were subjected to their structure–activity relationships (SAR) screening of anti-inflammatory activity in mouse mononuclear macrophage RAW264.7 cell line, and their cytotoxicities were determined after. Finally, an optimal compound, PIF_9, was identified. It decreased the mRNA levels of lipopolysaccharide (LPS)-induced interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX2). We also found that the anti-inflammatory effects might be contributed by its suppression on the nuclear factor-κB (NF-κB) and MAPKs signaling pathway. Moreover, PIF_9 also demonstrated potent anti-oxidative activity in RAW264.7 macrophages and the sepsis mouse model. Not surprisingly, with the benefits mentioned above, it ameliorated LPS-induced sepsis in C57BL/6J mice and reduced multi-organ toxicity. Taken together, PIF_9 was identified as a potential sepsis solution, targeting inflammation and oxidative stress through modulating MAPKs/NF-κB.

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.

Glycyrrhizin, the main active compound in liquorice, attenuates pro-inflammatory responses by interfering with membrane-dependent receptor signalling

2009 ◽  
Vol 421 (3) ◽  
pp. 473-482 ◽  
Author(s):  
Bärbel Schröfelbauer ◽  
Johanna Raffetseder ◽  
Maria Hauner ◽  
Andrea Wolkerstorfer ◽  
Wolfgang Ernst ◽  
...  
Keyword(s):  
Active Compound ◽  
Inflammatory Responses ◽  
Nuclear Factor Κb ◽  
Mitogen Activated Protein Kinase ◽  
Raw 264.7 Cells ◽  
Cpg Dna ◽  
Cellular Attachment ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory ◽  
Factor Α

The triterpene glycoside glycyrrhizin is the main active compound in liquorice. It is used as a herbal medicine owing to its anticancer, antiviral and anti-inflammatory properties. Its mode of action, however, remains widely unknown. In the present study, we aimed to elucidate the molecular mechanism of glycyrrhizin in attenuating inflammatory responses in macrophages. Using microarray analysis, we found that glycyrrhizin caused a broad block in the induction of pro-inflammatory mediators induced by the TLR (Toll-like receptor) 9 agonist CpG-DNA in RAW 264.7 cells. Furthermore, we found that glycyrrhizin also strongly attenuated inflammatory responses induced by TLR3 and TLR4 ligands. The inhibition was accompanied by decreased activation not only of the NF-κB (nuclear factor κB) pathway but also of the parallel MAPK (mitogen-activated protein kinase) signalling cascade upon stimulation with TLR9 and TLR4 agonists. Further analysis of upstream events revealed that glycyrrhizin treatment decreased cellular attachment and/or uptake of CpG-DNA and strongly impaired TLR4 internalization. Moreover, we found that the anti-inflammatory effects were specific for membrane-dependent receptor-mediated stimuli, as glycyrrhizin was ineffective in blocking Tnfa (tumour necrosis factor α gene) induction upon stimulation with PMA, a receptor- and membrane-independent stimulus. These observations suggest that the broad anti-inflammatory activity of glycyrrhizin is mediated by the interaction with the lipid bilayer, thereby attenuating receptor-mediated signalling.

scholarly journals (E)-9-Octadecenoic Acid Ethyl Ester Derived from Lotus Seedpod Ameliorates Inflammatory Responses by Regulating MAPKs and NF-κB Signalling Pathways in LPS-Induced RAW264.7 Macrophages

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Chuanqi Xie ◽  
Shufen Wang ◽  
Mingyuan Cao ◽  
Wei Xiong ◽  
Lei Wu
Keyword(s):  
Nitric Oxide ◽  
Ethyl Ester ◽  
Inflammatory Responses ◽  
Octadecenoic Acid ◽  
Acid Ethyl Ester ◽  
Signalling Pathways ◽  
Mrna Levels ◽  
Raw264.7 Macrophages ◽  
Anti Inflammatory ◽  
Lotus Seedpod

Inflammation is generally considered a key risk factor in the progress of several chronic diseases, such as arthritis, gastritis, and hepatitis. Natural products with anti-inflammatory ability have played a great role in the process of overcoming these inflammatory diseases. In this study, we evaluated the anti-inflammatory activities of ten natural compounds derived from lotus seedpod and discovered (E)-9-octadecenoic acid ethyl ester (E9OAEE) inhibited the production of nitric oxide (NO) optimally in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Furthermore, we explored the effects of E9OAEE on inflammatory responses and the underlying mechanisms in LPS-induced RAW264.7 macrophages. The results indicated that E9OAEE significantly suppressed the production of NO, prostaglandin E2 (PGE2), and tumour necrosis factor-α (TNFα) in a dose-dependent manner. The protein expression and mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) were inhibited by pretreatment of E9OAEE. Furthermore, E9OAEE restrained the phosphorylation of mitogen-activated protein kinase (MAPKs) family members, ERK, P38, and JNK stimulated by LPS-treated for 30 min and prevented the nuclear translocation of nuclear factor-kappa B (NF-κB) prompted by LPS-treated for 6 h in RAW264.7 macrophages. Taken together, we discovered an anti-inflammatory component from lotus seedpod and identified E9OAEE attenuated the inflammatory response in LPS-induced RAW264.7 macrophages probably by regulating the activation of MAPKs and NF-κB signalling pathways, which would provide some base for the development of new anti-inflammatory drugs.

scholarly journals Caragana rosea Turcz Methanol Extract Inhibits Lipopolysaccharide-Induced Inflammatory Responses by Suppressing the TLR4/NF-κB/IRF3 Signaling Pathways

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6660
Author(s):  
Ankita Mitra ◽  
Akash Ahuja ◽  
Laily Rahmawati ◽  
Han Gyung Kim ◽  
Byoung Young Woo ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Methanol Extract ◽  
Inflammatory Responses ◽  
Eastern China ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Raw264.7 Macrophages ◽  
Anti Inflammatory

Caragana rosea Turcz, which belongs to the Leguminosae family, is a small shrub found in Northern and Eastern China that is known to possess anti-inflammatory properties and is used to treat fever, asthma, and cough. However, the underlying molecular mechanisms of its anti-inflammatory effects are unknown. Therefore, we used lipopolysaccharide (LPS) in RAW264.7 macrophages to investigate the molecular mechanisms that underlie the anti-inflammatory activities of a methanol extract of Caragana rosea (Cr-ME). We showed that Cr-ME reduced the production of nitric oxide (NO) and mRNA levels of iNOS, TNF-α, and IL-6 in a concentration-dependent manner. We also found that Cr-ME blocked MyD88- and TBK1-induced NF-κB and IRF3 promoter activity, suggesting that it affects multiple targets. Moreover, Cr-ME reduced the phosphorylation levels of IκBα, IKKα/β and IRF3 in a time-dependent manner and regulated the upstream NF-κB proteins Syk and Src, and the IRF3 protein TBK1. Upon overexpression of Src and TBK1, Cr-ME stimulation attenuated the phosphorylation of the NF-κB subunits p50 and p65 and IRF3 signaling. Together, our results suggest that the anti-inflammatory activity of Cr-ME occurs by inhibiting the NF-κB and IRF3 signaling pathways.

scholarly journals Anti-Inflammatory Compounds from Atractylodes macrocephala

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1859 ◽  
Author(s):  
Dawoon Jeong ◽  
Guang-zhi Dong ◽  
Hwa Jin Lee ◽  
Jae-Ha Ryu
Keyword(s):  
Nitric Oxide ◽  
Nuclear Translocation ◽  
Inflammatory Diseases ◽  
Nuclear Factor Κb ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Mrna Levels ◽  
Anti Inflammatory ◽  
Atractylodes Macrocephala ◽  
Oxide Synthase

In relation to anti-inflammatory agents from medicinal plants, we have isolated three compounds from Atractylodes macrocephala; 1, 2-[(2E)-3,7-dimethyl-2,6-octadienyl]-6-methyl-2, 5-cyclohexadiene-1, 4-dione; 2, 1-acetoxy-tetradeca-6E,12E-diene-8, 10-diyne-3-ol; 3, 1,3-diacetoxy-tetradeca-6E, 12E-diene-8, 10-diyne. Compounds 1–3 showed concentration-dependent inhibitory effects on production of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Western blotting and RT-PCR analyses demonstrated that compounds 1–3 suppressed the protein and mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, compounds 1–3 inhibited transcriptional activity of nuclear factor-κB (NF-κB) and nuclear translocation of NF-κB in LPS-activated RAW 264.7 cells. The most active compound among them, compound 1, could reduce the mRNA levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and suppress the phosphorylation of MAPK including p38, JNK, and ERK1/2. Taken together, these results suggest that compounds 1–3 from A. macrocephala can be therapeutic candidates to treat inflammatory diseases.

scholarly journals Gymnema inodorum (Lour.) Decne. Extract Alleviates Oxidative Stress and Inflammatory Mediators Produced by RAW264.7 Macrophages

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Benjawan Dunkhunthod ◽  
Chutima Talabnin ◽  
Mark Murphy ◽  
Kanjana Thumanu ◽  
Patcharawan Sittisart ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Nuclear Translocation ◽  
Antioxidant Properties ◽  
Raw264.7 Cells ◽  
Mrna Levels ◽  
Ros Production ◽  
Raw264.7 Macrophages ◽  
Ifn Γ ◽  
Anti Inflammatory

Gymnema inodorum (Lour.) Decne. (G. inodorum) is widely used in Northern Thai cuisine as local vegetables and commercial herb tea products. In the present study, G. inodorum extract (GIE) was evaluated for its antioxidant and anti-inflammatory effects in LPS plus IFN-γ-induced RAW264.7 cells. Major compounds in GIE were evaluated using GC-MS and found 16 volatile compounds presenting in the extract. GIE exhibited antioxidant activity by scavenging the intracellular reactive oxygen species (ROS) production and increasing superoxide dismutase 2 (SOD2) mRNA expression in LPS plus IFN-γ-induced RAW264.7 cells. GIE showed anti-inflammatory activity through suppressing nitric oxide (NO), proinflammatory cytokine production interleukin 6 (IL-6) and also downregulation of the expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and IL-6 mRNA levels in LPS plus IFN-γ-induced RAW264.7 cells. Mechanism studies showed that GIE suppressed the NF-κB p65 nuclear translocation and slightly decreased the phosphorylation of NF-κB p65 (p-NF-κB p65) protein. Our studies applied the synchrotron radiation-based FTIR microspectroscopy (SR-FTIR), supported by multivariate analysis, to identify the FTIR spectral changes based on macromolecule alterations occurring in RAW264.7 cells. SR-FTIR results demonstrated that the presence of LPS plus IFN-γ in RAW264.7 cells associated with the increase of amide I/amide II ratio (contributing to the alteration of secondary protein structure) and lipid content, whereas glycogen and other carbohydrate content were decreased. These findings lead us to believe that GIE may prevent oxidative damage by scavenging intracellular ROS production and activating the antioxidant gene, SOD2, expression. Therefore, it is possible that the antioxidant properties of GIE could modulate the inflammation process by regulating the ROS levels, which lead to the suppression of proinflammatory cytokines and genes. Therefore, GIE could be developed into a novel antioxidant and anti-inflammatory agent to treat and prevent diseases related to oxidative stress and inflammation.

scholarly journals Nardochinoid B Inhibited the Activation of RAW264.7 Macrophages Stimulated by Lipopolysaccharide through Activating the Nrf2/HO-1 Pathway

Molecules ◽  
2019 ◽  
Vol 24 (13) ◽  
pp. 2482 ◽  
Author(s):  
Yun-Da Yao ◽  
Xiu-Yu Shen ◽  
Jorge Machado ◽  
Jin-Fang Luo ◽  
Yi Dai ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Inhibitory Effect ◽  
New Drugs ◽  
Raw264.7 Cells ◽  
Raw264.7 Macrophages ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Oxide Synthase

Nardochinoid B (NAB) is a new compound isolated from Nardostachys chinensis. Although our previous study reported that the NAB suppressed the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW264.7 cells, the specific mechanisms of anti-inflammatory action of NAB remains unknown. Thus, we examined the effects of NAB against LPS-induced inflammation. In this study, we found that NAB suppressed the LPS-induced inflammatory responses by restraining the expression of inducible nitric oxide synthase (iNOS) proteins and mRNA instead of cyclooxygenase-2 (COX-2) protein and mRNA in RAW264.7 cells, implying that NAB may have lower side effects compared with nonsteroidal anti-inflammatory drugs (NSAIDs). Besides, NAB upregulated the protein and mRNA expressions of heme oxygenase (HO)-1 when it exerted its anti-inflammatory effects. Also, NAB restrained the production of NO by increasing HO-1 expression in LPS-stimulated RAW264.7 cells. Thus, it is considered that the anti-inflammatory effect of NAB is associated with an induction of antioxidant protein HO-1, and thus NAB may be a potential HO-1 inducer for treating inflammatory diseases. Moreover, our study found that the inhibitory effect of NAB on NO is similar to that of the positive drug dexamethasone, suggesting that NAB has great potential for developing new drugs in treating inflammatory diseases.

scholarly journals 20-Hydroxy-3-Oxolupan-28-Oic Acid Attenuates Inflammatory Responses by Regulating PI3K–Akt and MAPKs Signaling Pathways in LPS-Stimulated RAW264.7 Macrophages

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 386 ◽  
Author(s):  
Yufeng Cao ◽  
Fu Li ◽  
Yanyan Luo ◽  
Liang Zhang ◽  
Shuya Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Nuclear Factor Κb ◽  
Activator Protein 1 ◽  
Raw264.7 Macrophages ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

20-Hydroxy-3-oxolupan-28-oic acid (HOA), a lupane-type triterpene, was obtained from the leaves of Mahonia bealei, which is described in the Chinese Pharmacopeia as a remedy for inflammation and related diseases. The anti-inflammatory mechanisms of HOA, however, have not yet been fully elucidated. Therefore, the objective of this study was to characterize the molecular mechanisms of HOA in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. HOA suppressed the release of nitric oxide (NO), pro-inflammatory cytokine tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 macrophages without affecting cell viability. Quantitative real-time reverse-transcription polymerase chain reaction (RT-qPCR) analysis indicated that HOA also suppressed the gene expression of inducible NO synthase (iNOS), TNF-α, and IL-6. Further analyses demonstrated that HOA inhibited the phosphorylation of upstream signaling molecules, including p85, PDK1, Akt, IκBα, ERK, and JNK, as well as the nuclear translocation of nuclear factor κB (NF-κB) p65. Interestingly, HOA had no effect on the LPS-induced nuclear translocation of activator protein 1 (AP-1). Taken together, these results suggest that HOA inhibits the production of cytokine by downregulating iNOS, TNF-α, and IL-6 gene expression via the downregulation of phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinases (MAPKs), and the inhibition of NF-κB activation. Our findings indicate that HOA could potentially be used as an anti-inflammatory agent for medical use.

scholarly journals Anti-Inflammatory Effect of 4,5-Dicaffeoylquinic Acid on RAW264.7 Cells and a Rat Model of Inflammation

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3537
Author(s):  
Goeun Jang ◽  
Seulah Lee ◽  
Joonho Hong ◽  
Boram Park ◽  
Dokyung Kim ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nuclear Factor Κb ◽  
Raw264.7 Cells ◽  
Dicaffeoylquinic Acid ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Oxide Synthase

Anti-inflammatory agents that are safer and more effective than the currently used non-steroidal anti-inflammatory drugs are urgently needed. The dicaffeoylquinic acid (diCQA) isomer 4,5-diCQA exhibits antioxidant activity and various other health-promoting benefits; however, its anti-inflammatory properties require further investigation. This study was conducted to evaluate the anti-inflammatory properties of 4,5-diCQA in vitro and in vivo using RAW264.7 cells and a carrageenan-induced inflammation model, respectively. In RAW264.7 cells, 4,5-diCQA pretreatment significantly inhibited lipopolysaccharide-induced expression of nitric oxide, prostaglandin E2, nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, interleukin-1β, and interleukin-6, without inducing cytotoxicity. The inhibitory effects of 4,5-diCQA were mediated by the suppression of nuclear factor-κB nuclear translocation and mitogen-activated protein kinase (MAPK) phosphorylation. Oral administration of 4,5-diCQA at doses of 5, 10, and 20 mg/kg of the body weight suppressed carrageenan-induced edema and the expression of nitric oxide synthase, cyclooxygenase-2, and tumor necrosis factor-α in a dose-dependent manner. Collectively, our results suggest that 4,5-diCQA exerts anti-inflammatory effects by suppressing activation of the nuclear factor-κB and MAPK pathways in vitro and reducing carrageenan-induced edema in vivo. Therefore, 4,5-diCQA shows potential as a natural alternative to non-steroidal anti-inflammatory drugs.

Inhibition of chikusetsusaponin IVa on inflammatory responses in RAW264.7 cell line via MAPK pathway

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Guangren Xu ◽  
Hongyu Lei ◽  
Qiaoling Yuan ◽  
Huiyu Chen ◽  
Jianming Su
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Responses ◽  
Mapk Pathway ◽  
Biological Activities ◽  
Interleukin 10 ◽  
Raw264.7 Cell ◽  
Anti Inflammatory ◽  
Underlying Mechanisms ◽  
Factor Α ◽  
Oxide Synthase

AbstractChikusetsusaponin IVa (CHS-IVa), a saponin from herb Panacis japonicas, possesses extensive biological activities. However, the roles and underlying mechanisms of CHS-IVa on inflammation have not been fully clarified in the setting of murine macrophages. In this study, we found that CHS-IVa effectively reduced the expression of inflammatory mediators, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-1β (IL-1β), cyclooxygenase (COX-2), inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated murine macrophage-like RAW264.7 cells. Meanwhile, CHS-IVa could also evidently bate the contents of nitric oxide (NO) and prostaglandin E2 (PGE2) in cell culture supernatants. Furthermore, the anti-inflammatory activity of CHS-IVa may be via diminishing the phosphorylation of extracellular regulated protein kinases (ERK), p38, and c-Jun N-terminal kinase (JNK). Collectively, these findings will help to understand of the anti-inflammatory effects and mechanisms of P. japonicas deeply, and suggest a validated therapeutic use as an anti-inflammatory medication.

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