scholarly journals Fucoidan Isolated from Saccharina japonica Inhibits LPS-Induced Inflammation in Macrophages via Blocking NF-κB, MAPK and JAK-STAT Pathways

Marine Drugs ◽  
2020 ◽  
Vol 18 (6) ◽  
pp. 328 ◽  
Author(s):  
Jing Ye ◽  
Donghui Chen ◽  
Zhicheng Ye ◽  
Yayan Huang ◽  
Na Zhang ◽  
...  
Keyword(s):  
High Performance ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Biological Activities ◽  
Saccharina Japonica ◽  
Janus Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Resonance Spectroscopy ◽  
Mechanism Study ◽  
Anti Inflammatory

Fucoidan has been reported to have a variety of biological activities. However, different algae species, extraction methods, harvesting seasons, and growth regions lead to the structural variation of fucoidan, which would affect the bioactivities of fucoidan. To date, the anti-inflammatory properties and the underlying mechanism of fucoidan from brown alga Saccharina japonica (S. japonica) remain limited. The aims of the present study were to investigate the structure, the anti-inflammatory properties, and the potential molecular mechanisms of fucoidan isolated from S. japonica (SF6) against lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. SF6 was characterized using high performance liquid gel permeation chromatography (HPGPC), Fourier transform infrared spectroscopy (FTIR), and nuclear magnetic resonance spectroscopy (NMR), and observed to be rich in fucose, galactose, and sulfate. Additionally, results showed that SF6 remarkably inhibited LPS-induced production of various inflammatory mediators and pro-inflammation cytokines, including nitric oxide (NO), NO synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-β (IL-β), and interleukin-6 (IL-6). A mechanism study showed that SF6 could effectively inhibit inflammatory responses through blocking LPS-induced inflammation pathways, including nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and Janus kinase (JAK)-2 and signal transducer and activator of transcription (STAT)-1/3 pathways. These results suggested that SF6 has the potential to be developed as an anti-inflammatory agent applied in functional food.

scholarly journals Compound traditional Chinese medicine dermatitis ointment ameliorates inflammatory responses and dysregulation of itch-related molecules in atopic dermatitis

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Rongrong Zhang ◽  
Hongyin Zhang ◽  
Shuai Shao ◽  
Yingxin Shen ◽  
Fengqin Xiao ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Liquid Chromatography ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
High Performance ◽  
Inflammatory Responses ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Hplc Fingerprint ◽  
Anti Inflammatory

Abstract Background Atopic dermatitis (AD) is a chronic inflammatory skin disease accompanied with itchy and scaly rash. Compound traditional Chinese medicine dermatitis ointment (CTCMDO) consists of a mixture of extracts from five plants, which had been used in AD treatment due to good anti-inflammatory and anti-allergic effects. Materials and methods In this study, high-performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometer (LC/MS) were performed to analyze the active ingredients of CTCMDO in detail and to establish its HPLC fingerprint. Furthermore, the anti-inflammatory and antipruritic activities of CTCMDO were studied in the treatment of DNCB-induced AD in mice. Results A total of 44 compounds including phenylpropionic acid compounds, alkaloid compounds, curcumin compounds and lignans were identified via combined HPLC and LC/MS. A fingerprint with 17 common peaks was established. In AD-like mice, DNCB-induced scratching behavior had been suppressed in the treatment of CTCMDO in a dose-dependent manner. Furthermore, the detailed experimental results indicated that the AD can be effectively improved via inhibiting the production of Th1/2 cytokines in serum, reversing the upregulation of substance P levels of itch-related genes in the skin, and suppressing the phosphorylation of JNK, ERK, and p38 in the skin. Conclusion This work indicated that CTCMDO can significantly improve AD via attenuating the pathological alterations of Th1/2 cytokines and itch-related mediators, as well as inhibiting the phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB).

scholarly journals Ergosta-7,9(11),22-trien-3β-ol Attenuates Inflammatory Responses via Inhibiting MAPK/AP-1 Induced IL-6/JAK/STAT Pathways and Activating Nrf2/HO-1 Signaling in LPS-Stimulated Macrophage-like Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1430
Author(s):  
Yi-Ping Huang ◽  
Dar-Ren Chen ◽  
Wen-Jen Lin ◽  
Yu-Hsien Lin ◽  
Jiann-Yeu Chen ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Interleukin 6 ◽  
Inflammatory Responses ◽  
Janus Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Raw 264.7 Cells ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Bv2 Cells ◽  
Anti Inflammatory

Chronic inflammation induces autoimmune disorders and chronic diseases. Several natural products activate nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, attenuating inflammatory responses. Ergosta-7,9(11),22-trien-3β-ol (EK100) isolated from Cordyceps militaris showed anti-inflammatory and antioxidative activity, but those mechanisms are still unclear. This study is the first to investigate EK100 on antioxidant Nrf2 relative genes expression in LPS-stimulated macrophage-like cell lines. The results showed that EK100 reduced IL-6 (interleukin-6) and tumor necrosis factor-α production. EK100 also attenuated a mitogen-activated protein kinase/activator protein-1 (MAPK/AP-1) pathway and interleukin-6/Janus kinase/signal transducer and activator of transcription (IL-6/JAK/STAT) pathway in LPS-stimulated cells. Toll-like receptor 4 (TLR4) inhibitor CLI-095 and MAPK inhibitors can synergize the anti-inflammatory response of EK100 in LPS-stimulated cells. Moreover, EK100 activated Nrf2/HO-1 (heme oxygenase-1) signaling in LPS-stimulated murine macrophage-like RAW 264.7 cells, murine microglial BV2 cells, and human monocytic leukemia THP-1 cells. However, Nrf2 small interfering RNA (Nrf2 siRNA) reversed EK100-induced antioxidative proteins expressions. In conclusion, EK100 showed anti-inflammatory responses via activating the antioxidative Nrf2/HO-1 signaling and inhibiting TLR4 related MAPK/AP-1 induced IL-6/JAK/STAT pathways in the LPS-stimulated cells in vitro. The results suggest EK100 acts as a novel antioxidant with multiple therapeutic targets that can potentially be developed to treat chronic inflammation-related diseases.

scholarly journals Anti-Inflammatory Mechanisms of Koreanaside A, a Lignan Isolated from the Flower of Forsythia koreana, against LPS-Induced Macrophage Activation and DSS-Induced Colitis Mice: The Crucial Role of AP-1, NF-κB, and JAK/STAT Signaling

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1163 ◽  
Author(s):  
Kim ◽  
Shin ◽  
Chung ◽  
Lee ◽  
Baek ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Inflammatory Responses ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Janus Kinase ◽  
Mesenchymal Transition ◽  
Stat Signaling ◽  
Anti Inflammatory

The current treatment options for inflammatory bowel disease (IBD) are unsatisfactory. Therefore, novel and safer therapies are needed. We previously reported that koreanaside A (KA) showed high radical scavenging activity and suppressed vascular cell adhesion molecule 1 (VCAM-1) expression in vascular smooth muscle cells. However, the molecular mechanisms involved in its anti-inflammatory effect have not been reported. KA inhibited pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nitric oxide (NO), and prostaglandin E2 (PGE2). KA inhibited the production and mRNA expression of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) induced by LPS. KA downregulated the myeloid differentiation primary response 88 (MyD88)-dependent inflammatory gene expressions in the MyD88-overexpressed cells. KA suppressed the LPS-induced transcriptional and DNA-binding activities of activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB). KA was found to inhibit the phosphorylation of Janus kinase 1/2 (JAK1/2) and signal transducers and activators of transcription 1/3 (STAT1/3). In DSS-induced colitis mice, KA relieved the symptoms of colitis by suppressing inflammatory cell infiltration, restoring tight junction (TJ)- and epithelial–mesenchymal transition (EMT)-related protein expression, and inactivating AP-1, NF-κB, and STAT1/3. Therefore, KA reduced inflammatory responses by downregulating AP-1, NF-κB, and JAK/STAT signaling in LPS-induced macrophages and DSS-induced colitis mice.

scholarly journals Luteolin-3′-O-Phosphate Inhibits Lipopolysaccharide-Induced Inflammatory Responses by Regulating NF-κB/MAPK Cascade Signaling in RAW 264.7 Cells

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7393
Author(s):  
Jung-Hwan Kim ◽  
Tae-Jin Park ◽  
Jin-Soo Park ◽  
Min-Seon Kim ◽  
Won-Jae Chi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Mitogen Activated Protein Kinase ◽  
Inflammatory Activity ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Luteolin (LT), present in most plants, has potent anti-inflammatory properties both in vitro and in vivo. Furthermore, some of its derivatives, such as luteolin-7-O-glucoside, also exhibit anti-inflammatory activity. However, the molecular mechanisms underlying luteolin-3′-O-phosphate (LTP)-mediated immune regulation are not fully understood. In this paper, we compared the anti-inflammatory properties of LT and LTP and analyzed their molecular mechanisms of action; we obtained LTP via the biorenovation of LT. We investigated the anti-inflammatory activities of LT and LTP in macrophage RAW 264.7 cells. We confirmed from previously reported literature that LT inhibits the production of nitric oxide and prostaglandin E2, as well as the expression of inducible NO synthetase and cyclooxygenase-2. In addition, expressions of inflammatory genes and mediators, such as tumor necrosis factor-α, interleukin-6, and interleukin-1β, were suppressed. LTP showed anti-inflammatory activity similar to LT, but better anti-inflammatory activity in all the experiments, while also inhibiting mitogen-activated protein kinase and nuclear factor-kappa B more effectively than LT. At a concentration of 10 μM, LTP showed differences of 2.1 to 44.5% in the activity compared to LT; it also showed higher anti-inflammatory activity. Our findings suggest that LTP has stronger anti-inflammatory activity than LT.

scholarly journals On the Mechanism of Action of Anti-Inflammatory Activity of Hypericin: An In Silico Study Pointing to the Relevance of Janus Kinases Inhibition

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3058 ◽  
Author(s):  
Luca Dellafiora ◽  
Gianni Galaverna ◽  
Gabriele Cruciani ◽  
Chiara Dall’Asta ◽  
Renato Bruni
Keyword(s):  
Molecular Mechanisms ◽  
Competitive Inhibitor ◽  
Janus Kinase ◽  
Inflammatory Activity ◽  
Docking Simulations ◽  
Janus Kinase 1 ◽  
In Silico Study ◽  
Hypericum Perforatum L ◽  
Actual Effectiveness ◽  
Anti Inflammatory

St. John’s Wort (Hypericum perforatum L.) flowers are commonly used in ethnomedical preparations with promising outcomes to treat inflammation both per os and by topical application. However, the underlying molecular mechanisms need to be described toward a rational, evidence-based, and reproducible use. For this purpose, the aptitude of the prominent Hypericum metabolite hypericin was assessed, along with that of its main congeners, to behave as an inhibitor of janus kinase 1, a relevant enzyme in inflammatory response. It was used a molecular modeling approach relying on docking simulations, pharmacophoric modeling, and molecular dynamics to estimate the capability of molecules to interact and persist within the enzyme pocket. Our results highlighted the capability of hypericin, and some of its analogues and metabolites, to behave as ATP-competitive inhibitor providing: (i) a likely mechanistic elucidation of anti-inflammatory activity of H. perforatum extracts containing hypericin and related compounds; and (ii) a rational-based prioritization of H. perforatum components to further characterize their actual effectiveness as anti-inflammatory agents.

scholarly journals MiR-155/GSK-3β mediates anti-inflammatory effect of Chikusetsusaponin IVa by inhibiting NF-κB signaling pathway in LPS-induced RAW264.7 cell

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yi Xin ◽  
Qin Yuan ◽  
Chaoqi Liu ◽  
Changcheng Zhang ◽  
Ding Yuan
Keyword(s):  
Signaling Pathway ◽  
Mouse Liver ◽  
Inflammatory Responses ◽  
Biological Activities ◽  
Raw264.7 Cells ◽  
Inflammation Model ◽  
Raw264.7 Cell ◽  
Anti Inflammatory ◽  
Gsk 3Β ◽  
Inflammatory Effect

Abstract It has been demonstrated that Chikusetsusaponin IVa (CsIVa) possesses abundant biological activities. Herein, using LPS to establish acute inflammation model of mouse liver and cell line inflammation model, we investigated whether miR-155/GSK-3β regulated NF-κB signaling pathway, and CsIVa exerted anti-inflammatory effects by regulating miR-155/GSK-3β signaling pathway. Our results showed that LPS induced high expression of miR-155 and miR-155 promoted macrophage activation through GSK-3β. In addition, CsIVa inhibited inflammatory responses in LPS-induced mouse liver and RAW264.7 cells. Furthermore, we demonstrated that CsIVa improved the inflammatory response in LPS-induced RAW264.7 cells by inhibiting miR-155, increasing GSK-3β expression, and inhibiting NF-κB signaling pathway. In conclusion, our study reveals that CsIVa suppresses LPS-triggered immune response by miR-155/GSK-3β-NF-κB signaling pathway.

scholarly journals Apoptosis Induction of Fibroblast-Like Synoviocytes Is an Important Molecular-Mechanism for Herbal Medicine along with its Active Components in Treating Rheumatoid Arthritis

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 795 ◽  
Author(s):  
Qing Zhang ◽  
Jia Liu ◽  
Mengmeng Zhang ◽  
Shujun Wei ◽  
Ruolan Li ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Mechanisms ◽  
Herbal Medicines ◽  
Janus Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Signal Pathways ◽  
Apoptosis Induction ◽  
Apoptotic Pathway ◽  
Induction Of Apoptosis ◽  
Fibroblast Like Synoviocytes

Rheumatoid arthritis (RA) is a known chronic autoimmune disease can cause joint deformity and even loss of joint function. Fibroblast-like synoviocytes (FLS), one of the main cell types in synovial tissues of RA patients, are key effector cells in the development of RA and are considered as promising therapeutic targets for treating RA. Herbal medicines are precious resources for finding novel agents for treating various diseases including RA. It is reported that induction of apoptosis in FLS is an important mechanism for the herbal medicines to treat RA. Consequently, this paper reviewed the current available references on pro-apoptotic effects of herbal medicines on FLS and summarized the related possible signal pathways. Taken together, the main related signal pathways are concluded as death receptors mediated apoptotic pathway, mitochondrial dependent apoptotic pathway, NF-κB mediated apoptotic pathways, mitogen-activated protein kinase (MAPK) mediated apoptotic pathway, endoplasmic reticulum stress (ERS) mediated apoptotic pathway, PI3K-Akt mediated apoptotic pathway, and other reported pathways such as janus kinase/signal transducers and activators of transcription (JAK-STAT) signal pathway. Understanding the apoptosis induction pathways in FLS of these herbal medicines will not only help clear molecular mechanisms of herbal medicines for treating RA but also be beneficial for finding novel candidate therapeutic drugs from natural herbal medicines. Thus, we expect the present review will highlight the importance of herbal medicines and its components for treating RA via induction of apoptosis in FLS, and provide some directions for the future development of these mentioned herbal medicines as anti-RA drugs in clinical.

scholarly journals The Immunomodulatory and Anti-Inflammatory Role of Polyphenols

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1618 ◽  
Author(s):  
Nour Yahfoufi ◽  
Nawal Alsadi ◽  
Majed Jambi ◽  
Chantal Matar
Keyword(s):  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Biologically Active ◽  
Mitogen Activated Protein Kinase ◽  
Clear Understanding ◽  
Akt Inhibitor ◽  
Amino Terminal ◽  
Anti Inflammatory ◽  
Arachidonic Acids

This review offers a systematic understanding about how polyphenols target multiple inflammatory components and lead to anti-inflammatory mechanisms. It provides a clear understanding of the molecular mechanisms of action of phenolic compounds. Polyphenols regulate immunity by interfering with immune cell regulation, proinflammatory cytokines’ synthesis, and gene expression. They inactivate NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and modulate mitogen-activated protein Kinase (MAPk) and arachidonic acids pathways. Polyphenolic compounds inhibit phosphatidylinositide 3-kinases/protein kinase B (PI3K/AkT), inhibitor of kappa kinase/c-Jun amino-terminal kinases (IKK/JNK), mammalian target of rapamycin complex 1 (mTORC1) which is a protein complex that controls protein synthesis, and JAK/STAT. They can suppress toll-like receptor (TLR) and pro-inflammatory genes’ expression. Their antioxidant activity and ability to inhibit enzymes involved in the production of eicosanoids contribute as well to their anti-inflammation properties. They inhibit certain enzymes involved in reactive oxygen species ROS production like xanthine oxidase and NADPH oxidase (NOX) while they upregulate other endogenous antioxidant enzymes like superoxide dismutase (SOD), catalase, and glutathione (GSH) peroxidase (Px). Furthermore, they inhibit phospholipase A2 (PLA2), cyclooxygenase (COX) and lipoxygenase (LOX) leading to a reduction in the production of prostaglandins (PGs) and leukotrienes (LTs) and inflammation antagonism. The effects of these biologically active compounds on the immune system are associated with extended health benefits for different chronic inflammatory diseases. Studies of plant extracts and compounds show that polyphenols can play a beneficial role in the prevention and the progress of chronic diseases related to inflammation such as diabetes, obesity, neurodegeneration, cancers, and cardiovascular diseases, among other conditions.

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 Treatment of inflammatory arthritis via targeting of tristetraprolin, a master regulator of pro-inflammatory gene expression

2016 ◽  
Vol 76 (3) ◽  
pp. 612-619 ◽  
Author(s):  
E A Ross ◽  
A J Naylor ◽  
J D O'Neil ◽  
T Crowley ◽  
M L Ridley ◽  
...  
Keyword(s):  
Inflammatory Arthritis ◽  
Inflammatory Responses ◽  
Vascular Endothelial Cells ◽  
Bone Erosion ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase ◽  
Critical Determinant ◽  
Anti Inflammatory

ObjectivesTristetraprolin (TTP), a negative regulator of many pro-inflammatory genes, is strongly expressed in rheumatoid synovial cells. The mitogen-activated protein kinase (MAPK) p38 pathway mediates the inactivation of TTP via phosphorylation of two serine residues. We wished to test the hypothesis that these phosphorylations contribute to the development of inflammatory arthritis, and that, conversely, joint inflammation may be inhibited by promoting the dephosphorylation and activation of TTP.MethodsThe expression of TTP and its relationship with MAPK p38 activity were examined in non-inflamed and rheumatoid arthritis (RA) synovial tissue. Experimental arthritis was induced in a genetically modified mouse strain, in which endogenous TTP cannot be phosphorylated and inactivated. In vitro and in vivo experiments were performed to test anti-inflammatory effects of compounds that activate the protein phosphatase 2A (PP2A) and promote dephosphorylation of TTP.ResultsTTP expression was significantly higher in RA than non-inflamed synovium, detected in macrophages, vascular endothelial cells and some fibroblasts and co-localised with MAPK p38 activation. Substitution of TTP phosphorylation sites conferred dramatic protection against inflammatory arthritis in mice. Two distinct PP2A agonists also reduced inflammation and prevented bone erosion. In vitro anti-inflammatory effects of PP2A agonism were mediated by TTP activation.ConclusionsThe phosphorylation state of TTP is a critical determinant of inflammatory responses, and a tractable target for novel anti-inflammatory treatments.

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