scholarly journals Salidroside Inhibits HMGB1 Acetylation and Release through Upregulation of SirT1 during Inflammation

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Zhilin Qi ◽  
Yao Zhang ◽  
Shimei Qi ◽  
Liefeng Ling ◽  
Lin Gui ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Inhibitory Effect ◽  
Signalling Pathway ◽  
Hmgb1 Level ◽  
Shrna Plasmid ◽  
Experimental Rat Model ◽  
Stat3 Signalling ◽  
Serum Hmgb1 Level ◽  
Inflammatory Effect

HMGB1, a highly conserved nonhistone DNA-binding protein, plays an important role in inflammatory diseases. Once released to the extracellular space, HMGB1 acts as a proinflammatory cytokine that triggers inflammatory reaction. Our previous study showed that salidroside exerts anti-inflammatory effect via inhibiting the JAK2-STAT3 signalling pathway. However, whether salidroside inhibits the release of HMGB1 is still unclear. In this study, we aim to study the effects of salidroside on HMGB1 release and then investigate the potential molecular mechanisms. In an experimental rat model of sepsis caused by CLP, salidroside administration significantly attenuated lung injury and reduced the serum HMGB1 level. In RAW264.7 cells, we investigated the effects of salidroside on LPS-induced HMGB1 release and then explored the underlying molecular mechanisms. We found that salidroside significantly inhibited LPS-induced HMGB1 release, and the inhibitory effect was correlated with the HMGB1 acetylation levels. Mechanismly, salidroside inhibits HMGB1 acetylation through the AMPK-SirT1 pathway. In addition, SirT1 overexpression attenuated LPS-induced HMGB1 acetylation and nucleocytoplasmic translocation. Furthermore, in SirT1 shRNA plasmid-transfected cells, salidroside treatment enhanced SirT1 expression and reduced LPS-activated HMGB1 acetylation and nucleocytoplasmic translocation. Collectively, these results demonstrated that salidroside might reduce HMGB1 release through the AMPK-SirT1 signalling pathway and suppress HMGB1 acetylation and nucleocytoplasmic translocation.

Lactobacillus fermentum IM12 attenuates inflammation in mice by inhibiting NF-κB-STAT3 signalling pathway

2017 ◽  
Vol 8 (3) ◽  
pp. 407-419 ◽  
Author(s):  
S.-M. Lim ◽  
H.M. Jang ◽  
S.-E. Jang ◽  
M.J. Han ◽  
D.-H. Kim
Keyword(s):  
Peritoneal Macrophages ◽  
Signalling Pathway ◽  
Lactobacillus Fermentum ◽  
Trinitrobenzene Sulfonic Acid ◽  
Myeloperoxidase Activity ◽  
Paw Oedema ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Stat3 Signalling ◽  
Inflammatory Effect

In the present study, we isolated Lactobacillus fermentum IM12 from human gut microbiota, which strongly inhibited interleukin (IL)-6 expression and STAT3 activation in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages, and examined its anti-inflammatory effect in mice with carrageenan-induced hind-paw oedema (CIE) or 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis (TIC). Oral administration of IM12 (0.2×109, 1×109 or 5×109 cfu/mouse, once a day for 3 days) in mice with CIE significantly suppressed the increase of oedema volume and thickness, as well as myeloperoxidase activity and IL-6, IL-17, NO, and prostaglandin E2 levels in the carrageenan-stimulated paw. Treatment with IM12 (1×109 cfu/mouse, once a day for 3 days) in mice with TIC significantly suppressed colon shortening, and myeloperoxidase activity and IL-6 and IL-17 levels. Treatment with IM12 in mice with CIE or TIC also suppressed the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, as well as activation of nuclear factor kappa beta (NF-κB) and signal transducer and activator of transcription 3 (STAT3). Furthermore, IM12 significantly inhibited the expression of iNOS, and COX-2, as well as activation of NF-κB in LPS-stimulated mouse peritoneal macrophages. The inflammatory effect of heat-inactivated IM12 was significantly different to that of live IM12 in mice with TIC, although anti-inflammatory effect of IM12 was reduced by heat treatment. Based on these findings, IM12 may attenuate inflammation by inhibiting NF-κB-STAT3 signalling pathway.

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 Targeting MAPK/NF-κB Pathways in Anti-Inflammatory Potential of Rutaecarpine: Impact on Src/FAK-Mediated Macrophage Migration

2021 ◽  
Vol 23 (1) ◽  
pp. 92
Author(s):  
Thanasekaran Jayakumar ◽  
Kao-Chang Lin ◽  
Chao-Chien Chang ◽  
Chih-Wei Hsia ◽  
Manjunath Manubolu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Inflammatory Diseases ◽  
Biological Activities ◽  
Inhibitory Effect ◽  
Vital Role ◽  
Raw 264.7 ◽  
Raw 264.7 Macrophages ◽  
Anti Inflammatory

Studies have discovered that different extracts of Evodia rutaecarpa and its phytochemicals show a variety of biological activities associated with inflammation. Although rutaecarpine, an alkaloid isolated from the unripe fruit of E. rutaecarpa, has been exposed to have anti-inflammatory properties, the mechanism of action has not been well studied. Thus, this study investigated the molecular mechanisms of rutaecarpine (RUT) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. RUT reserved the production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF-α), and interleukin (IL)-1β in the LPS-induced macrophages. RUT showed an inhibitory effect on the mitogen-activated protein kinases (MAPKs), and it also inhibited nuclear transcription factor kappa-B (NF-κB) by hindering IκBα and NF-κB p65 phosphorylation and p65 nuclear translocation. The phospho-PI3K and Akt was concentration-dependently suppressed by RUT. However, RUT not only suggestively reduced the migratory ability of macrophages and their numbers induced by LPS but also inhibited the phospho-Src, and FAK. Taken together, these results indicate that RUT participates a vital role in the inhibition of LPS-induced inflammatory processes in RAW 264.7 macrophages and that the mechanisms involve PI3K/Akt and MAPK-mediated downregulation of NF-κB signaling pathways. Notably, reducing the migration and number of cells induced by LPS via inhibiting of Src/FAK pathway was also included to the anti-inflammatory mechanism of RUT. Therefore, RUT may have potential benefits as a therapeutic agent against chronic inflammatory diseases.

scholarly journals Columbianadin Suppresses Lipopolysaccharide (LPS)-Induced Inflammation and Apoptosis through the NOD1 Pathway

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 549 ◽  
Author(s):  
Chao Zhang ◽  
Alan Hsu ◽  
He Pan ◽  
Yinuo Gu ◽  
Xu Zuo ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Therapeutic Agent ◽  
Inflammatory Diseases ◽  
Mechanisms Of Action ◽  
Bioactive Constituents ◽  
Cellular Apoptosis ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Columbianadin (CBN) is one of the main bioactive constituents isolated from the root of Angelica pubescens. Although the anti-inflammatory activity of CBN has been reported, the underpinning mechanism of this remains unclear. In this study, we investigated the anti-inflammatory effect of CBN on lipopolysaccharide (LPS)-stimulated THP-1 cells and explored the possible underlying molecular mechanisms. The results showed that CBN suppressed LPS-mediated inflammatory response mainly through the inactivation of the NOD1 and NF- κ B p65 signaling pathways. Knockdown of NOD1 reduced the degree to which inflammatory cytokines decreased following CBN treatment, whereas forced expression of NOD1 and CBN treatment reduced NF- κ B p65 activation and the secretion of inflammatory cytokines. Furthermore, CBN significantly reduced cellular apoptosis by inhibiting the NOD1 pathway. Collectively, our results indicate that CBN suppressed the LPS-mediated inflammatory response by inhibiting NOD1/NF- κ B activation. Further investigations are required to determine the mechanisms of action of CBN in the inhibition of NOD signaling: However, CBN may be employed as a therapeutic agent for multiple 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.

The Immunomodulatory Role of G2013 (α-L-Guluronic Acid) on the Expression of TLR2 and TLR4 in HT29 cell line

2019 ◽  
Vol 16 (1) ◽  
pp. 91-95 ◽  
Author(s):  
Hamid Farhang ◽  
Laleh Sharifi ◽  
Mohammad Mehdi Soltan Dallal ◽  
Mona Moshiri ◽  
Zahra Norouzbabaie ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Rna Extraction ◽  
Cell Plate ◽  
Inhibitory Effect ◽  
Control Group ◽  
Ht29 Cells ◽  
Guluronic Acid ◽  
Tlr4 Mrna

Background: The non-steroidal anti-inflammatory drugs (NSAIDs) play crucial role in the controlling of inflammatory diseases. Due to the vast side effects of NSAIDs, its use is limited. G2013 or &amp;#945;-L-Guluronic Acid is a new NSAID with immunomodulatory features. Objectives: Considering the leading role of TLRs in inflammatory responses, in this study, we aimed to evaluate G2013 cytotoxicity and its effect on the expression of TLR2 and TLR4 molecules. Methods: HEK293-TLR2 and HEK293-TLR4 cells were cultured and seeded on 96-well cell plate, and MTT assay was performed for detecting the viability of the cells after treatment with different concentrations of G2013. HT29 cells were grown and treated with low and high doses of G2013. After total RNA extraction and cDNA synthesis, quantitative real-time PCR were performed to assess the TLR2 and TLR4 mRNA synthesis. Results: We found that concentrations of ≤125 &amp;#181;g/ml of G2013 had no apparent cytotoxicity effect on the HEK293-TLR2 and -TLR4 cells. Our results indicated that after G2013 treatment (5 &amp;#181;g/ml) in HT29 cells, TLR2 and TLR4 mRNA expression decreased significantly compared with the untreated control group (p=0.02 and p=0.001 respectively). Conclusion: The results of this study revealed that G2013 can down regulate the TLR2 and TLR4 gene expression and exerts its inhibitory effect. Our findings are parallel to our previous finding which showed G2013 ability to down regulate the signaling pathway of TLRs. However, further studies are needed to identify the molecular mechanism of G2013.<p&gt;

Natural Products for Regulating Macrophages M2 Polarization

2020 ◽  
Vol 15 (7) ◽  
pp. 559-569 ◽  
Author(s):  
Zhen Chang ◽  
Youhan Wang ◽  
Chang Liu ◽  
Wanli Smith ◽  
Lingbo Kong
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Therapeutic Strategies ◽  
Research Progress ◽  
Cellular Mechanisms ◽  
Pharmacological Activities ◽  
Current Review ◽  
M2 Polarization ◽  
Macrophages Polarization ◽  
Herbal Plants

Macrophages M2 polarization have been taken as an anti-inflammatory progression during inflammation. Natural plant-derived products, with potential therapeutic and preventive activities against inflammatory diseases, have received increasing attention in recent years because of their whole regulative effects and specific pharmacological activities. However, the molecular mechanisms about how different kinds of natural compounds regulate macrophages polarization still unclear. Therefore, in the current review, we summarized the detailed research progress on the active compounds derived from herbal plants with regulating effects on macrophages, especially M2 polarization. These natural occurring compounds including flavonoids, terpenoids, glycosides, lignans, coumarins, alkaloids, polyphenols and quinones. In addition, we extensively discussed the cellular mechanisms underlying the M2 polarization for each compound, which could provide potential therapeutic strategies aiming macrophages M2 polarization.

Molecular Mechanisms of the Inhibitory Effects of Bupivacaine, Levobupivacaine, and Ropivacaine on Sarcolemmal Adenosine Triphosphate–sensitive Potassium Channels in the Cardiovascular System

2004 ◽  
Vol 101 (2) ◽  
pp. 390-398 ◽  
Author(s):  
Takashi Kawano ◽  
Shuzo Oshita ◽  
Akira Takahashi ◽  
Yasuo Tsutsumi ◽  
Yoshinobu Tomiyama ◽  
...  
Keyword(s):  
Cardiovascular System ◽  
Adenosine Triphosphate ◽  
Local Anesthetics ◽  
Molecular Mechanisms ◽  
Transmembrane Domain ◽  
Katp Channels ◽  
Inhibitory Effect ◽  
Amino Acid Residues ◽  
Sulfonylurea Receptor ◽  
Inhibitory Effects

Background Sarcolemmal adenosine triphosphate-sensitive potassium (KATP) channels in the cardiovascular system may be involved in bupivacaine-induced cardiovascular toxicity. The authors investigated the effects of local anesthetics on the activity of reconstituted KATP channels encoded by inwardly rectifying potassium channel (Kir6.0) and sulfonylurea receptor (SUR) subunits. Methods The authors used an inside-out patch clamp configuration to investigate the effects of bupivacaine, levobupivacaine, and ropivacaine on the activity of reconstituted KATP channels expressed in COS-7 cells and containing wild-type, mutant, or chimeric SURs. Results Bupivacaine inhibited the activities of cardiac KATP channels (IC50 = 52 microm) stereoselectively (levobupivacaine, IC50 = 168 microm; ropivacaine, IC50 = 249 microm). Local anesthetics also inhibited the activities of channels formed by the truncated isoform of Kir6.2 (Kir6.2 delta C36) stereoselectively. Mutations in the cytosolic end of the second transmembrane domain of Kir6.2 markedly decreased both the local anesthetics' affinity and stereoselectivity. The local anesthetics blocked cardiac KATP channels with approximately eightfold higher potency than vascular KATP channels; the potency depended on the SUR subtype. The 42 amino acid residues at the C-terminal tail of SUR2A, but not SUR1 or SUR2B, enhanced the inhibitory effect of bupivacaine on the Kir6.0 subunit. Conclusions Inhibitory effects of local anesthetics on KATP channels in the cardiovascular system are (1) stereoselective: bupivacaine was more potent than levobupivacaine and ropivacaine; and (2) tissue specific: local anesthetics blocked cardiac KATP channels more potently than vascular KATP channels, via the intracellular pore mouth of the Kir6.0 subunit and the 42 amino acids at the C-terminal tail of the SUR2A subunit, respectively.

scholarly journals Anti-inflammatory effect of Barringtonia angusta methanol extract is mediated by targeting of Src in the NF-κB signalling pathway

2021 ◽  
Vol 59 (1) ◽  
pp. 799-810
Author(s):  
Minkyeong Jo ◽  
Jongsung Lee ◽  
Han Gyung Kim ◽  
Jin Kyeong Kim ◽  
Haeyeop Kim ◽  
...  
Keyword(s):  
Methanol Extract ◽  
Signalling Pathway ◽  
Anti Inflammatory ◽  
Inflammatory Effect

scholarly journals Molecular Mechanisms of ZC3H12C/Reg-3 Biological Activity and Its Involvement in Psoriasis Pathology

2021 ◽  
Vol 22 (14) ◽  
pp. 7311
Author(s):  
Mateusz Wawro ◽  
Jakub Kochan ◽  
Weronika Sowinska ◽  
Aleksandra Solecka ◽  
Karolina Wawro ◽  
...  
Keyword(s):  
Family Member ◽  
Cellular Localization ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Association Studies ◽  
Psoriasis Patient ◽  
Genome Wide Association Studies ◽  
Mrna Levels ◽  
Transcript Levels

The members of the ZC3H12/MCPIP/Regnase family of RNases have emerged as important regulators of inflammation. In contrast to Regnase-1, -2 and -4, a thorough characterization of Regnase-3 (Reg-3) has not yet been explored. Here we demonstrate that Reg-3 differs from other family members in terms of NYN/PIN domain features, cellular localization pattern and substrate specificity. Together with Reg-1, the most comprehensively characterized family member, Reg-3 shared IL-6, IER-3 and Reg-1 mRNAs, but not IL-1β mRNA, as substrates. In addition, Reg-3 was found to be the only family member which regulates transcript levels of TNF, a cytokine implicated in chronic inflammatory diseases including psoriasis. Previous meta-analysis of genome-wide association studies revealed Reg-3 to be among new psoriasis susceptibility loci. Here we demonstrate that Reg-3 transcript levels are increased in psoriasis patient skin tissue and in an experimental model of psoriasis, supporting the immunomodulatory role of Reg-3 in psoriasis, possibly through degradation of mRNA for TNF and other factors such as Reg-1. On the other hand, Reg-1 was found to destabilize Reg-3 transcripts, suggesting reciprocal regulation between Reg-3 and Reg-1 in the skin. We found that either Reg-1 or Reg-3 were expressed in human keratinocytes in vitro. However, in contrast to robustly upregulated Reg-1 mRNA levels, Reg-3 expression was not affected in the epidermis of psoriasis patients. Taken together, these data suggest that epidermal levels of Reg-3 are negatively regulated by Reg-1 in psoriasis, and that Reg-1 and Reg-3 are both involved in psoriasis pathophysiology through controlling, at least in part different transcripts.

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