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.

Oxyresveratrol suppresses lipopolysaccharide-induced inflammatory responses in murine macrophages

2014 ◽  
Vol 34 (8) ◽  
pp. 808-818 ◽  
Author(s):  
HS Lee ◽  
DH Kim ◽  
JE Hong ◽  
J-Y Lee ◽  
EJ Kim
Keyword(s):  
Nitric Oxide ◽  
Messenger Rna ◽  
Inflammatory Responses ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Raw264.7 Cells ◽  
Line Production ◽  
Gm Csf ◽  
Protein Expressions ◽  
Cox 2

Excessive inflammation is considered a critical factor in many human diseases. Oxyresveratrol(trans-2,3′,4,5′-tetrahydroxystilbene), a natural hydroxystilbene, has been shown to possess antioxidant and free radical-scavenging activity. In this study, we investigated the effects of oxyresveratrol (OxyR) on the lipopolysaccharide (LPS)-induced production of inflammatory cytokines and mediators and further explored the mechanism of action in RAW264.7 murine macrophage cell line. Production of nitric oxide (NO), prostaglandin E2 (PGE2), messenger RNA (mRNA) and protein expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), and granulocyte macrophage colony-stimulating factor (GM-CSF), phosphorylation of mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38), and the activation of nuclear factor κ-light chain enhancer of activated B cells (NFκB) with OxyR were assayed in LPS-stimulated RAW264.7 cells. OxyR inhibited the productions of NO, PGE2, IL-6, and GM-CSF significantly in LPS-stimulated RAW264.7 cells. OxyR suppressed mRNA and protein expressions of iNOS, COX-2, IL-6, and GM-CSF in LPS-stimulated RAW264.7 cells. OxyR suppressed the phosphorylation of Akt and JNK and p38 MAPKs and the translocation of NFκB p65 subunit into the nucleus. These results indicate that OxyR inhibits LPS-stimulated inflammatory responses though the blocking of MAPK and NFκB signaling pathway in macrophages, and suggest that OxyR possesses anti-inflammatory effects.

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 Activation of the Cholinergic Anti-inflammatory Pathway Attenuated Angiotension II-Dependent Hypertension and Renal Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Shu-jie Wu ◽  
Zhe-wei Shi ◽  
Xue Wang ◽  
Fang-fang Ren ◽  
Zuo-yi Xie ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Inflammatory Responses ◽  
Autonomic Control ◽  
Inflammatory Pathway ◽  
Mesenchymal Transition ◽  
Matrix Deposition ◽  
Α7 Nachr ◽  
Induced Hypertension ◽  
Anti Inflammatory

Background: Angiotensin II (AngII) induces renal fibrosis, characterized by fibroblast proliferation, inflammatory cell infiltration and excessive extracellular matrix deposition, all of which was relevant closely to hypertension. The vagus nerve-related cholinergic anti-inflammatory pathway (CAP) modulates local and systemic inflammatory responses. The aim of present study was to determine the effect of CAP on renal inflammation and fibrosis.Methods and Results: AngII-induced hypertension was induced in vivo by 14-days low-dose AngII infusion from osmotic minipumps. We used GTS-21 dihydrochloride, a selective nicotinic acetylcholine receptor agonist. Daily intraperitoneal GTS-21 injection and/or vagotomy started after hypertension was confirmed and continued for 4 weeks. The elevated blood pressure caused by AngII was significantly attenuated by GTS-21. Improved baroreflex sensitivity was observed after GTS-21 administration. Masson stain and immunoblotting revealed that deposition of excessive fibrosis and overexpression of inflammatory cytokines induced by AngII was reduced by GTS-21. To determine the role of autonomic control in CAP, unilateral vagotomy was performed. Vagotomy weakened the effect of CAP on AngII-induced hypertension. In vitro, GTS-21 suppressed NF-κB activation, attenuated AngII-induced epithelial-mesenchymal transition and reduced inflammation and fibrosis in NRK-52E cells; α-bungarotoxin (α-Bgt, an α7-nAChR selective antagonist) partly inhibited these effects.Conclusion: CAP protected against AngII-induced hypertension via improvement in autonomic control, suppression of NF-κB activation, and reduction of renal fibrosis and inflammatory response.

scholarly journals Anti-Inflammatory Effects of Antarctic Lichen Umbilicaria antarctica Methanol Extract in Lipopolysaccharide-Stimulated RAW 264.7 Macrophage Cells and Zebrafish Model

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Ju-Mi Hong ◽  
Jung Eun Kim ◽  
Seul Ki Min ◽  
Kyung Hee Kim ◽  
Se Jong Han ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Protein Expression ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Zebrafish Model ◽  
In Vivo Models ◽  
Mrna And Protein Expression ◽  
Anti Inflammatory

Umbilicaria antarctica (UA) is a member of the family Umbilicariaceae. To the best of our knowledge, no studies on its anti-inflammatory effects have been reported yet. In the present study, we examined its ability to suppress inflammatory responses and the molecular mechanisms underlying these abilities using lipopolysaccharide- (LPS-) stimulated RAW 264.7 cells and a zebrafish model of inflammation. We investigated the effects of UA on the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated RAW 264.7 cells. To explore the anti-inflammatory mechanisms of UA, we measured the mRNA and protein expression of proinflammatory mediators in LPS-stimulated RAW 264.7 cells using quantitative RT-PCR and western blot analyses, respectively. UA significantly inhibited the production of NO, PGE2, interleukin- (IL-) 6, and tumor necrosis factor- (TNF-) α in the LPS-stimulated RAW 264.7 cells. It also suppressed the mRNA and protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor- (NF-) κB activation in LPS-stimulated RAW 264.7 cells and tail pin-cutting-induced zebrafish model. Collectively, these findings indicate that UA significantly inhibits LPS-stimulated inflammatory responses. These effects were considered to be strongly associated with the suppression of NF-κB activation. Overall, our results demonstrate that UA extract exerts strong anti-inflammatory activities in in vitro and in vivo models and suggest that UA may be an effective novel therapeutic agent for the treatment of inflammatory diseases.

scholarly journals Radical Scavenging Activity-Based and AP-1-Targeted Anti-Inflammatory Effects of Lutein in Macrophage-Like and Skin Keratinocytic Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Jueun Oh ◽  
Ji Hye Kim ◽  
Jae Gwang Park ◽  
Young-Su Yi ◽  
Kye Won Park ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Ros Scavenging ◽  
Intracellular Signaling Pathway ◽  
Anti Oxidant ◽  
Matrix Metallopeptidase ◽  
Anti Inflammatory

Lutein is a naturally occurring carotenoid with antioxidative, antitumorigenic, antiangiogenic, photoprotective, hepatoprotective, and neuroprotective properties. Although the anti-inflammatory effects of lutein have previously been described, the mechanism of its anti-inflammatory action has not been fully elucidated. Therefore, in the present study, we aimed to investigate the regulatory activity of lutein in the inflammatory responses of skin-derived keratinocytes or macrophages and to elucidate the mechanism of its inhibitory action. Lutein significantly reduced several skin inflammatory responses, including increased expression of interleukin-(IL-) 6 from LPS-treated macrophages, upregulation of cyclooxygenase-(COX-) 2 from interferon-γ/tumor necrosis-factor-(TNF-)α-treated HaCaT cells, and the enhancement of matrix-metallopeptidase-(MMP-) 9 level in UV-irradiated keratinocytes. By evaluating the intracellular signaling pathway and the nuclear transcription factor levels, we determined that lutein inhibited the activation of redox-sensitive AP-1 pathway by suppressing the activation of p38 and c-Jun-N-terminal kinase (JNK). Evaluation of the radical and ROS scavenging activities further revealed that lutein was able to act as a strong anti-oxidant. Taken together, our findings strongly suggest that lutein-mediated AP-1 suppression and anti-inflammatory activity are the result of its strong antioxidative and p38/JNK inhibitory activities. These findings can be applied for the preparation of anti-inflammatory and cosmetic remedies for inflammatory diseases of the skin.

NLRP3 Promotes Colorectal Cancer Cell Proliferation and Metastasis via Regulating Epithelial Mesenchymal Transformation

2020 ◽  
Vol 20 (7) ◽  
pp. 820-827 ◽  
Author(s):  
Xinyu Shao ◽  
Zhiyi Lei ◽  
Chunli Zhou
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Inflammatory Responses ◽  
Venous Invasion ◽  
Tnm Staging ◽  
Mesenchymal Transition ◽  
Mesenchymal Transformation

Background: Nucleotide-binding domain Leucine-rich Repeat Protein 3 (NLRP3) plays a regulatory role in the immune and inflammatory responses, and has been implicated in Colorectal Cancer (CRC) progression and metastasis. However, the underlying molecular mechanisms have not been fully elucidated. Methods: In this study, we analyzed the expression levels of NLRP3 in human CRC tissues, and performed functional assays in CRC cell lines and a subcutaneous tumor model to elucidate its role in the development and progression of CRC. Results: In this study, we found that NLRP3 was significantly upregulated in human CRC tissues and was associated with tumor size and invasion, lymph node metastasis, venous invasion, neural invasion and TNM staging. Furthermore, knockdown of NLRP3 in CRC cells inhibited their migration and growth in vitro and in vivo, and reversed Epithelial-Mesenchymal Transition (EMT) in vitro. Conclusion: Our findings indicate that NLRP3 likely regulates CRC metastasis by activating the EMT program, and is a potential therapeutic target.

scholarly journals Inhibitory Effects of Porphyra tenera Extract on Oxidation and Inflammatory Responses

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Chul Won Lee ◽  
Yong-Tae Ahn ◽  
Rongjie Zhao ◽  
Youn Sook Kim ◽  
Sang Mi Park ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Radical Scavenging Activity ◽  
Scientific Evidence ◽  
Radical Scavenging ◽  
Raw 264.7 Cells ◽  
Scavenging Activity ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Porphyra Tenera ◽  
Anti Inflammatory

Porphyra tenera (laver) has long been a popular and traditional seaweed food in Korea, Japan, and China. Historically, it was known as a marine medicinal herb to treat hemorrhoids and cholera morbus in Donguibogam. We investigated the effects of P. tenera extract (PTE) for its antioxidant and anti-inflammatory activities. These activities were measured using assays for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) radical scavenging and its superoxide dismutase- (SOD-) like activity, and through the inhibitory production of inflammatory mediators (prostaglandin E2 (PGE2), NO, tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6)) in lipopolysaccharide- (LPS-) stimulated Raw 264.7 cells. The antioxidant assay results showed that PTE displayed DPPH radical scavenging activity (46.44%), NO radical scavenging activity (67.14%), and SOD-like activity (80.29%) at a concentration of 5 mg/mL. In the anti-inflammatory assays, treatment with PTE (1 mg/mL) significantly inhibited expression levels of LPS-induced COX-2 and iNOS, as well as the production of PGE2, NO, TNF-α, and IL-6. These results show that PTE has antioxidant and anti-inflammatory properties and provide scientific evidence to explain the antioxidative and anti-inflammatory properties of PTE.

scholarly journals In vitro ANTI-INFLAMMATORY AND ANTIOXIDANT EVALUATION OF AN INDIGENOUS MEDICINAL PLANT – Pterospermum rubiginosum

2021 ◽  
Vol 9 (5) ◽  
pp. 687-696
Author(s):  
Rajamohanan J Anish ◽  
◽  
Arun A Rauf ◽  
Keyword(s):  
Nitric Oxide ◽  
Antioxidant Activity ◽  
Antioxidant Activities ◽  
Radical Scavenging Activity ◽  
Colorimetric Method ◽  
Radical Scavenging ◽  
Scavenging Activity ◽  
Cellular Viability ◽  
Anti Inflammatory

The current study was carried out to determine the antioxidant potential, anti-inflammatory activity, and cellular viability of Pterospermum rubiginosum (PR), a tropical tree endemic to the Western Ghats. The antioxidant activities of the PR bark methanolic (PRME) and aqueous extract (PRAQ) were tested using ABTS as well as superoxide, nitric oxide, and hydroxyl radical assays. Total antioxidant activity was evaluated by adopting the colorimetric method and correlation with their antioxidant activities was derived by Pearson co-efficient analysis. The PRME showed the highest ABTS radical scavenging activity, EC50 (46.09µg/ml) followed by PRAQ (52.08µg/ml). Furthermore, the PRME exhibited the highest scavenging activity against superoxide, nitric oxide, and hydroxyl radicals. The MTT assay results revealed good cellular viability up to a concentration of 100µg/ml with an EC50 (106.869µg/ml). The inflammatory mediators such as Cox-2, IL-1β, IL-6, and NF-kB were reduced during the treatment of PRME in LPS stimulated RAW cells. The stress marker in rat liver cells such as glutathione reductase (GR), glutathione peroxidase (GPx), and reduced glutathione (GSH) levels was found in normal levels when compared to the untreated group of rats. The antioxidant enzyme superoxide dismutase and catalase also exhibited notable bioactivity in PRME treated groups up to a concentration of 1000µg/ml. The present study showed excellent In vitro and In vivo antioxidant activity; the potent anti-inflammatory ability of PRME in reducing the LPS induced inflammation in cell culture conditions.

MiR-597 Targeting 14-3-3σ Enhances Cellular Invasion and EMT in Nasopharyngeal Carcinoma Cells

2019 ◽  
Vol 12 (2) ◽  
pp. 105-114 ◽  
Author(s):  
Lisha Xie ◽  
Tao Jiang ◽  
Ailan Cheng ◽  
Ting Zhang ◽  
Pin Huang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Western Blotting ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Suppressor Gene ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Downstream Target ◽  
Before And After

Background: Alterations in microRNAs (miRNAs) are related to the occurrence of nasopharyngeal carcinoma (NPC) and play an important role in the molecular mechanism of NPC. Our previous studies show low expression of 14-3-3σ (SFN) is related to the metastasis and differentiation of NPC, but the underlying molecular mechanisms remain unclear. Methods: Through bioinformatics analysis, we find miR-597 is the preferred target miRNA of 14-3-3σ. The expression level of 14-3-3σ in NPC cell lines was detected by Western blotting. The expression of miR-597 in NPC cell lines was detected by qRT-PCR. We transfected miR-597 mimic, miR-597 inhibitor and 14-3-3σ siRNA into 6-10B cells and then verified the expression of 14-3-3σ and EMT related proteins, including E-cadherin, N-cadherin and Vimentin by western blotting. The changes of migration and invasion ability of NPC cell lines before and after transfected were determined by wound healing assay and Transwell assay. Results: miR-597 expression was upregulated in NPC cell lines and repaired in related NPC cell lines, which exhibit a potent tumor-forming effect. After inhibiting the miR-597 expression, its effect on NPC cell line was obviously decreased. Moreover, 14-3-3σ acts as a tumor suppressor gene and its expression in NPC cell lines is negatively correlated with miR-597. Here 14-3-3σ was identified as a downstream target gene of miR-597, and its downregulation by miR-597 drives epithelial-mesenchymal transition (EMT) and promotes the migration and invasion of NPC. Conclusion: Based on these findings, our study will provide theoretical and experimental evidences for molecular targeted therapy of NPC.

Galectin-3: A factotum in carcinogenesis bestowing an archery for prevention

Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 77-96
Author(s):  
T. Jeethy Ram ◽  
Asha Lekshmi ◽  
Thara Somanathan ◽  
K. Sujathan
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Therapy Resistance ◽  
Cellular Level ◽  
Clinical Samples ◽  
Innovative Strategy ◽  
Mesenchymal Transition ◽  
Galectin 3

Cancer metastasis and therapy resistance are the foremost hurdles in oncology at the moment. This review aims to pinpoint the functional aspects of a unique multifaceted glycosylated molecule in both intracellular and extracellular compartments of a cell namely galectin-3 along with its metastatic potential in different types of cancer. All materials reviewed here were collected through the search engines PubMed, Scopus, and Google scholar. Among the 15 galectins identified, the chimeric gal-3 plays an indispensable role in the differentiation, transformation, and multi-step process of tumor metastasis. It has been implicated in the molecular mechanisms that allow the cancer cells to survive in the intravascular milieu and promote tumor cell extravasation, ultimately leading to metastasis. Gal-3 has also been found to have a pivotal role in immune surveillance and pro-angiogenesis and several studies have pointed out the importance of gal-3 in establishing a resistant phenotype, particularly through the epithelial-mesenchymal transition process. Additionally, some recent findings suggest the use of gal-3 inhibitors in overcoming therapeutic resistance. All these reports suggest that the deregulation of these specific lectins at the cellular level could inhibit cancer progression and metastasis. A more systematic study of glycosylation in clinical samples along with the development of selective gal-3 antagonists inhibiting the activity of these molecules at the cellular level offers an innovative strategy for primary cancer prevention.

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