scholarly journals Anti-Neuroinflammatory Property of Phlorotannins from Ecklonia cava on Aβ25-35-Induced Damage in PC12 Cells

Marine Drugs ◽  
2018 ◽  
Vol 17 (1) ◽  
pp. 7 ◽  
Author(s):  
Seungeun Lee ◽  
Kumju Youn ◽  
Dong Kim ◽  
Mok-Ryeon Ahn ◽  
Eunju Yoon ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Neurodegenerative Disorder ◽  
Brown Seaweed ◽  
Ecklonia Cava ◽  
Drug Candidate ◽  
Protein Levels ◽  
Tnf Α ◽  
Caspase Family ◽  
Anti Inflammatory ◽  
New Generation

Alzheimer disease (AD) is a neurodegenerative disorder characterized by excessive accumulation of amyloid-beta peptide (Aβ) and progressive loss of neurons. Therefore, the inhibition of Aβ-induced neurotoxicity is a potential therapeutic approach for the treatment of AD. Ecklonia cava is an edible brown seaweed, which has been recognized as a rich source of bioactive derivatives, mainly phlorotannins. In this study, phlorotannins including eckol, dieckol, 8,8′-bieckol were used as potential neuroprotective candidates for their anti-apoptotic and anti-inflammatory effects against Aβ25-35-induced damage in PC12 cells. Among the tested compounds, dieckol showed the highest effect in both suppressing intracellular oxidative stress and mitochondrial dysfunction and activation of caspase family. Three phlorotannins were found to inhibit TNF-α, IL-1β and PGE2 production at the protein levels. These result showed that the anti-inflammatory properties of our compounds are related to the down-regulation of proinflammatory enzymes, iNOS and COX-2, through the negative regulation of the NF-κB pathway in Aβ25-35-stimulated PC12 cells. Especially, dieckol showed the strong anti-inflammatory effects via suppression of p38, ERK and JNK. However, 8,8′-bieckol markedly decreased the phosphorylation of p38 and JNK and eckol suppressed the activation of p38. Therefore, the results of this study indicated that dieckol from E. cava might be applied as a drug candidate for the development of new generation therapeutic agents against AD.

AAnti-Inflammatory Effects of Plasma Circulating Exosomes Obtained from Normal-Weight and Obese Subjects on Hepatocytes

2020 ◽  
Vol 20 ◽  
Author(s):  
Reza Afrisham ◽  
Sahar Sadegh-Nejadi ◽  
Reza Meshkani ◽  
Solaleh Emamgholipour ◽  
Molood Bagherieh ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Hepg2 Cells ◽  
Human Liver ◽  
Liver Cells ◽  
Normal Weight ◽  
Protein Levels ◽  
Human Liver Cells ◽  
Tnf Α ◽  
Anti Inflammatory

Introduction: Obesity is a disorder with low-grade chronic inflammation that plays a key role in the hepatic inflammation and steatosis. Moreover, there are studies to support the role of exosomes in the cellular communications, the regulation of metabolic homeostasis and immunomodulatory activity. Accordingly, we aimed to evaluate the influence of plasma circulating exosomes derived from females with normal-weight and obesity on the secretion of inflammatory cytokines in human liver cells. Methods: Plasma circulating exosomes were isolated from four normal (N-Exo) and four obese (O-Exo) women. The exosomes were characterized and approved for CD63 expression (common exosomal protein marker) and morphology/size using the western blot and TEM methods, respectively. The exosomes were used for stimulation of HepG2 cells in vitro. After 24 h incubation, the protein levels of TNF-α,IL-6, and IL-1β were measured in the culture supernatant of HepG2 cells using the ELISA kit. Results: The protein levels of IL-6 and TNF-α in the cells treated with O-Exo and N-Exo reduced significantly in comparison with control group (P=0.039 and P<0.001 respectively), while significance differences were not found between normal and obese groups (P=0.808, and P=0.978 respectively). However, no significant differences were found between three groups in term of IL-1β levels (P=0.069). Based on the correlation analysis, the protein levels of IL-6 were positively correlated with TNF-α (r 0.978, P<0.001). Conclusion: These findings suggest that plasma circulating exosomes have probably anti-inflammatory properties independently from body mass index and may decrease the secretion of inflammatory cytokines in liver. However, further investigations in vitro and in vivo are needed to address the anti-inflammatory function of N-Exo and O-Exo in human liver cells and/or other cells.

scholarly journals Dexmedetomidine Induces Microglial Activation and Modulates Microglial M1/M2 Polarization in Attenuation of Chronic Morphine Tolerance in Cancer Pain

2022 ◽  
Author(s):  
Jianlong Bu ◽  
Wu Xiaohong ◽  
Deng Lin ◽  
Ma Chao ◽  
Shi Xiaoding ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Morphine Tolerance ◽  
Inflammatory Factor ◽  
Chronic Morphine ◽  
Protein Levels ◽  
M2 Polarization ◽  
Α2 Adrenoceptor ◽  
Adrenoceptor Agonist ◽  
Tnf Α ◽  
Anti Inflammatory

Abstract The pro-inflammatory (M1) and anti-inflammatory (M2) status of microglial determines the outcome of neuroinflammation, which contributes to the pathogenesis of chronic morphine tolerance. Studies report that α2-adrenoceptor agonist dexmedetomidine exerts anti-inflammatory effects in inhibiting morphine tolerance in normal and neuropathic pain animals, which has not been studied in cancer pain. Therefore, we investigate the effect of intrathecal DEX on morphine tolerance in cancer pain, and whether dexmedetomidine functions via modulating microglial activation and M1/M2 polarization. 54 Wistar rats with intrathecal catheterization were treated by morphine for 10 days. Test groups received intrathecal α2-adrenoceptor agonist dexmedetomidine or antagonist MK-467. The mRNA levels of TLR4 and NF-κB were tested by RT-PCR. The protein levels of TLR4, NF-κB, Iba-1, iNOS, CD206 were quantifed using Western blotting, and IL-10 and TNF-α were examined by ELISA. Dexmedetomidine attenuates mechanical threshold and thermal latency, and increased the expression of TLR4 and NF-κB in morphine tolerance of cancer pain. Dexmedetomidine attenuates mechanical and thermal nociception in morphine tolerance in cancer pain rats. Intrathecal DEX pre-treatment significantly increased the protein levels of microglia maker Iba-1, M2 marker CD206 and anti-inflammatory factor IL-10, while had no evident influence on the pro-inflammatory factor TNF-α and M1 marker iNOS in morphine tolerance. Our findings suggest that intrathecal dexmedetomidine attenuates morphine tolerance in cancer pain via α2-adrenoceptor pathway. Furthermore, dexmedetomidine upregulates TLR4/NF-κB pathway and induces microglia activation in chronic morphine tolerance of cancer pain. The anti-inflammatory effect of dexmedetomidine might be exerted by inducing microglia M2 polarization and increasing anti-inflammatory factor IL-10.

scholarly journals 4-Hydroxyisoleucine relieves inflammation through iRhom2-dependent pathway in co-cultured macrophages and adipocytes with LPS stimulation

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Cong Zhou ◽  
Rui Chen ◽  
Feng Gao ◽  
Jiaoyue Zhang ◽  
Furong Lu
Keyword(s):  
Culture System ◽  
Real Time Quantitative Pcr ◽  
Protein Levels ◽  
Raw264.7 Macrophages ◽  
Chemotactic Protein ◽  
Tnf Α ◽  
Mrna And Protein Expression ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Dependent Pathway

Abstract Background 4-Hydroxyisoleucine (4-HIL) is an active ingredient extracted from Trigonella foenum-graecum L., a Chinese traditional herbal medicine, which exerts the efficacy of anti-obesity and anti-diabetes. We previously reported that 4-HIL potentiates anti-inflammatory and anti-insulin resistance effects through down-regulation of TNF-α and TNF-α converting enzyme (TACE) in 3 T3-L1 adipocytes and HepG2 cells. In the present study, we further investigate the effects and mechanisms of 4-HIL on obesity-induced inflammation in RAW264.7 macrophages and 3 T3-L1 adipocytes co-culture system. Methods RAW264.7 macrophages and 3 T3-L1 adipocytes were co-cultured to mimic the microenvironment of adipose tissue. siRNA-iRhom2 transfection was performed to knockdown iRhom2 expression in RAW264.2 macrophages. The mRNA and protein expression of iRhom2 and TACE were measured by real-time quantitative PCR (RT-qPCR) and western blotting. The production of tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), IL-6 and IL-10 were evaluated by ELISA. The ratio of M2/M1 was detected by flow cytometry. Results 4-HIL significantly repressed the mRNA and protein levels of iRhom2 and TACE in RAW264.7 macrophages after LPS stimulated. Meanwhile, the levels of pro-inflammatory cytokines, including TNF-α, MCP-1, and IL-6, were substantially suppressed by 4-HIL in the co-culture system. Moreover, the level of anti-inflammatory cytokine IL-10 was increased significantly by 4-HIL in the co-culture system after LPS stimulation. Additionally, the ratio of M2/M1 was also increased by 4-HIL in the co-culture system after LPS stimulation. Finally, these effects of 4-HIL were largely enhanced by siRNA-iRhom2 transfection. Conclusion Taken together, our results indicated that obesity-induced inflammation was potently relieved by 4-HIL, most likely through the iRhom2-dependent pathway.

scholarly journals Isoorientin Inhibits Amyloid β25–35-Induced Neuronal Inflammation in BV2 Cells by Blocking the NF-κB Signaling Pathway

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 7056
Author(s):  
Buyun Kim ◽  
Ki Yong Lee ◽  
Byoungduck Park
Keyword(s):  
Neurodegenerative Disorder ◽  
Drug Candidate ◽  
Therapeutic Drug ◽  
Treatment And Prevention ◽  
Bv2 Cells ◽  
Tnf Α ◽  
Underlying Mechanisms ◽  
Induced Apoptosis ◽  
Factor Α ◽  
The Brain

Alzheimer’s disease (AD) is a severe neurodegenerative disorder. AD is pathologically characterized by the formation of intracellular neurofibrillary tangles, and extracellular amyloid plaques which were comprised of amyloid-beta (Aβ) peptides. Aβ induces neurodegeneration by activating microglia, which triggers neurotoxicity by releasing various inflammatory mediators and reactive oxygen species (ROS). Nuclear factor-kappa B (NF-κB) is expressed in human tissues including the brain and plays an important role in Aβ-mediated neuronal inflammation. Thus, the identification of molecules that inhibit the NF-κB pathway is considered an attractive strategy for the treatment and prevention of AD. Isoorientin (3′,4′,5,7-Tetrahydroxy-6-C-glucopyranosyl flavone; ISO), which can be extracted from several plant species, such as Philostachys and Patrinia is known to have various pharmacological activities such as anticancer, antioxidant, and antibacterial activity. However, the effect of ISO on Aβ-mediated inflammation and apoptosis in the brain has yet to be elucidated. In the present study, we investigated whether ISO regulated Aβ-induced neuroinflammation in microglial cells and further explored the underlying mechanisms. Our results showed that ISO inhibited the expression of iNOS and COX-2 induced by Aβ25–35. And, it inhibited the secretion of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). In addition, ISO reduced the ROS production in Aβ25–35-induced BV2 cells and inhibited NF-κB activation. Furthermore, ISO blocked Aβ25–35-induced apoptosis of BV2 cells. Based on these findings, we suggest that ISO represents a promising therapeutic drug candidate for the treatment and prevention of AD.

scholarly journals Azithromycin Selectively Reduces Tumor Necrosis Factor Alpha Levels in Cystic Fibrosis Airway Epithelial Cells

2007 ◽  
Vol 51 (3) ◽  
pp. 975-981 ◽  
Author(s):  
Cristina Cigana ◽  
Baroukh Maurice Assael ◽  
Paola Melotti
Keyword(s):  
Cystic Fibrosis ◽  
Dna Binding ◽  
Tumor Necrosis ◽  
Airway Epithelial ◽  
Necrosis Factor Alpha ◽  
Protein Levels ◽  
Tnf Α ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

ABSTRACT Azithromycin (AZM) ameliorates lung function in cystic fibrosis (CF) patients. This macrolide has been suggested to have anti-inflammatory properties as well as other effects potentially relevant for therapy of CF. In this study, we utilized three CF (IB3-1, 16HBE14o- AS3, and 2CFSMEo-) and two isogenic non-CF (C38 and 16HBE14o- S1) airway epithelial cell lines to investigate whether AZM could reduce tumor necrosis factor alpha (TNF-α) mRNA and protein levels by real-time quantitative PCR analysis and an enzyme-linked immunosorbent assay (ELISA), respectively. We studied the effects on the DNA binding of NF-κB and specificity protein 1 (Sp1) by an ELISA. Non-CF cells express significantly lower TNF-α mRNA and protein levels than an isogenic CF cell line. In CF cells, AZM treatment causes a 30% reduction of TNF-α mRNA levels (P < 0.05) and a 45% decrease in TNF-α secretion (P < 0.05), reaching approximately the levels of the untreated isogenic non-CF cells. In CF cells, NF-κB and Sp1 DNA binding activities were also significantly decreased (about 45 and 60%, respectively; P < 0.05) after AZM treatment. Josamycin, a macrolide lacking clinically described anti-inflammatory effects, was ineffective. Finally, AZM did not alter the mRNA expression levels of interleukin-6, a proinflammatory molecule not differentially expressed in CF and isogenic non-CF cells. The results of our study support the anti-inflammatory activities of this macrolide, since we show that AZM reduced the levels of TNF-α and propose inhibitions of NF-κB and Sp1 DNA binding as possible mechanisms of this effect.

scholarly journals Meroterpenoids from the Brown Alga Cystoseira usneoides as Potential Anti-Inflammatory and Lung Anticancer Agents

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 207 ◽  
Author(s):  
Hanaa Zbakh ◽  
Eva Zubía ◽  
Carolina de los Reyes ◽  
José M. Calderón-Montaño ◽  
Miguel López-Lázaro ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Therapeutic Potential ◽  
A549 Cells ◽  
Brown Seaweed ◽  
Normal Lung ◽  
Cytotoxic Activities ◽  
Anticancer Effects ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory

The anti-inflammatory and anticancer properties of eight meroterpenoids isolated from the brown seaweed Cystoseira usneoides have been evaluated. The algal meroterpenoids (AMTs) 1–8 were tested for their inhibitory effects on the production of the pro-inflammatory cytokines tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), and the expression of cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in LPS-stimulated THP-1 human macrophages. The anticancer effects were assessed by cytotoxicity assays against human lung adenocarcinoma A549 cells and normal lung fibroblastic MRC-5 cells, together with flow cytometry analysis of the effects of these AMTs on different phases of the cell cycle. The AMTs 1–8 significantly reduced the production of TNF-α, IL-6, and IL-1β, and suppressed the COX-2 and iNOS expression, in LPS-stimulated cells (p < 0.05). The AMTs 1–8 displayed higher cytotoxic activities against A549 cancer cells than against MRC-5 normal lung cells. Cell cycle analyses indicated that most of the AMTs caused the arrest of A549 cells at the G2/M and S phases. The AMTs 2 and 5 stand out by combining significant anti-inflammatory and anticancer activities, while 3 and 4 showed interesting selective anticancer effects. These findings suggest that the AMTs produced by C. usneoides may have therapeutic potential in inflammatory diseases and lung cancer.

scholarly journals Hydroxylumisterols, Photoproducts of Pre-Vitamin D3, Protect Human Keratinocytes against UVB-Induced Damage

2020 ◽  
Vol 21 (24) ◽  
pp. 9374 ◽  
Author(s):  
Anyamanee Chaiprasongsuk ◽  
Zorica Janjetovic ◽  
Tae-Kang Kim ◽  
Cynthia J. Schwartz ◽  
Robert C. Tuckey ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Human Keratinocytes ◽  
Inflammatory Activity ◽  
Orphan Receptors ◽  
Protein Levels ◽  
Tnf Α ◽  
Transglutaminase 1 ◽  
Anti Inflammatory ◽  
High Doses

Lumisterol (L3) is a stereoisomer of 7-dehydrocholesterol and is produced through the photochemical transformation of 7-dehydrocholesteol induced by high doses of UVB. L3 is enzymatically hydroxylated by CYP11A1, producing 20(OH)L3, 22(OH)L3, 20,22(OH)2L3, and 24(OH)L3. Hydroxylumisterols function as reverse agonists of the retinoic acid-related orphan receptors α and γ (RORα/γ) and can interact with the non-genomic binding site of the vitamin D receptor (VDR). These intracellular receptors are mediators of photoprotection and anti-inflammatory activity. In this study, we show that L3-hydroxyderivatives significantly increase the expression of VDR at the mRNA and protein levels in keratinocytes, both non-irradiated and after UVB irradiation. L3-hydroxyderivatives also altered mRNA and protein levels for RORα/γ in non-irradiated cells, while the expression was significantly decreased in UVB-irradiated cells. In UVB-irradiated keratinocytes, L3-hydroxyderivatives inhibited nuclear translocation of NFκB p65 by enhancing levels of IκBα in the cytosol. This anti-inflammatory activity mediated by L3-hydroxyderivatives through suppression of NFκB signaling resulted in the inhibition of the expression of UVB-induced inflammatory cytokines, including IL-17, IFN-γ, and TNF-α. The L3-hydroxyderivatives promoted differentiation of UVB-irradiated keratinocytes as determined from upregulation of the expression at the mRNA of involucrin (IVL), filaggrine (FLG), and keratin 14 (KRT14), downregulation of transglutaminase 1 (TGM1), keratins including KRT1, and KRT10, and stimulation of ILV expression at the protein level. We conclude that CYP11A1-derived hydroxylumisterols are promising photoprotective agents capable of suppressing UVB-induced inflammatory responses and restoring epidermal function through targeting the VDR and RORs.

scholarly journals Phenolic Compounds of Red Wine Aglianico del Vulture Modulate the Functional Activity of Macrophages via Inhibition of NF-κB and the Citrate Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Anna Santarsiero ◽  
Paolo Convertini ◽  
Antonio Vassallo ◽  
Valentina Santoro ◽  
Simona Todisco ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
Red Wine ◽  
Nuclear Translocation ◽  
Atp Citrate Lyase ◽  
Protein Levels ◽  
Metabolic Genes ◽  
Citrate Lyase ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine

Phenolic compounds of red wine powder (RWP) extracted from the Italian red wine Aglianico del Vulture have been investigated for the potential immunomodulatory and anti-inflammatory capacity on human macrophages. These compounds reduce the secretion of IL-1β, IL-6, and TNF-α proinflammatory cytokines and increase the release of IL-10 anti-inflammatory cytokine induced by lipopolysaccharide (LPS). In addition, RWP restores Annexin A1 levels, thus involving activation of proresolutive pathways. Noteworthy, RWP lowers NF-κB protein levels, promoter activity, and nuclear translocation. As a consequence of NF-κB inhibition, reduced promoter activities of SLC25A1—encoding the mitochondrial citrate carrier (CIC)—and ATP citrate lyase (ACLY) metabolic genes have been observed. CIC, ACLY, and citrate are components of the citrate pathway: in LPS-activated macrophages, the mitochondrial citrate is exported by CIC into the cytosol where it is cleaved by ACLY in oxaloacetate and acetyl-CoA, precursors for ROS, NO⋅, and PGE2 inflammatory mediators. We identify the citrate pathway as a RWP target in carrying out its anti-inflammatory activity since RWP reduces CIC and ACLY protein levels, ACLY enzymatic activity, the cytosolic citrate concentration, and in turn ROS, NO⋅, PGE2, and histone acetylation levels. Overall findings suggest that RWP potentially restores macrophage homeostasis by suppressing inflammatory pathways and activating proresolutive processes.

scholarly journals Virtual prediction of purple rice ferulic acid as anti-inflammatory of TNF-α signaling

2021 ◽  
Vol 27 (2) ◽  
pp. 59-66
Author(s):  
Ernanin Dyah Wijayanti ◽  
Anna Safitri ◽  
Dian Siswanto ◽  
Fatchiyah Fatchiyah
Keyword(s):  
Biological Activity ◽  
Ferulic Acid ◽  
Inhibition Mechanism ◽  
Drug Candidate ◽  
Inflammatory Drug ◽  
Lipinski’S Rule ◽  
Discovery Studio ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Docking Energy

Purple rice is one of the main sources of ferulic acid (FA). Some studies reported anti-inflammatory properties of FA, but the interaction of FA with TNF-α signaling has not been elucidated. TNF-α is a target for anti-inflammatory drug research due to its major role in the inflammatory process. This study aims to investigate the interaction of FA with TNF-α and TNF-α receptor (TNFR) through in silico study and evaluate the drug-like properties and biological activity of FA. The interactions among FA (CID 445858), TNF-α (2AZ5), and TNFR (1NCF) were docked by Hex 8.0.0 Cuda, then visualized by Discovery Studio 2020 and LigPlot V.1.4.5. Apigenin-7-glucuronide (AG, CID 5319484) was used as the positive control. The drug-like properties were predicted by Lipinski’s rule of five and the biological activity was analyzed by PASS online. FA showed good properties as a drug-like molecule and biological activity as an anti-inflammatory. FA also showed good interaction with TNF-α and TNFR. FA bound to TNF-α at Asn92(B), Val91(B), Leu93(B), Phe124(B), Phe124(D), and Leu93(D) residues with docking energy of -214.6 kJ/mol, and bound to TNFR at Pro16(A), Glu56(B), Cys55(B), Glu54(B) residues with docking energy of -191.1 kJ/mol. FA could inhibit TNF-α – TNFR interaction by binding to TNFR at Glu54 residue, the same inhibition mechanism to AG which bind to TNFR at Glu54 and Val90. The current study shows that FA has the potential as an anti-inflammatory of TNF-α signaling and can be developed as an oral anti-inflammatory drug candidate.

Anti-inflammatory Effects of Ecklonia cava by the Regulation of TSLP in TNF-α/IFN-γ-Stimulated Keratinocytes

2017 ◽  
Vol 22 (4) ◽  
pp. 248-253
Author(s):  
Nalae Kang ◽  
Ginnae Ahn ◽  
Eui Jeong Han ◽  
Eun-Ji Shin ◽  
Hee-Jin Han ◽  
...  
Keyword(s):  
Ecklonia Cava ◽  
Tnf Α ◽  
Ifn Γ ◽  
Anti Inflammatory
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