Effect of the Arctic terrestrial plant Ranunculus hyperboreus on LPS-induced inflammatory response via MAPK pathways

Abstract The Arctic flora hosts a limited number of species due to its extreme environmental conditions which also yield novel and unique secondary metabolites from withstanding plants. Considering a lack of research on bioactivity potential of Arctic flora, Ranunculus hyperboreus, an Arctic plant, was studied for its anti-inflammatory potential as a part of ongoing research on discovering novel natural bioactive products. Solvent-based fractions (H2O, n-BuOH, 85% aq. MeOH, n-hexane) from R. hyperboreus extract were observed to decrease the elevated nitrate amount during the inflammatory response of lipopolysaccharide-induced mouse macrophage RAW264.7 cells. To some extent, treatment with fractions was able to regulate the expression and protein levels of inflammation-related enzymes, iNOS and COX-2, and pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6. The most active fractions, H2O and 85% aq. MeOH, were suggested to exert their effect through suppressed activation of MAPK pathways, especially JNK. Based on the studies of same species, phenolic glycosides were suggested to be the main active ingredients. To our knowledge, this is the first report of any bioactivity of R. hyperboreus which could be a valuable source of natural bioactive agents against inflammation.

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Sorghum Fermented by Aspergillus oryzae NK Enhances Inhibition of Vascular Inflammation in TNF-α-stimulated Human Aortic Smooth Muscle Cells

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000496 ◽

2018 ◽

Vol 88 (5-6) ◽

pp. 309-318

Author(s):

Hae Seong Song ◽

Jung-Eun Kwon ◽

Hyun Jin Baek ◽

Chang Won Kim ◽

Hyelin Jeon ◽

...

Keyword(s):

Smooth Muscle ◽

Inflammatory Response ◽

Smooth Muscle Cells ◽

Adhesion Molecule ◽

Vascular Inflammation ◽

Muscle Cells ◽

Aortic Smooth Muscle Cells ◽

Aortic Smooth Muscle ◽

Tnf Α ◽

Cox 2

Abstract. Sorghum bicolor L. Moench is widely grown all over the world for food and feed. The effects of sorghum extracts on general inflammation have been previously studied, but its anti-vascular inflammatory effects are unknown. Therefore, this study investigated the anti-vascular inflammation effects of sorghum extract (SBE) and fermented extract of sorghum (fSBE) on human aortic smooth muscle cells (HASMCs). After the cytotoxicity test of the sorghum extract, a series of experiments were conducted. The inhibition effects of SBE and fSBE on the inflammatory response and adhesion molecule expression were measured using treatment with tumor necrosis factor-α (TNF-α), a crucial promoter for the development of atherosclerotic lesions, on HASMCs. After TNF-α (10 ng/mL) treatment for 2 h, then SBE and fSBE (100 and 200 μg/mL) were applied for 12h. Western blotting analysis showed that the expression of vascular cell adhesion molecule-1 (VCAM-1) (2.4-fold) and cyclooxygenase-2 (COX-2) (6.7-fold) decreased, and heme oxygenase-1 (HO-1) (3.5-fold) increased compared to the TNF-α control when treated with 200 μg/mL fSBE (P<0.05). In addition, the fSBE significantly increased the expression of HO-1 and significantly decreased the expression of VCAM-1 and COX-2 compared to the TNF-α control in mRNA level (P<0.05). These reasons of results might be due to the increased concentrations of procyanidin B1 (about 6-fold) and C1 (about 30-fold) produced through fermentation with Aspergillus oryzae NK for 48 h, at 37 °C. Overall, the results demonstrated that fSBE enhanced the inhibition of the inflammatory response and adherent molecule expression in HASMCs.

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4-(Phenylsulfanyl) Butan-2-One Attenuates the Inflammatory Response Induced by Amyloid-β Oligomers in Retinal Pigment Epithelium Cells

Marine Drugs ◽

10.3390/md19010001 ◽

2020 ◽

Vol 19 (1) ◽

pp. 1

Author(s):

Peeraporn Varinthra ◽

Shun-Ping Huang ◽

Supin Chompoopong ◽

Zhi-Hong Wen ◽

Ingrid Y. Liu

Keyword(s):

Retinal Pigment Epithelium ◽

Inflammatory Response ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Amyloid Β ◽

Age Related Macular Degeneration ◽

Epithelial Cell Line ◽

Age Related ◽

Tnf Α ◽

Cox 2

Age-related macular degeneration (AMD) is a progressive eye disease that causes irreversible impairment of central vision, and effective treatment is not yet available. Extracellular accumulation of amyloid-beta (Aβ) in drusen that lie under the retinal pigment epithelium (RPE) has been reported as one of the early signs of AMD and was found in more than 60% of Alzheimer’s disease (AD) patients. Extracellular deposition of Aβ can induce the expression of inflammatory cytokines such as IL-1β, TNF-α, COX-2, and iNOS in RPE cells. Thus, finding a compound that can effectively reduce the inflammatory response may help the treatment of AMD. In this research, we investigated the anti-inflammatory effect of the coral-derived compound 4-(phenylsulfanyl) butan-2-one (4-PSB-2) on Aβ1-42 oligomer (oAβ1-42) added to the human adult retinal pigment epithelial cell line (ARPE-19). Our results demonstrated that 4-PSB-2 can decrease the elevated expressions of TNF-α, COX-2, and iNOS via NF-κB signaling in ARPE-19 cells treated with oAβ1-42 without causing any cytotoxicity or notable side effects. This study suggests that 4-PSB-2 is a promising drug candidate for attenuation of AMD.

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Skullcapflavone II Suppresses TNF-α/IFN-γ-Induced TARC, MDC, and CTSS Production in HaCaT Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22126428 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6428

Author(s):

Hanon Lee ◽

Dong Hun Lee ◽

Jang-Hee Oh ◽

Jin Ho Chung

Keyword(s):

P38 Mapk ◽

Therapeutic Potential ◽

Inflammatory Diseases ◽

Mapk Signaling ◽

Hacat Cells ◽

Protein Levels ◽

Tnf Α ◽

Ifn Γ ◽

Mapk Signaling Pathways ◽

Pro Inflammatory Cytokines

Skullcapflavone II (SFII), a flavonoid derived from Scutellaria baicalensis, has been reported to have anti-inflammatory properties. However, its therapeutic potential for skin inflammatory diseases and its mechanism are unknown. Therefore, this study aimed to investigate the effect of SFII on TNF-α/IFN-γ-induced atopic dermatitis (AD)-associated cytokines, such as thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC). Co-stimulation with TNF-α/IFN-γ in HaCaT cells is a well-established model for induction of pro-inflammatory cytokines. We treated cells with SFII prior to TNF-α/IFN-γ-stimulation and confirmed that it significantly inhibited TARC and MDC expression at the mRNA and protein levels. Additionally, SFII also inhibited the expression of cathepsin S (CTSS), which is associated with itching in patients with AD. Using specific inhibitors, we demonstrated that STAT1, NF-κB, and p38 MAPK mediate TNF-α/IFN-γ-induced TARC and MDC, as well as CTSS expression. Finally, we confirmed that SFII significantly suppressed TNF-α/IFN-γ-induced phosphorylation of STAT1, NF-κB, and p38 MAPK. Taken together, our study indicates that SFII inhibits TNF-α/IFN-γ-induced TARC, MDC, and CTSS expression by regulating STAT1, NF-κB, and p38 MAPK signaling pathways.

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Let-7a-5p regulates the inflammatory response in chronic rhinosinusitis with nasal polyps

Diagnostic Pathology ◽

10.1186/s13000-021-01089-0 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Jianwei Zhang ◽

Lei Han ◽

Feng Chen

Keyword(s):

Inflammatory Response ◽

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Mapk Pathway ◽

Inhibitory Effect ◽

Luciferase Reporter ◽

Western Blot Assay ◽

Protein Levels ◽

Tnf Α

Abstract Background Let-7a-5p is demonstrated to be a tumor inhibitor in nasopharyngeal carcinoma. However, the role of let-7a-5p in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been reported. This study is designed to determine the pattern of expression and role of let-7a-5p in CRSwNP. Methods The expression level of let-7a-5p, TNF-α, IL-1β, and IL-6 in CRSwNP tissues and cells were detected by RT-qPCR. Western blot assay was carried out to measure the protein expression of the Ras-MAPK pathway. Dual luciferase reporter assay and RNA pull-down assay were used to explore the relationship between let-7a-5p and IL-6. Results Let-7a-5p was significantly downregulated in CRSwNP tissues and cells. Moreover, the mRNA expression of TNF-α, IL-1β and IL-6 was increased in CRSwNP tissues, while let-7a-5p mimic inhibited the expression of TNF-α, IL-1β and IL-6. Besides that, let-7a-5p was negatively correlated with TNF-α, IL-1β and IL-6 in CRSwNP tissues. In our study, IL-6 was found to be a target gene of let-7a-5p. Additionally, let-7-5p mimic obviously reduced the protein levels of Ras, p-Raf1, p-MEK1 and p-ERK1/2, while IL-6 overexpression destroyed the inhibitory effect of let-7a-5p on the Ras-MAPK pathway in CRSwNP. Conclusion We demonstrated that let-7a-5p/IL-6 interaction regulated the inflammatory response through the Ras-MAPK pathway in CRSwNP.

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Enhancement of the immune response against Salmonella infection of mice by heat-killed multispecies combinations of lactic acid bacteria

Journal of Medical Microbiology ◽

10.1099/jmm.0.061010-0 ◽

2013 ◽

Vol 62 (11) ◽

pp. 1657-1664 ◽

Cited By ~ 14

Author(s):

Chih-Yuan Chen ◽

Hau-Yang Tsen ◽

Chun-Li Lin ◽

Chien-Ku Lin ◽

Li-Tsen Chuang ◽

...

Keyword(s):

Lactic Acid ◽

Lactic Acid Bacteria ◽

Interleukin 12 ◽

Mouse Serum ◽

Immunomodulatory Activity ◽

Mouse Macrophage ◽

Macrophage Cells ◽

Tnf Α ◽

Anti Inflammatory Cytokine ◽

Pro Inflammatory Cytokines

Heat-killed lactic acid bacteria (LAB) has advantages over live LAB in that it has a long shelf‐life and is therefore easy to store and transport. From four LAB strains selected by immunomodulatory activity and adherent properties, we prepared the heat-killed multispecies combination of LAB (MLAB) and the cell walls from MLAB under two conditions (100 °C for 30 min and 121 °C for 15 min). Different effects on the adherent properties of these four LAB strains were observed, depending on the heating conditions. With mouse macrophage cells, the two heat-killed MLABs (HMLABs) showed significantly higher induction activities on the production of interleukin 12 (IL-12) than their individual strains did. Heat-killed MLABs and cell‐wall preparations were able to reduce the Salmonella invasion of Caco-2 and mouse macrophage cells. Feeding mice with HMLAB could inhibit the Salmonella invasion of mice significantly. For these mice, the expression level of pro-inflammatory cytokines, such as TNF-α and IL-6, in mouse serum was reduced while that of the anti-inflammatory cytokine, i.e. IL-10, was enhanced. The HMLABs developed in this study showed higher protective effect against Salmonella invasion either of Caco-2 cells or of mice, relative to the heat-killed lactobacilli, which consisted of Lactobacillus acidophilus strains selected at random. In conclusion, the HMLABs were potentially useful for the protection of mice against Salmonella infection and the induced inflammation.

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Cichoric Acid Ameliorates Monosodium Urate-Induced Inflammatory Response by Reducing NLRP3 Inflammasome Activation via Inhibition of NF-kB Signaling Pathway

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/8868527 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Qi Wang ◽

Bingfeng Lin ◽

Zhifeng Li ◽

Jie Su ◽

Yulin Feng

Keyword(s):

Inflammatory Response ◽

Signaling Pathway ◽

Nlrp3 Inflammasome ◽

Gouty Arthritis ◽

Inflammasome Activation ◽

Cichoric Acid ◽

Monosodium Urate ◽

Protein Levels ◽

Nlrp3 Inflammasome Activation ◽

Tnf Α

Gouty arthritis is characterized by the deposition of monosodium urate (MSU) within synovial joints and tissues due to increased urate concentrations. Here, we elucidated the role of the natural compound cichoric acid (CA) on the MSU crystal-stimulated inflammatory response. The THP-1-derived macrophages (THP-Ms) were pretreated with CA and then stimulated with MSU suspensions. The protein levels of p65 and IκBα, the activation of the NF-κB signaling pathway by measuring the expression of its downstream inflammatory cytokines, and the activity of NLRP3 inflammasome were measured by western blotting and ELISA. CA treatment markedly inhibited the degradation of IκBα and the activation of NF-κB signaling pathway and reduced the levels of its downstream inflammatory genes such as IL-1β, TNF-α, COX-2, and PGE2 in the MSU-stimulated THP-M cells. Therefore, we infer that CA effectively alleviated MSU-induced inflammation by suppressing the degradation of IκBα, thereby reducing the activation of the NF-κB signaling pathway and the NLRP3 inflammasome. These results suggest that CA could be a novel therapeutic strategy in averting acute episodes of gout.

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The Protective Effect of Picroside II on Isoflurane-Induced Neuronal Injury in Rats via Downregulating miR-195

NeuroImmunoModulation ◽

10.1159/000519779 ◽

2021 ◽

pp. 1-9

Author(s):

Hui Li ◽

Weijia Du ◽

Yawei Yuan ◽

Jingjing Xue ◽

Qiang Li ◽

...

Keyword(s):

Inflammatory Response ◽

Protective Effect ◽

Inflammatory Cytokines ◽

Escape Latency ◽

Neuronal Cells ◽

Neuronal Injury ◽

Morris Water Maze Test ◽

Picroside Ii ◽

Tnf Α ◽

Pro Inflammatory Cytokines

Introduction: Numerous pieces of evidence demonstrated that isoflurane induces hippocampal cell injury and cognitive impairments. Picroside II has been investigated for its anti-apoptosis and antioxidant neuroprotective effects. We aimed to explore the protective effects of picroside II and the role of microRNA-195 (miR-195) on isoflurane-induced neuronal injury in rats. Methods: The Morris water maze test was used to evaluate the effects of isoflurane on rats regarding escape latency and time in quadrant parameters. Real-time quantitative PCR was used to detect the expression levels of miR-195 and pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) mRNA, in the hippocampal tissues and neuronal cells. Results: The picroside II significantly improves isoflurane-induced higher escape latency and lower time spent in the quadrant compared with the control rats. Picroside II also promotes cell viability and suppresses cell apoptosis of isoflurane-induced neuronal cells. Besides, picroside II suppresses the expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and miR-195 in vivo and in vitro. Furthermore, overexpression of miR-195 abrogates the effects of picroside II on the expression of pro-inflammatory cytokines. The appropriate dose of picroside II is 20 mg/kg. Conclusion: Picroside II could protect the nervous system possibly through inhibiting the inflammatory response in the isoflurane-induced neuronal injury of rats. The protective effect of picroside II may be achieved by downregulating the expression of miR-195 and then inhibiting the inflammatory response.

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Tumor necrosis factor-α stimulates gastric epithelial cell proliferation

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00093.2004 ◽

2005 ◽

Vol 288 (1) ◽

pp. G32-G38 ◽

Cited By ~ 20

Author(s):

Jiing Chyuan Luo ◽

Vivian Yvonne Shin ◽

Ying Hua Yang ◽

William Ka Kei Wu ◽

Yi Ni Ye ◽

...

Keyword(s):

Cell Proliferation ◽

Epithelial Cell ◽

Mucosal Injury ◽

Epithelial Cell Line ◽

Epithelial Cell Proliferation ◽

Protein Levels ◽

Tnf Α ◽

Cox 2 ◽

Underlying Mechanisms ◽

Factor Α

TNF-α is a cytokine produced during gastric mucosal injury. We examined whether TNF-α could promote mucosal repair by stimulation of epithelial cell proliferation and explored further the underlying mechanisms in a rat gastric mucosal epithelial cell line (RGM-1). TNF-α treatment (1–10 ng/ml) for 12 or 24 h significantly increased cell proliferation but did not induce apoptosis in RGM-1 cells. TNF-α treatment significantly increased cytosolic phospholipase A2 and cyclooxygenase-2 (COX-2) protein expression and PGE2 level but did not affect the protein levels of EGF, basic fibroblast growth factor, and COX-1 in RGM-1 cells. The mRNA of TNF receptor (TNF-R) 2 but not of TNF-R1 was also increased. Dexamethasone dose dependently inhibited the stimulatory effect of TNF-α on cell proliferation, which was associated with a significant decrease in cellular COX-2 expression and PGE2 level. A selective COX-2 inhibitor 3-(3-fluorophenyl)-4-[4-(methylsulfonyl)phenyl]-5,5-dimethyl-5H-furan-2-one (DFU) by itself had no effect on basal cell proliferation but significantly reduced the stimulatory effect of TNF-α on RMG-1 cells. Combination of dexamethasone and DFU did not produce an additive effect. PGE2 significantly reversed the depressive action of dexamethasone on cell proliferation. These results suggest that TNF-α plays a regulatory role in epithelial cell repair in the gastric mucosa via the TNF-α receptor and activation of the arachidonic acid/PG pathway.

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Pentahydroxy flavonoid isolated from Madhuca indica ameliorated adjuvant-induced arthritis: Possible role of TNF-α, IL’s, NF-kβ, Ikβα, COX-2, P2X7

10.21203/rs.3.rs-413694/v1 ◽

2021 ◽

Author(s):

Yongliang Tang ◽

Daotao Xie ◽

Wenqing Gong ◽

Hongtao Wu ◽

Yi Qiang

Keyword(s):

Nitrosative Stress ◽

Autoimmune Disorder ◽

Significant Inhibition ◽

Withdrawal Threshold ◽

Protein Levels ◽

Intradermal Administration ◽

Tnf Α ◽

Female Wistar Rats ◽

Cox 2

Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disorder associated with progressive joint disability. Madhuca indica J. F. Gmel (family Sapotaceae) is an Indian medicinal plant reported to have an array of pharmacological properties. Objective To evaluate the anti-arthritic activity of isolated phytoconstituent from methanolic extract of Madhuca indica Leaves (MI-ALC) and its possible mechanism of action in FCA induced experimental arthritis. Materials and methods Polyarthritis was induced in female Wistar rats by intradermal administration of FCA (0.1 ml) into the tail. Polyarthritis was allowed to develop for the next 32 days. Then rats were treated with isolated phytoconstituent from MI-ALC (5, 10, and 20 mg/kg, p.o.) Results HPTLC, FTIR, and LC-MS spectral analysis of phytoconstituent isolated from MI-ALC confirmed the structure as 3,5,7,3′,4′- Pentahydroxy flavone (i.e., QTN). Treatment with QTN (10 and 20 mg/kg) showed significant inhibition (p < 0.05) in FCA-induced increased paw volume, joint diameter, paw withdrawal threshold, and latency. The elevated synovial oxido-nitrosative stress and protein levels of TNF-α, IL-1β, and IL-6 were significantly reduced (p < 0.05)by QTN. Western blot analysis revealed QNT significantly ameliorated (p < 0.05) up-regulated NF-kβ, Ikβα, COX-2, and P2X7 protein expressions. Conclusion QTN ameliorates FCA-induced hyperalgesia via inhibition of elevated oxido-nitrosative stress, inflammatory mediators (NF-kβ, Ikβα, COX-2, and P2X7), and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in experimental rats.

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Epigenetic targeting of the ACE2 and NRP1 viral receptors limits SARS-CoV-2 infectivity

Clinical Epigenetics ◽

10.1186/s13148-021-01168-5 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Maria Laura Saiz ◽

Marta L. De Diego ◽

Darío López-García ◽

Viviana Corte-Iglesias ◽

Aroa Baragaño Raneros ◽

...

Keyword(s):

Inflammatory Response ◽

Cell Lines ◽

Hdac Inhibitors ◽

Potential Candidate ◽

Dependent Manner ◽

Messenger Rnas ◽

N Protein ◽

Protein Levels ◽

Viral Spread ◽

Tnf Α

Abstract Background SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) and neuropilin-1 (NRP1) receptors for entry into cells, and the serine protease TMPRSS2 for S protein priming. Inhibition of protease activity or the engagement with ACE2 and NRP1 receptors has been shown to be an effective strategy for blocking infectivity and viral spreading. Valproic acid (VPA; 2-propylpentanoic acid) is an epigenetic drug approved for clinical use. It produces potent antiviral and anti-inflammatory effects through its function as a histone deacetylase (HDAC) inhibitor. Here, we propose VPA as a potential candidate to tackle COVID-19, in which rapid viral spread and replication, and hyperinflammation are crucial elements. Results We used diverse cell lines (HK-2, Huh-7, HUVEC, Caco-2, and BEAS-2B) to analyze the effect of VPA and other HDAC inhibitors on the expression of the ACE-2 and NRP-1 receptors and their ability to inhibit infectivity, viral production, and the inflammatory response. Treatment with VPA significantly reduced expression of the ACE2 and NRP1 host proteins in all cell lines through a mechanism mediated by its HDAC inhibitory activity. The effect is maintained after SARS-CoV-2 infection. Consequently, the treatment of cells with VPA before infection impairs production of SARS-CoV-2 infectious viruses, but not that of other ACE2- and NRP1-independent viruses (VSV and HCoV-229E). Moreover, the addition of VPA 1 h post-infection with SARS-CoV-2 reduces the production of infectious viruses in a dose-dependent manner without significantly modifying the genomic and subgenomic messenger RNAs (gRNA and sg mRNAs) or protein levels of N protein. The production of inflammatory cytokines (TNF-α and IL-6) induced by TNF-α and SARS-CoV-2 infection is diminished in the presence of VPA. Conclusions Our data showed that VPA blocks three essential processes determining the severity of COVID-19. It downregulates the expression of ACE2 and NRP1, reducing the infectivity of SARS-CoV-2; it decreases viral yields, probably because it affects virus budding or virions stability; and it dampens the triggered inflammatory response. Thus, administering VPA could be considered a safe treatment for COVID-19 patients until vaccines have been rolled out across the world.

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