• Biomedical Science Letters
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• v.29 no.4
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• pp.211-219
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• 2023

Caffeic acid phenethyl ester (CAPE) is an active component of propolis obtained from honeybee hives. CAPE possesses anti-mitogenic, anti-carcinogenic, anti-inflammatory, and immunomodulatory activities in diverse systems, which know as displays antioxidant activity and inhibits lipoxygenase activities, protein tyrosine kinase, and nuclear factor kappa B (NF-κB) activation. This study aimed to investigate the effect of CAPE on lipopolysaccharide (LPS)-induced human neutrophil phagocytosis. Human neutrophils were cultured with various concentrations of CAPE (1, 10, and 100 µM) with or without LPS. The pro-inflammatory proteins (tumor necrosis factor-alpha [TNF-α], interleukin [IL]-6 and IL-8) levels were measured after 4 h incubation. To investigate the intracellular signaling pathway, we measured the levels of mitogen-activated protein kinases (MAPK), including phosphorylation of p38, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinase (JNK). Next, to evaluate the potential phagocytosis, neutrophils were labeled with iron particles of superparamagnetic iron oxide nanoparticles (SPIONs, 40 nm) for 1 h in culture medium containing 5 mg/mL of iron. The labeling efficiency was determined by Prussian blue staining for intracellular iron and 3T-wighted magnetic resonance imaging. CAPE decreased the activation of intracellular signaling pathways, including ERK1/2 and c-Jun, and expression of pro-inflammatory cytokines, including TNF-α and IL-6, but had no effect on the signaling pathways of p38 and cytokine IL-8. Furthermore, images obtained after mannan-coated SPION treatment suggested that CAPE induced significantly higher signal intensities than the control or LPS group. Together, these results suggest that CAPE regulates LPS-mediated activation of human neutrophils to reduce phagocytosis.

• BMB Reports
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• v.45 no.6
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• pp.371-376
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• 2012

To investigate the therapeutic effect of a Korean herbal medicine Pulsatilla koreana as an anti-septic agent, anti-inflammatory effects of the herbal medicine were determined in lipopolysaccharide (LPS)-exposed rats. Treatment with a methanol extract from Pulsatilla koreana significantly inhibited LPS-induced inflammatory responses. Results from ELISA analysis showed that Pulsatilla koreana decreased the plasma and hepatic levels of pro-inflammatory cytokines such as IL-$1{\beta}$, IL-6, TNF-${\alpha}$ while increased the level of anti-inflammatory cytokine IL-10 in LPS-exposed rats. Pulsatilla koreana also decreased the plasma levels of other inflammatory mediators such as $NO_3{^-}/NO_2{^-}$, ICAM-1, $PGE_2$, and CINC-1 in LPS-exposed rats. Although no significant effects were observed in the phagocytic activities, the distribution of lymphocyte population was significantly shifted by the treatment with Pulsatilla koreana. All together, Pulsatilla koreana exerts anti-inflammatory activities in the immune-challenged animals implicating that this Korean herbal medicine is therapeutically useful for the treatment of inflammatory diseases like sepsis.

• Food Science of Animal Resources
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• v.35 no.3
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• pp.293-298
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• 2015

Porcine placenta extract (PPE) is known to possess anti-inflammatory properties owing to its high concentration of bioactive substances. However, the need to eliminate blood-borne infectious agents while maintaining biological efficacy raises concerns about the optimal method for sterilizing PPE. Therefore, the objective of this study was to compare the effects of the standard pressurized heat (autoclaving) method of sterilization with γ-irradiation on the anti-inflammatory effects of PPE. The anti-inflammatory actions of these two preparations of PPE were evaluated by measuring their inhibitory effects on the production of NO, the expression of iNOS protein, and the expression of iNOS, COX2, TNF-α, IL-1β, and IL-6 mRNA in lipopolysaccharide-stimulated RAW 264.7 cells. Compared with autoclaved PPE, γ-irradiated PPE showed significantly greater inhibition of NO production and iNOS protein expression, and produced a greater reduction in the expression of iNOS, COX2, TNF-α, IL-1β, and IL-6 mRNA. These results provide evidence that the sterilization process is crucial in determining the biological activity of PPE, especially its anti-inflammatory activity. Collectively, our data suggest that γ-irradiated PPE acts at the transcriptional level to effectively and potently suppresses the production of NO and the expression of pro-inflammatory cytokines.

• Journal of Applied Biological Chemistry
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• v.60 no.4
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• pp.363-372
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• 2017

Hypericum ascyron has long been used as medicinal plant and recent studies reported that H. ascyron has anti-diabetic, anti-oxidant, and anti-bacterial effects. In this study, inhibitory effect from H. ascyron on pro-inflammatory responses has been investigated. H. ascyron was extracted at optimal extraction condition. Total phenolic contents in water and 90% ethanol were 29.75 and 31.82 mg/g, respectively. Hyaluronidase inhibitory activity of H. ascyron extracts ($50-200{\mu}g/mL$ phenolics) was 0.00-14.81% and 15.33-47.49%, respectively. In cell viability, cell toxicity was shown at concentration of $100{\mu}g/mL$ and $30{\mu}g/mL$ of water and 90% ethanol extract. Therefore, $10-50{\mu}g/mL$ in water extracts and $5-20{\mu}g/mL$ in ethanol extracts was selected each for further study. Inducible nitric oxide synthase (iNOS) derived nitric oxide (NO) and cyclooxygenase (COX)-2-derived prostaglandin $E_2$ ($PGE_2$) protein expression inhibitory effect of extracts were inhibited in a dose dependent manner, significantly. Also, the pro-inflammatory cytokines inhibitory effect such as tumor necrosis $factor-{\alpha}$, nterleukin (IL)-6 and $IL-1{\beta}$ were decreased in the dose dependent manner. The results indicate that H. ascyron extracts reduced inflammatory responses in lipopolysaccharide-induced 264.7 cells via the regulation of the iNOS, COX-2, NO, $PGE_2$, and pro-inflammatory cytokines. Therefore, H. ascyron extracts have significant anti-inflammatory effect and a source as therapeutic materials.

• Proceedings of the Zoological Society Korea Conference
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• 2003.08a
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• pp.59-59
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• 2003

No Abstract, See Full Text

• Advances in Traditional Medicine
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• v.6 no.3
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• pp.161-166
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• 2006

Chrysanthemum morifolium (CM) is a herb widely used in medicine for the treatment of a variety of diseases. In this study, using mouse peritoneal macrophages, we have examined whether CM affects nitric oxide (NO), tumor necrosis factor $(TNF)-\alpha$ and interleukin (IL)-6 induced interferon $(IFN)-\gamma$ and lipopolysaccharide (LPS). CM inhibits $IFN-\gamma$ and LPS-induced NO in dose dependent manner. We also found that CM inhibits pro-inflammatory cytokine, $TNF-\alpha$ and IL-6. The expression of cyclooxygenase-2 was reduced by CM. These finding means that CM can be used in controlling macrophages-mediated inflammatory disease.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.4
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• pp.391-398
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• 2018

The aim of this study was to evaluate the in vitro anti-inflammatory and utero-relaxant effect of ${\alpha}$-bisabolol on the pregnant human myometrium. Samples from the pregnant human myometrium were used in functional tests to evaluate the inhibitory effect of ${\alpha}$-bisabolol (560, 860, 1,200 and $1,860{\mu}M$) on spontaneous myometrial contractions. The intracellular cyclic adenosine monophosphate (cAMP) levels generated in response to ${\alpha}$-bisabolol in human myometrial homogenates were measured by ELISA. The anti-inflammatory effect of ${\alpha}$-bisabolol was determined through the measurement of two pro-inflammatory cytokines, tumor necrosis factor-${\alpha}$ ($TNF{\alpha}$) and interleukin $(IL)-1{\beta}$, and the anti-inflammatory cytokine IL-10, in pregnant human myometrial explants stimulated with lipopolysaccharide (LPS). Forskolin was used as a positive control to evaluate the cAMP and cytokine levels. ${\alpha}$-Bisabolol was found to induce a significant inhibition of spontaneous myometrial contractions at the highest concentration level (p<0.05). ${\alpha}$-Bisabolol caused a concentration-dependent decrease in myometrial cAMP levels (p<0.05) and a concentration-dependent decrease in LPS-induced $TNF{\alpha}$ and $IL-1{\beta}$ production, while IL-10 production did not increase significantly (p>0.05). The anti-inflammatory and utero-relaxant effects induced by ${\alpha}$-bisabolol were not associated with an increase in cAMP levels in pregnant human myometrial samples. These properties place ${\alpha}$-bisabolol as a potentially safe and effective adjuvant agent in cases of preterm birth, an area of pharmacological treatment that requires urgent improvement.

• Journal of the East Asian Society of Dietary Life
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• v.27 no.1
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• pp.1-8
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• 2017

This study was conducted to investigate alterations of seaweed composition upon Lactobacillus rhamnosus GG (LGG) fermentation as well as potential anti-inflammatory effects and mechanism (s) of water extracts and fermented water extracts of Laminaria japonica (LJ) and Hizikia fusiforme (HF) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Total polyphenol, total sugar, and reducing sugar contents were measured in LJ and HF water extracts before and after fermentation by LGG. Alterations of inflammatory cytokine levels in cell culture media were measured by ELISA, and levels of phosphorylation of c-jun NH2-terminalkinase (JNK) and extra cellular signal regulated kinase (ERK) were examined by Western blot analysis. LGG fermentation of LJ and HF altered total polyphenol and sugar contents in water extracts of LJ and HF. LPS-induced production of pro-inflammatory cytokines such as IL-6 and $TNF-{\alpha}$ was significantly reduced by HF-f compared to control in RAW264.7 cells. Consistent with reduction of anti-inflammatory cytokine, interleukin (IL)-6, and tumor necrosis factor $(TNF)-{\alpha}$ levels by HF-f, HF-f also significantly reduced phosphorylation of ERK and JNK in LPS-stimulated RAW264.7 cells. In addition, LJ-f and HF also significantly reduced phosphorylation of JNK and ERK induced by LPS in RAW264.7 cells. Overall, our result suggests that HF-f among the four tested seaweed extracts is the most potent anti-inflammatory agent, and its mechanism of action is partially mediated by reduction of JNK and ERK phosphorylation as well as IL-6 and $TNF-{\alpha}$ production in LPS-stimulated RAW264.7 cells.

• BMB Reports
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• v.49 no.4
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• pp.232-237
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• 2016

Mulberry tree twigs (Ramulus mori) contain large amounts of oxyresveratrols and have traditionally been used as herbal medicines because of their anti-inflammatory properties. However, the signaling mechanism by which R. mori exerts its anti-inflammatory action remains to be elucidated. In this study, we observed that R. mori ethanol extracts (RME) exerted an inhibitory effect on the lipopolysaccharide (LPS)-induced production of the pro-inflammatory cytokine interleukin-6 (IL-6) in Raw264.7 macrophage cells. Additionally, RME inhibited IL-6 production by blocking the leukotriene B₄ receptor-2 (BLT2)-dependent-NADPH oxidase 1 (NOX1)-reactive oxygen species (ROS) cascade, leading to anti-inflammatory activity. Finally, RME suppressed the production of the BLT2 ligands LTB4 and 12(S)-HETE by inhibiting the p38 kinase-cytosolic phospholipase A₂-5-/12-lipoxygenase cascade in LPS-stimulated Raw264.7 cells. Overall, our results suggest that RME inhibits the 'BLT2 ligand-BLT2'-linked autocrine inflammatory axis, and that this BLT2-linked cascade is one of the targets of the anti-inflammatory action of R. mori.

• Food Science and Preservation
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• v.21 no.1
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• pp.114-120
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• 2014

Zizyphus jujube leaf fractions (ZLFs) showed no cytotoxic effects of up to $100{\mu}g/mL$, while the anti-inflammatory effects of ZLFs were analyzed by checking the productions of nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), cyclooxygenase-2 (COX-2), and inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 in the lipopolysaccharide (LPS)-stimulated Raw264.7 macrophage up to the concentration of $100{\mu}g/mL$. ZLFs ($100{\mu}g/mL$) demonstrated a strong anti-inflammatory activity that reduced 61~85% of NO and 71~100% of $PGE_2$ production in the LPS-stimulated Raw264.7 macrophage. Even the low ZLFs concentration of $1{\mu}g/mL$ have reduced NO and $PGE_2$ production by 34~64%. Expressions of COX-2 protein were also effectively inhibited by the ZLFs. Furthermore, the TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 production were significantly suppressed through the treatment of ZLFs at concentrations of 1, 10, and $100{\mu}g/mL$. In the order of the Zizyphus jujube leaf water fraction (ZLWF) < buthanol fraction (ZLBF) < ethyl acetate fraction (ZLEF) showed anti-inflammatory activity. In particular, the ethyl acetate fraction ZLEF at $100{\mu}g/mL$ showed an excellent anti-inflammatory activity by reducing the production of NO, $PGE_2$, COX-2, and inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$, IL-6) in the level of Raw264.7 macrophage without LPS-stimulation or even better. The results of our study suggest the potential of ZLEF for use as an excellent ant-inflammatory inhibiting mediator and may be used as a therapeutic approach to various inflammatory diseases.