• ALGAE
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• v.35 no.2
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• pp.201-212
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• 2020

The inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn disease are characterized by chronic inflammation throughout the gastrointestinal tract. The prevalence of IBD has been increasing worldwide, and has sometimes led to irreversible impairment of gastrointestinal structure and functions. In the present study, we identified a new sulfoquinovosylmonoacylglycerols (SQMG) (1) together with two known SQMGs (2 and 3) regulating intestinal inflammation from the brown alga Turbinaria ornata. The anti-inflammatory properties of two bioactive SQMGs, 1 and 2 were evaluated using an in vitro co-culture system consisting of human epithelial Caco-2 cells and PMA (phorbol 12-myristate 12-acetate)-differentiated THP-1 macrophages. Treatment with 1 or 2 inhibited the production nitric oxide and prostaglandin E₂ induced by lipopolysaccharide and interferon γ challenge. The expressions of inducible nitric oxide synthase and cyclooxygenase 2 were markedly down-regulated in response to inhibition of nuclear factor κB translocation to nucleus. These findings suggest the potential use of the brown alga T. ornata and its biologically active metabolites SQMGs as pharmaceutical adjuvants in the treatment of inflammation-related diseases, including IBD.

• Nutrition Research and Practice
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• v.11 no.5
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• pp.430-434
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• 2017

BACKGROUND/OBJECTIVE: Chronic hyperglycemia induces oxidative stress via accumulation of reactive oxygen species (ROS) and contributes to diabetic complications. Hyperglycemia induces mitochondrial superoxide anion production through the increased activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This study aimed to determine whether fisetin and luteolin treatments suppress the oxidative stress by modulating the expression of sirtuins (SIRTs) and forkhead box O3a (FOXO3a) under hyperglycemic conditions in human monocytes. MATERIALS/METHODS: Human monocytic cells (THP-1) were cultured under osmotic control (14.5 mmol/L mannitol), normoglycemic (NG, 5.5 mmol/L glucose), or hyperglycemic (HG, 20 mmol/L glucose) conditions, in the absence or presence of fisetin and luteolin for 48 h. To determine the effect of fisetin and luteolin treatments on high glucose-induced oxidative stress, western blotting and intracellular staining were performed. RESULTS: Hyperglycemic conditions increased the ROS production, as compared to normoglycemic condition. However, fisetin and luteolin treatments inhibited ROS production under hyperglycemia. To obtain further insight into ROS production in hyperglycemic conditions, evaluation of p47phox expression revealed that fisetin and luteolin treatments inhibited p47phox expression under hyperglycemic conditions. Conversely, the expression levels of SIRT1, SIRT3, SIRT6, and FOXO3a were decreased under high glucose conditions compared to normal glucose conditions, but exposure to fisetin and luteolin induced the expression of SIRT1, SIRT3, SIRT6, and FOXO3a. The above findings suggest that fisetin and luteolin inhibited high glucose-induced ROS production in monocytes through the activation of SIRTs and FOXO3a. CONCLUSIONS: The results of our study supports current researches that state fisetin and luteolin as potential agents for the development of novel strategies for diabetes.

• Journal of Periodontal and Implant Science
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• v.48 no.1
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• pp.60-68
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• 2018

Purpose: The aim of this study was to evaluate the ability of Porphyromonas gingivalis (P. gingivalis) to induce oxidation of high-density lipoprotein (HDL) and to determine whether the oxidized HDL induced by P. gingivalis exhibited altered antiatherogenic function or became proatherogenic. Methods: P. gingivalis and THP-1 monocytes were cultured, and the extent of HDL oxidation induced by P. gingivalis was evaluated by a thiobarbituric acid-reactive substances (TBARS) assay. To evaluate the altered antiatherogenic and proatherogenic properties of P. gingivalistreated HDL, lipid oxidation was quantified by the TBARS assay, and tumor necrosis factor alpha (TNF-${\alpha}$) levels and the gelatinolytic activity of matrix metalloproteinase (MMP)-9 were also measured. After incubating macrophages with HDL and P. gingivalis, Oil Red O staining was performed to examine foam cells. Results: P. gingivalis induced HDL oxidation. The HDL treated by P. gingivalis did not reduce lipid oxidation and may have enhanced the formation of MMP-9 and TNF-${\alpha}$. P. gingivalistreated macrophages exhibited more lipid aggregates than untreated macrophages. Conclusions: P. gingivalis induced HDL oxidation, impairing the atheroprotective function of HDL and making it proatherogenic by eliciting a proinflammatory response through its interaction with monocytes/macrophages.

• Journal of Ginseng Research
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• v.44 no.1
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• pp.145-153
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• 2020

Background: Panax ginseng Meyer (Araliaceae) is a highly valued medicinal plant in Asian regions, especially in Korea, China, and Japan. Chemical and biological studies on P. ginseng have focused primarily on its roots, whereas the seeds remain poorly understood. This study explores the phytochemical and biological properties of compounds from P. ginseng seeds. Methods: P. ginseng seeds were extracted with methanol, and 16 compounds were isolated using various chromatographic methods. The chemical structures of the isolates were determined by spectroscopic data. Antiinflammatory activities were evaluated for triterpene and steroidal saponins using lipopolysaccharide-stimulated RAW264.7 macrophages and THP-1 monocyte leukemia cells. Results: Phytochemical investigation of P. ginseng seeds led to the isolation of a novel triterpene saponin, pseudoginsenoside RT₈, along with 15 known compounds. Pseudoginsenoside RT₈ exhibited more potent antiinflammatory activity than the other saponins, attenuating lipopolysaccharide-mediated induction of proinflammatory genes such as interleukin-1β, interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2, and matrix metalloproteinase-9, and suppressed reactive oxygen species and nitric oxide generation in a dose-dependent manner. Conclusion: These findings indicate that pseudoginsenoside RT₈ has a pharmaceutical potential as an antiinflammatory agent and that P. ginseng seeds are a good natural source for discovering novel bioactive molecules.

• IMMUNE NETWORK
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• v.22 no.4
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• pp.33.1-33.17
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• 2022

Suppressors of cytokine signaling (SOCS) have emerged as potential regulators of macrophage function. We have investigated mechanisms of SOCS3 action on type 2 macrophage (M2) differentiation induced by glucocorticoid using human monocytic cell lines and mouse bone marrow-derived macrophages. Treatment of THP1 monocytic cells with dexamethasone (Dex) induced ROS generation and M2 polarization promoting IL-10 and TGF-β production, while suppressing IL-1β, TNF-α and IL-6 production. SOCS3 over-expression reduced, whereas SOCS3 ablation enhanced IL-10 and TGF-β induction with concomitant regulation of ROS. As a mediator of M2 differentiation, glucocorticoid-induced leucine zipper (GILZ) was down-regulated by SOCS3 and up-regulated by shSOCS3. The induction of GILZ and IL-10 by Dex was dependent on ROS and p38 MAPK activity. Importantly, GILZ ablation led to the inhibition of ROS generation and anti-inflammatory cytokine induction by Dex. Moreover, GILZ knock-down negated the up-regulation of IL-10 production induced by shSOCS3 transduction. Our data suggest that SOCS3 targets ROS- and p38-dependent GILZ expression to suppress Dex-induced M2 polarization.

• Biomedical Science Letters
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• v.16 no.2
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• pp.119-122
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• 2010

Interleukin-1${\beta}$ $(IL-1{\beta})$ is one of the key proinflammatory cytokines and it plays an important role for the antimycobacterial host defense mechanisms. In this study, we examined Mycobacterium tuberculosis (MTB)-stimulated induction of IL-1${\beta}$ and evaluated the associated signal transduction pathways. In PMA-differentiated THP-1 cells, MTB infection increased mRNA expression of IL-$1{\beta}$ in a dose-dependent manner. The expression of IL-1${\beta}$ mRNA began to be induced at 1.5 h after infection, and induced expression of IL-1${\beta}$ was retained for 48 h after MTB infection. The increase in expression of IL-1${\beta}$ caused by MTB was reduced in cells treated with Ro-31-8425 (an inhibitor of PK$C{\alpha}$, ${\beta}I$, ${\beta}II$, ${\gamma}$, ${\varepsilon}$) or PD98059 (an inhibitor of MEK1), meanwhile, pre-treatment with $G\ddot{o}6976$ (an inhibitor of $Ca^{2+}$ dependent PK$C{\alpha}$ and PK$C{\beta}I$) or Rottlerin (an inhibitor of PK$C{\delta}$) has no effect on MTB-induced expression of $IL-1{\beta}$ mRNA. These results show that the expression of $IL-1{\beta}$ mRNA caused by MTB may be mediated via MEK1 and PKC isoforms including PK$C{\beta}II$, $PKC{\gamma}$, or $PKC{\varepsilon}$. Further studies are required to determine whether other PKC isoforms $(PKC {\eta},\;{\theta},\;{\varepsilon},\;and\;{\lambda}/{\iota})$, except $PKC{\delta}$, $PKC{\alpha}$, and $PKC{\beta}I$, are also involved in $IL-1{\beta}$ mRNA expression after mycobacterial infection.

• Journal of Life Science
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• v.18 no.4
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• pp.537-541
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• 2008

White adipose tissue is now recognized as an important endocrine organ which secretes various signal factors and proteins termed 'adipokine'. Haptoglobin (Hp), which has been known as an acute phase protein, belongs to the adipokine. However, the function of Hp in adipose tissue remains unclear. To verify the role of Hp in preadipocytes, in this study, 3T3-L1 preadipocyte cells were stably transfected with human Hp gene and Hp-overexpressing cells were made. The Hp had no effect on cell growth of preadipocytes. By RT-PCR and Western blot analysis, the Hp inhibited gene expression of IL-6 and COX-2 and enhanced HO-1 synthesis in preadipocytes. Moreover, invasion assay showed the Hp suppressed migration of monocytes to preadipocytes. These findings suggest that the Hp may inhibit an inflammatory reaction in adipose tissue by regulating the expressions of pro-inflammatory and anti-inflammatory mediators, and by repressing monocytes/macrophages infiltration.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.27-39
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• 2023

Extensive research supported the therapeutic potential of curcumin, a naturally occurring compound, as a promising cytokine-suppressive anti-inflammatory drug. This study aimed to investigate the synergistic anti-inflammatory and anti-cytokine activities by combining 6-shogaol and 10-shogaol to curcumin, and associated mechanisms in modulating lipopolysaccharides and interferon-γ-induced proinflammatory signaling pathways. Our results showed that the combination of 6-shogaol-10-shogaolcurcumin synergistically reduced the production of nitric oxide, inducible nitric oxide synthase, tumor necrosis factor and interlukin-6 in lipopolysaccharides and interferon-γ-induced RAW 264.7 and THP-1 cells assessed by the combination index model. 6-shogaol-10-shogaol-curcumin also showed greater inhibition of cytokine profiling compared to that of 6-shogaol-10-shogaol or curcumin alone. The synergistic anti-inflammatory activity was associated with supressed NFκB translocation and downregulated TLR4-TRAF6-MAPK signaling pathway. In addition, SC also inhibited microRNA-155 expression which may be relevant to the inhibited NFκB translocation. Although 6-shogaol-10-shogaol-curcumin synergistically increased Nrf2 activity, the anti-inflammatory mechanism appeared to be independent from the induction of Nrf2. 6-shogaol-10-shogaol-curcumin provides a more potent therapeutic agent than curcumin alone in synergistically inhibiting lipopolysaccharides and interferon-γ induced proinflammatory mediators and cytokine array in macrophages. The action was mediated by the downregulation of TLR4/TRAF6/MAPK pathway and NFκB translocation.

• Korean Journal of Food Science and Technology
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• v.51 no.1
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• pp.70-80
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• 2019

The aim of this study was to investigate the effects of red ginseng-derived non-saponin fraction (NSF) on inflammatory responses and monocyte-to-macrophage differentiation in RAW264.7 and THP-1. NSF effectively inhibited inflammatory responses by downregulating nitric oxide (NO) production and protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). NSF ($2000{\mu}g/mL$) decreased the levels of NO, iNOS, and COX-2 by 33, 83, and 64%, respectively. NSF inhibited the differentiation of monocyte-to-macrophage by decreasing cell adherence along with downregulation of the cluster of differentiation molecule $11{\beta}$ ($CD11{\beta}$) and CD36. In addition, pro-inflammatory cytokines, such as tumor necrosis factor-alpha, interleukin 6, and monocyte chemoattractant protein 1 (MCP-1), were significantly reduced with NSF treatment. The NSF-mediated inhibition of inflammatory responses was due to the regulation of nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). NSF effectively suppressed the translocation of $NF-{\kappa}B$ into the nucleus, while nuclear Nrf2 and its target protein, heme oxygenase-1, levels were significantly increased.

• BMB Reports
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• v.28 no.6
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• pp.527-532
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• 1995

Human taurine transporter has 12 transmembrane domains and its molecular weight is 69.6 kDa. The long cytoplasmic carboxy and amino termini might function as regulatory attachment sites for other proteins. Six potential protein kinase C phosphorylation sites have been reported in human taurine transporter. In this report, we studied the effects of phorbol 12-myristate 13-acetate (PMA) and glucocorticoid hormone on taurine transportation in the RAW 264.7, mouse macrophage cell line. When the cells were incubated with $[^{3}H]taurine$ in the presence or absence of $Na^+$ ion for 40 min at $37^{\circ}C$, the [$[^{3}H]taurine$ uptake rate was 780-times higher in the $Na^{+}-containing$ buffer than in the $Na^{+}-deficient$ buffer, indicating that this cell line expresses taurine transporter protein on the cell surface. THP1, a human promonocyte cell line, also showed a similar property. The $[^{3}H]taurine$ uptake rate was not influenced by the inflammatory inducing cytokines such as interleukin-1, gamma-interferon or interleukin-1+gamma-interferon, but was decreased by the PMA in the RAW 264.7 cell line. This suggests that activation of protein kinase C inhibits taurine transporter activity directly or indirectly. The inhibition of $[^{3}H]taurine$ uptake by PMA was time-dependent. Maximal inhibition occurred in one hr stimulation with PMA Increasing the treatment time beyond one h reduced the $[^{3}H]taurine$ uptake inhibition due to the depletion or inactivation of protein kinase C. The cell line also showed concentration-dependent $[^{3}H]taurine$ uptake under PMA stimulation. The phorbol-ester caused 23% inhibition at the concentration of 1 ${\mu}m$ PMA. The inhibition was significant even at a concentration as low as 10 nM PMA The reduced $[^{3}H]taurine$ uptake could be recovered by treatment with glucocorticosteroid hormone. Dexamethasone led to recover of the reduced taurine uptake induced by phorbol-ester, recovering maximally after one hr. This may suggest that macrophage cells require higher taurine concentration in a stressed state, for the secretion of glucocorticoid hormone is increased by hypothalamo-pituitary-adrenocortical (HPA) axis activation in the blood stream.