• Biomolecules & Therapeutics
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• 제24권1호
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• pp.25-32
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• 2016

Lichens have been known to possess multiple biological activities, including anti-proliferative and anti-inflammatory activities. Vascular cell adhesion molecule-1 (VCAM-1) may play a role in the development of atherosclerosis. Hence, VCAM-1 is a possible therapeutic target in the treatment of the inflammatory disease. However, the effect of lobaric acid on VCAM-1 has not yet been investigated and characterized. For this study, we examined the effect of lobaric acid on the inhibition of VCAM-1 in tumor necrosis factor-alpha (TNF-${\alpha}$)-stimulated mouse vascular smooth muscle cells. Western blot and ELISA showed that the increased expression of VCAM-1 by TNF-${\alpha}$ was significantly suppressed by the pre-treatment of lobaric acid ($0.1-10{\mu}g/ml$) for 2 h. Lobaric acid abrogated TNF-${\alpha}$-induced NF-${\kappa}B$ activity through preventing the degradation of $I{\kappa}B$ and phosphorylation of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), and p38 mitogen activated protein (MAP) kinase. Lobaric acid also inhibited the expression of TNF-${\alpha}$ receptor 1 (TNF-R1). Overall, our results suggest that lobaric acid inhibited VCAM-1 expression through the inhibition of p38, ERK, JNK and NF-${\kappa}B$ signaling pathways, and downregulation of TNF-R1 expression. Therefore, it is implicated that lobaric acid may suppress inflammation by altering the physiology of the atherosclerotic lesion.

• Molecules and Cells
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• 제26권3호
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• pp.285-290
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• 2008

Estrogen-induced proliferation in estrogen receptor (ER)-positive breast cancer cells is primarily mediated through two distinct intracellular receptors, $ER{\alpha}$ and $ER{\beta}$. Although tumor necrosis factor alpha ($TNF{\alpha}$) and $E2/ER{\alpha}$ are known to exert opposing effects on cell proliferation in MCF-7 cells, the mechanism by which $TNF{\alpha}$ antagonizes $E2/ER{\alpha}$-mediated cell proliferation is not well understood. The present study suggests that reduced cell survival in response to $TNF{\alpha}$ treatment in MCF-7 cells may be associated with the down-regulation of $ER{\alpha}$ protein. The decrease in $ER{\alpha}$ protein level was accompanied by an inhibition of $ER{\alpha}$ gene transcription. Cell viability was decreased synergistically by the combined treatment with $ER{\alpha}$-siRNA and $TNF{\alpha}$. Furthermore, pretreatment of cells with the PI3-kinase (PI3K)/ Akt inhibitor, LY294002, markedly enhanced $TNF{\alpha}$-induced down-regulation of the $ER{\alpha}$ protein, suggesting that the PI3K/Akt pathway might be involved in control of the $ER{\alpha}$ level. Moreover, down-regulation of $ER{\alpha}$ by $TNF{\alpha}$ was not inhibited in cells that were pretreated with the proteasome inhibitors, MG132 and MG152, which suggests that proteasome-dependent proteolysis does not significantly influence $TNF{\alpha}$-induced down-regulation of $ER{\alpha}$ protein. In contrast, the effect of the PI3K/Akt inhibitor on $ER{\alpha}$ was blocked in cells that were treated with LY294002 in the presence of the proteasome inhibitors. Collectively, our findings show that the $TNF{\alpha}$ may partly regulate the growth of MCF-7 breast cancer cells through the down-regulation of $ER{\alpha}$ expression, which is primarily mediated by a PI3K/Akt signaling.

• 셀메드
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• 제6권2호
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• pp.13.1-13.7
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• 2016

Fatigue is a common complaint and affects the quality of life in modern people. Physical stress may induce activation of certain immune cells. Fermented porcine placenta (FPP) has been used to alleviate fatigue. Inflammatory cytokines are produced by physical stress and results in symptoms of fatigue. However, the role of FPP on fatigue-associated inflammatory cytokine production has not been elucidated yet. Thus, we estimated the anti-fatigue effect of FPP and its active components, leucine (Leu) and lysine (Lys) in activated RAW264.7 macrophages and forced swimming test (FST) fatigue animal model. Pretreatment with FPP, Leu, or Lys significantly inhibited the lipopolysaccharide (LPS)-induced tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 production without inducing cytotoxicity on LPS-stimulated RAW264.7 macrophages. FPP, Leu, or Lys inhibited the production of nitric oxide and downregulated the expression of inducible nitric oxide synthase on LPS-stimulated RAW264.7 macrophages. Furthermore, caspase-1 activities increased by LPS were significantly reduced by FPP, Leu, or Lys. In the FST, inflammatory cytokine levels of the mice administrated with FPP, Lys, and Leu were significantly reduced compared with the control group at 21 days. Collectively, these results show that anti-fatigue effect of FPP and its active components, Leu and Lys might be derived from the down-regulating of inflammatory mediators.

• Journal of Ginseng Research
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• 제44권4호
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• pp.619-626
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• 2020

Background: The effects of diol-ginsenoside fraction (Diol-GF) and triol-ginsenoside fraction (Triol-GF) from Korean Red Ginseng on the development of type 1 diabetes (T1D) were examined in diabetes-prone biobreeding (DP-BB) rats that spontaneously develop T1D through an autoimmune process. Methods: DP-BB female rats were treated with Diol-GF or Triol-GF daily from the age of 3-4 weeks up to 11-12 weeks (1 mg/g body weight). Results: Diol-GF delayed the onset, and reduced the incidence, of T1D. Islets of Diol-GF-treated DP-BB rats showed significantly lower insulitis and preserved higher plasma and pancreatic insulin levels. Diol-GF failed to change the proportion of lymphocyte subsets such as T cells, natural killer cells, and macrophages in the spleen and blood. Diol-GF had no effect on the ability of DP-BB rat splenocytes to induce diabetes in recipients. Diol-GF and diol-ginsenoside Rb1 significantly decreased tumor necrosis factor α production, whereas diol-ginsenosides Rb1 and Rd decreased interleukin 1β production in RAW264.7 cells. Furthermore, mixed cytokine- and chemical-induced β-cell cytotoxicity was greatly inhibited by Diol-GF and diol-ginsenosides Rc and Rd in RIN5mF cells. However, nitric oxide production in RAW264.7 cells was unaffected by diol-ginsenosides. Conclusion: Diol-GF, but not Triol-GF, significantly delayed the development of insulitis and T1D in DP-BB rats. The antidiabetogenic action of Diol-GF may result from the decrease in cytokine production and increase in β-cell resistance to cytokine/free radical-induced cytotoxicity.

• The Korean Journal of Physiology and Pharmacology
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• 제20권4호
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• pp.347-355
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• 2016

Cryptotanshinone (CPT) is a natural compound isolated from traditional Chinese medicine Salvia miltiorrhiza Bunge. In the present study, the regulatory effect and potential mechanisms of CPT on tumor necrosis factor alpha ($TNF-{\alpha}$) induced lectin-like receptor for oxidized low density lipoprotein (LOX-1) were investigated. Human umbilical vein endothelial cells (HUVECs) were cultured and the effect of $TNF-{\alpha}$ on LOX-1 expression at mRNA and protein levels was determined by Real-time PCR and Western blotting respectively. The formation of intracellular ROS was determined with fluorescence probe $CM-DCFH_2-DA$. The endothelial ox-LDL uptake was evaluated with DiI-ox-LDL. The effect of CPT on LOX-1 expression was also evaluated with SD rats. $TNF-{\alpha}$ induced LOX-1 expression in a dose- and time- dependent manner in endothelial cells. $TNF-{\alpha}$ induced ROS formation, phosphorylation of $NF-{\kappa}B$ p65 and ERK, and LOX-1 expression, which were suppressed by rotenone, DPI, NAC, and CPT. $NF-{\kappa}B$ inhibitor BAY11-7082 and ERK inhibitor PD98059 inhibited $TNF-{\alpha}-induced$ LOX-1 expression. CPT and NAC suppressed $TNF-{\alpha}-induced$ LOX-1 expression and phosphorylation of $NF-{\kappa}B$ p65 and ERK in rat aorta. These data suggested that $TNF-{\alpha}$ induced LOX-1 expression via ROS activated $NF-{\kappa}B/ERK$ pathway, which could be inhibited by CPT. This study provides new insights for the anti-atherosclerotic effect of CPT.

• 동아시아식생활학회지
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• 제14권5호
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• pp.425-437
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• 2004

Medicinal plants are of great importance in providing healthcare to a large portion of the population in Korea. A number of plants are described in Dong-Ui-Bo-Gam for use in the treatment of allergic disorders, namely psoriasis, eczema, bronchial asthma, etc. In this study, we evaluated the effect of AllerQ, which is multi-complexes of various plants extracts such like Mori folium, Scutellaria baicallensis, Glycyrrhiza uralnsis, Mentha sacharinensis and Poncirus trifoliata on compound 48/80 induced anaphylactic shock, ovalbumin induced asthma in vivo and anti-IgE antibody induced hypersensitivity in vitro. We found antianaphylactic or antiallergic properties of AllerQ when given orally. AllerQ for prophylactic treatment for anaphylactic shocks have produced good results. AllerQ may modulate various aspects of immune function and allergic inflammation. In the present study, we analyse the effects of AllerQ on mast cell degranulation, mortality, cAMP/cGMP, O₂, H₂O₂ level, cyokine production and on the elicitation of IgE-mediated mast cell-dependent allergic inflammation in vivo and in vitro. We have established that AllerQ inhibited histamine release, cAMP/cGMP, O₂, H₂O₂ level, IL-4, tumor necrosis factor-alpha(TNF-α) and IL-6 production without having any significant physical change. These effects have been observed in mast cell(in vitro) and serum(in vivo) derived from three different origins that were activated by either immunological or non-immunological stimuli. These results suggest that the antianaphylactic and antiasthma tic action of AllerQ may be associated with an increase in the intracellular inhibition of the cAMP phosphodiesterase. Furthermore, AllerQ identified as potent inhibitors on O₂, H₂O₂ and cytokine activity. these data suggest that AllerQ may have an inhibitory role in mast cell-mediated allergic inflammation, and thus might be considered as an useful functional food.

• 대한의생명과학회지
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• 제26권1호
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• pp.51-56
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• 2020

Soy sauce is one of the representatives of traditional fermented foods in Korea. However, studies on soy sauce are relatively insufficient in Korea compared to Japan. In this study, antioxidant and anti-inflammatory activities of polysaccharides were measured by polysaccharides isolated from two different soy sauces, Korean and Japanese (KSS-0 and JSS-0). KSS-0 was purified into two fractions using gel chromatography and named them as KSS-I and KSS-II. To investigate the antioxidant activity of the polysaccharides, we measured the polyphenol content and radical scavenging activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). To investigate the anti-inflammatory activity of polysaccharides, we used RAW 264.7 macrophage cells and induced inflammation using lipopolysaccharide (LPS). Then, we measured levels of inflammatory mediators such as nitric oxide (NO) and tumor necrosis factor (TNF)-α. Among the four polysaccharides, KSS-II showed the highest antioxidant activity and had good anti-inflammatory activity; KSS-II decreased inflammatory mediators in a dose-dependent manner. In conclusion, the polysaccharide isolated from Korean soy sauce (KSS-II) showed better anti-oxidant and anti-inflammatory activities than polysaccharides isolated from Japanese soy sauce, and may be useful as substances for functional foods.

• Journal of Microbiology and Biotechnology
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• 제26권8호
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• pp.1367-1374
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• 2016

The present study evaluated the total phenolic and flavonoid contents as well as total antioxidant capacity (TAC) of three cultivars of Actinidia arguta Planch. kiwi berries; cv. Mansoo (Mansoo), cv. Chiak (Chiak), and cv. Haeyeon (Haeyeon). In addition, the anti-inflammatory effects of the three cultivars of kiwi berries were investigated using a lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cell line. Mansoo had the highest total phenolic content and TAC among the three cultivars, whereas Chiak had the highest total flavonoid content. The total antioxidant capacities of the kiwi berry extracts were more strongly correlated with total phenolic content than with total flavonoid content. The kiwi berry extracts suppressed the secretion of pro-inflammatory cytokines, including interleukin-6 and tumor necrosis factor-α, from LPS-stimulated RAW 264.7 cells. The release of nitrite, an indirect indicator of nitric oxide, was also ameliorated by pre-treatment with the kiwi berry extracts in a dose-dependent manner. Cellular-based measurements of antioxidant capacity exhibited that the kiwi berry extracts had cellular antioxidant capacities. Such cellular antioxidant effects are possibly attributed to their direct antioxidant capacity or to the inhibition of reactive oxygen species generation via anti-inflammatory effects. Our findings suggest that kiwi berries are potential antioxidant and anti-inflammatory agents.

• Journal of Microbiology and Biotechnology
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• 제30권9호
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• pp.1282-1289
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• 2020

Previously, we performed an in silico analysis of the Periplaneta americana transcriptome. Antimicrobial peptide candidates were selected using an in silico antimicrobial peptide prediction method. It was found that periplanetasin-5 had antimicrobial activity against yeast and gram-positive and gram-negative bacteria. In the present study, we demonstrated the anti-inflammatory activities of periplanetasin-5 in mouse macrophage Raw264.7 cells. No cytotoxicity was observed at 60 ㎍/ml periplanetasin-5, and treatment decreased nitric oxide production in Raw264.7 cells exposed to lipopolysaccharide (LPS). In addition, quantitative RT-PCR and enzyme-linked immunosorbent assay revealed that periplanetasin-5 reduced cytokine (tumor necrosis factor-α, interleukin-6) expression levels in the Raw264.7 cells. Periplanetasin-5 controlled inflammation by inhibiting phosphorylation of MAPKs, an inflammatory signaling element, and reducing the degradation of IκB. Through LAL assay, LPS toxicity was found to decrease in a periplanetasin-5 dose-dependent manner. Collectively, these data showed that periplanetasin-5 had anti-inflammatory activities, exemplified in LPS-exposed Raw264.7 cells. Thus, we have provided a potentially useful antibacterial peptide candidate with anti-inflammatory activities.

• BMB Reports
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• 제52권10호
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• pp.613-618
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• 2019

Microglial cells are known as the main immune cells in the central nervous system, both regulating its immune response and maintaining its homeostasis. Furthermore, the antioxidant ${\alpha}-lipoic$ acid (LA) is a recognized therapeutic drug for diabetes because it can easily invade the blood-brain barrier. This study investigated the effect of ${\alpha}-LA$ on the inflammatory response in lipopolysaccharide (LPS)-treated BV-2 microglial cells. Our results revealed that ${\alpha}-LA$ significantly attenuated several inflammatory responses in BV-2 microglial cells, including pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ and interleukin (IL)-6, and other cytotoxic molecules, such as nitric oxide and reactive oxygen species. In addition, ${\alpha}-LA$ inhibited the LPS-induced phosphorylation of ERK and p38 and its pharmacological properties were facilitated via the inhibition of the nuclear factor kappa B signaling pathway. Moreover, ${\alpha}-LA$ suppressed the activation of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasomes, multiprotein complexes consisting of NLRP3 and caspase-1, which are involved in the innate immune response. Finally, ${\alpha}-LA$ decreased the genes accountable for the M1 phenotype, $IL-1{\beta}$ and ICAM1, whereas it increased the genes responsible for the M2 phenotype, MRC1 and ARG1. These findings suggest that ${\alpha}-LA$ alleviates the neuroinflammatory response by regulating microglial polarization.