• Journal of Life Science
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• v.29 no.11
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• pp.1218-1226
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• 2019

The white-spotted flower chafer Protaetia brevitarsis seulensis is a medicinally beneficial and important edible insect species. We previously performed an in silico analysis of the Protaetia brevitarsis seulensis transcriptome to identify putative antimicrobial peptides and then tested their antimicrobial and hemolytic activities. These peptides had potent antimicrobial activities against bacteria and yeast without inducing hemolysis. In the present study, the cationic antimicrobial peptide, protaetiamycine 2, was selected for further assessment of its anti-inflammatory properties in mouse macrophage Raw264.7 cells. Protaetiamycine 2 treatment of Raw264.7 cells suppressed LPS-induced nitric oxide production and reduced the expression of inducible nitric oxide synthase and cyclooxygenase-2, as determined by real-time PCR and western blotting. The expression of proinflammatory cytokines ($TNF-{\alpha}$, IL-6, and $IL-1{\beta}$) was also attenuated through the MAPKs and $NF-{\kappa}B$ signaling. We also confirmed that protaetiamycine 2 bound to bacterial cell membranes by a specific interaction with LPS. Collectively, these data obtained from LPS-induced Raw264.7 cells indicated that protaetiamycine 2 could have both antimicrobial and anti-inflammatory properties.

• Korean Journal of Plant Resources
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• v.24 no.3
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• pp.298-303
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• 2011

A large number of edible seaweeds are consumed by the coastal peoples of Asia. Some of them are used in traditional remedies in many parts of the world. In this study we investigated effects of supplementation with ethyl acetate extracts of the brown alga Eisenia bicyclis (EBE) on rat macrophage to evaluate the possibilities as immune-modulators. Twelve male SD rats were divided into two groups and the treatments were as follows: A, no Eisenia bicyclis extract (EBE) intake and distilled water ; B, oral supplemented with EBE 200 mg/kg. After 5 weeks of supplementation, rats were sacrificed to assess the effect on peritoneal macrophage functions. We showed no increasing effects on tumoricidal activity, phagocytic activity and NO production in macrophages in EBE supplementation group. However, EBE supplementation suppressed NO-iNOS production and p65 translocation into the nucleus in LPS-stimulated macrophages. Overall, these results suggest that the supplementation of EBE might have an anti-inflammatory effects on NO-iNOS production in macrophages throughout the inhibition of NF-${\kappa}B$ activation.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.146-156
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• 2018

Spermidine is a naturally occurring polyamine compound that has recently emerged with anti-aging properties and suppresses inflammation and oxidation. However, its mechanisms of action on anti-inflammatory and antioxidant effects have not been fully elucidated. In this study, the potential of spermidine for reducing pro-inflammatory and oxidative effects in lipopolysaccharide (LPS)-stimulated macrophages and zebrafish was explored. Our data indicate that spermidine significantly inhibited the production of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$), and cytokines including tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$ in RAW 264.7 macrophages without any significant cytotoxicity. The protective effects of spermidine accompanied by a marked suppression in their regulatory gene expression at the transcription levels. Spermidine also attenuated the nuclear translocation of $NF-{\kappa}B$ p65 subunit and reduced LPS-induced intracellular accumulation of reactive oxygen species (ROS) in RAW 264.7 macrophages. Moreover, spermidine prevented the LPS-induced NO production and ROS accumulation in zebrafish larvae and was found to be associated with a diminished recruitment of neutrophils and macrophages. Although more work is needed to fully understand the critical role of spermidine on the inhibition of inflammation-associated migration of immune cells, our findings clearly demonstrate that spermidine may be a potential therapeutic intervention for the treatment of inflammatory and oxidative disorders.

• Korean Journal of Organic Agriculture
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• v.27 no.4
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• pp.513-528
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• 2019

Coriandrum sativum L., an annual herbaceous plant of Apiaceae family. The present study evaluated the anti-oxidant activities and anti-inflammatory effects of ethanol extracts of C. sativum. The anti-oxidant activities of C. sativum were measured by total contents of polyphenol, flavonoid, DPPH and ABTS radical scavenging and reducing power activity. And anti-inflammatory effects of C. sativum were measured by LPS-induced RAW 264.7 cells. The results showed that the contents of total polyphenol and flavonoid were 76.03 ± 1.36 mg of gallic acid equivalents/g and 182.23 ± 4.32 mg of rutin equivalents/g at concentration 1 mg/mL of C. sativum. The DPPH radical scavenging activity was found to be 52.8% at 500 ㎍/mL. The ABTS radical scavenging activity was shown in 58.3% after exposure to 1,000 ㎍/mL. Reducing power activity was found to be 66.8% at 2,000 ㎍/mL. The inhibitory effect of NO production was found to be 65% concentration 500 ㎍/mL. In the generation quantity of inflammatory cytokines such as TNF-α and IL-1β in cell culture medium, the expression levels of inflammatory proteins in cells were showed decrease with the increase of concentration. Therefore, we suggest that the C. sativum should be a potential source of alternative anti-inflammatory drug with good anti-inflammatory effects.

• IMMUNE NETWORK
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• v.13 no.4
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• pp.123-132
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• 2013

Obesity is consistently increasing in prevalence and can trigger insulin resistance and type 2 diabetes. Many lines of evidence have shown that macrophages play a major role in inflammation associated with obesity. This study was conducted to determine metformin, a widely prescribed drug for type 2 diabetes, would regulate inflammation through down-regulation of scavenger receptors in macrophages from obesity-induced type 2 diabetes. RAW 264.7 cells and peritoneal macrophages were stimulated with LPS to induce inflammation, and C57BL/6N mice were fed a high-fat diet to generate obesity-induced type 2 diabetes mice. Metformin reduced the production of NO, $PGE_2$ and pro-inflammatory cytokines ($IL-1{\beta}$, IL-6 and $TNF-{\alpha}$) through down-regulation of $NF-{\kappa}B$ translocation in macrophages in a dose-dependent manner. On the other hand, the protein expressions of anti-inflammatory cytokines, IL-4 and IL-10, were enhanced or maintained by metformin. Also, metformin suppressed secretion of $TNF-{\alpha}$ and reduced the protein and mRNA expression of $TNF-{\alpha}$ in obese mice as well as in macrophages. The expression of scavenger receptors, CD36 and SR-A, were attenuated by metformin in macrophages and obese mice. These results suggest that metformin may attenuate inflammatory responses by suppressing the production of $TNF-{\alpha}$ and the expressions of scavenger receptors.

• Korean Journal of Pharmacognosy
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• v.39 no.2
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• pp.104-109
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• 2008

We previously reported that anti-inflammatory properties of poncirin, isolated from fruit of Poncirus trifoliata, might be the result from the inhibition of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis $factor-{\acute{a}}$ ($TNF-{\alpha}$) and interlukin-6 (IL-6) expression via the down-regulation of $NF{-\kappa}B$ binding activity. In this study, we investigated whether poncirin has an inhibitory effect on the production of pro-inflammatory mediators ex vivo and whether poncirin could relieve the symptoms of dextran sulfate sodium (DSS)-induced colitis in mice model of inflammatory bowel disease. Poncirin significantly inhibited the productions of NO, IL-6 and $TNF-{\alpha}$ in lipopolysaccharide (LPS)-induced mouse peritoneal macrophage. In addition, poncirin-treated mice when compared to control mice not receiving treatment recovered better from the weight loss caused by DSS-induced colitis. Changes in disease activity index (DAI) of poncirin-treated mice were also more favorable than for control mice and were comparable with mice treated with a typical anti-inflammatory-drug, 5-aminosalichylic acid (5-ASA). In addition, suppression of plasma NO and IL-6 productions of poncirin-treated mice was also observed in DSS-induced colitis. These results suggest that poncirin has potentially useful anti-inflammatory effects mediated by suppression of inflammatory mediator productions.

• Microbiology and Biotechnology Letters
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• v.43 no.1
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• pp.45-55
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• 2015

This study was carried out to demonstrate the anti-inflammatory effect of tuna oil (TO) using LPS-induced inflammation responses and mouse models. First, nitric oxide (NO) and pro-inflammatory cytokines levels were suppressed up to 50% with increasing concentrations of TO without causing any cytotoxicity. Also, the expression of a variety of proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB), was suppressed in a dosedependent manner by treatment with TO. Furthermore, TO also inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs), including c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 protein kinase (p38). Moreover, in in vivo testing the formation of ear edema was reduced at the highest dose tested compared to that in the control, and a reduction of ear thickness and the number of mast cells was observed in histological analysis. In acute toxicity test, no mortalities occurred in mice administrated 5,000 mg/kg body weight of TO over a two-week observation period. Our results suggest that TO has a considerable anti-inflammatory property through the suppression of inflammatory mediator productions and that it could prove to be useful as a potential anti-inflammatory therapeutic material.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.4
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• pp.365-372
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• 2015

Aripiprazole (ARI) is a commonly prescribed medication used to treat schizophrenia and bipolar disorder. To date, there have been no studies regarding the molecular pathological and immunotoxicological profiling of aripiprazole. Thus, in the present study, we prepared two different formulas of aripiprazole [Free base crystal of aripiprazole (ARPGCB) and cocrystal of aripiprazole (GCB3004)], and explored their effects on the patterns of survival and apoptosis-regulatory proteins under acute toxicity and cytotoxicity test conditions. Furthermore, we also evaluated the modulatory activity of the different formulations on the immunological responses in macrophages primed by various stimulators such as lipopolysaccharide (LPS), pam3CSK, and poly(I:C) via toll-like receptor 4 (TLR4), TLR2, and TLR3 pathways, respectively. In liver, both ARPGCB and GCB3004 produced similar toxicity profiles. In particular, these two formulas exhibited similar phospho-protein profiling of p65/nuclear factor $(NF)-{\kappa}B$, c-Jun/activator protein (AP)-1, ERK, JNK, p38, caspase 3, and bcl-2 in brain. In contrast, the patterns of these phospho-proteins were variable in other tissues. Moreover, these two formulas did not exhibit any cytotoxicity in C6 glioma cells. Finally, the two formulations at available in vivo concentrations did not block nitric oxide (NO) production from activated macrophage-like RAW264.7 cells stimulated with LPS, pam3CSK, or poly(I:C), nor did they alter the morphological changes of the activated macrophages. Taken together, our present work, as a comparative study of two different formulas of aripiprazole, suggests that these two formulas can be used to achieve similar functional activation of brain proteins related to cell survival and apoptosis and immunotoxicological activities of macrophages.

• The Korea Journal of Herbology
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• v.29 no.2
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• pp.1-6
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• 2014

Objectives : Reactive oxygen species (ROS) are involved in a wide spectrum of diseases including chronic inflammation and cancer. In this study, we investigated the antioxidant activities and anti-inflammatory effects of the extracts from the herbal teas such as Lonicera japonica Thunberg (L. japonica), Chrysanthemum morifolium Ramat (C. morifolium), Mentha arvensis L. (M. arvensis), and P.rhizoma. Methods : Anti-oxidant activity was evaluated using DPPH radical scavenging assay and $Fe^{2+}$ chelating assay. And DNA cleavage assay was performed to evaluate an anti-oxidative effect. Anti-inflammatory effect was performed using NO generation assay and western blot in LPS-stimulated RAW264.7 cell line. Results : L. japonica scavenged DPPH radical by 9.8% at 12.5 ${\mu}g/ml$, 24.8% at 25 ${\mu}g/ml$, 34.3% at 50 ${\mu}g/ml$, 61.1% at 100 ${\mu}g/ml$ and 75.8% at 200 ${\mu}g/ml$, respectively. In addition, C. morifolium and M. arvensis removed DPPH radical by 15.6% and 10.4% at 12.5 ${\mu}g/ml$, 34.8% and 22.8% at 25 ${\mu}g/ml$, 66.9% and 43.3% at 50 ${\mu}g/ml$, 87.4% and 69.1% at 100 ${\mu}g/ml$, and 92.1% and 73.2% at 200 ${\mu}g/ml$, respectively. However, P. rhizoma did not affect on DPPH radical scavenging. The $Fe^{2+}$ chelating activity was highest in L. japonica, but lowest in P. rhizoma among the herbal teas. In addition, the extracts from L. japonica, C. morifolium and M. arvensis inhibited oxidative DNA damage via its anti-oxidant activity. In anti-inflammatory effect, the extracts from C. morifolium inhibited NO production. In addition, it suppressed the $NF-{\kappa}B$ signaling pathway in LPS-stimulated RAW 264.7 cells. Conclusions : Together, this study indicates that L. japonica, M. arvensis and C. morifolium possess the protective effect against the oxidative DNA damage. Furthermore, C. morifolium exerts an anti-inflammatory effect.

• Microbiology and Biotechnology Letters
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• v.42 no.2
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• pp.170-176
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• 2014

In this study, the anti-oxidative and anti-inflammatory activities of Euptelea pleiosperma ethanol extract (EPEE) were evaluated using in vitro assays and cell culture model systems. EPEE possessed a more potent scavenging activity against 1,1-diphenyl-2-picryl hydrazyl than the ascorbic acid used as a positive control. EPEE effectively suppressed lipopolysaccharide (LPS), in addition to hydrogen peroxide induced reactive oxygen species on RAW 264.7 cells. Furthermore, EPEE induced the expression of the anti-oxidative enzyme heme oxygenase 1 (HO-1) and its upstream transcription factor, nuclear factor-E2-related factor 2 (Nrf2), dose and time dependently. The modulation of HO-1 and Nrf2 expression might be regulated by mitogen-activated protein kinases and phosphatidyl inositol 3 kinase/Akt as their upstream signaling pathways. On the other hand, EPEE inhibited LPS induced nitric oxide (NO) formation without cytotoxicity. Suppression of NO formation was the result of the down regulation of inducible NO synthase (iNOS) by EPEE. Suppression of NO and iNOS by EPEE may be modulated by their upstream transcription factor, nuclear factor ${\kappa}B$, and AP-1 pathways. Taken together, these results provide important new insights into E. pleiosperma, namely that it possesses anti-oxidative and anti-inflammatory activities, indicating that it could be utilized as a promising material in the field of nutraceuticals.