• Biomolecules & Therapeutics
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• 제22권1호
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• pp.10-16
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• 2014

Derivatives of caffeic acid have been reported to possess diverse pharmacological properties such as anti-inflammatory, anti-tumor, and neuroprotective effects. However, the biological activity of methyl p-hydroxycinnamate, an ester derivative of caffeic acid, has not been clearly demonstrated. This study aimed to elucidate the anti-inflammatory mechanism of methyl p-hydroxycinnamate in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Methyl p-hydroxycinnamate significantly inhibited LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and $PGE_2$ and the protein expression of iNOS and COX-2. Methyl p-hydroxycinnamate also suppressed LPS-induced overproduction of pro-inflammatory cytokines such as IL-$1{\beta}$ and TNF-${\alpha}$. In addition, methyl p-hydroxycinnamate significantly suppressed LPS-induced degradation of $I{\kappa}B$, which retains NF-${\kappa}B$ in the cytoplasm, consequently inhibiting the transcription of pro-inflammatory genes by NF-${\kappa}B$ in the nucleus. Methyl p-hydroxycinnamate exhibited significantly increased Akt phosphorylation in a concentration-dependent manner. Furthermore, inhibition of Akt signaling pathway with wortmaninn abolished methyl p-hydroxycinnamate-induced Akt phosphorylation. Taken together, the present study clearly demonstrates that methyl p-hydroxycinnamate exhibits anti-inflammatory activity through the activation of Akt signaling pathway in LPS-stimulated RAW264.7 macrophage cells.

• Biomolecules & Therapeutics
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• 제22권3호
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• pp.200-206
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• 2014

N-(p-Coumaryol) tryptamine (CT), a phenolic amide, has been reported to exhibit anti-oxidant and anti-inflammatory activities. However, the underlying mechanism by which CT exerts its pharmacological properties has not been clearly demonstrated. The objective of this study is to elucidate the anti-inflammatory mechanism of CT in lipopolysaccharide (LPS)-challenged RAW264.7 macrophage cells. CT significantly inhibited LPS-induced extracellular secretion of pro-inflammatory mediators such as nitric oxide (NO) and $PGE_2$, and protein expressions of iNOS and COX-2. In addition, CT significantly suppressed LPS-induced secretion of pro-inflammatory cytokines such as TNF-${\alpha}$ and IL-$1{\beta}$. To elucidate the underlying anti-inflammatory mechanism of CT, involvement of MAPK and Akt signaling pathways was examined. CT significantly attenuated LPS-induced activation of JNK/c-Jun, but not ERK and p38, in a concentration-dependent manner. Interestingly, CT appeared to suppress LPS-induced Akt phosphorylation. However, JNK inhibition, but not Akt inhibition, resulted in the suppression of LPS-induced responses, suggesting that JNK/c-Jun signaling pathway significantly contributes to LPS-induced inflammatory responses and that LPS-induced Akt phosphorylation might be a compensatory response to a stress condition. Taken together, the present study clearly demonstrates CT exerts anti-inflammatory activity through the suppression of JNK/c-Jun signaling pathway in LPS-challenged RAW264.7 macrophage cells.

• Biomolecules & Therapeutics
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• 제21권3호
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• pp.216-221
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• 2013

Aromadendrin, a flavonol, has been reported to possess a variety of pharmacological activities such as anti-inflammatory, antioxidant, and anti-diabetic properties. However, the underlying mechanism by which aromadendrin exerts its biological activity has not been extensively demonstrated. The objective of this study is to elucidate the anti-inflammatory mechanism of aromadedrin in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Aromadendrin significantly suppressed LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and $PGE_2$. In accordance, aromadendrin attenuated LPS-induced overexpression iNOS and COX-2. In addition, aromadendrin significantly suppressed LPS-induced degradation of $I{\kappa}B$, which sequesters NF-${\kappa}B$ in cytoplasm, consequently inhibiting the nuclear translocation of pro-inflammatory transcription factor NF-${\kappa}B$. To elucidate the underlying signaling mechanism of anti-inflammatory activity of aromadendrin, MAPK signaling pathway was examined. Aromadendrin significantly attenuated LPS-induced activation of JNK, but not ERK and p38, in a concentration-dependent manner. Taken together, the present study clearly demonstrates that aromadendrin exhibits anti-inflammatory activity through the suppression of nuclear translocation of NF-${\kappa}B$ and phosphorylation of JNK in LPS-stimulated RAW 264.7 macrophage cells.

• Restorative Dentistry and Endodontics
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• 제24권1호
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• pp.187-199
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• 1999

Bone remodeling is characterized by the continuing processes of osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Bone metabolism is tightly regulated at the local level by networks of hormones, cytokines, and other factors. In pathological conditions of bone remodeling, including osteoporosis and periodontal diseases, inflammatory cytokines and local mediators are responsible for enhancement of osteoclast resorption and inhibition of repair at the sites of bone resorption. TNF-${\alpha}$ is a pleiotropic hormone with actions on the differentiation, growth, and functional activities of normal and malignant cells from numerous tissues. TNF-${\alpha}$ has been proposed as a local mediator of the control of bone turnover in situations of chronic inflammation, and it has been assumed that the local source of TNF-${\alpha}$ is the monocyte in the adjacent bone marrow or the local circulation. TNF-${\alpha}$ is a potent inducer of bone resorption. TNF-${\alpha}$ is known to induce the activation of apoptotic signaling pathway, which leads to the apoptosis of bone cells. We demonstrated that treatment of murine osteoblastic MC3T3E1 cells with TNF-${\alpha}$ decreases proliferation as well as alkaline phosphatase (ALP) activity in a dose depenent manner. In addition, TNF-${\alpha}$ increases osteoclast-like cell formation in $1{\alpha}$, 25(OH)2D3 or PGE2-treated bone marrow cell culture. When cells were cultured in TNF-${\alpha}$ free ${\alpha}$-MEM, this inhibitory effect of ALP activity was reversible up to 10 ng/ml TNF-${\alpha}$, in contrast, at the 20 ng/ml TNF-${\alpha}$, irreversible. In this concentration, TNF-${\alpha}$ may induce apoptosis in MC3T3E1 cells. In this study, TNF-${\alpha}$ induces apoptosis resulting in chromosomal DNA fragmentation, preceded by JNK/SAPKs and caspase-3 activation. Our present results show that JNK/SAPKs and caspase-3 are activated by TNF-${\alpha}$, suggesting that the JNK/SAPKs and caspase-3 participate in the bone resorption, associated with apoptosis.

• Journal of Nutrition and Health
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• 제34권8호
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• pp.843-849
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• 2001

This study was performed to investigate the effect of n-3 fatty acids and dietary protein levels on renal function. Fifteen-month old male Sprague-Dawley rats were divided into 4 diet groups. Two-month old rats were used as a control group. The experimental diets contained either a% or 25% casein and lipid levels of the diets were 20% by weight. For the control group, the lipid was composed of beef tallow and corn oil on a 1:1 basis, and fish oil was comprised 75% of the fat mixture for the fish oil group. Rats were fed the diets ad libitum for 8 weeks. GFR and urinary protein excretion were higher in high protein groups, while fish oil exhibited no effects. Renal medulla TXB$_2$and PGE$_2$ concentrations tended to be higher in high protein groups and lower in fish oil groups. Light microscopic examinations showed that glomerulosclerosis, tubular atrophy, tubular cast, interstitial inflammation and interstitial fibrosis fended to be higher in aged rats and in high protein groups and lower in fish oil groups. Serum levels of total lipid, triglyceride and total cholesterol were higher in aged rats and lower in fish oil groups while serum HDL-cholesterol level was higher in young rats and in fish oil groups. However, dietary protein level had no effect on serum lipid levels. Serum TBARS concentration was higher in aged rats and in fish oil groups. In conclusion, fish oil caused changes in serum lipid concentrations and eicosanoids metabolism. The effect of fish oil on renal function was less obvious than dietary protein. However, fish oil seemed to be effective in lessening deterioration of renal function due to aging and/or high protein diets through changes in lipid and eicosanoids metabolism.

• Journal of Microbiology and Biotechnology
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• 제24권10호
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• pp.1346-1353
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• 2014

In the present study, an anthraquinone derivative, questinol was successfully isolated from the broth extract of the marine-derived fungus Eurotium amstelodami for the first time. The structure of questinol was determined based on the analysis of the MS and NMR spectral data as well as comparison of those data with the published data. Moreover, the anti-inflammatory effect of questinol in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells was investigated. The results showed that questinol did not exhibit cytotoxicity in LPS-stimulated RAW 264.7 cells up to $200{\mu}M$. Questinol could significantly inhibit NO and $PGE_2$ production at indicated concentrations. Questinol was also found to inhibit the production of pro-inflammatory cytokines, including TNF-${\alpha}$, IL-1${\beta}$, and IL-6. Furthermore, the western blot analysis showed that questinol suppressed the expression level of iNOS in a dose-dependent manner. However, questinol could slightly inhibit the expression of COX-2 at the concentration of $200{\mu}M$. Therefore, our study suggests that questinol might be selected as a promising agent for the prevention and therapy of inflammatory disease.

• Biomolecules & Therapeutics
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• 제24권6호
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• pp.610-615
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• 2016

Quercetin, a flavonol, has been reported to exhibit a wide range of biological properties including anti-oxidant and anti-inflammatory activities. However, pharmacological properties of quercetin-3-O-${\beta}$-D-glucuronide (QG), a glycoside derivative of quercetin, have not been extensively examined. The objective of this study is to elucidate the anti-inflammatory property and underlying mechanism of QG in lipopolysaccharide (LPS)-challenged RAW264.7 macrophage cells in comparison with quercetin. QG significantly suppressed LPS-induced extracellular secretion of pro-inflammatory mediators such as nitric oxide (NO) and $PGE_2$, and pro-inflammatory protein expressions of iNOS and COX-2. To elucidate the underlying mechanism of the anti-inflammatory property of QG, involvement of MAPK signaling pathways was examined. QG significantly attenuated LPS-induced activation of JNK and ERK in concentration-dependent manners with a negligible effect on p38. In conclusion, the present study demonstrates QG exerts anti-inflammatory activity through the suppression of JNK and ERK signaling pathways in LPS-challenged RAW264.7 macrophage cells.

• The Korean Journal of Physiology and Pharmacology
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• 제4권6호
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• pp.525-530
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• 2000

During reperfusion of skeletal muscle after ischemia, lipid mediators, mainly eicosanoids, are released and may have a role in the pathogenesis of reperfusion injury. To validate the role of eicosanoids in the ischemia-reperfusion induced functional deficits in skeletal muscle, we compared muscle edema and the changes of eicosanoid concentration in the rat hind limb after ischemia-reperfusion injury by application of tourniquet. After 4 hours of ischemia, reperfusion was established for 4 hours by releasing tourniquet. To assess tissue damage, edema, and wet/dry weight ratios were determined and the eicosanoid concnentrations were measured by the HPLC. The muscle edema and the release of cyclooxygenase metabolites were not induced by the ischemia itself rather they were significantly increased by reperfusion. Indomethacin treatment ameliorated limb edema and decreased the release of $6-keto-PGF_{1{\alpha}},$ thromboxane $B_2,$ and $PGE_2$ inducedby reperfusion. But the inhibitory effect of indomethacin on edema (35%) was relatively low than the inhibitory effect on release of cyclooxygenase metabolites (up to 69%) by reperfusion. These results support the view that cyclooxygenase products may play a significant role in the formation of muscle injury by ischemia-reperfusion and suggest that nonsteroidal antiinflammatory agents might be partially beneficial to the management of acute limb ischemia-reperfusion injury.

• 한국식품저장유통학회지
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• 제9권2호
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• pp.174-178
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• 2002

감초추출물의 농도를 100 ppm, 200 ppm, 300 ppm and 400 ppm로 조절하여 콩을 발아시켜 재배한 콩나물의 아미노산, 유기산 및 유리당 함량을 재배 2일, 3일 및 4일째에 분석하였다. 총 아미노산 함량은 100 ppm에서 3일간 재배하였을 때가 가장 높았고, 또한 재배일수가 길어질수록 aspartic acid 함량은 증가하지만, glutamic acid 함량은 오히려 감소하는 경향을 나타내었다. 총 유리당은 GGE 콩나물의 경우 대조군에 비하여 낮은 함량을 나타내었으며, 그러나 재배일수가 증가할수록 그 함량은 많아졌다 Sucrose함량은 재배일수가 길어질수록 감소하였으나, 다른 유리당은 오히려 증가하였다 총 유기산은 재배일수가 증가할수록 많은 함량을 나타내었으며, 200 ppm으로 재배한 콩나물이 가장 많은 함량을 나타내었다. 결론적으로 감초추출물은 콩나물의 품질증진을 위한 아미노산 및 유기산 함량을 증가시키는 발아 및 재배수로서 효과적일 것으로 판단된다.

• 운동영양학회지
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• 제25권4호
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• pp.45-53
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• 2021

[Purpose] In this study, we investigated whether a 70% ethanolic (EtOH) extract of Sargassum horneri had antioxidant and anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated macrophage-like RAW 264.7 cells. [Methods] The proximate composition, fatty acids, amino acids, and dietary fiber of S. horneri, various biologically active compounds, and antioxidant activity were analyzed. [Results] The DPPH and ABTS free radical scavenging activities, as well as the reduction power, of the S. horneri extract used here were significantly increased in a concentration-dependent manner. This indicates that S. horneri contains bioactive compounds, such as phenols and flavonoids, that have excellent antioxidant activity. The cellular viability and metabolic activity results confirmed that the extract had no discernible toxicity at concentrations up to 100 ㎍/mL. The levels of nitrites and cytokines (PGE₂, TNF-α and IL-6), which mediate pro-inflammatory effect, were significantly inhibited by treatment with either 50 or 100 ㎍/mL S. horneri extract, whereas that of IL-1β was significantly inhibited by treatment with 100 ㎍/mL of the extract. Similarly, the expression of iNOS and COX-2 proteins also decreased according to 50 or 100 ㎍/mL extract concentrations. NF-κB binding to DNA was also significantly inhibited by treatment with 100 ㎍/mL of extract. [Conclusion] These results suggest that 70% EtOH extracts of S. horneri can relieve inflammation caused by disease or high intensity exercise.