• Nutrition Research and Practice
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• 제9권3호
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• pp.219-226
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• 2015

BACKGROUND/OBJECTIVES: In this study, potential anti-inflammatory effect of enzymatic hydrolysates from Styela clava flesh tissue was assessed via nitric oxide (NO) production in lipopolysaccahride (LPS) induced RAW 264.7 macrophages and in vivo zebrafish model. MATERIALS/METHODS: We investigated the ability of enzymatic hydrolysates from Styela clava flesh tissue to inhibit LPS-induced expression of pro-inflammatory mediators in RAW 264.7 macrophages, and the molecular mechanism through which this inhibition occurred. In addition, we evaluated anti-inflammatory effect of enzymatic hydrolysates against a LPS-exposed in in vivo zebrafish model. RESULTS: Among the enzymatic hydrolysates, Protamex-proteolytic hydrolysate exhibited the highest NO inhibitory effect and was fractionated into three ranges of molecular weight by using ultrafiltration (UF) membranes (MWCO 5 kDa and 10 kDa). The above 10 kDa fraction down-regulated LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), thereby reducing production of NO and prostaglandin $E_2$ ($PGE_2$) in LPS-activated RAW 264.7 macrophages. The above 10 kDa fraction suppressed LPS-induced production of pro-inflammatory cytokines, including interleukin $(IL)-1{\beta}$, IL-6, and tumor necrosis factor $(TNF)-{\alpha}$. In addition, the above 10 kDa fraction inhibited LPS-induced phosphorylation of extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinase (JNK), and p38. Furthermore, NO production in live zebrafish induced by LPS was reduced by addition of the above 10 kDa fraction from S. clava enzymatic hydrolysate. CONCLUSION: The results of this study suggested that hydrolysates derived from S. clava flesh tissue would be new anti-inflammation materials in functional resources.

• 대한본초학회지
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• 제26권4호
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• pp.31-37
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• 2011

Objectives : Chrysanthemum boreale flower is widely distributed in Korea, Japan, China, and Eastern countries. C. boreale flower is also one of the herbs used for the treatment of various inflammatory disease in Korean Medicine. So, this research was designed to study anti-inflammatory effect of C. boreale flower and its mechanism. Methods : We investigated nitro oxide (NO) and prostaglandin $E_2$ ($PGE_2$) production by ELISA. And expressions of inducible nitric oxide synthase (iNOS), Cyclooxygenase-2 (COX-2) and nuclear factor-${\kappa}B$ P50/65 (NF-${\kappa}B$ P50, NF-${\kappa}B$ P65) were measured in RAW 264.7 murine macrophage cells induced by LPS. Results : MeOH ex., EtOAc fr., $CHCl_3$ fr. and Water fr. of C. boreale flower showed anti-inflammatory effect through inhibition of NO and PGE expression respectively. Among them, EtOAc fr. and $CHCl_3$ fr. inhibited production of NO and $PGE_2$ through inhibition of iNOS and COX-2 expression. And MeOH ex., EtOAc fr. and $CHCl_3$ fr. inhibited translocation of NF-${\kappa}B$ P65, NF-${\kappa}B$ P50 by inhibiting phosphrylation of $I{\kappa}B$. Conclusions : MeOH ex. EtOAc fr, $CHCl_3$ fr., and Water fr. of the C. boreale flower have anti-inflammatory activity.

• 대한임상검사과학회지
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• 제48권3호
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• pp.176-182
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• 2016

대식세포에서 염증반응이 진행되면, interleukin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) 등의 cytokine들이 발현되어 inducible nitric oxide synthase (iNOS), prostaglandin E2(PGE2) 등의 염증유발인자가 생성된다. 오가피, 우슬, 두충 각각의 추출물이 어느 정도의 항 염증 효능을 보이며 어떤 pro-inflammatory cytokine의 발현을 억제하는지에 대한 연구를 진행하였다. 오가피, 우슬, 두충은 물 추출하고 동결 건조시켰다. 각각의 추출물의 구성 성분들이 잘 추출되었는지 확인하기 위하여 지표물질인 acanthoside D, 20-hydroxyecdysone, pinoresinol diglucoside를 HPLC로 분석하였다. 항 염증 효능을 확인하기 위하여 lipopolysaccharide (LPS)로 RAW 264.7 세포주를 자극하여 염증 반응을 일으킨 상태에서 각각의 추출물을 농도 별로 처리하고 NO assay를 통해 항 염증 효능을 확인하였으며 real time PCR로 pro-inflammatory cytokine들의 발현량을 측정하였다. 결과적으로 각각의 추출물은 지표성분들이 검출되었으며 오가피와 우슬이 두충보다 NO assay에서 높은 활성을 보였다. Cytokine 발현량 측정에서는 오가피와 우슬은 iNOS와 IL-6의 발현을 억제하였고, 우슬은 TNF-${\alpha}$의 발현을 억제하였다. 우리나라는 전통적으로 약재를 조합하여 처방하여 왔다. 본 연구는 관절염에 전통적으로 사용해 오던 약재들이 어떤 기전에 의하여 항 염증 반응을 보이는지 확인하고 이들을 조합하여 사용하였을 때 어떤 근거에 의하여 시너지 효능을 보이는지 확인하였다.

• Biomolecules & Therapeutics
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• 제31권1호
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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.

• Natural Product Sciences
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• 제24권3호
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• pp.171-180
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• 2018

Artemisia capillaris has been widely used as an alternative therapy for treating obesity and atopic dermatitis. It has been used as a hepatoprotactant. It is also used for ameliorating inflammatory reactions. Although there are several investigations on other Artemisia species, there is no systematic study describing the role of A. capillaris MeOH extract, its solvent soluble fractions, or derived anti-inflammatory principal components in regulating inflammatory conditions. Therefore, the objective of this study was to elucidate anti-inflammatory mechanisms of A. capillaris. Results revealed that MeOH extract of A. capillaris could decrease LPS-stimulated NO secretion. Of tested fractions, $CH_2Cl_2$, EtOAc, and n-BuOH strongly inhibited NO release from RAW264.7 cells. Bioactive mediators derived from $CH_2Cl_2$ and n-BuOH fractions elicited potent anti-inflammatory actions and strikingly abrogated LPS-triggered NO accumulation in RAW264.7 cells. Of particular interest, capillin and isoscopoletin possessed the most potent NO suppressive effects. Western blot analysis validated the molecular mechanism of NO inhibition and showed that capillin and isoscopoletin significantly down-regulated iNOS and COX-2 protein expression. Taken together, our results provide the first evidence that MeOH extract, $CH_2Cl_2$, EtOAc, and n-BuOH fractions from A. capillaris and its derived lead candidates can potently suppress inflammatory responses in macrophages by hampering NO release and down-regulating iNOS and COX-2 signaling.

• 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.

• Molecules and Cells
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• 제41권8호
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• pp.762-770
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• 2018

Adiponectin, a hormone produced by adipose tissue, is very abundant in plasma, and its anti- and pro-inflammatory effects are reported. However, the mechanisms of these pro- and anti-inflammatory effects are not fully defined. Herein, we evaluated the dual inflammatory response mechanism of adiponectin in macrophages. Short-term globular adiponectin (gAd) treatment induced $I{\kappa}B{\alpha}$ degradation, $NF-{\kappa}B$ nuclear translocation, and $TNF-{\alpha}$ production in RAW 264.7 cells. Polymyxin B pretreatment did not block gAd-induced $I{\kappa}B{\alpha}$ degradation, and heated gAd was unable to degrade $I{\kappa}B{\alpha}$, suggesting that the effects of gAd were not due to endotoxin contamination. gAd activated IKK and Akt, and inhibition of either IKK or Akt by dominant-negative $IKK{\beta}$ ($DN-IKK{\beta}$) or DN-Akt overexpression blocked gAd-induced $I{\kappa}B{\alpha}$ degradation, suggesting that short-term incubation with gAd mediates inflammatory responses by activating the $I{\kappa}B/NF-{\kappa}B$ and PI3K/Akt pathways. Contrastingly, long-term stimulation with gAd induced, upon subsequent stimulation, tolerance to gAd, lipopolysaccharide, and CpG-oligodeoxynucleotide, which is associated with gAd-induced downregulation of IL-receptor-associated kinase-1 (IRAK-1) due to IRAK-1 transcriptional repression. Conclusively, our findings demonstrate that the pro- and anti-inflammatory responses to gAd in innate immune cells are time-dependent, and mediated by the activation of the $I{\kappa}B/NF-{\kappa}B$ pathway, and IRAK-1 downregulation, respectively.

• 동의생리병리학회지
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• 제17권4호
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• pp.1101-1111
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• 2003

Our study shows that EC extract has inhibitory effect on pro-inflammatory cytokines such as TNF-α, IL-1, IL-6, iNOS and COX2 in hFLSs. IL-1β, IL-6, iNOS and COX2 mRNA expression is suppressed at a low dasage (1㎍/ml) of EC extract. TNF-α was also suppressed at higher dosages (10 ㎍/ml, 100㎍/ml). EC extract also inhibited TNF-α, IL-1β and IL-6 production in pro-inflammatory cytokine stimulated-hFLSs. Expecially IL-1β(p<0.05) production are suppressed significantly. On the other hand, EC extract did not show any cytotoxicity. Thses data suggest that EC extract has anti-inflammatory effect mostly by inhibiting IL-1β production, and thus could be used to prevent or treat some inflammatory disease such as RA. It remains to be known what are the major components responsible for anti-inflammatory effect and what is the main mechanism.

• The Korean Journal of Physiology and Pharmacology
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• 제22권1호
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• pp.1-15
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• 2018

Inflammasomes are intracellular multiprotein complexes that coordinate anti-pathogenic host defense during inflammatory responses in myeloid cells, especially macrophages. Inflammasome activation leads to activation of caspase-1, resulting in the induction of pyroptosis and the secretion of pro-inflammatory cytokines including interleukin $(IL)-1{\beta}$ and IL-18. Although the inflammatory response is an innate host defense mechanism, chronic inflammation is the main cause of rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and $Sj{\ddot{o}}gren^{\prime}s$ syndrome (SS). Since rheumatic diseases are inflammatory/autoimmune disorders, it is reasonable to hypothesize that inflammasomes activated during the inflammatory response play a pivotal role in development and progression of these diseases. Indeed, previous studies have provided important observations that inflammasomes are actively involved in the pathogenesis of inflammatory/autoimmune rheumatic diseases. In this review, we summarize the current knowledge on several types of inflammasomes during macrophage-mediated inflammatory responses and discuss recent research regarding the role of inflammasomes in the pathogenesis of inflammatory/autoimmune rheumatic diseases. This avenue of research could provide new insights for the development of promising therapeutics to treat inflammatory/autoimmune rheumatic diseases.

• 생명과학회지
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• 제33권12호
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• pp.978-986
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• 2023

선천면역체계에 의한 염증은 감염에 의해 매개되는 환경적 위험 요인에 대한 보호 메커니즘이며 암 발병을 포함한 다양한 인간 질병의 발병 원인이기도 하다. 지의류는 다양한 질병을 치료할 수 있는 가능성을 지닌 다양한 생체 활성분자를 가지고 있다는 측면에서 점점 더 주목받고 있다. 이끼류의 2차 대사산물이 지닌 항산화, 항염증 그리고 항암 활성에 대해서 널리 보고되었지만 아직까지 구체적인 메커니즘은 밝혀지지 않았다. 본 연구에서는 남극 지의류 Usnea aurantiaco-atra의 메탄올 추출물에 대한 항염증 및 항암 활성의 분자적 메커니즘을 조사하고자 하였다. 본 연구결과에 의하면 메탄올 추출물은 COX-2, IL-6, iNOS, TNF-α 및 NO 생성과 같은 주요 염증 지표들에 대해 농도 의존적으로 조절함으로써 항염증 활성을 나타냈다. 또한, 추출물이 농도 의존적으로 HCT116 결장암 세포에 대해 세포독성 활성을 가지며, caspase-3 활성화에 의한 세포사멸 유도를 통해 암세포의 증식을 현저히 감소시키는 것을 관찰했다. 이 연구에서 남극 이끼류인 Usnea aurantiaco-atra의 메탄올 추출물이 항염증과 항암 활성을 갖는다는 사실을 처음으로 보였으며 이러한 결과는 염증과 암 사이의 연관성을 뒷받침하는 분자 메커니즘에 대한 새로운 통찰력을 보여준다.