• Journal of Applied Biological Chemistry
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• 제65권3호
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• pp.203-213
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• 2022

미선나무(Abeliophyllum distichum) 1속 1종의 한반도 고유식물이다. 꽃잎색의 변이에 따라 미선(백색), 분홍미선, 상아미선 그리고 연노랑색의 옥황1호 품종 등으로 구분된다. 본 연구에서는 4종류의 꽃 추출물(FAD)로부터 생리활성물질의 함량과 항염증 활성 차이를 비교·분석하였다. FAD의 생리활성 물질은 LC/MS 분석을 통해 rutin, hirsutrin, 그리고 acteoside를 분석하였다. DPPH와 ABTS 라디칼 소거활성을 통한 항산화 활성을 분석하였으며, 항산화 활성은 각 추출물의 생리활성 물질의 함량에 따라 유의성 있는 활성을 나타내었다. FAD는 LPS로 유도된 RAW 264.7 세포에서 염증 유발 매개체(산화질소, iNOS, COX-2)의 발현을 감소시켰다. 또한 NF-κB와 MAPK 신호전달 경로 조절을 통한 항염증 효과를 확인하였다.

• 한국임상수의학회지
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• 제28권1호
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• pp.52-56
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• 2011

Acute renal injury induced by ischemia is a major cause of high morbidity and mortality in hospitalized patients and a common complication in hospitalized patients. Thus, the work with acute renal failure and renal ischemia has been studied for many years. Although serum creatinine concentration that is widely used as an index of renal function performs fairly well for estimating kidney function in patients with stable chronic kidney disease, it performs poorly in the setting of acute disease. Thus, an ideal biomarker for acute kidney injury would help clinicians and scientists diagnose the most common form of acute kidney injury in hospitalized patients, acute tubular necrosis, early and accurately, and may aid to risk-stratify patients with acute kidney injury by predicting the need for renal replacement therapy, the duration of acute kidney injury, the length of stay and mortality. In this study, renal ischemia and reperfusion were performed by clapming and un-clamping right renal artery in miniature pigs. Plasma blood urea nitrogen (BUN) and creatinine were examined at pre- clamping, after-clamping at 0, 1 and 3 hours. And we searched initial indicators in these samples. Also, renal tissue was collected and searched the initial indicator by PCR and western blotting. As a result, hypoxia inducible factor $1{\alpha}$ ($HIF1{\alpha}$), nuclear factor kappa-B ($NF{\kappa}B$), $I{\kappa}B$, erythropoietin (EPO), erythropoietin receptor (EPOR), angiopoietin-1 and vascular endothelial growth factor (VEGF) were showed significant changes among the renal protein. $HIF1{\alpha}$, EPO, and EPOR were showed significant changes among the renal gene. Thus, these markers will be used as initial diagnosis of acute renal failure.

• 생약학회지
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• 제51권4호
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• pp.244-254
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• 2020

Atractylodes macrocephala is a perennial herb and is a member of the Compositae family. This plant is known to contain various bioactive constituents indicating anti-inflammatory, neuroprotective, anti-oxidant, immunological enhancement, and gastroprotective effects. In this investigation, we isolated four compounds with similar chemical structures from A. macrocephala, and evaluated their anti-inflammatory effects. Among the four compounds, compound 2(atractylenolide II) showed the second-best inhibitory effect on the lipopolysaccharide(LPS)-induced production of nitric oxide in RAW264.7 macrophages and BV2 microglial cells. Compound 2 also inhibited the LPS-induced the production of prostaglandin E2(PGE2), and the expression of inducible nitric oxide synthase(iNOS) and cyclooxygenase(COX)-2 proteins in both cells. In addition, compound 2 suppressed the production of pro-inflammatory cytokines including interleukin(IL)-1β, IL-6, and tumor necrosis factor(TNF)-α. These inhibitory effects were contributed by inactivation of nuclear factor kappa B(NF-κB) and mitogen-activated protein kinases(MAPKs) pathways by treatment with compound 2. This compound did not induce the expression of heme oxygenase(HO)-1 protein indicating that the anti-inflammatory effect of compound 2 was independent with HO-1 protein. Taken together, these results suggested that atractylenolide II can be a candidate material to treat inflammatory diseases.

• 한국자원식물학회지
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• 제33권5호
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• pp.460-466
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• 2020

본 연구 결과들을 바탕으로 도깨비부채 잎(RPL)은 GSK3β활성화를 통해 IκB-α를 인산화시켜 단백질 분해를 유도하고 IκB-α분해로 인해 p65 핵내 전이를 유도하여 NF-κB 신호전달을 활성화시킨다. 이러한 NF-κB 신호전달 활성화를 통해 대장암의 세포생육을 억제하는 것으로 추정된다. 본 결과는 도깨비부채 잎을 소재로 항암을 목적으로 한 천연치료제 및 대체보완소재 개발에 활용할 수 있다고 판단된다. 그러나 도깨비부채 잎의 대장암에 대한 세포생육 억제와 작용기전의 정확한 관련성과 세포생육 억제활성 물질 분석을 위해 추가적인 연구가 필요할 것으로 사료된다.

• Biomolecules & Therapeutics
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• 제22권5호
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• pp.390-399
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• 2014

Chalcones (1,3-diaryl-2-propen-1-ones), a flavonoid subfamily, are widely known for their anti-inflammatory properties. Propenone moiety in chalcones is known to play an important role in generating biological responses by chalcones. In the present study, we synthesized chalcone derivatives structurally modified in propenone moiety and examined inhibitory effect on nitric oxide (NO) production and its potential mechanisms. Among the chalcone derivatives used for this study, TI-I-174 (3-(2-Hydroxyphenyl)-1-(thiophen-3-yl)prop-2-en-1-one) most potently inhibited lipopolysaccharide (LPS)-stimulated nitrite production in RAW 264.7 macrophages. TI-I-174 treatment also markedly inhibited inducible nitric oxide synthase (iNOS) expression. However, TI-I-174 did not significantly affect production of IL-6, cyclooxygenase-2 (COX-2) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), implying that TI-I-174 inhibits production of inflammatory mediators in a selective manner. Treatment of macrophages with TI-I-174 significantly inhibited transcriptional activity of activator protein-1 (AP-1) as determined by luciferase reporter gene assay, whereas nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity was not affected by TI-I-1744. In addition, TI-I-174 significantly inhibited activation of c-Jun-N-Terminal kinase (JNK) without affecting ERK1/2 and p38MAPK, indicating that down-regulation of iNOS gene expression by TI-I-174 is mainly attributed by blockade of JNK/AP-1 activation. We also demonstrated that TI-I-174 treatment led to an increase in heme oxygenase-1 (HO-1) expression both at mRNA and protein level. Transfection of siRNA targeting HO-1 reversed TI-I-174-mediated inhibition of nitrite production. Taken together, these results indicate that TI-I-174 suppresses NO production in LPS-stimulated RAW 264.7 macrophages via induction of HO-1 and blockade of AP-1 activation.

• Biomolecules & Therapeutics
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• 제26권2호
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• pp.210-217
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• 2018

Neuroinflammation is an immune response within the central nervous system against various proinflammatory stimuli. Abnormal activation of this response contributes to neurodegenerative diseases such as Parkinson disease, Alzheimer's disease, and Huntington disease. Therefore, pharmacologic modulation of abnormal neuroinflammation is thought to be a promising approach to amelioration of neurodegenerative diseases. In this study, we evaluated the synthetic flavone derivative 3',4'-dihydroxyflavone, investigating its anti-neuroinflammatory activity in BV2 microglial cells and in a mouse model. In BV2 microglial cells, 3',4'-dihydroxyflavone successfully inhibited production of chemokines such as nitric oxide and prostaglandin $E_2$ and proinflammatory cytokines such as tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in BV2 microglia. It also inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor $(NF)-{\kappa}B$ activation. This indicates that the anti-inflammatory activities of 3',4'-dihydroxyflavone might be related to suppression of the proinflammatory MAPK and $NF-{\kappa}B$ signaling pathways. Similar anti-neuroinflammatory activities of the compound were observed in the mouse model. These findings suggest that 3',4'-dihydroxyflavone is a potential drug candidate for the treatment of microglia-related neuroinflammatory diseases.

• 약학회지
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• 제52권5호
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• pp.402-406
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• 2008

Previously, we have shown that 1-furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) has an anti-inflammatory activity in a rat paw-edema model. In the present study, we investigated an inhibitory effect of FPP-3 on the tumor necrosis factor (TNF)-${\apha}$-induced inflammatory cytokine response in HT-29 human colon epithelial cells. Treatment with FPP-3 significantly prevented the TNF-${\apha}$-induced attachment of leukocytes to HT-29 colon epithelial cells, which is one of the pathologic hallmarks in colon inflammation. The effect of FPP-3 was markedly superior than that of 5-aminosalicylic acid (5-ASA), a commonly used drug for the treatment of inflammatory bowel disease (IBD). The pretreatment with FPP-3 inhibited TNF-${\apha}$- induced monocyte chemoattractant protein (MCP)-1, interleukin (IL)-8 mRNA expressions. In addition, FPP-3 significantly suppressed TNF-${\apha}$-induced nuclear factor (NF)-${\kappa}B$ transcription activity. These results demonstrate that FPP-3 modulates intestinal inflammation via suppressing the NF-${\kappa}B$ dependent expressions of MCP-1 and IL-8, and suggest that FPP-3 may be a valuable agent for the treatment of IBD.

• 한국약용작물학회지
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• 제19권4호
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• pp.217-226
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• 2011

The study was conducted to investigate candidate materials as anti-inflammation agent from plant resources. Activities of 33 plant parts extracts with the final concentration of 5${\mu}g/ml$ were evaluated on the several inflammation-related markers such as the release of proinflammatoty cytokine [tumor necrosis factor-alpha (TNF-${\alpha}$) & interleukin-6 (IL-6)], nitric oxide (NO), the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and inhibitor of nuclear factor kappa-B alpha ($I{\kappa}-B{\alpha}$) in lipopolysaccharide (LPS)-treated RAW 264.7 cells. The extracts in the final concentration of 10 ${\mu}g/ml$ were also screened on peroxynitrite (ONOO$^-$) scavenging activity. Eleven extracts selected from the screening assay were verified on the inhibition activity on peroxynitrite and total reactive species oxygen (ROS) in the several concentrations. As results, Alpinia officinarum Hance (rhizome), Inula britannica var. chinensis Regel (flower), Ulmus arvifolia Jacq (trunk peel) and Aster scaber Thunb. (aerial part) showed comparatively potent anti-inflammatory activities in vitro cells or chemical level systems, and then these four plant parts should be studied on the antiinflammatory mechanism by further studies.

• The Korean Journal of Physiology and Pharmacology
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• 제19권1호
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• pp.1-7
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• 2015

Our previous study has shown berberine prevents damage to the intestinal mucosal barrier during early phase of sepsis in rat through mechanisms independent of the NOD-like receptors signaling pathway. In this study, we explored the regulatory effects of berberine on Toll-like receptors during the intestinal mucosal damaging process in rats. Male Sprague-Dawlay (SD) rats were treated with berberine for 5 d before undergoing cecal ligation and puncture (CLP) to induce polymicrobial sepsis. The expression of Toll-like receptor 2 (TLR 2), TLR 4, TLR 9, the activity of nuclear factor-kappa B ($NF-{\kappa}B$), the levels of selected cytokines and chemokines, percentage of cell death in intestinal epithelial cells, and mucosal permeability were investigated at 0, 2, 6, 12 and 24 h after CLP. Results showed that the tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) level were significantly lower in berberine-treated rats compared to the control animals. Conversely, the expression level of tight junction proteins, percentage of cell death in intestinal epithelial cells and the mucosal permeability were significantly higher in berberine-treated rats. The mRNA expression of TLR 2, TLR 4, and TLR 9 were significantly affected by berberine treatment. Our results indicate that pretreatment with berberine attenuates tissue injury and protects the intestinal mucosal barrier in early phase of sepsis and this may possibly have been mediated through the TLRs pathway.

• 동의생리병리학회지
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• 제25권2호
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• pp.270-274
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• 2011

The prevalence of atopic dermatitis has markedly increased in recent years but the mechanism has not been clearly revealed. Recent study exhibited that atopic dermatitis was exacerbated by the increase of proteinase-activated receptor (PAR)-2 expression, which activated $I{\kappa}B$ kinase --> nuclear factor kappa B. Therefore, we determined whether the allergens of dust mites induced the expression of PAR-2, intercellular adhesion molecule-1 (ICAM-1, adehision molecule), interleukins (IL)-6 in HaCaT keratocytes and which herbal 1,3-butylene glycol extracts (Mori Cortex Radicis, Sanguisorba officinalis L., Arctium lappa Linne, Torilis japonica DC, Melia azedarach Linne var. japoinca Makino) suppressed their expression. Dust mite allergen increased PAR-2, ICAM-1 and IL-6 expression in HaCaT cells in a dose-dependent manner up to $3{\mu}g/mL$ but their expression reached the plateau over the dosages. The allergen ($3{\mu}g/mL$) also secreted more cytokines such as tumor necrosis factor (TNF)-${\alpha}$ and IL-6 into the media. Among five different herbal extracts ($50{\mu}g/mL$), Mori Cortex Radicis and Sanguisorba officinalis L. suppressed the PAR-2, ICAM-1 and IL-6 expression in HaCaT cells, which was activated by dust mite allergen ($3{\mu}g/mL$) and they also reduced the secretion of TNF-${\alpha}$ and IL-6 into the media. In conclusion, Mori Cortex Radicis and Sanguisorba officinalis L. can effectively reduce the prevalence and progression of atopic dermatitis by dute mite allergen.