• BMB Reports
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• 제35권1호
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• pp.28-40
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• 2002

Apoptosis is a mode of cell death that plays an important role in both pathological and physiological processes. Research during the last decade has delineated the entire machinery needed for cell death, and its constituents were found to pre-exist in cells. The apoptotic cascade is triggered when cells are exposed to an apoptotic stimulus. It has been known for several years that inhibitors of protein synthesis can potentiate apoptosis that is induced by cytokines and other inducers. Until 1996, it was not understood why protein synthesis inhibitors potentiate apoptosis. Then three reports appeared that suggested the role of the transcription factor NF-${\kappa}B$ activation in protecting the cells from TNF-induced apoptosis. Since then several proteins have been identified that are regulated by NF-${\kappa}B$ and are involved in cell survival, proliferation, and protection from apoptosis. It now seems that when a cell is attacked by an apoptotic stimulus, the cell responds first by activating anti-apoptotic mechanisms, which mayor may not be followed by apoptosis. Whether or not a cell undergoes proliferation, the survival, or apoptosis, appears to involve a balance between the two mechanisms. Inhibitors of protein synthesis seem to suppress the appearance of protein that are involved in anti-apoptosis. The present review discusses how NF-${\kappa}B$ controls apoptosis.

• 생명과학회지
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• 제20권2호
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• pp.275-280
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• 2010

Sulforaphane은 십자가화 채소에 존재하는 화합물로 항염증, 항암 및 신생혈관 생성의 억제 효과가 알려짐으로써 최근 많은 연구가 활발히 이루어지고 있으나, LPS에 의한 MMP-9 활성 조절에 대한 연구는 매우 미흡한 편이다. 따라서 본 연구에서 sulforaphane이 LPS 유도에 의한 MMP-9 활성에 미치는 영향에 대해서 조사해 보았다. Raw 264.7 세포에 sulforaphane을 전처리 한 후 LPS를 처리하여 gelatin zymography를 실시해 본 결과, LPS에 의해 유도된 MMP-9 활성 증가가 sulforaphane 농도 의존적으로 감소됨을 확인 하였다. 또한 RT-PCR과 MMP-9의 luciferase assay를 통한 실험에서 sulforaphane의 MMP-9 억제효과가 전사단계에서 조절됨을 추측 할 수 있었다. MMP-9 promoter 부위에 여러 가지의 전사조절인자 결합부위가 존재한다. 특히 AP-1과 NF-${\kappa}B$가 중요 전사조절인자로 작용하여 MMP-9 발현조절에 관여한다. 본 실험에서 sulforaphane에 의한 MMP-9 억제효과 기전에 이들 전사조절인자들의 중요한 역할을 조사하였다. AP-1과 NF-${\kappa}B$ 결합부위를 변형 시킨 vector를 transfection하여 MMP-9의 promoter 활성을 측정한 결과, 정상 vector에 비해 그 활성도가 현저히 떨어짐을 확인하였고, LPS에 의해 증가되는 AP-1과 NF-${\kappa}B$의 basal promoter 활성 또한 sulforaphane에 의해 감소됨을 관찰 할 수 있었다. 이상의 결과에서 sulforaphane의 MMP-9 활성억제효과는 AP-1과 NF-${\kappa}B$와 같은 전사인자들이 MMP-9의 전사를 조절함으로써 일어나는 것임을 알 수 있었다. 그리고 sulforaphane은 세포의 invasion능력 또한 효과적으로 억제시킴을 관찰 할 수 있었는데 이는 MMP-9 활성억제효과와 밀접한 관련이 있음을 추측 할 수 있었다.

• 대한한방내과학회지
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• 제35권3호
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• pp.262-273
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• 2014

Objectives: This study was carried out to investigate the protective effect of Coptidis Rhizoma steamed with rice wine (CR) against gastroduodenal mucosal injury through inhibiting inducible nitric oxide synthase (iNOS) activation. Methods: In in vitro experiment, LPS-induced RAW 264.7 macrophages were treated with CR(0.4, 0.6, 0.8, 1.0 mg/ml) and iNOS mRNA expression and nitric oxide (NO) production were measured. In in vivo experiment normal group mice were treated with neither ethanol nor CR. Both control and sample group mice were orally administrated with ethanol. Five hours after ethanol administration control group mice were orally administrated with distilled water, sample group mice were orally administrated with CR. After three days administration, gastroduodenal mucosa of mice was observed histopathologically and iNOS, nuclear factor-kappa B (NF-${\kappa}B$) activation were observed immunohistochemically. Results: In in vitro experiment iNOS mRNA expression and NO production in LPS-induced RAW 264.7 macrophages were decreased by CR dose-dependently. In in vivo experiment, gastroduodenal mucosal injury was repaired by CR and iNOS, NF-${\kappa}B$ activation in gastroduodenal mucosa were decreased by CR. Conclusions: Coptidis Rhizoma steamed with rice wine has a protective effect against gastroduodenal mucosal injury through inhibiting iNOS activation.

• Preventive Nutrition and Food Science
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• 제15권1호
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• pp.14-18
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• 2010

Stevia rebaudiana (SR) is an herb used traditionally as a sweetener in Paraguay and Brazil, whose use is spreading to other countries, such as Japan, Korea and China. In addition to its low calorie sweet taste, SR appears to have other beneficial properties, such as hypotensive capabilities and inflammation reduction. To identify the bioactive natural constituents exerting anti-inflammatory activities, we examined the EtOAc fraction of SR. In the inflammatory mediator inhibitory assay from lipopolysaccharide (LPS)-activated macrophages, the EtOAc fraction significantly, and dose dependently, inhibited the enhanced production of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) expression. We also found that treatment of cells with the EtOAc fraction significantly inhibited LPS-stimulated nuclear factor-${\kappa}B$ (NF-${\kappa}B$) reporter gene expression. Such inhibition of NF-${\kappa}B$ was closely associated with the inhibition of interleukin-6 (IL-6) and the monocyte chemoattractant protein-1 (MCP-1). Therefore, we suggest that SR has the potential for development as a functional food for the treatment of immune diseases, such as rheumatoid arthritis and lupus.

• Biomolecules & Therapeutics
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• 제19권3호
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• pp.331-335
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• 2011

In this study, we determined the anti-inflammatory activity and mechanism of action of a hexane fraction (hWRF) obtained from white Rosa hybrida flowers by employing various assays such as quantitative real-time PCR, Western blotting, and Electrophoretic-Mobility Shift Assay (EMSA). The results revealed that the hWRF had excellent anti-inflammatory potency by reducing inflammatory repertoires, such as inducible nitric oxide synthase (iNOS), interleukin-$1{\beta}$, and cyclooxygenase-2 (COX-2) in RAW264.7 cells when stimulated with lipopolysaccharide (LPS), a pro-inflammatory mediator. The reduction of nitric oxide (NO) release from RAW 264.7 cells supported the anti-inflammatory effect of hWRF. Interestingly, hWRF effectively inhibited LPS-mediated nuclear factor-${\kappa}B$ (NF-${\kappa}B$) p65 subunit translocation into the nucleus and extracellular signal-regulated kinase (ERK)1/2 phosphorylation, suggesting that hWRF anti-inflammatory activity may be based on inhibition of the NF-${\kappa}B$ and MAPK pathways. Based on the findings described in this study, hWRF holds promise for use as a potential anti-inflammatory agent for either therapeutic or functional adjuvant purposes.

• The Korean Journal of Physiology and Pharmacology
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• 제20권3호
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• pp.229-236
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• 2016

Resveratrol (RSV) may provide numerous protective effects against chronic inflammatory diseases. Due to local hypoxia and hypertonicity, the renal medulla is subject to extreme oxidative stress, and aldehyde products formed during lipid peroxidation, such as 4-hydroxy-2-hexenal (HHE), might be responsible for tubular injury. This study aimed at investigating the effects of RSV on renal and its signaling mechanisms. While HHE treatment resulted in decreased expression of Sirt1, AQP2, and nuclear factor erythroid 2-related factor 2 (Nrf2), mouse cortical collecting duct cells (M1) cells treated with HHE exhibited increased activation of p38 MAPK, extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and increased expression of NOX4, $p47^{phox}$, Kelch ECH associating protein 1 (Keap1) and COX2. HHE treatment also induced $NF-{\kappa}B$ activation by promoting $I{\kappa}B-{\alpha}$ degradation. Meanwhile, the observed increases in nuclear $NF-{\kappa}B$, NOX4, $p47^{phox}$, and COX2 expression were attenuated by treatment with Bay 117082, N-acetyl-l-cysteine (NAC), or RSV. Our findings indicate that RSV inhibits the expression of inflammatory proteins and the production of reactive oxygen species in M1 cells by inhibiting $NF-{\kappa}B$ activation.

• Journal of Nutrition and Health
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• 제49권4호
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• pp.241-246
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• 2016

Purpose: Aloe-emodin (AE), an ingredient of aloe, is known to exhibit anti-inflammatory activities. However, little is known about the underlying molecular mechanisms of its inflammatory modulatory activity in vitro. In the present study, we investigated the anti-inflammatory potential of AE using $Pam_3CSK_4$-stimulated macrophages. Methods: RAW 264.7 macrophages were treated with AE (0~20 mM) for 1 h, followed by treatment with $Pam_3CSK_4$ for 1 h. After incubation, mRNA expression levels of cytokines were measured. The effect of AE on TLR2-related molecules was also investigated in $Pam_3CSK_4$-stimulated RAW 264.7 macrophages. Results: AE attenuated $Pam_3CSK_4$-stimulated expression of proinflammatory cytokines, including tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-6 (IL-6), and interleukin-$1{\beta}$ ($IL-1{\beta}$) in RAW 264.7 macrophages. Two concentrations of AE ($10{\mu}M$ and $20{\mu}M$) effectively reduced mRNA expression of TLR2 by 41.18% and 54.43%, respectively, compared to that in control cells (p < 0.05). AE also decreased nuclear factor-kappa B ($NF-{\kappa}B$) activation and mitogen-activated protein kinase (MAPK) phosphorylation. Phosphorylation levels of ERK1/2, p38, and JNK were markedly reduced by $20{\mu}M$ AE. In particular, AE decreased phosphorylation of ERK in a dose-dependent manner in $Pam_3CSK_4$-stimulated RAW 264.7 macrophages. Conclusion: Our data indicate that AE exerts its anti-inflammatory effect by suppressing TLR2-mediated activation of $NF-{\kappa}B$ and MAPK signaling pathways in macrophages.

• 대한한의학회지
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• 제37권2호
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• pp.62-75
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• 2016

Objectives: This study examined whether Lycii Radicis Cortex has an inhibitory effect on inflammatory response through an oxidative stress and advanced glycation endproducts (AGEs)-mediated pathway in streptozotocin (STZ)-induced type 1 diabetic rats. Methods: Lycii Radicis Cortex was orally administered to STZ-induced diabetic rats in doses of 80 or 160 mg/kg body weight/day for 2 weeks, and its effects were compared with those of diabetic control and normal rats. Results: The administration of Lycii Radicis Cortex decreased the elevated serum urea nitrogen and renal reactive oxygen species (ROS), and reduced the increased AGEs in the serum and kidney. The elevated protein expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits in the kidney of diabetic control rats were significantly decreased after Lycii Radicis Cortex treatments. Moreover, the kidney of diabetic rats exhibited the up-regulation of receptor for AGEs (RAGE) and AGEs-related proteins; however, Lycii Radicis Cortex treatment also significantly reduced those expressions (excepted RAGE). In addition, the diabetic rats exhibited an up-regulation of the expression of proteins related to inflammation in the kidney, but Lycii Radicis Cortex administration reduced significantly the expression of the inflammatory proteins through the nuclear factor-kappa B (NF-${\kappa}B$) and activator protein-1 (AP-1) pathways. Conclusions: This study provides scientific evidence that Lycii Radicis Cortex exerts the antidiabetic effect by inhibiting the expressions of AGEs and NF-${\kappa}B$ in the STZ-induced diabetic rats.

• The Korean Journal of Physiology and Pharmacology
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• 제23권6호
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• pp.493-499
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• 2019

Macrophage-associated inflammation is crucial for the pathogenesis of diverse diseases including metabolic disorders. Rhodanthpyrone (Rho) is an active component of Gentiana rhodantha, which has been used in traditional Chinese medicine to treat inflammation. Although synthesis procedures of RhoA and RhoB were reported, the biological effects of the specific compounds have never been explored. In this study, the anti-inflammatory activity and mechanisms of action of RhoA and RhoB were studied in lipopolysaccharide (LPS)-stimulated macrophages. Pretreatment with RhoA and RhoB decreased inducible nitric oxide synthase and cyclooxygenase-2 expressions in RAW 264.7 cells and in thioglycollate-elicited mouse peritoneal macrophages. In addition, it downregulated transcript levels of several inflammatory genes in LPS-stimulated RAW 264.7 cells, including inflammatory cytokines/chemokines (Tnfa, Il6, and Ccl2) and inflammatory mediators (Nos2 and Ptgs2). Macrophage chemotaxis was also inhibited by treatment with the compounds. Mechanistic studies revealed that RhoA and RhoB suppressed the nuclear factor $(NF)-{\kappa}B$ pathway, but not the canonical mitogen activated protein kinase pathway, in LPS-stimulated condition. Moreover, the inhibitory effect of RhoA and RhoB on inflammatory gene expressions was attenuated by treatment with an $NF-{\kappa}B$ inhibitor. Our findings suggest that RhoA and RhoB play an anti-inflammatory role at least in part by suppressing the $NF-{\kappa}B$ pathway during macrophage-mediated inflammation.

• 생약학회지
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• 제49권4호
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• pp.305-311
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• 2018

Osteoarthritis (OA) is the most common form of joint disease, characterized by articular cartilage, osteonecrosis, and osteochondral bone erosion. It is an early, progressive disease that combines joint stiffness and joint pain and reduces cartilage function and condition. Interleukin-1 beta ($IL-1{\beta}$) is thought to be important to the pathogenesis of OA and significantly increases the expression of matrix metalloproteinases (MMPs), which play an important role in cartilage degradation in OA. Sparassis crispa (Wulf.) is an edible / medicinal mushroom that has been reported to variety of biological activities. In this study, investigated the Anti-inflammatory effect of Sparassis crispa (Wulf.) ethanol extract (SCE) on $IL-1{\beta}$ stimulated SW1353 chondrocytes. SCE decreased the expression and activity of MMPs by $IL-1{\beta}$ and decreased the levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) associated with the inhibition of prostaglandin E2($PGE_2$) in $IL-1{\beta}$ stimulated SW-1353 chondrocytes. In addition, SCE inhibits the expression of MAPK (mitogen-activated protein kinase) and $NF-{\kappa}B$ (nuclear factor-kappa B) signaling in $IL-1{\beta}$ stimulated SW-1353 cells, and SCE inhibits the production of reactive oxygen species (ROS) through heme oxygenase-1 (HO-1) expression. Thus, it is suggested that SCE has a potential as an anti-inflammatory agent in osteoarthritis treatments.