• 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.

• 미생물학회지
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• 제44권2호
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• pp.140-146
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• 2008

다양한 염증 질환을 유발하는 사람세포거대바이러스(Human cytomegalovirus: HCMV)는 단핵구 세포주인 THP-1 세포에서 염증반응의 중요한 매개체인 세포간부착분자-1(intercellular adhesion molecule: ICAM-1) 발현을 촉진한다. ICAM-1 발현은 자외선으로 불활화시킨 HCMV (UV-HCMV)에 의해서도 촉진되므로 이 과정에 HCMV 유전자발현은 꼭 필요하지는 않은 것 같다. HCMV에 감염된 THP-1 세포 배양액을 감염되지 않은 THP-1 세포에 처리하거나 공유하게 하였을 시 감염되지 않은 세포에서도 ICAM-1 발현이 증가하였다. 감염된 세포 배양액에 의한 ICAM-1 발현 증가는 $NF-{\kappa}B$ 경로를 거친다. UV-HCMV에 감염된 세포의 배양액은 ICAM-1 발현을 촉진시키지 못하였다. 따라서 HCMV에 의한 THP-1 세포에서 ICAM-1 발현 증가는 바이러스 유전자 발현을 필요로 하지 않지만, 감염된 세포에서 ICAM-1 발현을 촉진하는 물질을 분비하는 과정에는 바이러스 유전자 발현이 필요한 것으로 생각된다.

• International Journal of Oral Biology
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• 제30권4호
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• pp.143-148
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• 2005

Osteoclasts are multinucleated cells with bone resorbing activity and differentiated from hematopoietic cell lineages of monocyte/macrophages in the presence of receptor activator of NF-${\kappa}B$ ligand (RANKL) and M-CSF. However, the exact molecular mechanisms through which RANKL stimulates osteoclastogenesis remain to be elucidated. Here we report that activation of cAMP-response elementbinding protein (CREB) is not involved in osteoclastogenesis from osteoclast precursors in response to RANKL. RANKL induced CREB activation in osteoclast precursors. Using pharmacological inhibitors, we found that RANKL-induced CREB activation is dependent on p38 MAPK pathways. We also found that ectopic expressions of wild type and dominant negative forms of CREB in osteoclast precursors did not affect RANKL-induced osteoclast formation and bone resorbing activity. Furthermore, dominant negative forms of CREB did not alter the expression levels of osteoclast-specific marker genes. Taken together, these data suggest that CREB is dispensable for differentiation and resorbing activity of osteoclasts.

• 한방안이비인후피부과학회지
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• 제31권4호
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• pp.1-12
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• 2018

Objectives : This study investigated the anti-oxidant and anti-inflammatory activities of Changchulgeumryeontang (CCGRT) extract. Methods : The macrophage cell line RAW 264.7 cells were used and MTT assay was performed to measure the cell viabilities at the various concentrations of CCGRT ($25-200{\mu}g/m{\ell}$). Nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) were measured in LPS-induced RAW 264.7 cells. Expressions of iNOS, $NF-{\kappa}B$, $IL-1{\alpha}$, $IL-1{\beta}$ and IL-6 were also performed by real-time PCR. The anti-oxidant activities of CCGRT was measured by DPPH radical scavenging activity. Results : 1. there was no cytotoxicity in RAW264.7 cells treated with CCGRT compared to the control. 2. CCGRT treated group significantly inhibited NO and $PGE_2$ production compared to the LPS treated group. 3. CCGRT treated group significantly decreased mRNA expressions of iNOS, $NF-{\kappa}B$, $IL-1{\alpha}$, $IL-1{\beta}$ and IL-6 compared to the LPS treated group. 4. CCGTR was found to have high DPPH free radical scavenging ability. Conclusions : According to the above results, CCGRT may be a potentional choice for the treatment of inflammatory skin disease. Conclusions : According to the above results, CCGRT may be a potentional choice for the treatment of inflammatory skin disease.

• 혜화의학회지
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• 제15권2호
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• pp.105-119
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• 2006

This study aimed to investigate the effects of Sesami Semen on the itching and anti-allergic inflammation mechanism related with cytokine, chemokine, histamine, $\beta$-hexosaminidase, NF-$\kappa$B, and free radical, and it was concluded as follows : 1. Sesami Semen did not show any cytotoxicity at the range of con-centration (1-250 ${\mu}g/m\ell$) on the human fibroblast cell (hFCs). 2. Sesami Semen reduced the gene expressions of IL-8, TNF-$\alpha$, IL-6 mRNA comparing with control. 3. Sesami Semen reduced the levels of IL-6, IL-8, MCP-1 within THP-1 cell depending on the concentration, and especially significantly reduced the the levels of IL-6, MCP-1 at all the concentration. 4. Sesami Semen significantly decreased the histamine secretion on HMC-1 at all the concentration. 5. Sesami Semen decreased the $\beta$-Hexosaminidase secretion 6.2% at 10 ${\mu}g$/ml conc., 58.3% at 100 ${\mu}g$/ml conc. and 63.2% at 200 ${\mu}g$/ml conc., respectively. And IC50 (${\mu}g$/ml) was 158.25 ${\mu}g$/ml. 6. Sesami Semen significantly suppressed the activity of NF-$\kappa$B promoter depending on the concentration. 7. Sesami Semen decreased the production of reactive oxygen species (ROS) and DPPH generation depending on the concentration. As judged with above results, the effects of Sesami Semen on the anti-allergic inflamation would be recognized, and it could be applied on the medicinal sources for prevention or treatment of several allergy disease. And more studies are needed furthermore with the seperation of effective materials.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2010년도 정기총회 및 추계학술발표회
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• pp.7-7
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• 2010

전 세계적으로 폭발적으로 증가하고 있는 비만은 만병의 근원이다. 동시에 대사성질환의 발병을 증가시키는 결정적인 역할을 하고 있다. 이러한 상황을 극복할 수 있는 안전하고 효능이 우수한 약의 개발이 매우 시급하다. 시판되는 약들은 예견할 수 없는 지방변으로 실제생활을 매우 불편하게 하는 부작용과 우울증 및 자살충동 등의 심각한 부작용을 유발시키고 있다. 특히 생명을 위협하는 약은 시판이 금지되었다. 200여종의 한약재들을 In vitro screening (pancreatic lipase inhibition, PDE inhibition, c-AMP activity), ex vivo screening (lipolytic action on fat pad), short term animal screening(혈중 TG 함량 분석)을 토대로 long term animal model에서비만 예방 및 치료 효능을 검증하기 위하여 호장근 부탄올 분획을 선정하였다. 고지방 사료로 비만을 유도한 rat (Diet induced obesty (DIO) rat)에서 비만 치료 효능이, 고지방 사료로 비만을 유도한 ICR-mice에서 비만 예방 효능이 우수함을 입증하였다 (체중감소, 지방세포의 크기억제, 지방간 예방/치료(간무게, TG함량, 간 색상, 고지혈증 증상억제), 혈중 TNF-a, IL-6, leptin, adponectin 등, 간 조직에서의 pAMPK, SOCS, NF-${\kappa}B$ DNA biding activity, ACC level, FAS expression, CPT-1 activity의 정상화). 호장근 부탄올 분획의 이러한 효능은 AMPK 작용과 CPT-1 작용을 활성화하고 동시에 지방산 합성 억제와 지방산 산화를 촉진함으로 인함임을 규명하였다. 동시에 비만으로 인한 pancreatic beta cell의 파괴를 예방함으로 인슐린 내성을 예방(치료)함을 입증하였다. 이는 AMPK 활성화와 SOCS-3 단백질 억제와 NF-${\kappa}B$-DNA 결합 억제로 인함임을 증명하였다. 3T3-L1 지방 세포주에서 lipogenesis 예방(치료) 및 lipolytic effect에 관여하는 인자들의 변화를 확인하였다. 이는 Multi-compounds-multi-targets에 의한 시너지 효과임을 알 수 있었다.

• 대한한의학회지
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• 제26권1호
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• pp.46-58
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• 2005

Objective : This study on Sipimikwanjung-tang was undertaken to evaluate its antioxidant capacities and antiperoxidation activities in rat liver tissues. Sipimikwanjung-tang which has been one of the prescriptions in sasang constitutional medicine is usually applied for the therapy of various liver diseases. It is elucidated that Sipimikwanjung-tang has antioxidants on liver tissue of rat and the cytotoxic effects on human hepatoblastoma Hep G2 cells. Methods: Sipimikwanjung-tang extract in antioxidant effects of Hep G2 cells is evaluated by MTT assay, DAPI staining, DNA fragmentation assays and FACS can analysis. Results: Sipimikwanjung-tang induced apoptosis in Hep G2 cells, and induced G1 and G2M arrest of the cell cycle as well as a significant increase in PARP and caspase-3 activity. It induced an increase in $H_2O_2$ generation and the subsequent $NF-{\kappa}B$ activation and also induced cell apoptosis through the caspase-3-dependent pathways in the low concentration of Sipimikwanjung-tang extracts. However, the high dose of Sipimikwanjung-tang extract in Hep G2 cells inhibited $TGF-{\beta}l-induced$ apoptosis via increase in cellular $H_2O_2$, formation and $NF-{\kappa}B$ activation in human hepatoblastoma Hep G2 cells. Conclusion: From this study, the possibility that Sipimikwanjung-tang extracts apply to antioxidant and apoptotic treatment of disease is revealed.

• The Korean Journal of Physiology and Pharmacology
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• 제19권3호
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• pp.291-297
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• 2015

An oral environment is constantly exposed to environmental factors and microorganisms. The periodontal ligament (PDL) fibroblasts within this environment are subject to bacterial infection and allergic reaction. However, how these condition affect PDL fibroblasts has yet to be elucidated. PDL fibroblasts were isolated from healthy donors. We examined using reverse transcription-polymerase chain reaction and measuring the intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$). This study investigated the receptors activated by exogenous bacterial pathogens (Lipopolysaccharide and peptidoglycan) and allergens (German cockroach extract and house dust mite) as well as these pathogenic mediators-induced effects on the intracellular $Ca^{2+}$ signaling in human PDL fibroblasts. Moreover, we evaluated the expression of pro-inflammatory cytokines (interleukin (IL)-$1{\beta}$, IL-6, and IL-8) and bone remodeling mediators (receptor activator of NF-${\kappa}B$ ligand and osteoprotegerin) and intracellular $Ca^{2+}$-involved effect. Bacterial pathogens and allergic mediators induced increased expression of pro-inflammatory cytokines, and these results are dependent on intracellular $Ca^{2+}$. However, bacterial pathogens and allergic mediators did not lead to increased expression of bone remodeling mediators, except lipopolysaccharide-induced effect on receptor activator of NF-${\kappa}B$ ligand expression. These experiments provide evidence that a pathogens and allergens-induced increase in $[Ca^{2+}]_i$ affects the inflammatory response in human PDL fibroblasts.

• Journal of Microbiology and Biotechnology
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• 제19권6호
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• pp.616-621
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• 2009

To evaluate the effects of lactic acid bacteria (LAB) in inflammatory bowel diseases (IBD), we measured the inhibitory effect of several LAB isolated from intestinal microflora and commercial probiotics against the glycosaminoglycan (GAG) degradation by intestinal bacteria. Bifidobacterium longum HY8004 and Lactobacillus plantarum AK8-4 exhibited the most potent inhibition. These LAB inhibited colon shortening and myeloperoxidase production in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced experimental colitic mice. These LAB also blocked the expression of the proinflammatory cytokines, IL-$1{\beta}$ and TNF-$\alpha$, as well as of COX-2, in the colon. LAB also blocked activation of the transcription factor, NF-${\kappa}B$, and expression of TLR-4 induced by TNBS. In addition, LAB reduced the TNBS-induced bacterial degradation activities of chondroitin sulfate and hyaluronic acid. These findings suggest that GAG degradation-inhibitory LAB may improve colitis by inhibiting inflammatory cytokine expression via TLR-4-linked NF-${\kappa}B$ activation and by inhibiting intestinal bacterial GAG degradation.

• Journal of Acupuncture Research
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• 제23권2호
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• pp.33-46
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• 2006

Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disease associated with aging in the human population. This disease is characterized by the extracellular deposition of beta-amyloid peptide $(A{\beta})$ in cerebral plaques. $A{\beta}$ is derived from the ${\beta}-amyloid$ precursor protein (APP) by the enzymes, ${\beta}-$ and ${\eta}o-secretase$. Compounds that ${\beta}-$ or ${\eta}o-secretase$ inhibit activity, can reduce the production of $A{\beta}$ peptides, and thus have therapeutic potential in the treatment of AD. Increasing body of evidence has been demonstrated that Bee Venom(BV) Acupuncture could compete with complex protein involving in multiple step of $NF-{\kappa}B$ activation and exert the anti-inflammatory potential of combined inhibition of the prostanoid and nitric oxide synthesis systems by inhibition of IKK and $NF-{\kappa}B$. In this study, I investigated possible effects of BV on memory dysfunction caused by lipopolysaccharide (LPS) and $A{\beta}$ through inhibition of secretases activities and $A{\beta}$ aggregation. I examined the improving effect of BV on the LPS (2.5 mg/Kg, i.p.)-induced memory dysfunction using passive avoidance response and water maze tests in the mice. BV (0.84, $1.67\;{\mu}g/ml$) reversed the LPS-induced memorial dysfunction in dose dependent manner. BV also dose-dependently attenuated LPS-induced ${\beta}$ and ${\eta}o-secretase$ activities in cerebral cortex and hippocampus of the mice brain. This study therefore suggests that BV acupuncture method may be useful for prevention of development or progression of AD.