• Natural Product Sciences
• /
• 제22권4호
• /
• pp.282-286
• /
• 2016

Cyanidin-$3{\beta}$-D-glycoside (C3G), which is widely distributed in herbal medicines and functional foods, exhibits anti-inflammatory, anti-oxidant, and anti-scratching behavioral effects. Orally administered C3G is metabolized to protocatechuic acid (PA) by gut microbiota. Therefore, we compared the anti-colitic effect of C3G to that of PA in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. Orally administered C3G and PA preventively and curatively ameliorated TNBS-induced colitis parameters, including macroscopic colitis score, colon shortening, and increase of myeloperoxidase activity. Treatment with C3G or PA also inhibited the expression of cyclooxygenase-2, inducible NO synthatase, $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$ and the activation of $NF-{\kappa}B$ in the colon of mice with TNBS-induced colitis. Furthermore, these also inhibited lipopolysaccharide-induced $NF-{\kappa}B$ activation and $TNF-{\alpha}$ expression in peritoneal macrophages. The anti-colitic effect of PA was more effective than C3G. Orally administered PA more potently attenuate colitis than C3G by inhibiting $NF-{\kappa}B$ activation and the anti-colitic efficacy of C3G may be dependent on the biotransformation of C3G to PA by gut microbiota.

• 동의생리병리학회지
• /
• 제25권3호
• /
• pp.406-416
• /
• 2011

In this study, we have verified the memory and cognitive enhancing effect of Longanae Arillus, the fruit of Euphoria longana Lamarck, which has been used as a tonic and for the treatment of amnesia, insomnia, and palpitations in oriental medicine. To investigate the effect of Longanae Arillus water extract(LAE) on the memory and cognitive dysfunction, scopolamine (1 mg/kg, i.p.) was injected in C57BL/6 mice and several behavior tests including Y-maze, Morris water-maze, passive avoidance and fear conditioning tests were conducted. Administration of LAE (100 or 200 mg/kg/day, p.o.) effectively improved scopolamine-induced memory impairment and dysfunction. To further determine the possible molecule mechanism of LAE, we have examined the activity and/or mRNA expression of diverse proteins involved in the acetylcholine metabolism. LAE particularly increased the amount of acetylcholine in the cortex which was mediated by suppression of acetylcholine esterase (AchE) activity. In addition, LAE elevated the mRNA expression of muscarinic acetylcholine receptors (mAchRs) without affecting the mRNA levels of choline acetyltransferase (ChAT) and acetylcholine esterase (AchE). In another experiment, LAE effectively inhibited mRNA expression of pro-inflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-$1{\beta}$ (IL1-${\beta}$), which seemed to be mediated by inhibition of upstream transcription factor NF-${\kappa}B$ and extracellular-regulated kinase 1/2 (ERK1/2). These results demonstrate that Longanae Arillus can increase acetylcholine amount the cortex via regulation of AchE activity as well as mAchRs expression and decrease pro-inflammatory responses via inhibition of NF-${\kappa}B$ signaling pathway, thereby having therapeutic potential to improve memory and cognitive deficit in amnesia.

• Tuberculosis and Respiratory Diseases
• /
• 제54권4호
• /
• pp.449-458
• /
• 2003

연구배경 : Cyclosporin A(CsA)와 tacrolimus(FK506)은 현재 임상에서 널리 쓰이는 면역억제제이다. CsA와 FK506이 $I{\kappa}B/NF-{\kappa}B$ 경로에 미치는 영향에는 세포에 따라 다양한 효과가 알려져 있다. 그러나 CsA와 FK506이 기관지 상피세포에서 $I{\kappa}B/NF-{\kappa}B$ 경로에 미치는 효과에 관해서는 알려져 있지 않고, 각종 염증 세포에서의 차이에 관해서도 보고가 미미한 실정이다. 본 연구에서는 비염증세포인 기관지상피세포와, 폐의 염증에 중요한 역할을 하는 염증 세포(폐포대식세포, 단핵구, 림프구)에서 CsA와 FK506이 $I{\kappa}B{\alpha}$의 분해에 미치는 영향과 그 기전을 평가하였다. 방 법 : 비염증세포로는 BEAS-2B와 A549 세포주를 이용하였다. FK506 또는 CsA 전처치 후 TNF-${\alpha}$로 자극하고 anti-$I{\kappa}B{\alpha}$ 항체를 이용한 Western blot으로 $I{\kappa}B{\alpha}$의 분해 여부를 관찰하였다. 염증세포로는 폐포대식세포, 말초혈액 단핵구 및 림프구를 이용하였고, 역시 FK506 또는 CsA 전처치 후 TNF-${\alpha}$, IL-$1{\beta}$, LPS로 자극하고 anti-$I{\kappa}B{\alpha}$ 항체를 이용한 Western blot으로 $I{\kappa}B{\alpha}$의 분해 여부를 관찰하였다. IKK의 활성도는 GST-$I{\kappa}B{\alpha}$를 기질로 이용한 in vitro immune complex kinase assay로 평가하였다. 결 과 : 사용된 모든 세포에서 CsA와 FK506은 $I{\kappa}B{\alpha}$의 발현에 영향을 미치지 않았다. 기관지 상피세포에서 TNF-${\alpha}$ 자극에 의한 $I{\kappa}B{\alpha}$의 분해는 CsA의 전처치로 억제되었으나, FK506의 전처치로는 억제되지 않았다. 단핵구, 림프구 및 폐포대식세포에서 외부자극에 의한 $I{\kappa}B{\alpha}$의 분해는 CsA 또는 FK506의 전처치로 억제되었으나 IKK활성은 억제되지 않았다. 결 론 : CsA와 FK506은 각각 기관지 상피세포와 단핵구, 림프구, 폐포대식세포에서 외부 자극에 의한 $I{\kappa}B{\alpha}$의 분해를 억제하는데, 이는 IKK 활성화의 억제가 아닌 다른 경로를 통하는 것으로 생각된다.

• 한국식품영양과학회지
• /
• 제46권6호
• /
• pp.681-687
• /
• 2017

본 연구는 그라비올라 잎 에탄올 추출물(AME)의 항염증 효과에 관하여 알아보기 위하여 LPS에 의해 유도되는 대식세포 염증모델에 AME를 병용 처리하여 다양한 염증매개인자들의 분비능 및 염증억제 기전에 관하여 알아보았다. LPS의 처리에 따라 염증반응이 유도된 RAW 264.7 대식세포에 AME를 병용 처리하였을 때, NO 및 염증성 cytokine(IL-6, $TNF-{\alpha}$ 및 $IL-1{\beta}$)의 분비능이 유의적으로(P<0.05) 감소하는 것을 확인하였다. 또한, AME의 처리에 따라 염증반응의 매개인자인 iNOS 및 COX-2 발현이 유의적으로(P<0.05) 감소하는 것으로 나타났으며, 이러한 항염증 활성의 기전에 관하여 분석한 결과 염증성 단백질 발현의 전사인자인 $NF-{\kappa}B$와 MAPKs 신호전달 경로 억제를 통하여 추출물의 항염증 활성이 나타난다는 사실을 관찰할 수 있었다. 따라서 이러한 결과를 통하여 AME의 처리는 염증반응의 전사인자인 $NF-{\kappa}B$의 발현을 조절함으로써 iNOS 및 COX-2의 발현을 억제하고, 염증성 매개인자인 NO 및 cytokine(IL-6, $TNF-{\alpha}$ 및 $IL-1{\beta}$)의 분비를 억제한다고 판단된다.

• 한국자원식물학회지
• /
• 제31권2호
• /
• pp.117-123
• /
• 2018

비지는 대두 가공 시 생산되는 부산물로 대부분 폐기되고 있는 실정이지만, 최근 비지를 유용한 자원으로 이용하기 위한 기능성 연구가 진행되고 있다. 그러나 비지의 항염증에 대한 연구가 미비하여 본 연구진은 비지추출물이 마우스 대식세포인 RAW264.7에 LPS에 의한 염증 반응에 미치는 영향을 평가하였다. 본 연구에서 비지추출물은 NF-${\kappa}B$와 p38의 활성 억제를 통해 만성염증 유발인자인 NO, iNOS, $PGE_2$, COX-2, TNF-${\alpha}$ 및 IL-$1{\beta}$의 발현을 억제하는 것으로 확인되었다. 따라서 비지는 독성과 부작용이 적은 항염증 관련 식의약 소재로 활용될 수 있을 것으로 사료된다.

• 한국식품과학회지
• /
• 제49권4호
• /
• pp.453-458
• /
• 2017

본 연구는 가시여지 잎 에탄올 추출물(ALE) 및 조다당 추출물(ALP)의 면역 활성에 관하여 비교하기 위하여, 선천 및 적응면역에서 중추적인 역할을 수행하는 큰포식세포에 ALE 및 ALP를 처리하여 세포 증식률, 산화질소 분비능, 사이토카인(종양괴사인자, IL-6, $IL-1{\beta}$) 분비능 및 기전 분석을 통한 신호전달에 관하여 관찰하였다. ALE 및 ALP를 큰포식세포에 처리하여 면역활성에 관하여 비교하였을 때, 큰포식세포 면역활성의 바이오-마커인 산화질소, 사이토카인의 분비능 및 iNOS의 세포내 발현이 ALP 처리구에서 유의적으로 증가되는 것으로 관찰되었으며, 기전분석결과, ALP의 처리는 MPAKs의 인산화 및 $NF-{\kappa}B$의 핵내 이동성을 증가시켜 면역활성을 증가시키는 것으로 관찰되었다. 따라서, ALP의 높은 면역활성은 MPAKs의 인산화 및 $NF-{\kappa}B$의 활성과 밀접한 관련이 있는 것으로 판단된다.

• Journal of Microbiology and Biotechnology
• /
• 제28권3호
• /
• pp.349-356
• /
• 2018

Asterias amurensis is a marine organism that causes damage to the fishing industry worldwide; however, it has been considered a promising source of functional components. The present study aimed to investigate the immune-enhancing effects of fatty acids from three organs of A. amurensis on murine macrophages (RAW 264.7 cells). A. amurensis fatty acids boosted production of immune-associated factors such as nitric oxide (NO) and prostaglandin E2 in RAW 264.7 cells. A. amurensis fatty acids also enhanced the expression of critical immune-associated genes, including iNOS, $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6, as well as COX-2. Western blotting showed that A. amurensis fatty acids stimulated the $NF-{\kappa}B$ and MAPK pathways by phosphorylation of $NF-{\kappa}B$ p-65, p38, ERK1/2, and JNK. A. amurensis fatty acids from different tissues resulted in different levels of $NF-{\kappa}B$ and MAPK phosphorylation in RAW 264.7 cells. The results increase our understanding of how A. amurensis fatty acids boost immunity in a physiological system, as a potential functional material.

• Fisheries and Aquatic Sciences
• /
• 제14권4호
• /
• pp.267-274
• /
• 2011

Bacterial lipopolysaccharide (LPS) induces expression of pro-inflammatory cytokines and enzymes producing nitric oxide (NO) and prostaglandins (PGs) in immune cells. This process is mediated by the activation of nuclear factor kappaB (NF-${\kappa}B$). In this study, we investigated the anti-inflammatory characteristics of Codium fragile ethanolic extract (CFE) mediated by the regulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) using LPS-stimulated murine macrophage RAW 264.7 cells. CFE significantly inhibited LPS-induced NO and $PGE_2$ production in a dose-dependent manner and suppressed the expression of iNOS and COX-2 proteins in LPS-stimulated RAW 264.7 cells with no cytotoxicity. Pro-inflammatory cytokines, such as interleukin (IL)-$1{\beta}$, IL-6, and tumor necrosis factor-${\alpha}$, were significantly reduced by treatment of CFE in LPS-stimulated RAW 264.7 cells. CFE inhibited the promoter activity of (NF)-${\kappa}B$ in LPS-stimulated macrophages. Treatment with CFE suppressed translocation of the NF-${\kappa}B$ p65 subunit by preventing proteolytic degradation of inhibitor of ${\kappa}B-{\alpha}$. These results indicate that the CFE-mediated inhibition of NO and $PGE_2$ production in LPS-stimulated RAW 264.7 cells is mediated through the NF-${\kappa}B$-dependent transcriptional downregulation of iNOS and COX-2, suggesting the potential of CFE as a nutraceutical with anti-inflammatory activity.

• 대한본초학회지
• /
• 제24권4호
• /
• pp.39-47
• /
• 2009

Objectives : Hwangnyeonhaedok-tang (Huanglian Jiedu Tang; HHT) has been widely used for purging' 'fire' and lessening virulence of any pathogenic organism. However it has been rarely conducted to evaluate the immuno-biological activity. In this study, we evaluated anti-inflammatory effects of HHT in LPS-activated Raw264.7 cells. Methods : Cells were treated with $1\;{\mu}g/ml$ of LPS 1 h prior to the addition of HHT. Cell viability was measured by MTT assay. The production of NO was determined by reacting cultured medium with Griess reagent. PGE2 and proinflammatory cytokines were detected by ELISA. Expression of iNOS, COX-2, $I{\kappa}B{\alpha}$ and NF-${\kappa}B$ were analyzed by immunoblot analysis. Results : All three doses of HHT (0.03, 0.10 and 0.30 mg/ml) had no significant cytotoxicity during the entire experimental period. The levels of NO and PGE2 were dramatically augmented by LPS compared to control. However, HHT extract dose-dependently reduced these increases. Expression of iNOS and COX-2 protein were also decreased by treatment with HHT extract. Furthermore, HHT extract significantly reduced the nuclear translocation of NF-${\kappa}B$ which is critical in regulating inflammation through transcription of iNOS and COX-2. In addition, HHT extract reduced the elevated production of inflammatory cytokines including TNF-$\alpha$, IL-$1{\beta}$ and IL-6. Conclusions : The results in this study demonstrate that HHT extract exerts anti-inflammatory activities through the inhibition of NO, PGE2 and proinflammatory cytokines production via the suppression of NF-${\kappa}B$.

• Molecules and Cells
• /
• 제37권10호
• /
• pp.747-752
• /
• 2014

Protein kinase C (PKC) family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. However, the role of PKC in receptor activator of NF-${\kappa}B$ ligand (RANKL) signaling has remained elusive. We now demonstrate that $PKC{\beta}$ acts as a positive regulator which inactivates glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$) and promotes NFATc1 induction during RANKL-induced osteoclastogenesis. Among PKCs, $PKC{\beta}$ expression is increased by RANKL. Pharmacological inhibition of $PKC{\beta}$ decreased the formation of osteoclasts which was caused by the inhibition of NFATc1 induction. Importantly, the phosphorylation of GSK-$3{\beta}$ was decreased by $PKC{\beta}$ inhibition. Likewise, down-regulation of $PKC{\beta}$ by RNA interference suppressed osteoclast differentiation, NFATc1 induction, and GSK-$3{\beta}$ phosphorylation. The administration of PKC inhibitor to the RANKL-injected mouse calvaria efficiently protected RANKL-induced bone destruction. Thus, the $PKC{\beta}$ pathway, leading to GSK-$3{\beta}$ inactivation and NFATc1 induction, has a key role in the differentiation of osteoclasts. Our results also provide a further rationale for $PKC{\beta}$'s therapeutic targeting to treat inflammation-related bone diseases.