• Journal of Applied Biological Chemistry
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• 제66권
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• pp.519-526
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• 2023

본 연구는 마우스 대식세포 유래 Raw264.7 세포주에서 황기와 산초 1:1 혼합물(AZM-1:1)의 면역 증진 효능을 탐색하였다. Raw264.7 세포에 100-400 ㎍/mL의 A ZM-1:1 처치는 세포 생존율의 변화 없이 inducible nitric oxide synthase mRNA의 발현 증가와 함께 nitric oxide의 생성을 통계적으로 유의하게 증가시켰다. 더불어 A ZM-1:1은 처치 농도 의존적으로 cyclooxygenase-2 mRNA의 유도와 함께 세포 배양액 중 prostaglandin E₂의 함량을 증가시켰다. 또한, AZM-1:1은 tumor necrosis factor-α, interleukin-1β, interleukin-6 및 monocyte chemoattractant protein-1의 전사를 촉진하였다. Immunoblot 분석을 통하여 AZM-1:1은 mitogen-activated protein kinase의 인산화를 증가시키고, inhibitory-κBα의 인산화를 매개한 분해를 촉진하며, p65의 인산화를 증가시킬 수 있음을 확인하였다. AZM-1:1의 처치는 녹색 형광으로 표지된 대장균 파편의 탐식작용을 촉진하였다. 따라서, 이상의 결과는 A ZM-1:1가 대식세포를 포함한 내재면역을 증진시키는 기능성 식의약 소재가 될 수 있음을 나타낸다.

• BMB Reports
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• 제49권1호
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• pp.57-62
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• 2016

Up-regulation of adhesion molecules plays an important role in the infiltration of leukocytes into the skin during the development of various inflammatory skin diseases, such as atopic dermatitis. In this study, we investigated the modulatory effects of 2,3-dimethoxy-2′-hydroxychalcone (DMHC) on tumor necrosis factor (TNF)-α-induced intercellular adhesion molecule-1 (ICAM-1) expression and monocyte adhesiveness, as well as the molecular mechanisms underlying its action in the HaCaT human keratinocyte cell line. Pre-treating HaCaT cells with DMHC significantly suppressed TNF-α-induced ICAM-1 expression and subsequent monocyte adhesiveness. DMHC inhibited TNF-α-induced activation of NF-ᴋB. In addition, DMHC induced HO-1 expression as well as NRF2 activation. Furthermore, HO-1 knockdown using siRNA reversed the inhibitory effect of DMHC on TNF-α-induced ICAM-1 expression and adhesion of monocytes to keratinocytes. These results suggest that DMHC may inhibit TNF-α-induced ICAM-1 expression and adhesion of monocytes to keratinocytes by suppressing the signaling cascades leading to NF-ᴋB activation and inducing HO-1 expression in keratinocytes. [BMB Reports 2016; 49(1): 57-62]

• Journal of Dental Anesthesia and Pain Medicine
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• 제19권6호
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• pp.343-351
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• 2019

Background: Preterm labor and miscarriage may occur in stressful situations, such as a surgical operation or infection during pregnancy. Pharyngeal and buccal abscess and facial bone fractures are inevitable dental surgeries in pregnant patients. Remifentanil is an opioid analgesic that is commonly used for general anesthesia and sedation. Nonetheless, no study has investigated the effects of remifentanil on amniotic epithelial cells. This study evaluated the effects of remifentanil on the factors related to uterine contraction and its mechanism of action on amniotic epithelial cells. Methods: Amniotic epithelial cells were preconditioned at various concentrations of remifentanil for 1 h, followed by 24-h lipopolysaccharide (LPS) exposure. MTT assays were performed to assess the cell viability in each group. The effects of remifentanil on factors related to uterine contractions in amniotic epithelial cells were assessed using a nitric oxide (NO) assay, western blot examinations of the expression of nuclear factor-kappa B (NF-κB), cyclooxygenase 2 (COX2), and prostaglandin E2 (PGE₂), and RT-PCR examinations of the expression of the proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor-alpha (TNF-α). Results: Remifentanil did not affect viability and nitric oxide production of amniotic epithelial cells. Western blot analysis revealed that remifentanil preconditioning resulted in decreased expressions of NF-κB and PGE2 in the cells in LPS-induced inflammation, and a tendency of decreased COX2 expression. The results were statistically significant only at high concentration. RT-PCR revealed reduced expressions of IL-1β and TNF-α. Conclusions: Preconditioning with remifentanil does not affect the viability of amniotic epithelial cells but reduces the expression of factors related to uterine contractions in situations where cell inflammation is induced by LPS, which is an important inducer of preterm labor. These findings provide evidence that remifentanil may inhibit preterm labor in clinical settings.

• Nutrition Research and Practice
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• 제8권3호
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• pp.249-256
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• 2014

BACKGROUND/OBJECTIVES: The traditional Korean diet is plant-based and rich in antioxidants. Previous studies have investigated the potential health benefits of individual nutrients of Korean foods. However, the cumulative effects of a Korean diet on inflammation remain poorly understood. Therefore, the aim of this study was to investigate the anti-inflammatory effects of a plant-based Korean diet. MATERIALS/METHODS: Using data from the Fifth Korean National Health and Nutrition Examination Survey, 75 individual plant food items were selected which represent over 1% of the total diet intake of the Korean diet. These items were classified into ten different food groups, and the vegetable (Veg) and fruit (Fruit) groups were studied based on their high antioxidant capacity. For comparison, a mixture of all ten groups (Mix) was prepared. To produce a model of inflammation with which to test these Veg, Fruit, and Mix plant-based Korean food extracts (PKE), RAW264.7 macrophages were treated with lipopolysaccharide (LPS). RESULTS: Levels of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$), as well as protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were found to be lower following PKE treatment. Furthermore, PKE treatment was found to suppress tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) via the nuclear transcription factor kappa-B ($NF-{\kappa}B$) signaling pathway. Overall, the Mix group exhibited the greatest anti-inflammatory effects compared with Veg and Fruit PKE group. CONCLUSIONS: Inhibition of LPS-induced pro-inflammatory mediators by the PKE tested was found to involve an inhibition of NF-kB activation. Moreover, PKE tested have the potential to ameliorate various inflammation-related diseases by limiting the excessive production of pro-inflammatory mediators.

• Journal of Ginseng Research
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• 제39권4호
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• pp.376-383
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• 2015

Background: Panax ginseng has a wide range of biological activities including anti-inflammatory, antioxidant, and immunomodulatory functions. Wild ginseng cambial meristematic cells (CMCs) were obtained from P. ginseng cambium. This study examined the protective mechanism of wild ginseng CMCs against $\small{D}$-galactosamine (GalN)-induced liver injury. GalN, a well-known hepatotoxicant, causes severe hepatocellular inflammatory damage and clinical features similar to those of human viral hepatitis in experimental animals. Methods: Hepatotoxicity was induced in rats using GalN (700 mg/kg, i.p.). Wild ginseng CMCs was administered orally once a day for 2 wks, and then 2 h prior to and 6 h after GalN injection. Results: Wild ginseng CMCs attenuated the increase in serum aminotransferase activity that occurs 24 h after GalN injection. Wild ginseng CMCs also attenuated the GalN-induced increase in serum tumor necrosis factor-${\alpha}$, interleukin-6 level, and hepatic cyclooxygenase-2 protein and mRNA expression. Wild ginseng CMCs augmented the increase in serum interleukin -10 and hepatic heme oxygenase-1 protein and mRNA expression that was induced by GalN, inhibited the increase in the nuclear level of nuclear factor-kappa B, and enhanced the increase in NF-E2-related factor 2. Conclusion: Our findings suggest that wild ginseng CMCs protects liver against GalN-induced inflammation by suppressing proinflammatory mediators and enhancing production of anti-inflammatory mediators.

• Journal of Microbiology and Biotechnology
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• 제30권12호
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• pp.1896-1904
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• 2020

Muscle atrophy, characterized by a reduced number and size of myofibers, occurs due to immobilization, aging, and several chronic diseases. Leonurus japonicus, belonging to the Labiatae family, is widely used as a traditional medicine in Korea, China, and Japan. Previous studies have reported that L. japonicus has various physiological activities, such as anti-bacteria, anti-cancer, and liver protection. Leonurine, which is a major bioactive in L. japonicas, is known to possess biological effects including anti-inflammation, anti-fibrosis, anti-angiogenesis, and anti-diabetes. However, the preventive effects of L. japonicas and leonurine on muscle have not been reported. The current study aimed to determine the inhibitory effects of standardized L. japonicus extract (LJE) and leonurine on muscle atrophy by clarifying their underlying molecular mechanisms in tumor necrosis factor-alpha (TNF-α)-stimulated L6 myotubes. LJE and leonurine stimulated the phosphatidylinositol 3-kinase/Akt pathway that was reduced by TNF-α treatment. LJE and leonurine not only increased the mammalian target of rapamycin pathway for protein anabolism but also decreased the mRNA expression of E3 ubiquitin ligases by blocking the translocation of Forkhead box O, which is closely linked with proteolysis. Additionally, LJE and leonurine alleviated inflammatory responses by downregulating TNF-α and interleukin-6 mRNA expression and reducing the protein expression of nuclear factor-kappa B, a major transcriptional factor of proinflammatory cytokines. Collectively, LJE and leonurine have potential as therapeutic candidates for inhibiting the development of skeletal muscle atrophy by activating the PI3K/Akt pathway and reducing inflammatory responses.

• Animal Bioscience
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• 제35권6호
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• pp.858-868
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• 2022

Objective: This study was conducted to evaluate the effects of dietary yeast hydrolysate (YH) supplementation on intestinal morphology, barrier, and anti-inflammatory functions of broilers. Methods: A total of 320 one day old male broilers were randomly allocated into four groups with eight replicates of ten broilers each. The broilers were supplemented with a basal diet (the control group) or basal diets adding 50, 100, 150 mg/kg YH, respectively. This trial lasted for 42 days. The orthogonal polynomial contrasts were used to determine the linear and quadratic effects of increasing levels of YH. Results: In our previous research, supplementing YH improved growth performance by enhancing body weight gain but decreased feed-to-gain ratio. In this study, compared with the control group, dietary YH addition linearly and quadratically decreased serum diamine oxidase activity (p<0.05). Additionally, supplementing YH linearly and/or quadratically decreased jejunal crypt depth (CD), tumor necrosis factor-alpha (TNF-α) concentration as well as mucin 2, interleukin-6 (IL-6), IL-1β, TNF-α, nuclear factor kappa B, and myeloid differentiation factor 88 gene expression levels (p<0.05). Whereas the jejunal villus height (VH), VH/CD, IL-10 concentration as well as zonula occludens-1 and IL-10 gene expression levels were linearly and/or quadratically increased by YH supplementation (p<0.05). Conclusion: Dietary YH supplementation improved intestinal morphology, barrier and anti-inflammatory functions while decreased intestinal permeability of broilers, which might be related with altering pertinent genes expression. This study provides evidence of YH as a promising feed additive for broilers.

• 한국식품영양과학회지
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• 제37권9호
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• pp.1126-1135
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• 2008

본 연구에서는 내독소인 LPS로 산화적 스트레스를 유발시킨 BALB/c mice에 genistein을 투여하였을 때 TNF-$\alpha$, TBARS, superoxide anion 농도와 GSH, 항산화 효소계 활성, 그리고 NF-${\kappa}B$ transactivation에 미치는 영향을 조사하여 genistein이 내독소에 의한 산화적 스트레스와 염증반응을 억제하는 효과가 있는지 알아보고자 하였다. 평균체중 20 g인 BALB/c mice 암컷 120수를 30수씩 완전임의배치로 4군으로 분류하여 PBS군(대조군)은 PBS를 복강 속으로 투여 후 30분경과 후에 다시 PBS를 투여하였으며, genistein군은 genistein을 체중 kg당 200 mg으로 투여한 30분 후 PBS를 투여하였다. LPS군은 LPS를 처리한 군으로 PBS 투여 30분 후 LPS를 체중 kg당 100 mg 농도로 복강 투여하였고, genistein+LPS군은 체중 kg당 genistein 200 mg을 투여 30분 후 LPS를 체중 kg당 100 mg을 투여하였다. 마지막 투여 1시간, 4시간, 8시간 경과 후 mouse의 안와정맥으로부터 혈액을, 복강으로부터 복강대식세포와 간을 취하였다. LPS 투여 8시간 경과 후 LPS군의 ${O_2}^-$ 생성량은 현저하게 증가하였으며 geinstein+LPS군은 genistein 대조군, PBS군과 비슷한 수준을 유지하였다. 반면 SOD 활성은 geinstein+LPS군이 LPS군에 비해 유의적으로 높은 수준이었다. 혈장에서의 TNF-$\alpha$ 수준은 LPS 투여 8시간 후 genstein+LPS군이 LPS군보다 유의적으로 낮은 수준을 보였다. LPS 투여는 항산화 효소계 활성과 GSH의 수준을 감소하였으나, genistein을 투여한 genistein+LPS군은 LPS군에 비해 GSH 농도와 catalase, GSH-px, GSH-reductase 활성이 모두 유의적으로 증가하는 결과를 보였다. 간에서의 NF-${\kappa}B$ transactivation 정도는 LPS 투여 후 1시간, 4시간 경과 후에 PBS군에 비해 LPS군과 genistein+LPS군에서 유의적으로 높은 수준이었으나 8시간 경과 후 LPS군은 증가하는 반면 genistein+LPS군은 변화하지 않았다. 이상의 결과를 요약해보면 LPS의 투여는 혈장과 간의 산화적 스트레스와 염증반응을 촉진하는 것으로 나타났으며 LPS 투여 전 공급한 genistein은 LPS로 유도된 산화적 스트레스와 염증반응을 항산화 효소계 활성 증가와 NF-${\kappa}B$ transactivation 억제, TNF-$\alpha$ 생성 저하 등의 기작으로 세포내의 과산화수준을 수준을 낮추고 GSH를 증가시켜 산화적 스트레스를 억제하는 것으로 사료된다.

• 한국식품영양과학회지
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• 제45권8호
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• pp.1090-1098
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• 2016

본 연구는 해조류 중에서도 홍조류인 주름까막살 에탄올 추출물(GCEE)의 항염증 효과를 확인하기 위한 실험으로 proinflammatory cytokines의 분비량 및 iNOS, COX-2, $NF-{\kappa}B$와 MAPKs의 발현량을 관찰하고 마우스모델에서 항염증 효과를 확인하였다. GCEE가 세포 생존율에 있어 독성을 나타내지 않음을 MTT assay를 통해 확인한 후 같은 농도로 추후실험을 진행하였다. NO 분비량이 GCEE에 의해 농도 의존적으로 감소하였으며 전염증성 매개물질인 사이토카인(IL-6, $TNF-{\alpha}$ 및 $IL-1{\beta}$)의 분비량 또한 유의적으로 감소하였다. 이러한 결과가 전염증성 매개인자의 전사인자인 $NF-{\kappa}B$와 MAPKs 경로에 의한 것인지 확인하기 위하여 발현량을 관찰한 결과, GCEE가 LPS 처리로 현저히 증가한 염증 관련 효소인 iNOS와 COX-2의 단백질 발현을 농도 의존적으로 유의성 있게 억제하였고 전사인자인 $NF-{\kappa}B$ 및 MAPKs의 발현을 억제하였다. 또한, GCEE는 croton oil로 부종을 유발한 마우스모델에서 귀 부종 억제 효과를 나타내었고 250 mg/kg 농도에서 조직의 경피 및 진피 두께의 발달을 prednisolone 50 mg/kg 처리구와 유사한 정도까지 현저히 억제하고 염증성 세포인 mast cell의 침윤 억제 효과도 확인하였다. 이를 통해 주름까막살 에탄올 추출물은 염증반응의 전사인자인 $NF-{\kappa}B$와 MAPKs의 발현을 조절함으로써 iNOS와 COX-2의 발현을 억제하고 그에 따라 전염증성 매 개인자인 NO, IL-6, $TNF-{\alpha}$ 및 $IL-1{\beta}$의 분비를 억제하여 항염증 활성을 가지는 것을 확인하였으며, 이 결과를 종합해 볼 때 주름까막살 에탄올 추출물이 염증 치료제의 소재로 이용될 가치가 충분할 것으로 생각한다.

• Journal of Nutrition and Health
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• 제51권6호
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• pp.507-514
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• 2018

본 연구에서는 모자반목 모자반과 갈조류인 괭생이 모자반의 3가지 서로 다른 추출물의 면역활성 가능성을 비교연구하기 위하여 RWA264.7 대식세포에 서로 다른 괭생이 모자반 추출물을 처리하여 $TNF-{\alpha}$, IL-6 및 NO 분비능과 MAPK 신호전달경로 및 $NF-{\kappa}B$ 활성화 수준을 측정하였다. 괭생이 모자반 열수추출물, 주정추출물, 그리고 초임계추출물 중 괭생이 모자반 열수추출물이 세포독성은 없는 농도 ($50{\mu}g/mL$)에서 $TNF-{\alpha}$, IL-6의 생성뿐 아니라 iNOS 활성화를 통한 NO 분비를 촉진하였다. 이러한 괭생이 모자반 열수추출물의 면역증진 효과는 MAPK 신호전달경로 및 $NF-{\kappa}B$ 활성화를 통해 이루어지고 있음을 확인하였다. 본 연구결과는 괭생이 모자반 열수추출물의 면역활성 증진 가능성을 제시하여 향후 대식세포의 활성 유도를 통한 면역증진 치료에 유용하게 사용될 수 있음을 보여주는 것이다.