• The Journal of Pediatrics of Korean Medicine
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• v.26 no.4
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• pp.10-23
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• 2012

Objectives: Gagamyanggyeoksan (G-YGS) has been used to suppress allergic reaction, however, the cellular target of G-YGS and its mode of action remain unclear. The present study was designed to investigate the effect of extracted G-YGS on the PMA and lonomycin (PI)-induced activation of RBL-2H3. Methods: For this investigation, We examined IL-4, IL-13 mRNA expression by Real-Time PCR, IL-4, IL-13 production by ELISA analysis and manifestations of GATA-1, GATA-2, NF-AT1, NF-AT2, AP-1 and NF-${\kappa}B$ p65 transcription factors by western blotting, OVA-specific IgE, IL-4, IL-13 by mouse be sensitive to OVA. Results: Here we showed that treatment of RBL-2H3 mast cells with G-YGS, suppressed PI-induced production of Th2 cytokines including IL-4 and IL-13 in a dose dependent manner. The mRNA expression of IL-4 were completely abolished by G-YGS at the concentration of $100{\mu}g/ml$. Data from a stable cell lines consistently expressing IL-4. And the mRNA expression of IL-13 were abolished by G-YGS at the $200{\mu}g/ml$. But there is no difference between the $50{\mu}g/ml$, the $100{\mu}g/ml$ and the comparison. Results from the western blot analysis of transcription factors involving IL-4 and IL-13 expression indicated that it prominently decreased the expression of mast cell specific transcricption factors including GATA-1, GATA-2, NF-AT2, c-Jun, NF-${\kappa}B$ p65 but not c-Fos. And G-YGS suppressed IgE, IL-4, IL-13 in mouse be sensitive to OVA. Conclusions We suggested the anti-allergic activities of G-YGS might be mediated by down-regulation of Th2 cytokines such as IL-4 and IL-13 through the regulation of transcription factors as GATA-1, GATA-2, NF-AT2, c-Jun, NF-${\kappa}B$ p65.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.9
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• pp.1226-1234
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• 2012

3,4,3',5'-Tetrahydroxy-trans-stilbene (piceatannol) is a derivative of resveratrol with a variety of biological activities, including anti-inflammatory, anti-proliferative, and anti-cancer activities. We assessed the mechanisms by which piceatannol inhibits inflammatory responses using lipopolysaccharide (LPS)-treated Raw264.7 murine macrophages. Piceatannol (0~10 ${\mu}mol/L$) decreased LPS-induced release of nitric oxide, tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, IL-$1{\beta}$, and inhibited LPS-induced protein expression of inducible nitric oxide synthase (iNOS). Activation of nuclear factor-kappaB (NF-${\kappa}B$), activator protein (AP)-1, and signal transducer and activator of transcription 3 (STAT3) are crucial steps during an inflammatory response. Piceatannol prevented LPS-induced degradation of inhibitor of ${\kappa}B$ ($I{\kappa}B$), translocation of p65 to the nucleus, and phosphorylation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK). Additionally, piceatannol inhibited LPS-induced phosphorylation of STAT3 and IL-6-induced translocation of STAT3 to the nucleus. Furthermore, piceatannol increased the protein and mRNA levels of hemeoxygenase (HO)-1, the rate-limiting enzyme of heme catabolism that plays a critical role in mediating antioxidant and anti-inflammatory effects. Piceatannol further induced antioxidant response elements (ARE)-driven luciferase activity in Raw264.7 cells transfected with an ARE-luciferase reporter construct containing the enhancer 2 and minimal promoter region of HO-1. These results suggest that piceatannol exerts anti-inflammatory effects via the down-regulation of iNOS expression and up-regulation of HO-1 expression.

• Proceedings of the Korean Society for Agricultural Machinery Conference
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• 2017.04a
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• pp.169-169
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• 2017

스마트 돈사 내의 열환경 분석에 필수적으로 고려되어야 인자는 가축의 복사 에너지 변화로 볼 수 있다. 열환경 제어의 대상이기도 하지만 회귀적으로 열환경 변화의 인자이기도 하다. 이러한 가축의 복사 에너지 분석을 위하여 시설 내에 용이하게 배포가 가능한 열화상 계측 시스템을 개발하였다. 초소형 마이크로 열화상 계측 시스템에 부가적으로 IOT(Internet of Thing) 기반 기술을 이용한 모듈화 개발을 병행하였다. 열화상 계측 센서로 LWIR(Longwave infrared)영역에 해당하는 $8{\mu}m{\sim}4{\mu}m$의 영역에서 $0.05^{\circ}C$의 분해능을 보이는 $Lepton^{TM}$ (500-0690-00, FLIR, Goleta, CA)모델을 사용하였다. SPI(Serial Peripheral Interface) 속도 2 Mhz로 마이크로프로세서(NanoPi NEO Air, FrendlyArm, CA, USA)와 고속 통신을 수행하여 9 Hz의 계측이 가능하다. 열화상 센서와 마이컴으로 구성되는 단위 계측 시스템의 통신 기능 확장을 위하여 다음과 같이 세 단계의 정보 전달 시나리오를 설계하였다. 1) 단독적으로 열화상을 계측 하고 내장된 메모리에 저장하는 형식 2) 인접한 사용자 인터페이스에서 1번 단독 모듈에 접속하여 열화상을 실시간으로 전송하여 화면에 도시하는 형식 3) 2번 사용자 도시모듈과 병행적으로 Local WI-FI 통신을 이용한 모바일 기기에 화면을 도시하는 형식. 이와 같은 계층적이며 모듈화된 계측 시스템을 구성하기 위해서 1번 모듈에 공개 소프트웨어인 Hostapd 2.5(http://w1.fi/hostapd)버전을 설치하였다. 외부 인터넷 환경이 없는 상황에 1번 모듈 단독으로 AP(Access Point) 기능을 제공하여 지근 거리에 있는 2번 모듈과 3번 모바일 기기의 접속을 관리할 수 있다. 2번 모듈의 경우 화면 다수의 1번 모듈에 접속을 교차적으로 수행하는 방식과 2번 모듈 자체가 AP가 되어 1번 모듈의 접속을 허용하는 형태로 구성되어 있다. 계측 시스템의 계측 매트릭스 구성에 따라 선택적으로 결정할 수 있다. 1번 2번 모듈 공통적으로 TCP/IP Listener와 Client 서비스를 병렬적으로 수행할 수 있도록 개발을 하였다. 3번 모바일 기기에서 사용자 인터페이스 구현을 위하여 범용 Android 기반 GUI 프로그램과 Socket 통신을 연동시켰다. 1개의 열화상 Frame의 전송량은 9,600 Byte ($=80{\times}60{\times}2Byte$) 로 WI-FI 통신 전송 시 2회 ~ 6회 정도 내외로 가변적인 통신 수행 횟수를 나타내었다. 센서 계측 시스템과 정보 전송 시스템을 병렬적으로 구성한 모듈화 된 계측시스템의 전 요소에서 센서에서 제공하는 최대 계측 주기인 9 Hz 구현이 일반적으로 가능하였다. 이를 이용한 추후 연구를 통해 가축 객체의 열복사 정보와 돈사 내 열환경 간의 역학성을 연구할 것이다.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.4
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• pp.171-176
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• 2008

Heat shock proteins (HSPs) serve as molecular chaperones and play a role in cell protection from damage in response to stress stimuli. The aim of this article is to investigate whether HSP22 affects IL-8 expression in vascular smooth muscle cells (VSMCs), and which cellular factors are involved in the HSP-mediated IL-8 induction in that cell type in terms of mitogen activated protein kinase (MAPK) and transcription element. Exposure of aortic smooth muscle cells (AoSMCs) to HSP22 not only enhanced IL-8 release but also induced IL-8 transcript via promoter activation. HSP22 activated ERK and p38 MAPK in AoSMCs. HSP22-induced IL-8 release was inhibited by U0126, but not by SB202190. A mutation in the IL-8 promoter region at the binding site of NF-${\kappa}$ B, but not AP-1 or C/EBP, impaired promoter activation in response to HSP22. Delivery of I ${\kappa}$ B, but not dominant negative c-Jun, lowered HSP22-induced IL-8 release from AoSMCs. These results suggest that HS P22 induces IL-8 in VSMCs via ERK1/2, and that transcription factor NF-kB may be required for the HSP22-induced IL-8 up-regulation.

• Biomolecules & Therapeutics
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• v.24 no.6
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• pp.595-603
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• 2016

(E)-3-Phenyl-1-(2-pyrrolyl)-2-propenone (PPP) is a pyrrole derivative of chalcone, in which the B-ring of chalcone linked to ${\beta}$-carbon is replaced by pyrrole group. While pyrrole has been studied for possible Src inhibition activity, chalcone, especially the substituents on the B-ring, has shown pharmaceutical, anti-inflammatory, and anti-oxidant properties via inhibition of NF-${\kappa}B$ activity. Our study is aimed to investigate whether this novel synthetic compound retains or enhances the pharmaceutically beneficial activities from the both structures. For this purpose, inflammatory responses of lipopolysaccharide (LPS)-treated RAW264.7 cells were analyzed. Nitric oxide (NO) production, inducible NO synthase (iNOS) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) mRNA expression, and the intracellular inflammatory signaling cascade were measured. Interestingly, PPP strongly inhibited NO release in a dose-dependent manner. To further investigate this anti-inflammatory activity, we identified molecular pathways by immunoblot analyses of nuclear fractions and whole cell lysates prepared from LPS-stimulated RAW264.7 cells with or without PPP pretreatment. The nuclear levels of p50, c-Jun, and c-Fos were significantly inhibited when cells were exposed to PPP. Moreover, according to the luciferase reporter gene assay after cotransfection with either TRIF or MyD88 in HEK293 cells, NF-${\kappa}B$-mediated luciferase activity dose-dependently diminished. Additionally, it was confirmed that PPP dampens the upstream signaling cascade of NF-${\kappa}B$ and AP-1 activation. Thus, PPP inhibited Syk, Src, and TAK1 activities induced by LPS or induced by overexpression of these genes. Therefore, our results suggest that PPP displays anti-inflammatory activity via inhibition of Syk, Src, and TAK1 activity, which may be developed as a novel anti-inflammatory drug.

• Journal of Life Science
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• v.26 no.8
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• pp.875-880
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• 2016

The plasma membrane plays a crucial role in relaying signals from the outside environment to the inside of the cells. In eukaryotic cells, the inner leaflets of the plasma membrane are composed mostly of phospholipids, including phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylinositides (PIs). In this study, we tried to analyze the morphological changes induced by EGFP-fused membrane binding proteins, which are targeted to the plasma membrane via specific phospholipids binding. As a result, we found that overexpression of EGFP-P4M-SidM, a specific PI4P binding protein, or EGFP alone, did not induce any morphological changes. On the other hand, overexpression of EGFP-PLCδ1(PH), which is a specific PI(4,5)P₂ binding protein, EGFP-AKT1(PH) which binds to PI(3,4,5)P₃, or EGFP-OSH2(PH)×2 which binds to PI4P and PI(4,5)P₂, could induce the filopodia and lamilapodia formation as well as cell shrinkage. Overexpression of Lact-C2-EGFP which is a specific PS-binding probe, EGFP fused Aplysia phosphodiesterase 4 (ApPDE4) long-form (L(N20)-EGFP) which is localized to the plasma membrane via hydrophobic interaction, or EGFP fused Aplysia PDE4 short-form (S(N-UCR1-2)-EGFP) which is localized to the plasma membrane via electrostatic interaction, could induce cell shrinkage, but not filopodia or lamilapodia formation. Taken together, our data support that the different phospholipid bindings in the plasma membrane could induce different characteristic morphological changes. Thus, we can analyze, characterize, and classify the cellular morphological changes induced by the various phospholipid binding proteins.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.4
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• pp.365-372
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• 2015

Aripiprazole (ARI) is a commonly prescribed medication used to treat schizophrenia and bipolar disorder. To date, there have been no studies regarding the molecular pathological and immunotoxicological profiling of aripiprazole. Thus, in the present study, we prepared two different formulas of aripiprazole [Free base crystal of aripiprazole (ARPGCB) and cocrystal of aripiprazole (GCB3004)], and explored their effects on the patterns of survival and apoptosis-regulatory proteins under acute toxicity and cytotoxicity test conditions. Furthermore, we also evaluated the modulatory activity of the different formulations on the immunological responses in macrophages primed by various stimulators such as lipopolysaccharide (LPS), pam3CSK, and poly(I:C) via toll-like receptor 4 (TLR4), TLR2, and TLR3 pathways, respectively. In liver, both ARPGCB and GCB3004 produced similar toxicity profiles. In particular, these two formulas exhibited similar phospho-protein profiling of p65/nuclear factor $(NF)-{\kappa}B$, c-Jun/activator protein (AP)-1, ERK, JNK, p38, caspase 3, and bcl-2 in brain. In contrast, the patterns of these phospho-proteins were variable in other tissues. Moreover, these two formulas did not exhibit any cytotoxicity in C6 glioma cells. Finally, the two formulations at available in vivo concentrations did not block nitric oxide (NO) production from activated macrophage-like RAW264.7 cells stimulated with LPS, pam3CSK, or poly(I:C), nor did they alter the morphological changes of the activated macrophages. Taken together, our present work, as a comparative study of two different formulas of aripiprazole, suggests that these two formulas can be used to achieve similar functional activation of brain proteins related to cell survival and apoptosis and immunotoxicological activities of macrophages.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.183-192
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• 2023

Viral infections are known as one of the major factors causing death. Ginseng is a medicinal plant that demonstrated a wide range of antiviral potential, and saponins are the major bioactive ingredients in the genus Panax with vast therapeutic potential. Studies focusing on the antiviral activity of the genus Panax plant-derived agents (extracts and saponins) and their mechanisms were identified and summarized, including contributions mainly from January 2016 until January 2022. P. ginseng, P. notoginseng, and P. quinquefolius were included in the review as valuable medicinal herbs against infections with 14 types of viruses. Reports from 9 extracts and 12 bioactive saponins were included, with 6 types of protopanaxadiol (PPD) ginsenosides and 6 types of protopanaxatriol (PPT) ginsenosides. The mechanisms mainly involved the inhibition of viral attachment and replication, the modulation of immune response by regulating signaling pathways, including the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, cystathionine γ-lyase (CSE)/hydrogen sulfide (H₂S) pathway, phosphoinositide-dependent kinase-1 (PDK1)/ protein kinase B (Akt) signaling pathway, c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) pathway, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. This review includes detailed information about the mentioned antiviral effects of the genus Panax extracts and saponins in vitro and in vivo, and in human clinical trials, which provides a scientific basis for ginseng as an adjunctive therapeutic drug or nutraceutical.

• Nutritional Sciences
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• v.9 no.4
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• pp.267-272
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• 2006

The effect of methanol extract from Agaricus blazei Murill on the hepatotoxicity was investigated $CCl_4$ is one of the oldest and most widely used toxins for the induction of hepatic damages and fibrosis in experimental animals. In this study, male Sprague-Dawley(SD) rats were randomly divided into 6 groups of the control(C), $CCl_4(T),\;CCl_4$ and high fat group(TL) with matching sub-groups of Agaricus blazei Murill extract-fed groups of CA, TA and TLA. Methanol extracts of Agaricus blazei Murill were fed 50 mg/kg B.W daily via drinking water. A 1.2 mL of $CCl_4/kg$ body weight was administered by oral intubation twice a week for total of six times. The levels of total-cholesterol, TG, LDL and LDL-phospholipids were elevated by $CCl_4$ treatment as compared to the control(C). However, Agaricus blazei Murill methanol extract feeding in the group of TA and TLA significantly(p<0.05) decreased TG by 53.1 % and 17.9% compared to the internal control of T and TL, respectively. Triglyceride of TL was increased by 3.33 times(p<0.05) compared to the control(C) with $CCl_4$ and high fat administration from 3.78 mg/g to 12.60 mg/g liver. The extract(CA) also reduced kidney weight compared to the control(C). With the administration of high fat and $CCl_4$(TLA), the extract reduced the organ weight of both liver and kidney and further, significantly reduced TG, total cholesterol and GTP activity. Hepatoprotective effects of Agaricus blazei Murill on GOT, GPT, AP and LDH activities were enhanced by the extract feeding. Electronmicrograph showed that $CCl_4$ deteriorated the structure of cytoplasmic matrix with its uneven distribution. However, the extract reconstituted the damaged cytoplasm and stimulated mitochondriogenesis. The above results suggest that Agaricus blazei Murill may have a possible protective effect against chemically induced liver damage and further help to reduce the symptoms of fatty liver.

• The Journal of Pediatrics of Korean Medicine
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• v.28 no.2
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• pp.23-39
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• 2014

Objectives PRAL (Prunus armniaca Linne Var) is a herbal formula in Oriental Medicine, known for its anti-inflammatory and anti-allergenic properties. However, its mechanism of action and the cellular targets have not yet been found enough. The purpose of this study is to investigate the effects of PRAL on Th2 cytokines expression in MC/9 mast cells. Methods The effect of PRAL was analyzed by ELISA, Real-time PCR, Western blot in MC/9 mast cells. mRNA levels of GM-CSF, IL-4, IL-5, IL-6, IL-13, TNF-${\alpha}$ were analyzed with Real-time PCR. Levels of IL-13, MIP-$1{\alpha}$ were measured using enzyme-linked immunosorbent assays (ELISA). NFAT, AP-1 and NF-${\kappa}B$ p65 were examined by Western blot analysis. Results PRAL inhibited GM-CSF, IL-4, IL-5, IL-6, IL-13, TNF-${\alpha}$ mRNA expression in a dose dependent manner. GM-CSF, IL-4, IL-5 mRNA expression were inhibited significantly in comparison to DNP-IgE control group at concentration of 100 ${\mu}g/ml$ and IL-6, IL-13, TNF-${\alpha}$ mRNA expression were inhibited at concentration of 50 ${\mu}g/ml$, 100 ${\mu}g/ml$. PRAL also inhibited the IL-13, MIP-$1{\alpha}$ production significantly in comparison to DNP-IgE control group in a dose dependent manner. IL-13 production was inhibited at a concentration of 200 ${\mu}g/ml$, 400 ${\mu}g/ml$ and MIP-$1{\alpha}$ was inhibited at a concentration of 100 ${\mu}g/ml$, 200 ${\mu}g/ml$, 400 ${\mu}g/ml$. Western blot analysis of transcription factors involving Th2 cytokines expression revealed prominent decrease of the mast cell specific transcription factors including NFAT-1, c-Jun as well as NF-${\kappa}B$ p65 but not NFAT-2 and c-Fos. Conclusion These results indicate that PRAL has the effect of suppressing Th2 cytokines production in the MC/9 mast cells. These data represent that PRAL potentiates therapeutic activities to the allergic disease by regulating Th2 cytokines in the MC/9 mast cells.