• Title/Summary/Keyword: Immune Activation

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Inhibitory Effect of Dioscorea Bulbifera MeOH Extract on Pro-inflammatory Mediator In Vitro and In Vivo (황약자(黃藥子) 메탄올 추출물의 염증억제 효과)

  • Jung, Ji-Yun;Lee, Jong-Rok;Byun, Sung-Hui;Jung, Ji-Wook;Kim, Yong-Han;Kim, Sang-Chan
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.2
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    • pp.310-318
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    • 2010
  • Dioscorea bulbifera is one of the traditional medicinal herb. It commonly used in the treatment of hematemesis, epistaxis, tuberculous cervical lymphadenitis, laryngitis, acute infectious disease in East Asia. In the present study, we have demonstrated the anti-inflammatory effects of Dioscorea bulbifera MeOH extract (DBME) in macrophage cell line. To investigate mechanism of the anti-inflammatory activity, we examined the effects of the lipopolysaccaride (LPS)-induced production of nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), pro-inflammatory cytokines and expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), p-inhibitory ${\kappa}B{\alpha}$ (p-$I{\kappa}B{\alpha}$), and nuclear factor-${\kappa}B$ (NF-${\kappa}B$) in a murine macrophage cell line RAW 264.7. The RAW 264.7 cells were cultured in DMEM + serum medium for 24 hrs. After serum starvation for 24 hrs, the cells were treated with DBME 0.03, 0.10, 0.30 mg/$m{\ell}$ for 1 h, followed by stimulation with LPS (1 ${\mu}g/m{\ell}$) for activation of immune response. After treatment, cell viability was measured by MTT assay, and NO production was monitored by measuring the nitrite content in culture medium. The protein band of iNOS, COX-2, p-$I{\kappa}B{\alpha}$, and NF-${\kappa}B$ was determined by immunoblot analysis and levels of cytokine were analyzed by sandwich immunoassays. There were three experimental groups: carrageenan, DBME 0.3, 1.0 g/kg. Rats were administrated either carrageenan (40% PEG) or carrageenan + DBME (0.3, 1.0 g/kg body weight) for 4 days (p.o.). To induce acute paw edema, rats were injected 1% carrageenan (100 ${\mu}{\ell}$/rat, dissolved in sterilized saline). The effect of DBME in the carrageenan-induced rat paw edema. As results, DBME has an inhibitory effect on the production of NO, PGE2, TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 and on the expression of iNOS, COX-2, p-$I{\kappa}B{\alpha}$ and translocation of NF-${\kappa}B$ to nuclear from cytosol. In addition, DBME effectively inhibited the increases of paw edema induced by carrageenan treatment in vivo. These results suggest that DBME can inhibit production of pro-inflammatory mediators and might be a useful source for treatment of acute inflammatory disease.

Th 17 Cells and Nesfatin-1 are associated with Spontaneous Abortion in the CBA/j×DBA/2 Mouse Model

  • Chung, Yiwa;Kim, Heejeong;Im, Eunji;Kim, Philjae;Yang, Hyunwon
    • Development and Reproduction
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    • v.19 no.4
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    • pp.243-252
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    • 2015
  • The pregnancy and abortion process involves a complex mechanism with various immune cells present in the implantation sites and several hormones associated with pregnancy, such as leptin, ghrelin and nesfatin-1. However, the mechanism underlying spontaneous abortion by maternal T helper 17 (Th17) present in the implantation sites and nesfatin-1, which is of anorexigenic hormones, is not fully understood so far. Therefore, the purpose of this study was to examine the possible roles of Th17 cells present in the implantation sites and nesfatin-1 expressed in the uterus on spontaneous abortion using the $CBA/j{\times}DBA/2$ mouse model. Th17 transcription factor, ROR-${\gamma}t$ mRNA expression was significantly increased in the abortion sites compared with the implantation sites of abortion model mice on day 14.5 and 19.5 of pregnancy. In addition, the expression levels of IL-17A mRNA were significantly higher in abortion sites than in implantation sites on day 14.5 and 19.5. Moreover, the nesfatin-1/NUCB2 protein and mRNA levels were increased in abortion sites compared with levels in implantation sites of both normal pregnant and abortion model mice on day 14.5 of pregnancy. Interestingly, nesfatin-1/NUCB2 serum levels were not changed throughout the whole pregnancy in abortion model mice, but its serum level was dramatically increased on day 14.5, and then rapidly decreased on day 19.5 in normal pregnant mice. In this study, we showed for the first time the expression of nesfatin-1/NUCB2 mRNA and protein in implantation sites during pregnancy. The present results suggest that Th17 cells in the uterus may play an important role in the period of implantation and for maintenance of pregnancy. Furthermore, the present results suggest that Th17 cells in implantation sites may be a key regulator for maintenance of pregnancy and provides evidence that activation of these cells may be regulated by nesfatin-1/NUCB2. Further study is needed to elucidate the role of nesfatin-1 expressed in the uterus during pregnancy.

Inflammation and Insufficient or Disordered Sleep (염증 반응과 수면 장애)

  • Lee, Suk Jun;Kim, Jinkwan
    • Korean Journal of Clinical Laboratory Science
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    • v.47 no.3
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    • pp.97-104
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    • 2015
  • Sleep is not only an essential physiological function, but also serves important roles in promoting growth, maturation, and overall health of humans. There is increasing interest regarding the impact of sleep and its disorders on the regulation of inflammatory processes and end-organ morbidities, particularly in the context of metabolic and cardiovascular diseases (CVD) and their complications. Obstructive sleep apnea syndrome (OSAS) is an increasingly common health problem in children. In the last decade, the emergence of increasing obesity rates has further led to remarkable increases in the prevalence of OSAS, along with more prominent neurocognitive, behavioral, cardiovascular and metabolic morbidities. Although the underlying mechanisms leading to OSAS-induced morbidities are likely multifactorial and remain to be fully elucidated, activation of inflammatory pathways by OSAS has emerged as an important pathophysiological component of the end-organ injury associated with this disorder. To this effect, it would appear that OSAS could be viewed as a chronic, low-grade inflammatory disorder. Furthermore, the concurrent presence of obesity and OSAS poses a theoretically increased risk of OSAS-related complications. In this study, we will critically review the current state of research regarding the impact of insufficient and disrupted sleep and OSAS on the immune processes and inflammatory pathways that underlie childhood OSAS as a distinctive systemic inflammatory condition in children, and will explore potential interactions between OSAS and obesity.

Anti-cancer Properties and Relevant Mechanisms of Cordycepin, an Active Ingredient of the Insect Fungus Cordyceps spp., (동충하초 유래 cordycepin의 항암 활성 기전 최근 연구 동향)

  • Jeong, Jin-Woo;Choi, Yung Hyun
    • Journal of Life Science
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    • v.25 no.5
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    • pp.607-614
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    • 2015
  • Cancers are the largest cause of mortality and morbidity all over the world. Cordycepin, an adenosine analog, is a major functional component of the Cordyceps species, which has been widely used in traditional Oriental medicine. Over the last decade, this compound has been reported to possess many pharmacological properties, such as an ability to enhance immune function, as well as anti-inflammatory, antioxidant and anti-cancer effects. Recently, numerous studies have reported interesting properties of cordycepin as a chemopreventive agent as well. There is an accumulating body of experimental evidences suggesting that cordycepin impedes cancer progression by promoting apoptosis, inducing cell cycle arrest, modulating intracellular signaling pathways, and inhibiting invasion and metastasis of cancer cells. In many cancer cell lines, cordycepin inhibits growth and cell cycle progression by inducing arrest of the G2/M phase, resulting from the inhibition of retinoblastoma protein phosphorylation and induction of cyclin-dependent kinase inhibitors. To induce apoptosis, cordycepin activates the extrinsic and intrinsic pathways, which promotes reactive oxygen species generation and the downstream activation of kinase cascades. Cordycepin also can activate alternative pathways to cell death such autophagy. In addition, cordycepin can inhibit the pro-metastatic processes of cancer cell detachment, migration, and invasion through a variety of mechanisms, including the nuclear factor-kappa B and activated protein-1 signaling pathways. In this review, we summarized the variety of action mechanisms by which cordycepin may mediate chemopreventive effects on cancer and discussed the potential of this natural product as a promising therapeutic inhibitor of cancer development.

Anti-obesity and Anti-inflammation Effects of Cheonggukjang in C57Bl/6 mice with High Fat Diet Induced Obesity (고지방식이로 유도된 비만 마우스에서 청국장의 항비만 및 항염증 효과)

  • Kim, Jiyoung
    • Journal of Life Science
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    • v.27 no.11
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    • pp.1357-1368
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    • 2017
  • The purpose of this study was to investigate the anti-obesity and anti-inflammation effect of the cheonggukjang (a soybean paste fermented for only a few days) in diet induced obesity mice. Weight gain was significantly decreased in the mice fed cheonggukjang compared High Fat Diets (HFD). The HFD plus cheonggukjang (CGJ) were also effective in improving the lipid metabolism. The levels of plasma triglyceride, cholesterol, ALT, AST, leptin, glucose, and insulin were significantly lower in CGJ than HFD group (p<0.05). The adiponectin level of CGJ group was significantly increased compared to the HFD group (p<0.05). In the CGJ group, the mRNA expression of adipogenic genes in the liver and adipose tissues, which are transcription factors crucial for adipogenesis, were significantly suppressed (p<0.05). The number of $CD11b^+F4/80^+$ T cells, $Gr-1^{int}CD11b^{high}$ cells, and $Gr-1^{int}CD11b^{high}$ cells were significantly higher in HFD group than CGJ group (p<0.05). The size of adipocyte was significantly reduced in CGJ group compared to HFD group. In addition, the contents of liver lipid droplets were significantly downregulated in the CGJ mice than HFD mice (p<0.05). Collectively, these data suggest the novel function of cheonggukjang in modulating adipogenesis through an immune function-alteration involving downregulation of adipogenic transcription factors and macrophage activation.

Application model research on visualizing anti-inflammation effects by using the virtual cell (가상세포를 활용한 항염증 효능 응용모델 연구)

  • Kim, Chul;Yea, Sang-Jun;Kim, Jin-Hyun;Kim, Sang-Kyun;Jang, Hyun-Chul;Kim, An-Na;Nam, Ky-Youb;Song, Mi-Young
    • Herbal Formula Science
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    • v.18 no.2
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    • pp.227-239
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    • 2010
  • Objective : The purpose of this study was to develop the simulator which can analyze the anti-inflammatory effects of herbs based on e-cell, or the virtual cell. Method : We have ensured the medical herbs and its active compounds by investigating the oriental medicine records and NBCI(Biomedicine database). Also we have developed the web-based search system for confirming database related to anti-inflammation. We have researched the cell signal pathway related with inflammatory response control and established the mathematical model of herb interaction on selected signal pathway in e-cell. Finally we have developed the prototype which can confirm the result of this model visibly. Results : We constructed the database of 62 cases of anti-inflammatory active compounds in 61 cases of medical herbs which have been known anti-inflammation effects in the paper, 16 cases of inflammatory factors, 10 cases of signal pathways related with inflammatory response and 6,834 cases of URL(Uniform Resource Locator) of referenced papers. And we embodied the web-based research system, which can research this database. User can search basic and detailed information of medical plants related with anti-inflammatory by using information system. And user can acquire information on an active compounds, a signal pathway and a link URL of related paper. Among investigated ten pathways, we selected NF-${\kappa}B$, which plays important role in activation of immune system, and we searched the mechanisms of actions of proteins which could be components of this pathway. We reduced total network into IKK-$I{\kappa}B$ - NF-${\kappa}B$, and completed mathematic modeling by using ordinary differential equations and response variables of $I{\kappa}B-NF-{\kappa}B$ signaling model network which is suggested by Baltimore Group. We designed OED(Ordinary Differential Equation) for response of IKK, $I{\kappa}B$, $NF-{\kappa}B$ in e-cell's cytoplasm and nucleus, and measured whether an active compound of medicinal plants which is inputted by an user would have a anti-inflammation effects in obedience to change in concentration over time. The proposed model was verified by using experimental results of the papers which are listed on NCBI.

Antimicrobial and Antioxidant Activities and Inhibition of Nitric Oxide Synthesis of Oak Wood Vinegar (참나무 목초액의 항균 및 항산화 활성과 일산화질소 합성 저해연구)

  • Jung, Il-Sun;Kim, Yu-Jung;Gal, Sang-Wan;Choi, Young-Ju
    • Journal of Life Science
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    • v.17 no.1 s.81
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    • pp.105-109
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    • 2007
  • This study was carried out to investigate the biological effects oak wood vinegar. Antimicrobial activity was tested in five microbial species at the concentration of 5 to $50{\mu}l$ of oak wood vinegar by paper disc method. Growth of P. oleovoranse, P. vulgaris, E. coli, S. aureus and Prevotella intermedia was inhibited at a dose of as low as $50{\mu}l$ of oak wood vinegar. Antioxidant activities were measured by using DPPH radical scavenging and SOD-like activity. DPPH radical scavenging and SOD-like activities were 90% and 65% at the concentration of $25{\mu}l\;and\;50{\mu}l$ of oak wood vinegar, respectively. Stimulation of the macrophages RAW264.7 cells with lipopolysaccharide (LPS) resulted in increased production of nitric oxide (NO) in the medium. However, the oak wood vinegar showed marked inhibition of NO synthesis in a dose-dependent manner. This result suggest that oak wood vinegar plays significant role for activation of immune system in the pathogenesis of inflammatory diseases.

Mode of Action of Antimicrobial Peptides Identified from Insects (곤충 유래 항균 펩타이드의 작용 기작)

  • Lee, Heejeong;Lee, Dong Gun
    • Journal of Life Science
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    • v.25 no.6
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    • pp.715-723
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    • 2015
  • Insects represent the largest class within the animal kingdom in terms of species number. Humans had been utilized insect in the broad area, including food, agriculture, industry, pharmaceuticals and so on. At present, insects are emerging as a leading group for identifying and extracting novel bioactive substances due to enormous number and a high nutritional value. Insects rely on a suite of systemic response to resist infection such as immune cells, hemocytes, activation of enzymes cascades, and antimicrobial peptide/protein. Among the substances, antimicrobial peptides (AMPs) are main components of potent antimircrobial innate defense system into the insect hemolymph. AMPs raise influential candidate as avenue to resolve the development of antibiotic-resistant microbial organism. Insect AMPs are classified into four main classes: cecropins, insect defensins, glycine/proline-rich peptides. Insect AMPs have been purified, over 150. In this review, AMPs derived from several insects were summarized including honey bee, dung beetle, butterfly and longicorn beetle. These peptides almost exhibited potent antimicrobial activities against human microbial pathogens without causing remarkable hemolysis to erythrocytes excluding melittin, and their mode of action(s) are based on disruption of the plasma membrane or fungal apoptosis. Therefore, study of insect AMPs is expected to be useful for designing novel therapeutic antimicrobial applications.

Apoptotic Cell Death of Human Leukemia U937 Cells by Essential Oil purified from Schisandrae Semen (오미자 종자 정유에 의한 인체백혈병 U937 세포의 apoptosis 유도)

  • Choi, Yung Hyun
    • Journal of Life Science
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    • v.25 no.2
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    • pp.249-255
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    • 2015
  • Schisandrae fructus [Schizandra chinensis (Turcz.) Baillon] is a medicinal herb widely used for treating various inflammatory and immune diseases in East Asian countries. The Schisandrae Semen essential oil (SSeo) from this plant has pharmacological activities, including antioxidant, antimicrobial, and antitumoral activities. Nevertheless, the biological activities and underlying molecular mechanisms of the potential anti-cancer effects of this oil remain unclear. In the present study, we investigated the potential inhibition of apoptosis signaling pathways by SSeo in human leukemia U937 cells and evaluated the underlying molecular mechanism. Exposure to SSeo resulted in a concentration-dependent growth inhibition due to apoptosis, which was verified by DNA fragmentation, the presence of apoptotic bodies, and an increase in the sub-G1 ratio. Induction of apoptotic cell death by SSeo was correlated with the down-regulation of members of the inhibitor of apoptosis protein (IAP) family (including X-linked inhibitor of apoptosis protein (XIAP), cIAP-1, and surviving) and anti-apoptotic Bcl-2, and with up-regulation of death receptor (DR) 4 and DR5, depending on dosage. SSeo treatment also induced Bid truncation, mitochondrial dysfunction, proteolytic activation of caspase-3, -8 and -9, and concomitant degradation of activated caspase-3 target proteins such as poly (ADP-ribose) polymerase. Taken together, these findings suggest that SSeo may be a potential chemotherapeutic agent for use in the control of human leukemia cells. Further studies are needed to identify its active compounds.

Antioxidant and Anti-Inflammatory Activities of Extracts of Traditional Medicinal Plants Mixtures 1 and 2 (약용식물 복합 추출물 TMP1과 TMP2의 항산화능과 염증 억제 효과)

  • Cho, Eun-Kyung;Choi, Young-Ju
    • Journal of Life Science
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    • v.21 no.4
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    • pp.596-603
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    • 2011
  • This study was conducted to investigate traditional medicinal plants (TMP) 1 and 2, two different multi-herbal mixtures consisting of 24 herbs. Regarding the contents of flavonoid compounds, the ethanol extract (EE) of TMP2 yielded the highest content of flavonoid compounds (40.981 mg/g), followed by EE of TMP1 (28.23 mg/g), hot water extract of TMP2 (WE, 10.046 mg/g), and WE of TMP1 (6.59 mg/g). Antioxidant activities of EE and WE of TMP1 and TMP2 were measured based on DPPH radical scavenging activity. At 1 mg/ml, the highest DPPH radical scavenging activity was shown in EE of TMP2 (96%), followed by EE of TMP1 (94%). Nitric oxide (NO) production by RAW264.7 macrophage cells stimulated with lipopolysaccharide (LPS) was reduced to 82, 77, 86, and 47% by addition of $500\;{\mu}g/ml$ of EE and WE of TMP1 and TMP2, respectively. These results were not due to the cytotoxicity of the extracts. NO synthesis was increased by 2.3, 3.6, 3.0, and 1.8 fold by addition of $500\;{\mu}g/ml$ of EE and WE of TMP1 and TMP2, respectively. These results show that medicinal plants play a significant role in antioxidative activity and activation of the immune system in the pathogenesis of inflammatory diseases, and different mixtures of the medicinal plants showed different effects.