• Title/Summary/Keyword: 억제인자

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Anti-Inflammatory Effect of Licochalcone E, a Constituent of Licorice, on Lipopolysaccharide-Induced Inflammatory Responses in Murine Macrophages (Licochalcone E의 항염증 효과와 그 기전에 대한 연구)

  • Park, Geun-Mook;Jun, Jong-Gab;Kim, Jin-Kyung
    • Journal of Life Science
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    • v.21 no.5
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    • pp.656-663
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    • 2011
  • Licochalcone, a major phenolic constituent of the licorice species Glycyrrhiza inflata, a constituent of licorice, exhibits various biological properties, including chemopreventive-, antibacterial-, and anti-spasmodic activities. Recently, Licochalcone E (LicE) was isolated from the roots of Glycyrrhiza inflate, however its biological functions have not been fully examined. In the present study, we investigated the ability of LicE to regulate inflammation reactions in macrophages. Our in vitro experiments using murine macrophages, RAW264.7 cells, showed that LicE suppressed not only nitric oxide (NO) and prostaglandin $E_2$ generation, but also the expression of inducible NO synthase and cyclooxygenase-2 induced by lipopolysaccharide (LPS). Similarly, LicE inhibited the release of proinflammatory cytokines induced by LPS in RAW264.7 cells, including tumor necrosis factor-${\alpha}$ and interleukin-6. The underlying mechanism of LicE on anti-inflammatory action correlated with down-regulation of the nuclear factor-${\kappa}$B. Our data collectively indicate that LicE inhibited the production of several inflammatory mediators and might be used in the treatment of various inflammatory diseases.

Effects of Glucose Degradation Products on Human Peritoneal Mesothelial Cells (포도당분해산물이 사람 복막중피세포 활성화에 미치는 영향)

  • Song, Jae-Sook;Lee, Kyung-Lim;Ha, Hunjoo
    • Microbiology and Biotechnology Letters
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    • v.33 no.4
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    • pp.308-314
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    • 2005
  • Both high glucose and glucose degradation products (GDP) have been implicated in alterations of peritoneal membrane structure and function during long-term peritoneal dialysis (PD). The present study examined the role of GDP including methylglyoxal (MGO), acetaldehyde, and 3,4-dideoxyglucosone (3,4-DGE) in HPMC activation with respect to membrane hyperpermeability or fibrosis. The role of reactive oxygen species (ROS) and activation of protein kinase C (PKC) in GDP-induced HPMC activation were also examined. Using M199 culture medium as control, growth arrested and synchronized HPMC were continuously stimulated by MGO, acetaldehyde, and 3,4-DGE for 48 hours. Vascular endothelial growth factor (VEGF) was quantified as a marker of peritoneal membrane hyperpermeability and fibronectin and heat shock protein 47 (hsp47) as markers of fibrosis. Involvement of ROS and PKC was examined by the inhibitory effect of N-acetylcystein (NAC) or calphostin C, respectively. MGO significantly increased VEGF (1.9-fold), fibronectin (1.5-fold), and hsp47 (1.3-fold) secretion compared with control M199. NAC and calphostin C effectively inhibited MGO-induced VEGF upregulation. Acetaldehyde stimulated and 3,4-DGE inhibited VEGF secretion. Fibronectin secretion and hsp47 expression in HPMC were not affected by acetaldehyde or 3,4-DGE In conclusion, MGO upregulated VEGF and fibronectin secretion and hsp47 expression in HPMC, and PKC as well as ROS mediate MGO-induced VEGF secretion by HPMC. This implies that PKC activation and ROS generation by GDP may constitute important signals for activation of HPMC leading to progressive membrane hyperpermeability and accumulation of extracellular matrix and eventual peritoneal fibrosis.

Effect of dietary changes from high-fat diet to normal diet on breast cancer growth and metastasis (고지방식이에서 일반식이로의 전환이 유방암의 성장 및 전이에 미치는 영향)

  • Park, Seung hwa;Jung, InKyung;Kim, Jung-Hyun
    • Journal of Nutrition and Health
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    • v.53 no.4
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    • pp.369-380
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    • 2020
  • Purpose: It has been previously reported that breast tumor incidence, growth, and metastasis are stimulated by high-fat diet but reduced by caloric restriction. However, few studies have elucidated the effects of dietary change from a high-fat diet after breast cancer initiation. Therefore, in this study, we attempted to provide practical assistance to breast cancer prevention and management by investigating the effects of dietary change from a high-fat diet to normal diet on breast cancer growth and metastasis. Methods: The experimental animals were divided into 2 groups (high-fat diet control [HFC] group and diet restriction [DR] group) and consumed a high-fat diet for 8 weeks. 4T1 cells were transplanted into subcutaneous fat or tail vein to measure the growth and metastasis of breast cancer. The HFC and DR groups continuously ingested either high-fat diet or AIG-93G diet for 5 weeks or 3 weeks, respectively. Cell proliferation and apoptosis markers from tumor tissues were analyzed by Western blot analysis. The data were analyzed using the SPSS 25.0 package program. Results: The results show that the DR group significantly reduced breast tumor initiation, growth, and tumor tissue weight compared to the HFC group. The DR group suppressed tumor growth by decreasing proliferation and inducing apoptosis through down-regulation of Bcl-xL and up-regulation of caspase-3 activity. Furthermore, the DR group significantly reduced numbers of metastasized tumors in lung tissues. Conclusion: These results suggest that dietary change from a high-fat diet to normal diet decreased breast growth by reducing cell proliferation and inducing apoptosis and metastasis. Taken together, these results indicate that dietary change to a low-fat and balanced diet might suppress breast tumor growth and metastasis even after tumor diagnosis.

Effect of Calpain Inhibitors on $Ca^{2+}-Induced$ Suppression of Neurite Outgrowth in Isolated Hippocampal Pyramidal Neurons (해마추상체 신경세포에서 칼슘에 의한 신경섬유 성장억제에 대한 칼파인 억제제의 영향)

  • Song, Dong-Keun;Kater, Stanley B.;Mykles, Donald L.
    • The Korean Journal of Pharmacology
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    • v.29 no.2
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    • pp.165-174
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    • 1993
  • $Ca^{2+}$ is an important regulator of neurite elongation and growth cone movements but the mechanism(s) mediating these $Ca^{2+}-dependent$ effects is unclear. Since cytoskeletal proteins are rapidly degraded by $Ca^{2+}-dependent $ proteinases (calpains) in vitro and in vivo, we investigated whether $Ca^{2+}-induced$ pruning or regression of neuronal processes is mediated by calpains. Isolated hippocampal pyramidal-like neurons were cultured and the ability of the membrane-permeable calpain inhibitors EST (etyl (+)-(2S,3S)-3-[(S)-methyl-1-(3-methlbutylcarbamoyl)-butylcarbamoyl]2-oxiranecarboxylate) and MDL28170 (carbobenzoxyl-Val-Phe-H) to block the $Ca^{2+}$ ionophore A23187-induced suppression in neurite outgrowth was investigated. Addition of 100 nM A23187 to the culture medium resulted in a retraction of dendrites without altering axonal elongation. The addition of 300 nM A23187 to the culture medium resulted in a signiciant decrease in the rate of axonal elongation as well as a retraction of dendritic processes. Administration of EST $(5\;or\;20{\mu}M)$ to the culture medium completely blocked the pruning effect of 100 nM A23187 on dendrites and of 300 nM A23187 on axons, while EST alone did not significantly affect neurite outgrowth rate. MDL 28170 $(20\;{\mu}M)$ showed the same effect as EST in preventing ionophore-induced pruning of dendrites and axons at 100 nM and 300 nM concentrations, respectively, of A23187. EST $(20\;{\mu}M)$ did not block the A23187-induced rise of $[Ca^{2+}]_{i}$ as measured with fura-2. These results show that $Ca^{2+}-induced$ pruning of neurites in isolated hippocampal pyramidal neurons is mediated by calpains.

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Suppressive Effects of Chrysanthemum zawadskii var. latilobum Flower Extracts on Nitric Oxide Production and Inducible Nitric Oxide Synthase Expression (구절초 꽃 추출물의 Nitric Oxide 생성과 Inducible Nitric Oxide Synthase 발현 억제 효과)

  • Han, Ji-Young;Kim, Young-Hwa;Sung, Jee-Hye;Um, Yu-Rry;Lee, Yi;Lee, Jun-Soo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.12
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    • pp.1685-1690
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    • 2009
  • In this study, we investigated the effect of C. zawadskii extract on nitric oxide (NO) production, prostaglandin E2 (PGE2) production, protein and mRNA expression of inducible nitric oxide synthase (iNOS) in LPS-induced RAW 264.7 macrophage cells. C. zawadskii extract (5~50 μg/mL) significantly inhibited LPS-induced NO production in a concentration-dependent manner ranging from 23.3% to 100%. Consistent with the inhibitory effect on NO production, C. zawadskii extract inhibited the protein expression and mRNA expression of iNOS. Although flower extracts of C. zawadskii was not effective on the expression of PGE2 and COX-2, flower extracts of C. zawadskii, however, showed a strong anti-inflammatory activity through inhibition of NO production and iNOS expression. The present results suggest that C. zawadskii extract has an inhibitory effect on NO production, and thus can be used as an anti-inflammatory agent.

ACE Inhibitory Materials from Raja kenojei (홍어의 항고혈압 활성물질)

  • 임현수
    • Journal of Life Science
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    • v.13 no.5
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    • pp.668-674
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    • 2003
  • This study was carried out to investigate the ACE inhibitory materials of Raja kenojei. Raja kenojei was sperated to fillet and viscera, and these were extracted with hot water. Antihypertensive activity was examined by mesearing angiotensin converting enzyme ACE inhibitory activity. ACE inhibitory activity of viscera at the concentration of 2% for Day 0 showed the highest value by 71.0%. But ACE inhibitory activity of fillet at 2% showed by 29%, which was lower antihypertensive activity than viscera. The protein content of viscerial hot water extracts in proximate composition showed the highest. And also, there was a large amount of aromatic and branched aliphatic amino acids in viscera than those in fillet. For the purification of antihypertensive material in visceral hot water extracts, it was separated and collected by Sephadex G-25 gel chromatography. The fraction (B) of 111 to 160 showed the highest ACE inhibitory activity by 65.1% at the concentration of 0.05%. But the other fractions (A and C) showed lower activity than B. These results demonstrate that crude hot water extracts of viscera from Raj kenojei may be useful as functional food ingredient with antihypertensive property.

Mcl-1 is a Binding Partner of hNoxa (Mcl-1 단백질은 Noxa 단백질의 결합 파트너이다.)

  • Park, Sun-Young;Kim, Tae-Hyoung
    • Journal of Life Science
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    • v.17 no.8 s.88
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    • pp.1063-1067
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    • 2007
  • The Bcl-2 family proteins play critical roles in regulation of apoptosis, and the balanced interaction of pro- and anti-death members is a key factor in determining the cell fate. Noxa, a BH3-only Bcl-2-family member, has been originally identified as a target gene of p53. To understand the mechanism by which human Noxa (hNoxa) regulates the cell death, we screened the hNoxa binding partner using the yeast two hybrid screening and found that anti-death protein Mcl-1 binds to hNoxa. The binding of hNoxa to Mcl-1 was confirmed by immunoprecipitation in human colon cancer cell line HCT 116 cells. Mcl-1 significantly inhibited the hNoxa-induced cell death in HCT 116 cells. During the cell death induced by hNoxa, Mcl-1 protein was degraded. Its degradation was inhibited by z-VAD-fmk, a pancaspase inhibitor, suggesting caspase is responsible for Mcl-1 degradation in response to hNoxa. Together, the results indicate that hNoxa binds to Mcl-1 that is degraded by cas-pases during hNoxa-induced cell death.

Effects of Ethanol Extract from Lathyrus palustris on Anti-inflammation Response of RAW 264.7 Cell (RAW 264.7 대식세포 염증반응에 대한 털연리초 에탄올 추출물의 항염증 효과)

  • Nam, Jung Hwan
    • Korean Journal of Plant Resources
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    • v.33 no.4
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    • pp.287-292
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    • 2020
  • Lathyrus palustris often used as a treatment for inflammation of the kidneys in Korean traditional medication. Generally, drugs for arthritis have anti-inflammatory and antinociceptive properties. However, the validity of the anti-inflammatory effect has not been scientifically investigated so far. Therefore, the purpose of the research was to investigate the latent anti-inflammatory ability of L. palustris using the ethanol extract. To evaluate the anti-inflammatory activities, we examined the inflammatory arbitrators such as a nitric oxide (NO) and prostaglandin E2 (PGE2) on RAW 264.7 cells. Our results indicated that ethanol extract significantly inhibited the lipopolysaccharide E (LPS) derived PGE2 production in RAW 264.7 cell. The inhibitory activity of ethanol extract for PGE2 tests with inhibition ratio showed in 40 ㎍/mL. Overall, PGE2 tests had a higher inhibitory effect on inflammation than NO tests. This result anticipated that the ethanol extract from L. palustris is a good candidate for developing the origin of anti-inflammatory agents.

Inhibition of Cell Proliferation and Induction of Apoptosis by Ethanolic Extract of Lespedeza cuneata G. Don in Human Colorectal Cancer HT-29 cells (야관문의 에탄올 추출물에 의한 대장암세포의 성장억제 및 세포사멸유도)

  • Zhao, Qian;Kim, Yeah-Un;Han, In-Hwa;Yun, Jung-Mi
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.6
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    • pp.911-917
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    • 2016
  • Lespedeza cuneata G. Don is an edible perennial herb used in traditional Korean medicine. We investigated the anti-proliferative properties and mechanism of L. cuneata extract. The ethanolic extract of L. cuneata dose-and time-dependently inhibited human colorectal cancer cell proliferation. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to test the effect of the extract on proliferation of HT-29 colorectal cancer cells. The extract inhibited HT-29 cell proliferation with an $IC_{50}$ value of $554.26{\pm}8.81{\mu}g/mL$. L. cuneata extract suppressed production of pro-inflammatory cytokines interleukin-6 and tumor necrosis $factor-{\alpha}$. Apoptosis was evaluated by analysis of DNA fragmentation, poly(ADP-ribose) polymerase cleavage, caspase-3 activity, and protein expression of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2). Our results demonstrated that the extract induced DNA fragmentation and characteristic morphological changes associated with apoptosis in HT-29 colorectal cancer cells. The extract also time- and dose-dependently up-regulated expression of the Bax and down-regulated expression of the Bcl-2. Furthermore, the extract dose- and time-dependently enhanced caspase-3 activity. Our findings provide evidence that L. cuneata extract may mediate its anti-proliferative effect via modulation of apoptosis.

Interleukin-$1{\beta}$ induces bone resorption by regulation of prostaglandin $E_2$ synthesis and plasminogen activator activity, and TGF-$\beta$ inhibits bone resorption of rat bone cells (쥐의 골세포에서 $PGE_2$ 합성과 plasminogen activator 활성 조절에 의한 IL-$1{\beta}$의 골 흡수유도와 TGF-$\beta$에 의한 골 흡수 억제 기전에 관한 연구)

  • Kim, Young-Hun;Lee, Young-Jun;Chung, Kyu-Rhim;Park, Young-Guk
    • The korean journal of orthodontics
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    • v.30 no.6 s.83
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    • pp.713-721
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    • 2000
  • Bone cells produce multiple growth factors and cytokines that have effects on bone metabolism and can be incorporated into the bone matrix. The present study was designed to extend these observations by examining the interactions between transforming growth factor-$\beta$(TGF-$\beta$) or interleukin-$1\beta$(rhIL-$1\beta$) and bone cells in a rat long bone culture model. IL-$1\beta$ regulates several activities of the osteoblast cells derived from rat long bone explants in vitro. IL-$1\beta$ stimulated cellular proliferation as well as the synthesis of prostaglandin $E_2$ and Plasminogen activator activity in the cultured cells in a dose-dependent manner. TGF-$\beta$ is present in the bone matrix and potentially released during bone resorption. TGF-$\beta$ reduced basal bone resorption and inhibited vitamin $D_3[1,25(OH)_2D_3]$-induced bone resorption in rat long bone cells. These results support the role of IL-$1\beta$ in the pathological modulation of bone cell metabolism, with regard to implication in the Pathogenesis of osteoporosis by IL-$1\beta$, and that TGF-$\beta$ positively inhibits the bone resorption.

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