• Title/Summary/Keyword: PAF

Search Result 178, Processing Time 0.027 seconds

Screening of Platelet Activating Factor(PAF) Antagonist from Medicinal Plants (수종의 생약으로부터 혈소판 활성화인자 길항제 검색)

  • Son, Kun-Ho;Kim, So-Hee;Jung, Keun-Young;Chang, Hyeun-Wook
    • Korean Journal of Pharmacognosy
    • /
    • v.25 no.2
    • /
    • pp.167-170
    • /
    • 1994
  • The platelet activating factor (PAF) is a newly discovered chemical mediator, the chemical structure of which is 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine. Since PAF has potent and broad activities, its pathophysiological roles have received much attention. To develope a new PAF antagonist from medicinal plants, extracts of twenty medicinal herb were screened using PAF receptor binding, $[^{14}C]$ serotonin release and platelet aggregation.

  • PDF

Gene Expression of Surfactant Protein A, Band C in Platelet-activating Factor(PAF) Treated Rats (Platelet-activating Factor 기도내 투여 후 Surfactant Protein A, B 및 C의 유전자 발현에 관한 연구)

  • Sohn, Jang-Won;Shin, Dong-Ho;Park, Sung-Soo;Lee, Jung-Hee
    • Tuberculosis and Respiratory Diseases
    • /
    • v.45 no.2
    • /
    • pp.369-379
    • /
    • 1998
  • Background: Platelet-activating factor(PAF) might play an important role in the development of acute respiratory distress syndrome. Since PAF induced lung injury is similar to changes of acute respiratory distress gyndrome, and abnormalities in surfactant function have been described in acute respiratory distress syndrome, the authors investigated the effects of PAF on the regulation of surfactant protein A, B and C mRNA accumulation Method: The effects of PAF on gene expression of surfactant protein A, B and C in 24 hours after intratracheal injection of PAF in rats. Surfactant protein A, B and C mRNAs were measured by filter hybridization. Results: The accumulation of SP-A mRNA in PAF treated group was significantly decreased by 37.1 % and 41.6%, respectively compared to the control group and the group treated with Lyso-PAF(p<0.025, p<0.01). The accumulation of SP-B mRNA in PAF treated group was decreased by 18.7% and 32.2 %, respectively compared to the control group and the group treated with Lyso-PAF but statistically not significant. The accumulation of SP-C mRNA in PAF treated group was significantly decreased by 30.7% and 38.5%, respectively compared to the control group and the group treated with Lyso-PAF(p<0.l, p<0.01). Conclusion: These findings represent a marked inhibitory effects of platelet-activating factor on surfactant proteins expression in vivo. This supports, in turn, 'platelet-activating factor might be related to pathogenesis of acute respiratory distress syndrome.

  • PDF

Inhibitory Effects of Herbal Medicines on the Platelet-Activating Factor(PAF) Receptor Binding

  • Kang, Young-Hwa
    • Natural Product Sciences
    • /
    • v.11 no.3
    • /
    • pp.131-135
    • /
    • 2005
  • Methanolic extracts of ninety-five medicinal plants were screened for platelet-activating factor (PAF) receptor binding inhibitory activity using rabbit platelet. Alpinia officinarum, Belamcanda chinensis, Leonurus heterophyllus, Pinus densiflora, Polygonatum sibiricum and Sambucus williamsii showed significant inhibitory effects on the platelet-activating factor (PAF) receptor binding.

PAF in Pulmonary Surfactant Contributes to Neutrophilic Oxidative Stress-Induced Acute Lung Injury of Rats Given LPS Intratracheally (흰쥐에서 내독소로 유도된 급성폐손상에서 surfactant내 PAF의 역할)

  • Lee, Young-Man
    • Journal of Life Science
    • /
    • v.22 no.10
    • /
    • pp.1352-1358
    • /
    • 2012
  • In acute lung injury (ALI) by lipopolysaccharide (LPS), the underlying cause of infiltration and migration of neutrophils into the alveoli is considered to be from increased production of platelet-activating factor (PAF) in the pulmonary surfactant lining the alveolar lumen. In this study I partially confirmed this concept. LPS increased lung leak and the infiltration of neutrophils in the lung of rats given LPS intratracheally. The migration of neutrophils into the lung, which had caused oxidative stress, was also morphologically identified. I verified that the metabolism of the pulmonary surfactant was affected and that there was increased production of PAF in the pulmonary surfactant, both of which are considered to contribute to ALI by LPS in rats.

Cytosolic Phospholipase A2 Activity in Neutrophilic Oxidative Stress of Platelet-activating Factor-induced Acute Lung Injury (Platelet-activating Factor에 의한 급성폐손상에서 호중구성 산화성 스트레스에 관여하는 Cytosolic Phospholipase A2 활성도의 변화)

  • Kwon, Young Shik;Hyun, Dae Sung;Lee, Young Man
    • Tuberculosis and Respiratory Diseases
    • /
    • v.63 no.6
    • /
    • pp.497-506
    • /
    • 2007
  • Background: The present investigation was performed in rats and isolated human neutrophils in order to confirm the presumptive role of the positive feedback loop of cytosolic phospholipase $A_2$ ($cPLA_2$) activation by plateletactivating factor (PAF). Methods: The possible formation of the positive feedback loop of the $cPLA_2$ activation and neutrophilic respiratory burst was investigated in vivo and in vitro by measurement of the parameters denoting acute lung injury. In addition, morphological examinations and electron microscopic cytochemistry were performed for the detection of free radicals in the lung. Results: Five hours after intratracheal instillation of PAF ($5{\mu}g/rat$), the lung leak index, lung myeloperoxidase (MPO) activity, the number of neutrophils and the concentration of cytokine-induced neutrophil chemoattractant (CINC) in bronchoalveolar lavage fluid were increased by PAF as compared with those of control rats. The NBT assay and cytochrome-c reduction assay revealed an increased neutrophilic respiratory burst in isolated human neutrophils following exposure to PAF. Lung and neutrophilic $cPLA_2$ activity were increased following PAF exposure and exposure to hydrogen peroxide increased $cPLA_2$ activity in the lung. Histologically, inflammatory findings of the lung were observed after PAF treatment. Remarkably, as determined by $CeCl_3$ cytochemical electron microscopy, increased production of hydrogen peroxide was identified in the lung after PAF treatment. Conclusion: PAF mediates acute oxidative lung injury by the activation of $cPLA_2$, which may provoke the generation of free radicals in neutrophils.

Role of Nuclear Factor (NF)-κB Activation in Tumor Growth and Metastasis (종양의 성장 및 전이에 있어서 NF-κB의 역할)

  • Ko, Hyun-Mi;Choi, Jung-Hwa;Ra, Myung-Suk;Im, Suhn-Young
    • IMMUNE NETWORK
    • /
    • v.3 no.1
    • /
    • pp.38-46
    • /
    • 2003
  • Background: Platelet-activating factor (PAF) induces nuclear factor $(NF)-{\kappa}B$ activation and angiogenesis and increases tumor growth and pulmonary tumor metastasis in vivo. The role of $NF-{\kappa}B$ activation in PAF-induced angiogenesis in a mouse model of Matrigel implantation, and in PAF-mediated pulmonary tumor metastasis were investigated. Methods: Angiogenesis using Matrigel and experimental pulmonary tumor metastasis were tested in a mouse model. Electrophoretic mobility shift assay was done for the assessment of $NF-{\kappa}B$ translocation to the nucleus. Expression of angiogenic factors, such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\alpha}$, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were tested by RT-PCR and ELISA. Results: PAF induced a dose- and time-dependent angiogenic response. PAF-induced angiogenesis was significantly blocked by PAF antagonist, CV6209, and inhibitors of $NF-{\kappa}B$ expression or action, including antisense oligonucleotides to p65 subunit of $NF-{\kappa}B$ (p65 AS) and antioxidants such as ${\alpha}$-tocopherol and N-acetyl-L-cysteine. In vitro, PAF activated the transcription factor, $NF-{\kappa}B$ and induced mRNA expression of $TNF-{\alpha}$, $IL-1{\alpha}$, bFGF, VEGF, and its receptor, KDR. The PAF-induced expression of the above mentioned factors was inhibited by p65 AS or antioxidants. Also, protein synthesis of VEGF was increased by PAF and inhibited by p65 AS or antioxidants. The angiogenic effect of PAF was blocked when anti-VEGF antibodies was treated or antibodies against $TNF-{\alpha}$, $IL-1{\alpha}$, and bFGF was co-administrated, but not by antibodies against $TNF-{\alpha}$, $IL-1{\alpha}$, and bFGF each alone. PAF-augmented pulmonary tumor metastasis was inhibited by p65 AS or antioxidants. Conclusion: These data indicate that PAF increases angiogenesis and pulmonary tumor metastasis through $NF-{\kappa}B$ activation and expression of $NF-{\kappa}B$-dependent angiogenic factors.

Stimulation of Platelet-Activating Factor (PAF) Synthesis in Human Intestinal Epithelial Cell Line by Aerolysin from Aeromonas encheleia

  • Nam In-Young;Cho Jae-Chang;Myung Hee-Joon;Joh Ki-Seong
    • Journal of Microbiology and Biotechnology
    • /
    • v.16 no.8
    • /
    • pp.1292-1300
    • /
    • 2006
  • Aeromonas encheleia, a potential human intestinal pathogen, was shown to infect a human intestinal epithelial cell line (Caco-2) in a noninvasive manner. The transcriptional profile of the Caco-2 cells after infection with the bacteria revealed an upregulated expression of genes involved in chloride secretion, including that of phospholipase A2 (PLA2) and platelet-activating factor (PAF) acetylhydrolase (PAFAH2). This was also confirmed by a real-time RT-PCR analysis. As expected from PLA2 induction, PAF was produced when the Caco-2 cells were infected with the bacteria, and PAF was also produced when the cells were treated with a bacterial culture supernatant including bacterial extracellular proteins, yet lacking lipopolysaccharides. Bacterial aerolysin was shown to induce the production of PAF.

Inhibitory Effects of Chinese Medicinal Plants on the Platelet-Activating Factor (PAF) Receptor Binding (중국 약용식물의 혈소판 활성화인자 수용체 결합 억제활성)

  • Kang, Young-Hwa
    • Korean Journal of Medicinal Crop Science
    • /
    • v.13 no.4
    • /
    • pp.178-181
    • /
    • 2005
  • Methanolic extracts of fifteen Chinese medicinal plants were screened for platelet-activating factor (PAF) receptor binding inhibitory activity using rabbit platelet. Campsis grandiflora, Dalbergia odorifera, Vaccaria segetalis and Zanthoxylum nitidum showed significant inhibitory effects on the platelet-activating factor (PAF) receptor binding. Campsis grandiflora, Dalbergia odorifera, Vaccaria segetalis and Zanthoxylum nitidum inhibited 52%, 56%, 70%, and 66% respectively at the concentration of 0.2 mg/ml.

Terpene-Strengthened Ginkgo biloba Extract as a Platelet-Activating Factor Antagonist

  • Quan, Zhe-Jiu;Moon, Tae-Chul;Yang, Ju-Hye;Chang, Hyeun-Wook;Park, Young-Hyun;Kim, Young-Ha;Lee, Kyung-Hee;Chi, Yeon-Sook;Lim, Hyun;Kim, Hyoung-Chun;Kim, Hyun-Pyo
    • Biomolecules & Therapeutics
    • /
    • v.14 no.3
    • /
    • pp.160-165
    • /
    • 2006
  • Since platelet-activating factor (PAF) is involved in inflammation, allergic response and anaphylactic shock, PAF receptor antagonists may have potential for controlling these disease conditions. The extract of the leaves of Ginkgo biloba having a higher content of terpenoids (12%) with flavonoids (24%) (YY1224) was prepared in order to obtain the increasing PAF antagonistic activity. As expected, YY1224 showed a higher PAF antagonistic binding affinity ($IC_{50}\;=\;0.09\;{\mu}g/ml$) using $[^3H]PAF$ and rabbit platelets as ligand and receptor source, compared with an $IC_{50}$ of $>\;100\;{\mu}g/ml$ by Egb 761, a standardized extract. YY1224 also showed a higher inhibitory activity against PAF-induced platelet aggregation and NO production from lipopolysaccharide-treated RAW 264.7 cells. In addition, it protected PAF-induced death in mice by oral administration at 15 mg/kg. All these results suggest that YY1224 may show favorable effects on PAF-related disorders.

Effect of Platelet Activating Factor on the Secretion of Progesterone in the Rabbit (혈소판 활성인자가 백서의 Progesterone 생성에 미치는 영향)

  • Cho, Soo-Hyun;Chung, Sung-Ro;Hwang, Yeoun-Young;Moon, Hyung
    • Clinical and Experimental Reproductive Medicine
    • /
    • v.19 no.1
    • /
    • pp.9-14
    • /
    • 1992
  • Platelet activating factor(PAF) has been reported to play a significant role in ovulation, establishment and maintnance of early pregnancy. The object of this study was to investigate the influence of PAF on progesterone secretion in rabbit by measurement of pheripheral blood concentration of progesterone. PAF had no effect on progesterone secretion and did not induce decidual reaction in nonovulatory rabbit. But 8th day of hCG induced pesudopregnant rabbit, PAF significantly increase progesterone secretion. Progesterone level was significantly increased at 0.5 and 4 hours after treatment with $10^{-8}$ M PAF on days 2, 4, 6, 8 of gestation as compared than those treated with normal saline. When PAF was injected 2 days after coitus, progesterone levels on days 4, 6, 10, 14 of gestation was significantly increased than those with saline injected group. These results suggest that PAF increase progesterone secretion from the hCG-primed ovary and during pregnancy in rabbit.

  • PDF