• Natural Product Sciences
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• v.7 no.2
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• pp.33-37
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• 2001

Methanol extracts of eighty Chinese medicinal plants were investigated for platelet-activating factor (PAF) receptor binding inhibitory activity using rabbit platelet. Extracts of Cratoxylon ligustrinum, Kalimeris indica, Euonymus japonica, Ophiopogon japonicus, Gleditsia sinensis, Clausena lansium, Agave sisalana were found to exhibit significant inhibitory effects. Chloroform partition of the Methanol extract of Kalimeris indica was further fractionated by column chromatography to afford one strong active subfraction with 93.6% inhibition at a concentration of $100{\mu}g/ml$.

• YAKHAK HOEJI
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• v.38 no.4
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• pp.462-468
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• 1994

Hot aqueous extracts of 130 herbal medicines were screened for platelet activating factor (PAE) receptor binding antagonistic activity using rabbit platelet. The results suggested that 4 medicinal plants including Biota orientalis are potential sources of PAF antagonists.

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.1-8
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• 1993

To elucidate involvement of platelet-activating factor (PAF) in cerebral ischemia-reperfusion injury, male Sprague-Dawley rats and albino mice of either sex were subjected to a 10-min bilateral carotid artery occlusion and 6-hr recirculation. The McGraw stroke index in mice was markedly inhibited by PAF antagonists, BN 52021 and CV 6209 (1 mg/kg, i.p., each) When they were administered 10 min before bilateral carotid artery occlusion or 1 hr after reperfusion. The increases in brain water content were significantly attenuated by treatment with BN 52021 or CV 6209 in both animals. BN 52021 exhibited a significant improvement in the postischemic blood pressure change in association with a beneficial effect on the delayed dilatation of pial arterioles after 10 min of ischemia. Thus it is suggested that PAF plays an important role as an endogenous mediator in development of cerebral ischemia-reperfusion injury, and further, specific antagonists to PAF will be able to prevent or reverse the pathological sequelae of cerebral ischemia.

• The Korean Journal of Physiology
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• v.29 no.2
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• pp.251-257
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• 1995

The objective of the present study was to test the effect of platelet-activating factor (PAF) on rat alveolar macrophages. PAF alone did not stimulate superoxide secretion from alveolar macrophages. However, PAF $(10^{-5}\;M)$ significantly enhanced phagocytic activator zymosan-induced superoxide secretion from alveolar macrophages. This enhancement of PAF plus zymosan was 30% above the sum of the separate effects of PAF and zymosan. Similarly, PAF $1.3{\times}(10^{-5}\;M)$ was not a direct stimulant of alveolar macrophages, as it had no stimulatory effect on chemiluminescence generation, but potentiated zymosan-induced activation of chemiluminescence, i.e., 162% above the separate effects of each stimulant. PAF $10^{-16}{\pm}10^{-6}\;M$ also failed to stimulate IL-1 production from alveolar macrophages. In contrast, when both PAF $10^{-10}\;M$ and lipopolysaccharide(LPS) $(1 {\mu}g/ml)$ were added together at the initiation of the culture, IL-1 production was significantly increased indicating the potentiative effects of PAF on IL-1 production by alveolar macrophages. Collectively, these data suggest that PAF alone does not activate the release of bioactive products from alveolar macrophages. However, PAF appears to act as a priming mediator that potentiates stimuli-induced macrophage activity. These novel actions of PAF prove its role as a potent mediator of inflammatory and immune responses in the lung.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.369-379
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• 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.

• YAKHAK HOEJI
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• v.39 no.1
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• pp.1-5
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• 1995

As a continuation of the previous study, a second group of sixty two aqueous extracts(freeze dried) from natural products was screened for the inhibitory effect of platelet activating factor(PAF) binding to rabbit platelet using 0.6 nM [$^{3}$H]PAF as a radioligand. The results demonstrated that three medicinal plants inhibited 40~50% of [$^{3}$H]PAF equilibrium binding at the concentration of 200 $\mu\textrm{g}$/ml.

• Journal of Yeungnam Medical Science
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• v.25 no.1
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• pp.41-49
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• 2008

Background : The central physiological derangement of hemorrhagic fever with renal syndrome (HFRS) caused by hantaan virus (HTNV) is a vascular dysfunction, manifested by hemorrhage, impaired vascular tone and increased vascular permeability. Platelet activating factor (PAF), whose actions are mediated through a specific receptor, is a potent bioactive lipid. PAF has diverse biological functions in the vascular system, such as increasing vascular permeability, adhesion of leukocytes to the endothelium and reduction of cardiac output, which result in hypotension and shock. The goal of the present study was to investigate whether PAF is involved in the pathogenesis of HFRS. For this purpose, we evaluated the effect of HTNV on the expression of PAF receptor (PAF-R) and on the activity of PAF-acetylhydrolase (PAF-AH) instead of PAF because PAF is rapidly degraded by PAF-AH in vivo. Materials and methods : To evaluate the expression of PAF-R, we performed reverse-transcription PCR, western blot and FACS analyses using HTNV-infected human umbilical vein endothelial cells (HUVECs) and non-infected (control) HUVECs. In addition, we measured the activity of plasma PAF-AH in HFRS patients and normal healthy persons. Results : The mRNA and protein expression of PAF-R was increased in HTNV-infected HUVECs compared with control HUVECs at 2 and 3 days post-infection (d.p.i.). FACS analysis showed that HTNV induced the surface expression of PAF-R in HUVECs from 2 d.p.i. The activity of plasma PAF-AH was 2.5-fold lower in HFRS patients than in normal healthy persons. Conclusion : Increased PAF-R expression by HTNV might increase the responsiveness to PAF in endothelial cells. Reduced PAF-AH activity in the blood of HFRS patients might delay PAF degradation. These results suggest that changes in PAF-R and PAF-AH by HTNV might influence to PAF activity and might be involved in the vascular dysfunction of HFRS.

• Journal of Embryo Transfer
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• v.6 no.1
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• pp.46-55
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• 1991

본연구의 목적은 흰쥐의 임신 초기에 있어서 착상의 유발에 PAF의 관련여부를 PAF의 수용체 길항제인 BN-52021d의 작용과 비교하여 결정하기 위함이다. 임신초기 각일에 점증하는 용량의 BN-52021 (체중 200g당 10$\mu$g 내지 1.25mg)이 근육내로 주사되었을때 10$\mu$g내지 250$\mu$g 용량에서는 대조구에 비하여 착상부위의 수 혹은 이것을 가진 흰쥐의 수에 대하여 현저한 영향을 미치지 아니하였으나 1.25mg투여 경우에는 현저히 감소된 효과를 나타내었다.(P<0.05). PAF(1$\mu$g) 경우에는 대조구와 비교하여 현저한 차이는 없었다. 임신 초기 각일에 BN-52021(1.25mg)과 검증하는 용량의 PAF(0.04$\mu$g 내지 1.0$\mu$g)가 동시에 투여된 경우에는 PAF의 농도가 증가함에 따라서 착상 부위의 수도 증가하는 경향이었으나 현저하지는 아니하였다. 본 실험 결과는 PAF는 흰쥐의 임신 초기 반응에 관련된다는 사실을 보여준다.

• Archives of Pharmacal Research
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• v.21 no.4
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• pp.436-439
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• 1998

In order to find out anti-platelet activating factor (PAF) from natural resources, Korean medicinal plants used for the treatments of peripheral circulation disorders were tested for their possible protective effects on PAF-induced anaphylactic shock. From the above screening, the methanol extract of Gentiana scabra showed a potent antagonistic activity against PAF. Water suspension of the extract was partitioned with $CH_2$$CI_2$ and EtOAc, successively. The EtOAc fraction which showed the highest activity was chromatographed on silica gel to yield 6 fractions. From the fraction which showed higher PAF-antagonistic activity than the other fractions, compound 1 was isolated by recrystallization. On the basis of spectral data, compound 1 was identified as 2-hydroxy-3-methoxybenzoic acid glucose ester. The compound prevented the mice from the PAF-induced death at a dose of 300 $\mu\textrm{g}$/mouse.

• Biomedical Science Letters
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• v.10 no.2
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• pp.143-151
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• 2004

Matrix metalloproteinases (MMPs) are capable of degrading extracellular matrix, a process that is necessary for angiogenesis, tumor invasion and metastasis. Platelet-activating factor (PAP) increases angiogenesis, tumor growth and metastasis through nuclear factor (NF)-$\kappa$B activation. Based on these facts, the involvement of MMPs in PAF-induced pulmonary metastasis was investigated in murine sarcoma cells, MMSV-BALB/3T3. Messenger RNA expression and enzymatic activity of MMP-9 were assessed by RT-PCR and zymography, and cell migration and metastasis were done for the detection of MMP-9 functional activity. PAP induced mRNA expression and enzymatic activity of MMP-9, and its effects were either inhibited by the PAP antagonist, WEB 2170 or by the NF-$\kappa$B inhibitor, parthenolide, or p65 antisense oligonucleotide in a dose-dependent manner. In addition, PAF induced promoter activity of MMP-9, which was inhibited by WEB 2170, phenanthroline, NAC, PDTC. These results indicate that PAF induces mRNA expression and enzymatic activity of MMP-9 in NF-$\kappa$B dependent manner. Cell migration assay showed that PAF induced MMSV-BALB/3T3 migration, and its effect was significantly inhibited by treatment with phenanthroline. PAF enhanced pulmonary metastasis of murine sarcoma cells, MMSV-BALB/3T3 was also reduced by phenanthroline. These results suggest that PAF-enhanced cell migration and pulmonary metastasis is mediated through the expression of MMP. In conclusion, It is suggested that PAF enhances pulmonary metastasis by inducing MMP-9 expression via the activation of NF-$\kappa$B.