Effect of a Ginkgolide Mixture (Bn 52063) in Antagonising Skin and Platelet Responses to Platelet Activating Factor in Man

Chung, Kian Fan; McCusker, Monica; Page, Clive; Dent, Gordon; Guinot, Philippe; Barnes, Peter J.

doi:10.1016/s0140-6736(87)90066-3

Cited by 258 publications

(86 citation statements)

References 18 publications

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“…In comparison to our findings, BN 52063 showed an inhibitory effect on weal-and-flare response to intradermal injection of PAF and in vitro PAF-induced platelet aggregation [18]. However, one of the most investigated PAF-receptor antagonists, WEB 2086, did not alter allergen challenge responses [19,20], or show differences when compared to placebo, in reducing glucocorticosteroid demands in atopic asthmatics [21].…”

Section: Discussioncontrasting

confidence: 80%

Effect of a platelet-activating factor (PAF) antagonist, SR 27417A, on PAF-induced gas exchange abnormalities in mild asthma

Roca²,

Barberà³

et al. 1998

Eur Respir J

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Platelet-activating factor (PAF) [1] is a potent etherlinked phospholipid mediator of inflammation which is considered to have a potential role in the pathogenesis of bronchial asthma. Recently, we have shown that PAF (dosage range 24-12 µg) disturbed pulmonary gas exchange in normal individuals [2][3][4] and in patients with mild asthma [5,6] in an identical manner to the entire spectrum of ventilation-perfusion (V 'A/Q ') mismatching shown in patients with bronchial asthma [7,8]. We suggested that the V 'A/Q ' defects could be preferentially related to an augmented bronchial vascular permeability due to post-capillary venoconstriction induced by PAF, thereby supporting the notion that PAF may play a key role, as a putative potent mediator of inflammation in human airways [5,8]. However, negative results have been obtained over the last few years, in stable patients with mild to moderate asthma with different PAF antagonists, and these question the role of PAF in the pathobiology of asthma.The compound SR 27417A (N-(2-dimethylaminoethyl)-N-(pyridinylmethyl)(4-(2,4,6 triisopropylphenyl) thiazol-2-yl)) amine difumarate is a novel class of anti-PAF medication that has been shown to be a potent, long-lasting and selective second generation PAF antagonist [9,10]. The present study was undertaken to assess the efficacy of this new PAF receptor antagonist, SR 27471A, in attenuating or preventing the PAF-induced systemic, neutropenic, lung mechanical and pulmonary gas exchange effects observed in patients with mild asthma [5,6]. To our knowledge, the efficacy of this class of anti-asthma compounds on pulmonary gas exchange abnormalities provoked by PAF has not been investigated previously. Methods Study populationTwelve patients with mild asthma (table 1) were recruited from our Outpatient Department for the study, which was approved by the Ethical Research Committee of the Hospital Clinic. All subjects gave informed written consent after the purpose, risks and potential benefits of the study were explained to them. The inclusion criteria were: no respiratory infection or exacerbation of asthma within the preceding 6 weeks; forced expiratory volume in one second (FEV1) Š80% predicted and positive methacholine bronchial challenge; maintenance therapy with aerosol short-acting beta-adrenergics and/or inhaled corticosteroids, but no previous treatment with oral corticosteroids; and absence of any systemic or cardiopulmonary disease We conclude that SR 27417A is effective in inhibiting systemic, cellular and pulmonary effects after platelet-activating factor challenge in patients with mild bronchial asthma.

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Section: Discussioncontrasting

confidence: 80%

Effect of a platelet-activating factor (PAF) antagonist, SR 27417A, on PAF-induced gas exchange abnormalities in mild asthma

Roca²,

Barberà³

et al. 1998

Eur Respir J

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“…It is also noteworthy that an advantage of using whole extracts seems likely to appear unexpected efficacy caused by unknown compounds in the whole extracts. Many studies have shown that such synergistic effects from unknown compounds in whole extracts occasionally render the crude extract more efficacious when comparing to a single compound isolated at the equivalent dose [8,18].…”

Section: Resultsmentioning

confidence: 99%

Extract from Prunus mume Sieb. et Zucc. Fruit Prevents LPS-induced Homotypic Aggregation of Monocytic THP-1 Cells via Suppression of Nitric Oxide Production and NF-κB Activation

Lee¹,

Park²,

Lee³

et al. 2015

Journal of Life Science

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Homotypic cell adhesion (homotypic aggregation) in activated monocytes plays a central role in physiological and pathological processes including inflammatory responses, differentiation and migration. The extract of the Prunus mume Sieb. et Zucc. fruit (Maesil) has potential benefits to human health; such as anti-viral, anti-microbial, and anti-cancer activities. Indeed, Maesil extract may modulate inflammatory responses via interference with homotypic aggregation in monocytes. In the present study, the molecular mechanisms underpinning the therapeutic efficacy of Maesil extract in inflammatory diseases were investigated. It was found that Maesil extract inhibited homotypic aggregation in lipopolysaccharide (LPS)-activated monocytes. This was mediated by reduction of nitric oxide (NO) production, partly via inhibition of inducible nitric oxide synthase (iNOS) expression in LPS-activated THP-1 cells. It was confirmed that NO inhibition is a key mechanism in Maesil induced blockade of monocyte aggregation through identification of reversal of this inhibitory effect by the NO-producing agent S-nitroso-N-acetyl penicillamine (SNAP). In addition, Maesil extract significantly attenuated LPS-induced IκB-α phosphorylation and NF-κB translocation into the nucleus. In conclusion, Maesil extract exerts anti-inflammatory effects via inhibition of homotypic aggregation of LPS-activated monocytes through mechanisms involving the suppression of NO production and NF-κB activity, suggesting Maesil extract as a potential therapeutic candidate for the prevention and treatment of chronic inflammatory diseases.

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“…BN 52021 has been tested in man for its ability to inhibit skin and platelet responses to Paf. At the maximal dose tested (120mg orally), partial suppression of Paf-induced weal and flare and ex vivo platelet aggregation were observed (Chung et al, 1987).…”

Section: Discussionmentioning

confidence: 97%

Antagonism of Paf‐induced oedema formation in rabbit skin: a comparison of different antagonists

Hellewell

Williams

1989

British J Pharmacology

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Effect of a Ginkgolide Mixture (Bn 52063) in Antagonising Skin and Platelet Responses to Platelet Activating Factor in Man

Cited by 258 publications

References 18 publications

Effect of a platelet-activating factor (PAF) antagonist, SR 27417A, on PAF-induced gas exchange abnormalities in mild asthma

Effect of a platelet-activating factor (PAF) antagonist, SR 27417A, on PAF-induced gas exchange abnormalities in mild asthma

Extract from Prunus mume Sieb. et Zucc. Fruit Prevents LPS-induced Homotypic Aggregation of Monocytic THP-1 Cells via Suppression of Nitric Oxide Production and NF-κB Activation

Antagonism of Paf‐induced oedema formation in rabbit skin: a comparison of different antagonists

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