Comparison of three paf-acether receptor antagonist ginkgolides

Korth, Ruth-Maria; Nunez, Daniele; Bidault, Jocelyne; Benveniste, Jacques

doi:10.1016/0014-2999(88)90840-0

Cited by 35 publications

(19 citation statements)

References 24 publications

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“…Bilobalide (BB), ginkgolide A (GA), ginkgolide B (GB), ginkgolide C (GC), quercetin (QCT), kaempferol (KMF), and isorhamnetin (ISR) are the main compounds for quality control (QC) of GBTs. Flavonols in G. biloba leaf extracts have been proven to have scavenging free radical effects (EllnainWojtaszek et al, 2003), and terpene lactones are platelet-activating factor (PAF) antagonists (Korth et al, 1988). Du et al (2013) studied the biological effects of bioactive compounds in GBTs and showed that the flavonols, mainly including QCT, KMF, and ISR, have remarkable antioxidant effects, and terpene lactones have anti-platelet aggregation activity.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous determination by UPLC-MS/MS of seven bioactive compounds in rat plasma after oral administration of Ginkgo biloba tablets: application to a pharmacokinetic study

Wang

Liu

Kang

et al. 2014

J. Zhejiang Univ. Sci. B

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A rapid, reliable, and sensitive method was developed using ultra-performance liquid chromatographytandem mass spectrometry (UPLC-MS/MS) with an electrospray ionization (ESI) source for determination of seven bioactive compounds in rat plasma after oral administration of Ginkgo biloba tablets (GBTs). The method simultaneously detects bilobalide (BB), ginkgolide A (GA), ginkgolide B (GB), ginkgolide C (GC), quercetin (QCT), kaempferol (KMF), and isorhamnetin (ISR) for pharmacokinetic study. The analytes and internal standard (IS) were extracted from rat plasma by acetidin. An MS/MS detection was conducted using multiple reaction monitoring (MRM) and operating in the negative ionization mode. The calibration curve ranges were 5-500, 5-500, 2.5-250, 1-100, 1-100, 1-100, and 1-100 ng/ml for BB, GA, GB, GC, QCT, KMF, and ISR, respectively. The mean recovery of the analytes ranged from 68.11% to 84.42%. The intra-and inter-day precisions were in the range of 2.33%-9.86% and the accuracies were between 87.67% and 108.37%. The method was used successfully in a pharmacokinetic study of GBTs. The pharmacokinetic parameters of seven compounds were analyzed using a non-compartment model. Plasma concentrations of the seven compounds were determined up to 48 h after administration, and their pharmacokinetic parameters were in agreement with previous studies.

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Section: Introductionmentioning

confidence: 99%

Simultaneous determination by UPLC-MS/MS of seven bioactive compounds in rat plasma after oral administration of Ginkgo biloba tablets: application to a pharmacokinetic study

Wang

Liu

Kang

et al. 2014

J. Zhejiang Univ. Sci. B

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“…Several putative antagonists of Paf have recently been described, such as CV 3988 (Terashita et al, 1983), Kadsurenone , BN 52021, a chemically-defined extract from Ginkgo biloba (Braquet, 1984;Nunez et al, 1986; and the Ginkgolide-mixture BN 52063 (Guinot et al, 1986;Korth et al, 1988b). The Ginkgolides specifically inhibit platelet aggregation, produce a shift in Paf concentration-response curves and displace labelled Paf from platelets in a concentration-and time-dependent manner suggesting competition at the binding site (Korth et al, 1988b).…”

Section: Introductionmentioning

confidence: 99%

“…The Ginkgolides specifically inhibit platelet aggregation, produce a shift in Paf concentration-response curves and displace labelled Paf from platelets in a concentration-and time-dependent manner suggesting competition at the binding site (Korth et al, 1988b). Certain calcium channel antagonist drugs also inhibit Paf binding (Wade et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

“…Firstly, Paf elicits vascular effects even in the absence of blood cells (Casals-Stenzel, 1987a); secondly, endothelial cells possess Paf receptors with a higher affinity than those in platelets and thirdly, Paf receptor antagonists specifically inhibit vascular effects in vivo and in vitro (Guinot et al, 1986;Casals-Stenzel et al, 1987a;Hwang et al, 1986). The shape change, the Ca2 + flux and the release of prostacyclin from endothelial cells in response to Paf (Bussolino et al, 1985;Brock & Gimbrone, 1986;D'Humieres et al, 1986;Grigorian & Ryan, 1987;Hirafuji et al, 1988), as well as the Paf-mediated adherence of inflammatory cells (McIntyre et al, 1986;Kimani et al, 1988), could explain the important pathophysiological role of the mediator in allergy and inflammation (Chung & Barnes, 1988;Arnoux et al, 1988 Korth et al, 1988b). For binding studies platelets were incubated in Tyrode buffer containing Aspegic (0.1 mM) for 30 min before the last of three washing procedures.…”

Section: Introductionmentioning

confidence: 99%

“…The platelet count in the solution was adjusted to 1 x 109mlP' as determined with a Coulter Counter. Platelets for aggregation studies were prepared either by the method of Mustard et al (1972) or that described by Korth et al (1988b [2H]-Pafbinding studies in intact human platelets…”

Section: Introductionmentioning

confidence: 99%

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Interaction of the Paf antagonist WEB 2086 and its hetrazepine analogues with human platelets and endothelial cells

Korth

Hirafuji

Keraly

et al. 1989

British J Pharmacology

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Intact platelets and confluent human umbilical vein endothelial cells bound [3H]‐Paf‐acether (platelet activating factor, [3H]‐Paf) at 20°C in the presence of 0.25% (w/v) bovine serum albumin (BSA). [3H]‐Paf binding to platelets was inhibited in a concentration‐dependent manner by WEB 2086. An excess of WEB 2086 indicated the presence of specific, saturable Paf binding which reached a maximum of 28.3 ± 3.7 fmol [3H]‐Paf per 5 × 107 platelets. In platelets, different hetrazepines (WEB 2098, 2105, but not 2118) also inhibited [3H]‐Paf binding in a concentration‐dependent manner. WEB 2086 partially displaced platelet‐bound [3H]‐Paf in a concentration‐dependent manner reaching a plateau at 400 nM WEB 2086. No further displacement was observed when WEB 2086 and an excess of unlabelled Paf were added together. The hetrazepines inhibited platelet aggregation. Platelet aggregation IC50 values correlated well with the IC50 values of the hetrazepines against [3H]‐Paf binding (r2 = 0.99). WEB 2086 shifted the Paf dose‐response curve rightwards in a parallel manner. Tested against platelet aggregation the pA2 obtained for WEB 2086 was 7.9. WEB 2086 inhibited [3H]‐Paf binding to endothelial cells in a concentration‐dependent manner. WEB 2086 also inhibited the Paf‐mediated cytosolic calcium increase in endothelial cells with an IC50 value of 23.1 ± 10.4 nM as compared with an IC50 of 21.6 ± 10.4 nM WEB 2086 for platelet aggregation. These results demonstrate an inhibition of [3H]‐Paf binding to platelets and endothelial cells by different hetrazepines, most probably at the Paf receptor level.

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