Cardiac ultrastructural effects of the platelet-activating factor and its antagonist BN 52021

Kecskeméti, Valéria; Balogh, I

doi:10.1016/s0940-2993(11)80329-5

Cited by 5 publications

(3 citation statements)

References 22 publications

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“…It is thought that ginkgolide B (C 20 H 24 O 10 ) elicits cardiac protective properties against ischemic heart diseases and arrhythmias [3,9,10] possibly related to its capacity as a specific platelet activating factor (PAF) receptor antagonist. This is consistent with the beneficial effect of ginkgolide B in PAF-induced ischemic damage [11] . Nevertheless, the impact of ginkgolide B on heart function or cardiac electromechanical function is still uncertain.…”

Section: Introductionsupporting

confidence: 89%

Paradoxical effects of ginkgolide B on cardiomyocyte contractile function in normal and high-glucose environments

Kim

Fang

et al. 2006

Acta Pharmacologica Sinica

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Aim: Ginkgo biloba extract is a natural product used widely for cerebral and cardiovascular diseases. It is mainly composed of terpene lactones (ginkgolide A and B) and flavone glycosides (eg quercetin and kaempferol). To better understand the cardiac electromechanical action of Ginkgo biloba extract in normal and diabetic states, this study was designed to examine the effect of ginkgolide B on cardiomyocyte contractile function under normal and high‐glucose environments. Methods: Isolated adult rat ventricular myocytes were cultured for 6 h in a serum‐free medium containing either normal (NG; 5.5 mmol/L) or high (HG; 25.5 mmol/L) glucose with or without ginkgolide B (0.5–2.0 ug/mL). Mechanical properties were evaluated using the IonOptix MyoCam system. Contractile properties analyzed included peak shortening (PS), maximal velocity of shortening/relengthening (±dl/dt), time‐to‐PS (TPS) and time‐to‐90% relengthening (TR90). Levels of essential Ca2+ regulatory proteins sarco(endo)plasmic reticulum Ca2+‐ATPase (SERCA2a), phospholamban (PLB) and Na+‐Ca2+ exchanger (NCX) were assessed by Western blotting. Results: Ginkgolide B nullified HG‐induced prolongation in TR90. However, ginkgolide B depressed PS, ±dl/dt and shortened TPS in NG and HG cells. Ginkgolide B also prolonged TR90 in NG cells. Western blot analysis revealed that HG upregulated SERCA2a and downregulated PLB expression without affecting that of NCX. Ginkgolide B disrupted the NG‐HG response pattern in SERCA2a and NCX without affecting that of PLB. Conclusion: Ginkgolide B affects cardiomyocyte contractile function under NG or HG environments in a paradoxical manner, which may be attributed to uneven action on Ca2+ regulatory proteins under NG and HG conditions.

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Section: Introductionsupporting

confidence: 89%

Paradoxical effects of ginkgolide B on cardiomyocyte contractile function in normal and high-glucose environments

Kim

Fang

et al. 2006

Acta Pharmacologica Sinica

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“…Ginkgolide B (GB) could antagonize PAF receptors, preventing thus the ischemical damage of myocardial cells (Keeskemeti & Balogh, 2001). Experimental results obtained with GB revealed that it prevented cardiac arrhythmias induced by the ischemiareperfusion protocol (Wainwright et al, 1989;Koltai et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Electrocardiographic profile of guinea pig heart submitted to Ginkgo biloba extract and its terpenoids

Santos

Souza

Conde-Garcia

et al. 2014

Rev. bras. plantas med.

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Electrocardiographic effects produced by Ginkgo biloba extract (EGb) and by ginkgolides A (GA) and B (GB), and bilobalide (BB) were investigated in guinea pig heart mounted in Langendorff apparatus (Tyrode, 34 ± 0.1 o C, 95% O 2 , 5% CO 2 ). Electrocardiographic parameters were evaluated in the conditions: 1) control with Tyrode and DMSO, 2) EGb (n=4), GA (n=5), GB (n=5) or BB (n=6), and 3) washout. The results showed that 0.1 and 1.0 mg/ml of EGb do not change the electrocardiographic parameters. However, 10 mg/ml of EGb increased the PR interval (PRi) at 21% (p<0.001). This increase was also observed for 50 mM GA (20%, p<0.001) and 70 mM BB (13%, p<0.001), which indicates Ca 2+ channel block. However, the 50 mM GB reduced the PRi at 11 % (p<0.001). The GA (23%, p<0.001), GB (16%, p<0.001), and BB (40%, p<0.001) reduced the QT interval (QTi), which suggests the activation of the potassium channel. However, EGb increased QTi (6%, p<0.001). The EGb (28%, p<0.05) and GB (13%, p<0.05) reduced the heart rate. Atrioventricular (AV) block was observed with EGb, GA, and BB. We can conclude that EGb and its terpenoids alter the ECG parameters inducing AV block, which indicates possible arrhythmogenic potential.Keywords: Ginkgo biloba, ginkgolide A, ginkgolide B, bilobalide, heart. RESUMO. Perfil eletrocardiográfico do coração de cobaia submetido ao extrato de Ginkgo biloba e seus terpenóides. Os efeitos eletrocardiográficos produzidos pelo extrato de Ginkgo biloba (EGb) e gingkolídeos A (GA) e B (GB), e bilobalide (BB) foram investigados em coração de cobaia montado sistema de Langendorff (Tyrode, 34 ± 0.1 o C, 95% O 2 , 5% CO 2 ). Os parâmetros do ECG foram avaliados nas condições: 1) Tyrode e DMSO, 2) EGb (n=4), GA (n=5), GB (n=5) ou BB (n=6) diluídos em DMSO e 3) washout. Os resultados demonstram que 0,1 e 1,0 mg/ mL de EGb não alteraram os parâmetros eletrocardiográficos. Entretanto, 10 mg/ml de EGb aumentaram o intervalo PR (PRi) em 21% (p<0.001). Esse aumento também foi observado com GA a 50µM (20%, p<0,001) e BB a 70 mM (13%, p<0,001) indicando bloqueio de canais de cálcio. Por outro lado, GB reduziu o PRi (11%, p<0,001). O intervalo QT (QTi) foi reduzido por GA (23%, p<0,001), GB (16%, p<0,001) e BB (40%, p < 0.001) sugerindo uma ativação de canais de potássio. Entretanto, EGb aumentou o QTi (6%, p<0.001). A frequência cardíaca foi reduzida por EGb (28%, p<0.05) e GB (13%, p<0.05). Bloqueios átrio-ventriculares (BAV) foram observados com EGb, GA e BB. Podemos concluir que EGb e os terpenos alteram parâmetros eletrocardiográficos induzindo BAV e demonstrando possível potencial arritmogênico. Palavras-chave:Ginkgo biloba, ginkgolídeo A, ginkgolídeo B, bilobalide, coração.

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“…Ginkgolide B is one of the major constituents of the terpenoid fraction of GbE. Numerous studies demonstrate that ginkgolide B, as a specific antagonist of platelet-activating factor (PAF), presents beneficial effects on various PAF-related diseases and specially has neuroprotective effects in the CNS [3][4][5][6] . Recent evidence suggests that GbE protects against neuronal death in global brain ischemia and in glutamate-induced excitotoxicity [7] .…”

Section: Introductionmentioning

confidence: 99%

Effects of ginkgolide B on neuronal discharges in paraventricular nucleus of rat hypothalamic slices

Lin

Wang

et al. 2008

Neurosci. Bull.

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Objective To study the central role of ginkgolide B (BN52021) in regulating cardiovascular function of nerve center by examining the effects of ginkgolide B on the electrical activity of rat paraventricular nucleus (PVN) neurons in hypothalamic slice preparation and to elucidate the mechanism involved. Methods Extracellular single-unit discharge recording technique. Results (1) In response to the application of ginkgolide B (0.1, 1, 10 μmol/L; n = 27) into the perfusate for 2 min, the spontaneous discharge rates (SDR) of 26 (26/27, 96.30%) neurons were significantly decreased in a dose-dependent manner.(2) Pretreatment with L-glutamate (L-Glu, 0.2 mmol/L) led to a marked increase in the SDR of all 8 (100%) neurons in an epileptiform pattern. The increased discharges were suppressed significantly after ginkgolide B (1 μmol/L) was applied into the perfusate for 2 min. (3) In 8 neurons, perfusion of the selective L-type calcium channel agonist, Bay K 8644 (0.1 μmol/L), induced a significant increase in the discharge rates of 8 (8/8, 100%) neurons, while ginkgolide B (1 μmol/L) applied into the perfusate, could inhibit the discharges of 8 (100%) neurons. (4) In 8 neurons, the broad potassium channels blocker, tetraethylammonium (TEA, 1 mmol/L) completely blocked the inhibitory effect of ginkgolide B (1 μmol/L). Conclusion These results suggest that ginkgolide B can inhibit the electrical activity of paraventricular neurons. The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and potentially concerned with delayed rectifier potassium channel (K DR ).

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Cardiac ultrastructural effects of the platelet-activating factor and its antagonist BN 52021

Cited by 5 publications

References 22 publications

Paradoxical effects of ginkgolide B on cardiomyocyte contractile function in normal and high-glucose environments

Paradoxical effects of ginkgolide B on cardiomyocyte contractile function in normal and high-glucose environments

Electrocardiographic profile of guinea pig heart submitted to Ginkgo biloba extract and its terpenoids

Effects of ginkgolide B on neuronal discharges in paraventricular nucleus of rat hypothalamic slices

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