Effect of curcumin on platelet aggregation and vascular prostacyclin synthesis

In vitro and ex vivo effects of 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (diferuloylmethane, curcumin) and acetylsalicylic acid (ASA) on the synthesis of prostacyclin (PGI2) and on platelet aggregation has been studied in rat. Both drugs inhibited adenosine diphosphate (ADP)-, epinephrine (adrenaline)- and collagen-induced platelet aggregation in monkey plasma. Pretreatment with ASA (25-100 mg/kg), but not curcumin (100-300 mg/kg), inhibited PGI2 synthesis in rat aorta. In the in vitro system, too, curcumin caused a slight increase in the synthesis of PGI2, while ASA inhibited it. Curcumin may, therefore, be preferable in patients prone to vascular thrombosis and requiring antiarthritic therapy.     

Inhibition of arterial PGI2 generation and platelet aggregation by aspirin in rabbits ex vivo

In 63 rabbits the generation of prostacyclin (PGI2) by coeliac and mesenteric arteries and arachidonate-induced platelet aggregation in platelet rich plasma (PRP) were studied at 24th, 48th and 72nd hour after oral administration of single doses of acetyl salicylic acid (ASA) (15, 25 and 50 mg/kg). Only at the lowest dose ASA caused a selective inhibition of platelet cyclo-oxygenase. ASA at this dose had a cumulative inhibitory effect on arterial cyclo-oxygenase when it was administered in an ineffective single daily dose during three days every 24h. It is concluded that in vivo ASA can be hardly considered as a preferential inhibitor of platelet cyclo-oxygenase.     

Adrenergic modulation of vascular prostacyclin (PGI2) secretion

An in vitro model for the study of adrenoreceptor-prostacyclin (PGI2) relationships in the rat aorta is described. PGI2 synthesis was stimulated by adrenergic agonists (rank order of potency: epinephrine greater than norepinephrine greater than phenylephrine greater than methoxamine). Isoproterenol, UK 14304, clonidine and salbutamol were without effect. Epinephrine (3 X 10(-7) M)-stimulated PGI2 synthesis was inhibited by adrenoreceptor antagonists (rank order of potency: yohimbine greater than prazosin greater than phentolamine greater than corynanthine much greater than propranolol). The absence of calcium in incubation media abolished epinephrine-stimulated PGI2 synthesis as did the calcium channel blocker, verapamil, in a dose-dependent manner. Calcium ionophore A23187 (10(-5) M)-stimulated PGI2 synthesis was inhibited by verapamil (in a dose-dependent manner), but not by prazosin, phentolamine or yohimbine. It is concluded that epinephrine-mediated rat aortic PGI2 synthesis is alpha-adrenoceptor- and not beta-adrenoceptor-mediated, calcium-dependent, and that the alpha-adrenoceptor antagonists evaluated do not have verapamil-like calcium channel blocking activities. These findings may be relevant to contraction-relaxation cycles of vascular tissue.     

Effect of a single oral dose of aspirin on the platelet aggregation response to arachidonic acid.

1 The platelet aggregation response to arachidonic acid ex vivo was measured in six volunteers daily before and for 10 days after a single oral dose of 600 mg aspirin. 2 Arachidonic acid induced aggregation of platelets from all subjects before aspirin and aggregation occurred after an interval which varied inversely with the concentration of arachidonic acid. No aggregation occurred for 4 days after aspirin; a reduced response, compared with pre-aspirin values, was obtained on the 5th, 6th and 8th day. The values on days 7, 9 and 10 were not consistently different from the pre-aspirin values. In 6 subjects 24 h after aspirin ingestion the addition of 10--25% v/v normal platelets restored the aggregation response. 3 It is concluded that aspirin has an effect on the platelet precursors in the marrow in addition to its effect on circulating platelets.     

雷公藤内酯醇诱导兔血小板聚集作用

雷公藤内酯醇 (Ｔｒｉｐｔｏｌｉｄｅ ,Ｔｒｉ)具有抗肿瘤、免疫抑制、抗炎等生物活性 ;临床上用于治疗银屑病 ,类风湿性关节炎及白血病[1] 。但在动物实验和临床应用中发现其静脉注射会引起严重的血栓性浅静脉炎 ;为探讨其引起血栓性浅静脉炎的机制 ,我们观察了Ｔｒｉ对兔血小板功能的影响。1　材料与方法1.1　材料　Ｔｒｉ由本所提取 ,纯度 99 9% ,使用时以 2 %丙二醇配成所需浓度。ＡＤＰ美国Ｓｉｇｍａ生产 ;5 ＨＴ瑞士Ｆｌｕ ｋａ生产 ;ＴＸＢ2 放免药盒 ,中国医学科学院基础所提供 ;ｃＡＭＰ和ｃＧＭＰ放免药盒 ,中国原子能研究所提…     

Effect of low-dose aspirin treatment on human platelet aggregation

1. The effect of aspirin 50 mg/day during 28 days on human platelet aggregation (PAG) induced by ADP and collagen has been studied in 12 healthy volunteers. 2. The results show that aspirin treatment reduces both ADP and collagen-induced PAG (P less than 0.01). 3. Maximal inhibition of PAG appears in the second week of treatment for ADP-induced PAG (41.1%) and in the fourth week for collagen-induced PAG (50.2%). No significant differences exist between the controls taken along the treatment during the 28 days of the study. 4. The data suggest that the low-dose of aspirin tested provides adequate PAG inhibition to be used in the prophylaxis of thromboembolism patients, thus avoiding intolerances to higher dosages.     

Anti-aggregatory effect of prostacyclin (PGI2) in vivo.

Prostacyclin (PGI2) when infused intravenously reduced the mortality of rabbits given high intravenous doses of arachidonic acid (AA). Prostaglandins E1 and D2 were ineffective. Indomethacin pretreatment abolished the toxic AA effect. Since the lethal effect of AA is partly due to the formation of platelet aggregates it is concluded that PGI2 is a most potent anti-aggregatory prostaglandin in vivo.     

Thromboxane A2 analogue (U-46619) stimulates vascular PGI2 synthesis

Since platelet release reaction products (e.g. serotonin, ADP) stimulate prostacyclin (PGI2) release in vitro, we have investigated whether thromboxane A2 (TXA2) also has a similar effect. An analogue, U-46619, was used for the experiments, since TXA2 is extremely unstable. U-46619 stimulated rat aortic PGI2 release; this stimulation was abolished by (a) EDTA and (b) verapamil. We conclude that TXA2 is a calcium-dependent stimulator of PGI2 release; this property may be relevant to the limitation of platelet aggregates in vivo and to vascular injury.     

Recirculation of prostacyclin (PGI2) in the dog.

1 The inactivation of prostacyclin (PGI2) in the circulation of anaesthetized dogs has been studied by the blood-bathed organ bioassay technique. 2 Spiral strips of bovine coronary and rabbit coeliac or mesenteric artery detected concentrations of PGI2 of 2 to 5 ng/ml. These tissues were insensitive to concentrations at least 200 fold higher of 15-oxo-PGI2 and 6-oxo-PGF1alpha. 3 PGI2 assayed on bovine coronary artery, rabbit coeliac artery or rat stomach strip, had a half life in blood of 3.0 +/- 0.3 min, indicating non-enzymatic degradation. 4 No disappearance could be detected by bovine coronary artery when PGI2 was infused across the lungs (0.1 to 0.5 microgram kg-1 min-1). However, PGI2 was partially inactivated in passage through vascular beds of hindquarters and liver. 5 Of PGI2 infused into the aorta 35 to 65% escaped inactivation in one complete circulation. Therefore, endogenous PGI2 released from the lungs may function as a circulating hormone.     

Effect of clonixin and aspirin on platelet aggregation in human volunteers.

The effect of clonixin and aspirin on platelet function was assessed in healthy volunteers. Both drugs inhibited secondary platelet aggregation and prolonged bleeding time, but the effect of clonixin was significantly less than that of aspirin. Hemorrhagic complications are less likely after clonixin than after aspirin.     

Anti-hypoxic effect of centrally and systemically administered prostacyclin (PGI2)

Prostacyclin (PGI2) induced a dose-dependent prolongation of survival time of mice subjected to hypoxic and anoxic hypoxia, when administered either intracerebroventricularly (i.c.v., 0.001-10 micrograms/mouse), intravenously (i.v., 0.5-500 micrograms/kg) or intraperitoneally (i.p., 50-500 micrograms/kg). The effects of a single dose of 50 micrograms/kg i.v. or i.p. and of 1 microgram/mouse i.c.v. persisted for about 30 min. The anti-hypoxic effect of PGI2 is most likely due to an action upon the CNS.     

融斑通脉颗粒对家兔血小板聚集的影响

目的观察融斑通脉颗粒对家兔血小板聚集的影响。方法使用二磷酸腺苷(ADP),花生四烯酸和胶原等促凝剂促进血小板凝聚,采用Born氏比浊法,观察融斑通脉颗粒对家兔血小板聚集的影响,并与对照组及阿司匹林组比较。结果家兔连续7 d灌胃给药,融斑通脉颗粒明显降低胶原,ADP诱导的家兔血小板聚集率(P<0.05~0.01),对花生四烯酸诱导的家兔血小板聚集率有降低趋势。结论融斑通脉颗粒具有抑制血小板聚集的作用,为其临床治疗缺血性心脏病提供了实验依据。     

Effects of sulphinpyrazone and aspirin on prostaglandin I2 (prostacyclin) synthesis by endothelial cells.

Synthesis of prostaglandin I2, (PGI2, prostacyclin) by vascular endothelium (assayed by the ability of cultured endothelial cells to inhibit platelet aggregation) was inhibited by aspirin. At 100 mumol/l aspirin completely blocked measurable PGI2 production, but endothelial cells had substantially recovered their ability to synthesize PGI2 24 h after removal of the drug. In contrast, the effect of 1 mmol/l aspirin was still evident 24 h after drug withdrawal. Sulphinpyrazone also inhibited PGI2 synthesis, but was about 100 fold less potent than aspirin, and the effect of the drug was lost within 24 h of its addition, even when endothelial cells were left in contact with the drug during this period.     

Vasodilation produced by prostacyclin (PGI2) and 9(O)-thiaprostacyclin (PGI2-S) in the canine femoral circulation.

The action of 9(0)-thiaprostacyclin (PGI2-S) was compared with that of prostacyclin (PGI2) and papaverine in the femoral circulation of dogs. PGI2-S, injected into the dog femoral artery in a dose of 0.1 microgram or higher, produced marked vasodilation in the femoral artery without any change in blood pressure. The potentcy of PGI2-S was one tenth that of PGI2, and was a hundred times that of papaverine. The stability of PGI2-S in neutral solution was forty times that of PGI2.