RESUMO
The stereochemistry of new acetophenones, cynandione B-D (2-4), isolated from Cynanchum taiwanianum, elucidated by computer modelling calculation and NOESY spectrum. It establishes the absolute configurations of cynandiones B-D (2-4) as 7R; 7"S, 7S; 7"S and 7R; 7"R, respectively. Cynandione B (2) strongly inhibited the release of beta-glucuronidase and lysozyme in formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated rat neutrophils in a concentration-dependent manner with IC50 values of 1.5 +/- 0.2 and 1.6 +/- 0.2 microM, respectively. 2,5-Dihydroxyacetophenone (6) strongly inhibited the aggregation of washed rabbit platelets induced by arachidonic acid in a concentration-dependent manner with an IC50 value of about 4.8 microM. In human citrated platelet-rich plasma, 2,5-dihydroxyacetophenone (6) inhibited the secondary phase, but not the primary phase, of aggregation induced by adrenaline and ADP. These results suggest that the antiplatelet effect of 2,5-dihydroxyacetophenone (6) is due to inhibition of the formation of thromboxane A2.
Assuntos
Acetofenonas/química , Acetofenonas/farmacologia , Plantas Medicinais , Acetofenonas/isolamento & purificação , Difosfato de Adenosina/farmacologia , Animais , Degranulação Celular/efeitos dos fármacos , Colágeno/farmacologia , Epinefrina/farmacologia , Humanos , Técnicas In Vitro , Mastócitos/efeitos dos fármacos , Mastócitos/fisiologia , Modelos Moleculares , Neutrófilos/efeitos dos fármacos , Neutrófilos/fisiologia , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/isolamento & purificação , Inibidores da Agregação Plaquetária/farmacologia , Coelhos , Ratos , Estereoisomerismo , Relação Estrutura-Atividade , Superóxidos/metabolismoRESUMO
The homozygous deletion allele (DD) of the angiotensin-I converting enzyme (ACE) gene and the T235 homozygote of the angiotensinogen (AGT) gene have been reported to be correlated with an increased prevalence of coronary artery disease (CAD) and myocardial infarction (MI). The importance of the DD genotype and T235 homozygote as genetic risk factors for CAD in Chinese remains uncertain. This study included 426 patients who underwent coronary angiography and 180 healthy subjects without clinical evidence of CAD. Coronary angiography identified 268 patients with CAD (CAD group) and 158 patients without CAD. The healthy subjects and patients without angiographic evidence of CAD constituted the control group. Three polymorphisms were studied: an insertion/deletion (I/D) polymorphism of the ACE gene and the T174 M and M235T polymorphisms of the AGT gene. No association was found between any of the three studied polymorphisms and the risk of CAD or MI in Chinese using univariate or multivariate analysis. In multivariate analysis, the relative risks were 1.20 (95% confidence interval = 0.91-1.61, P = 0.20) for the DD genotype, 1.05 (95% CI = 0.82-1.35, P = 0.69) for the T174 homozygote, and 1.19 (95% CI = 0.91-1.55, P = 0.20) for the T235 homozygote. Similarly, no significant difference was found in the frequencies of the DD genotype and the T174 and T235 homozygotes between the control group, the CAD group, the non-MI group, and the MI group when analyzed according to sex, age, or degree of risk. Our data suggest that neither the DD genotype of the ACE I/D polymorphism nor the T174 and T235 homozygotes of the AGT gene confer significant risk for CAD or MI in Chinese.