RESUMO
Oxidation of low density lipoprotein (LDL) is strongly implicated as a key process in the onset of atherosclerosis. In this study, nine alkylated (C10-C5) flavonoids from Sophora flavescens were examined for their inhibitory effects on copper-induced LDL oxidation. Of the flavonoids tested, sophoraflavanone G (1), kurarinone (2), kurarinol (3), norkurarinol (4), and kuraridin (9) inhibited the generation of thiobarbituric acid reactive substances (TBARS) with IC50s of 7.9, 14.5, 22.0, 26.9, and 17.5 microM, respectively. The most potent inhibitor, compound 1, also demonstrated significant activities in complementary in vitro investigations, such as lag time (130 min at 5 microM), relative electrophoretic mobility (REM) of ox-LDL (80% inhibition at 20 microM), and fragmentation of apoB-100 (inhibition of 71% at 20 microM). Analysis of the structures of these compounds reveals that a resorcinol moiety in the B-ring is strongly correlated with protection of LDL-oxidation.
Assuntos
Antioxidantes/farmacologia , Flavonoides/farmacologia , Lipoproteínas LDL/química , Sophora/química , Antioxidantes/química , Antioxidantes/isolamento & purificação , Apolipoproteína B-100/química , Cromatografia Líquida de Alta Pressão , Sulfato de Cobre/farmacologia , Ensaio de Desvio de Mobilidade Eletroforética , Flavonoides/química , Flavonoides/isolamento & purificação , Humanos , Lipoproteínas LDL/sangue , Estrutura Molecular , Oxirredução , Raízes de Plantas/química , Relação Estrutura-Atividade , Substâncias Reativas com Ácido Tiobarbitúrico/análiseRESUMO
The sesquineolignan, saucerneol B (1), and dineolignans, manassantin A (2), and manassantin B (3), were isolated from the methanol extracts of Saururus chinensis root and elucidated by their spectroscopic data analysis. Compounds 1-3 inhibited hACAT-1 and hACAT-2 with IC(50) values of 43.0 and 124.0 microM for 1, of 39.0 and 8.0 microM for 2, of 82.0 microM and only 32% inhibition at 1mM for 3, respectively. The EtOAc-soluble fraction, which contained compounds 1-3, of methanol extracts of S. chinensis exhibited strong cholesterol-lowering effect in high cholesterol-fed mice.
Assuntos
Furanos/farmacologia , Lignanas/farmacologia , Saururaceae , Esterol O-Aciltransferase/antagonistas & inibidores , Animais , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Furanos/química , Furanos/isolamento & purificação , Humanos , Lignanas/química , Lignanas/isolamento & purificação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Raízes de Plantas , Esterol O-Aciltransferase/metabolismo , Esterol O-Aciltransferase 2RESUMO
A series of pyrazoline derivatives were prepared for evaluating their acyl-CoA:cholesterol acyltransferase activities. 3-(3,5-Di-tert-butyl-4-hydroxyphenyl)-5-(multi-substituted 4-hydroxyphenyl)-2-pyrazolines 4a-i were shown in vitro inhibitory activity on hACAT-1 and -2.
