15-hydroxy-11-alpha-9-alpha-(epoxymethano)prosta-5-13-dienoic-acid and aporphine

Five aporphine alkaloids, N-acetylanonaine ( 1), N-acetylxylopine ( 2), N-formylanonaine ( 3), liriodenine ( 4), and lanuginosine ( 5) as the antiplatelet constituents, were isolated from the methanol extract of leaves of Magnolia obovata. This is the first reported occurrence of 2 and 3 from genus Magnolia and 5 was isolated from this plant for the first time. Compounds 1, 2 and 3 showed 60 approximately 264-fold stronger inhibitory effects than acetylsalicylic acid (ASA) to rat platelet aggregation induced by collagen, epinephrine, arachidonic acid (AA), or U46619.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Alkaloids; Animals; Aporphines; Arachidonic Acid; Collagen; Epinephrine; Humans; Inhibitory Concentration 50; Magnolia; Phytotherapy; Plant Extracts; Plant Leaves; Platelet Aggregation; Platelet Aggregation Inhibitors; Rats

Two aporphines (boldine and laurolitsine) and five phenanthrene alkaloids (litebamine, secoboldine, N-cyanosecoboldine, N-methylsecoglaucine and N-methylsecopredicentrine) were evaluated in-vitro for their ability to inhibit platelet aggregation. All seven alkaloids inhibited aggregation of rabbit platelets and inhibited the release of ATP induced by arachidonic acid and collagen in rabbit platelets. Those aggregations induced by platelet-activating factor (PAF), thrombin, U46619 and ADP were inhibited by the three N-substituted secoboldine derivatives only. Thromboxane B2 formation caused by arachidonic acid was also suppressed by these compounds. They did not affect the generation of [3H]inositol monophosphate caused by collagen, PAF and thrombin in the presence of indomethacin. Platelet cyclic AMP level was unaffected by litebamine, but was increased by N-methylsecoglaucine. Litebamine suppressed the secondary aggregation, but not the primary aggregation, induced by ADP and adrenaline in platelet-rich plasma from man, whereas N-methylsecoglaucine inhibited both primary and secondary aggregation. It is concluded that the antiplatelet effect of these seven aporphine and phenanthrene alkaloids is mainly a result of inhibition of thromboxane A2 formation; N-methylsecoglaucine has additional antiplatelet activity as a result of increasing the levels of platelet cyclic AMP.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adenosine Diphosphate; Adenosine Triphosphate; Animals; Aporphines; Arachidonic Acid; Blood Platelets; Collagen; Cyclic AMP; Guaiacol; Humans; Isoquinolines; Isotope Labeling; Lipoxygenase Inhibitors; Male; Phenanthrenes; Platelet Activating Factor; Platelet Aggregation Inhibitors; Quinolines; Rabbits; Radioimmunoassay; Structure-Activity Relationship; Thrombin; Thromboxane B2; Vasoconstrictor Agents