Bakkenolide G, a Natural PAF-receptor Antagonist
| Autor: | Che-Ming Teng, Feng Nien Ko, Chang-Hui Liao, Tian Shung Wu |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Blood Platelets
Platelet Aggregation medicine.drug_class Inositol Phosphates Pharmaceutical Science Receptors Cell Surface Platelet Membrane Glycoproteins In Vitro Techniques Pharmacology Biology Receptors G-Protein-Coupled chemistry.chemical_compound Adenosine Triphosphate 4-Butyrolactone medicine Animals Dimethyl Sulfoxide Spiro Compounds Platelet Platelet activation Arachidonic Acid Dose-Response Relationship Drug Molecular Structure Platelet-activating factor Thrombin Antagonist Receptor antagonist Thromboxane B2 Schild regression chemistry Biochemistry 15-Hydroxy-11 alpha 9 alpha-(epoxymethano)prosta-5 13-dienoic Acid Calcium Arachidonic acid Collagen Rabbits Sesquiterpenes Platelet Aggregation Inhibitors |
| Zdroj: | Journal of Pharmacy and Pharmacology. 49:1248-1253 |
| ISSN: | 2042-7158 0022-3573 |
| DOI: | 10.1111/j.2042-7158.1997.tb06079.x |
| Popis: | Because platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) participates in many physiopathological responses, including inflammatory reaction, endotoxic shock, allergic diseases and platelet aggregation, PAF-receptor antagonists are important in the treatment of these diseases. A biologically active compound, bakkenolide G, extracted from the plant Petasites formosanus selectively and concentration-dependently inhibited PAF-induced platelet aggregation and ATP release. The IC50 of bakkenolide G for PAF (2 ng mL−1)-induced platelet aggregation was 5.6 ± 0.9 μm. Bakkenolide G also concentration-dependently inhibited PAF-induced intracellular signal transductions, including thromboxane B2 formation, and increased intra-cellular calcium concentration and phosphoinositide breakdown without affecting those caused by thrombin (01 units mL−1), collagen (10 μg mL−1), arachidonic acid (100 μm) and U46619 (1 μm). Bakkenolide G shifted the concentration-response curves of PAF-induced platelet aggregation parallel to the right; the Schild plot slope and the pA2 value were 1.31 ± 0.31 and 6.21 ± 0.75, respectively. Moreover, bakkenolide G concentration-dependently competed with [3H]PAF binding to platelets, with an IC50 value of 2.5 ± 0.4 μm. These data strongly indicate that bakkenolide G is a specific PAF-receptor antagonist as an antiplatelet aggregatory agent. |
| Databáze: | OpenAIRE |
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