title: Anti-thrombotic and anti-inflammatory activities of protopine.
abstract: The effects of protopine on human platelet aggregation and arachidonic acid (AA) metabolism via cyclooxygenase (COX) and lipoxygenase (LOP) enzymes were examined. Platelet aggregation induced by various platelet agonists (AA, ADP, collagen and PAF) was strongly inhibited by protopine in a concentration-related manner. The IC50 values (microM) of protopine (mean +/- SEM) against: AA; 12 +/- 2: ADP; 9 +/- 2: collagen; 16 +/- 2 and PAF; 11 +/- 1, were much less than those observed for aspirin. In addition, protopine selectively inhibited the synthesis of thromboxane A2 (TXA2) via COX pathway and had no effect on the LOP pathway in platelets. In vivo, pretreatment with protopine (50-100 mg kg-1) protected rabbits from the lethal effects of AA (2 mg kg-1) or PAF (11 micrograms kg-1) in dose-dependent fashion. Protopine (50-100 mg kg-1) also inhibited carrageenan-induced rat paw oedema with a potency of three-fold as compared to aspirin. These results are suggestive that protopine acts as a potent inhibitor of thromboxane synthesis and PAF with anti-inflammatory properties.
authors.affiliation: Department of Physiology and Pharmacology, Aga Khan University Medical College, Karachi, Pakistan.
authors.forename: S A
authors.initials: SA
authors.lastname: Saeed
authors.forename: A H
authors.initials: AH
authors.lastname: Gilani
authors.forename: R U
authors.initials: RU
authors.lastname: Majoo
authors.forename: B H
authors.initials: BH
authors.lastname: Shah
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000097:blood / Q000494:pharmacology; D053119:Benzophenanthridines; D001600:Berberine Alkaloids; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000096:biosynthesis
chemical_list: D000470:Alkaloids; D000893:Anti-Inflammatory Agents; D053119:Benzophenanthridines; D001600:Berberine Alkaloids; D005343:Fibrinolytic Agents; D006634:Histamine H1 Antagonists; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D002351:Carrageenan; D011451:Prostaglandin-Endoperoxide Synthases; C009093:protopine