title: Antiplatelet activity of beta-carboline alkaloids from Perganum harmala: a possible mechanism through inhibiting PLCgamma2 phosphorylation.
abstract: Beta-carboline alkaloids including harmalol, harmaline, norharmane, harmol, harmine and harmane are important constituents of the medicinal plant, Perganum harmala L. (Zygophylaceae), which has been used in traditional medicine. In the present study, the antiplatelet activities of six beta-carboline alkaloid compounds were investigated in vitro. At a concentration of 200 microM, these compounds have no effect on arachidonic acid (AA)-, thrombin- and U46619 (a thromboxane A2 mimic)-stimulated platelet aggregation. On the contrary, it was revealed that collagen-induced platelet aggregation could be inhibited by these compounds with different potencies (harmane and harmine were most potent, harmol had medium potency, and harmol, norharmane, harmalol and harmaline had a weak, non significant effect), indicating a selective inhibition on collagen-mediated platelet activation. Consistently, further study revealed that collagen-mediated phospholipase (PL) Cgamma2 and protein tyrosine phosphorylation, cytosolic calcium mobilization and arachidonic acid liberation were completely inhibited by harmane and harmine in a concentration-dependent manner, while the other compounds were only partially or not effective at all. Taken together, these results indicate that three of these six beta-carboline alkaloids can selectively affect collagen-induced platelet aggregation with different potencies; in particular, harmane and harmine were most potent, and their antiplatelet activities may be mediated by inhibiting PLCgamma2 and protein tyrosine phosphorylation with sequential suppression of cytosolic calcium mobilization and arachidonic acid liberation, indicating that harmane and harmine have a potential to be developed as a novel agent for atherothrombotic diseases.
authors.affiliation: College of Pharmacy, Research Center for Bioresource and Health, Chungbuk National University, Cheongju, 361-763, Republic of Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Im
authors.forename: Yong-Ri
authors.initials: YR
authors.lastname: Jin
authors.forename: Jung-Jin
authors.initials: JJ
authors.lastname: Lee
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Yu
authors.forename: Xiang-Hua
authors.initials: XH
authors.lastname: Han
authors.forename: Se-Hyuk
authors.initials: SH
authors.lastname: Im
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Hwan-Soo
authors.initials: HS
authors.lastname: Yoo
authors.forename: Myoung-Yun
authors.initials: MY
authors.lastname: Pyo
authors.forename: Yeo-Pyo
authors.initials: YP
authors.lastname: Yun
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002243:Carbolines / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D015394:Molecular Structure; D032443:Peganum; D051966:Phospholipase C gamma / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011817:Rabbits; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D002243:Carbolines; D010936:Plant Extracts; D010975:Platelet Aggregation Inhibitors; D019000:Phosphotyrosine; D016718:Arachidonic Acid; D051966:Phospholipase C gamma; D002118:Calcium