title: Modulation of platelet aggregation by areca nut and betel leaf ingredients: roles of reactive oxygen species and cyclooxygenase.
abstract: There are 2 to 6 billion betel quid (BQ) chewers in the world. Areca nut (AN), a BQ component, modulates arachidonic acid (AA) metabolism, which is crucial for platelet function. AN extract (1 and 2 mg/ml) stimulated rabbit platelet aggregation, with induction of thromboxane B2 (TXB2) production. Contrastingly, Piper betle leaf (PBL) extract inhibited AA-, collagen-, and U46619-induced platelet aggregation, and TXB2 and prostaglandin-D2 (PGD2) production. PBL extract also inhibited platelet TXB2 and PGD2 production triggered by thrombin, platelet activating factor (PAF), and adenosine diphosphate (ADP), whereas little effect on platelet aggregation was noted. Moreover, PBL is a scavenger of O2(*-) and *OH, and inhibits xanthine oxidase activity and the (*)OH-induced PUC18 DNA breaks. Deferoxamine, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) and neomycin prevented AN-induced platelet aggregation and TXB2 production. Indomethacin, genistein, and PBL extract inhibited only TXB2 production, but not platelet aggregation. Catalase, superoxide dismutase, and dimethylthiourea (DMT) showed little effect on AN-induced platelet aggregation, whereas catalase and DMT inhibited the AN-induced TXB2 production. These results suggest that AN-induced platelet aggregation is associated with iron-mediated reactive oxygen species production, calcium mobilization, phospholipase C activation, and TXB2 production. PBL inhibited platelet aggregation via both its antioxidative effects and effects on TXB2 and PGD2 production. Effects of AN and PBL on platelet aggregation and AA metabolism is crucial for platelet activation in the oral mucosa and cardiovascular system in BQ chewers.
authors.affiliation: Laboratory of Dental Pharmacology and Toxicology, Graduate Institute of Clinical Dental Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Jiiang-Huei
authors.initials: JH
authors.lastname: Jeng
authors.forename: Shiao-Yun
authors.initials: SY
authors.lastname: Chen
authors.forename: Chang-Hui
authors.initials: CH
authors.lastname: Liao
authors.forename: Yuan-Yii
authors.initials: YY
authors.lastname: Tung
authors.forename: Bor-Ru
authors.initials: BR
authors.lastname: Lin
authors.forename: Liang-Jiunn
authors.initials: LJ
authors.lastname: Hahn
authors.forename: Mei-Chi
authors.initials: MC
authors.lastname: Chang
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001114:Areca / Q000737:chemistry*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism; D010084:Oxidation-Reduction; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
chemical_list: D016166:Free Radical Scavengers; D010936:Plant Extracts; D010975:Platelet Aggregation Inhibitors; D017382:Reactive Oxygen Species; D013481:Superoxides; D016718:Arachidonic Acid; D017665:Hydroxyl Radical; D013929:Thromboxane B2; D003094:Collagen; D011451:Prostaglandin-Endoperoxide Synthases; D014969:Xanthine Oxidase; D015230:Prostaglandin D2