title: Amarogentin, a secoiridoid glycoside, abrogates platelet activation through PLC γ 2-PKC and MAPK pathways.
abstract: Amarogentin, an active principle of Gentiana lutea, possess antitumorigenic, antidiabetic, and antioxidative properties. Activation of platelets is associated with intravascular thrombosis and cardiovascular diseases. The present study examined the effects of amarogentin on platelet activation. Amarogentin treatment (15~60  μM) inhibited platelet aggregation induced by collagen, but not thrombin, arachidonic acid, and U46619. Amarogentin inhibited collagen-induced phosphorylation of phospholipase C (PLC) γ2, protein kinase C (PKC), and mitogen-activated protein kinases (MAPKs). It also inhibits in vivo thrombus formation in mice. In addition, neither the guanylate cyclase inhibitor ODQ nor the adenylate cyclase inhibitor SQ22536 affected the amarogentin-mediated inhibition of platelet aggregation, which suggests that amarogentin does not regulate the levels of cyclic AMP and cyclic GMP. In conclusion, amarogentin prevents platelet activation through the inhibition of PLC γ2-PKC cascade and MAPK pathway. Our findings suggest that amarogentin may offer therapeutic potential for preventing or treating thromboembolic disorders.
authors.affiliation: Graduate Institute of Medical Sciences and Department of Pharmacology, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan.
authors.forename: Ting-Lin
authors.initials: TL
authors.lastname: Yen
authors.affiliation: Graduate Institute of Medical Sciences and Department of Pharmacology, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan.
authors.forename: Wan-Jung
authors.initials: WJ
authors.lastname: Lu
authors.affiliation: School of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan ; Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, 95 Wen-Chang Road, Taipei 111, Taiwan.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Lien
authors.affiliation: Department of Microbiology, Institute of Ophthalmology, Joseph Eye Hospital, 138 Melapudur, Tiruchirappalli, Tamil Nadu 620 001, India.
authors.forename: Philip Aloysius
authors.initials: PA
authors.lastname: Thomas
authors.affiliation: Graduate Institute of Medical Sciences and Department of Pharmacology, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan.
authors.forename: Tzu-Yin
authors.initials: TY
authors.lastname: Lee
authors.affiliation: Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, 95 Wen-Chang Road, Taipei 111, Taiwan ; College of Medicine, Fu-Jen Catholic University, 510 Zhongzheng Road, New Taipei City 242, Taiwan.
authors.forename: Hou-Chang
authors.initials: HC
authors.lastname: Chiu
authors.affiliation: Graduate Institute of Medical Sciences and Department of Pharmacology, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan.
authors.forename: Joen-Rong
authors.initials: JR
authors.lastname: Sheu
authors.affiliation: Graduate Institute of Medical Sciences and Department of Pharmacology, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan ; Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, 95 Wen-Chang Road, Taipei 111, Taiwan.
authors.forename: Kuan-Hung
authors.identifier: 0000-0003-1519-1797
authors.initials: KH
authors.lastname: Lin
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000737:chemistry; D000225:Adenine / Q000031:analogs & derivatives / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry; D003094:Collagen / Q000737:chemistry; D006152:Cyclic GMP / Q000378:metabolism; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006801:Humans; D039823:Iridoids / Q000737:chemistry*; D020935:MAP Kinase Signaling System; D051379:Mice; D010069:Oxadiazoles / Q000737:chemistry; D051966:Phospholipase C gamma / Q000378:metabolism*; D010936:Plant Extracts / Q000737:chemistry; D015539:Platelet Activation / Q000187:drug effects*; D011493:Protein Kinase C / Q000378:metabolism*; D011810:Quinoxalines / Q000737:chemistry; D013917:Thrombin / Q000737:chemistry; D013923:Thromboembolism / Q000188:drug therapy / Q000517:prevention & control; D013927:Thrombosis / Q000188:drug therapy
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D039823:Iridoids; D010069:Oxadiazoles; D010936:Plant Extracts; D011810:Quinoxalines; C017759:9-(tetrahydro-2-furyl)-adenine; D016718:Arachidonic Acid; C102609:amarogentin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate; D003094:Collagen; D011493:Protein Kinase C; D051966:Phospholipase C gamma; D013917:Thrombin; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D000225:Adenine