![]() ![]() Calcitonin gene-related peptide-mediated depressor effect and inhibiting vascular hypertrophy of rutaecarpine in renovascular hypertensive rats. Qin X.P., Zeng S.Y., Li D., Chen Q.Q., Luo D., Zhang Z., Hu G.Y., Deng H.W., Li Y.J. Studies of the cellular mechanisms underlying the vasorelaxant effects of rutaecarpine, a bioactive component extracted from an herbal drug. ![]() Pharmacological effects of rutaecarpine, an alkaloid isolated from Evodia eutaecarpa. B, * p < 0.05 and *** p < 0.001 compared with the 0.1% DMSO-treated group. A, *** p < 0.001, compared with the Tyrode’s solution only (resting group) # p < 0.001, compared with the 0.1% DMSO-treated group. Data are presented as the mean ± standard error of the mean ( A, n = 4 B, C, n = 8). ( C) The bleeding time was measured through mouse tail transection after 30 min of intraperitoneal administration of 0.1% DMSO or Rut (0.7 and 1.5 mg/kg). The photographs shown are representative of eight similar experiments, and red arrows indicate platelet plug formation. Microscopic images (400× magnification) of the 0.1% DMSO-treated group and Rut (0.7 and 1.5 mg/kg)-treated group were recorded at 5 and 150 s after irradiation, respectively. ( B) Mice were administered an intraperitoneal bolus of the solvent control (0.1% DMSO) or Rut (0.7 and 1.5 mg/kg), and the mesenteric venules were irradiated to induce microthrombus formation (occlusion time). Profiles are representative of four similar experiments. ( A) Washed platelets (3.6 × 10 8 cells/mL) were preincubated with (a) Tyrode’s solution only (resting group) or preincubated with (b) 0.1% DMSO or Rut (c, 2.5 d, 5 µM) subsequently, collagen (1 μg/mL) was added to trigger hydroxyl radical (*) formation. Inhibitory effect of Rut on hydroxyl radical formation in human platelets and microvascular thrombus formation as well as tail bleeding time in mice. MAPK PI3K/Akt/GSK3β VASP cyclic nucleotide human platelets hydroxyl radical microvascular thrombosis rutaecarpine. Thus, Rut can be a potential therapeutic agent for thromboembolic disorders. The findings demonstrated that Rut exerts a strong effect against platelet activation through the PLCγ2/PKC and PI3K/Akt/GSK3β pathways. Rut significantly increased the occlusion time of fluorescence irradiated thrombotic platelet plug formation. Rut was not directly responding to vasodilator-stimulated phosphoprotein phosphorylation. SQ22536 (an adenylate cyclase inhibitor) or ODQ (a guanylate cyclase inhibitor) did not reverse Rut-mediated antiplatelet aggregation. Rut markedly inhibited P-selectin expression adenosine triphosphate release i mobilization hydroxyl radical formation and phospholipase C (PLC)γ2/protein kinase C (PKC), mitogen-activated protein kinase, and phosphoinositide 3-kinase (PI3K)/Akt/glycogen synthase kinase-3β (GSK3β) phosphorylation stimulated by collagen. At low concentrations (1-5 μM), Rut strongly inhibited collagen-induced platelet aggregation, whereas it exerted only a slight or no effect on platelets stimulated with other agonists (e.g., thrombin). To address a research gap, we investigated the inhibitory mechanisms of Rut in washed human platelets and experimental mice. Evodia rutaecarpa (Wu-Chu-Yu) is a well-known Chinese medicine, and rutaecarpine (Rut) is a main bioactive component with substantial beneficial properties including vasodilation. Therefore, antiplatelet drugs significantly reduce the risk of severe CVDs. The role of activated platelets in acute and chronic cardiovascular diseases (CVDs) is well established. ![]() ![]() 9 School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan.8 Department of Cardiovascular Center, Cathay General Hospital, Taipei 106, Taiwan.7 Department of Zoology, Bharathiar University, Coimbatore 641046, Tamil Nadu, India.Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. 5 Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.4 Department of Nutrition, Chung Shan Medical University, Taichung 402, Taiwan.3 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.2 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.1 Department of Anesthesiology and Integrative Research Center for Critical Care, Wan Fang Hospital, Taipei Medical University, Taipei 110, Taiwan. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |