Rutin present in Alibertia edulis extract acts on human platelet aggregation through inhibition of cyclooxygenase/thromboxane

Author(s)

Lescano, Caroline Honaiser ^[1] ; de Lima, Fernando Freitas ^[2] ; Cardoso, Claudia Andrea Lima ^[3] ; Vieira, Silvia Cristina Heredia ^[4] ; Monica, Fabiola Zakia ^[1] ; de Oliveira, Ivan Pires ^[5]

Affiliation

^[1] Univ Estadual Campinas, Fac Med Sci, Dept Pharmacol, Campinas - Brazil

^[2] Inst Food Technol, Ctr Dairy Technol, Campinas - Brazil

^[3] Univ Mato Grosso, Ctr Nat Resource Studies, Dourados, MS - Brazil

^[4] Anhanguera Uniderp Univ, Environm & Reg Dev Postgrad Program, Campo Grande, MS - Brazil

^[5] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo - Brazil

• Document type: Journal article
• Source: FOOD & FUNCTION; v. 12, n. 2, p. 802-814, JAN 21 2021.
• Web of Science Citations: 0

Abstract

Alibertia edulis leaf extract is commonly used in folk medicine, with rutin caffeic and vanillic acids being its major compounds. The Alibertia edulis leaf extract was investigated for its pharmacological effects via platelet aggregation, calcium mobilization, cyclic nucleotides levels, vasodilator-stimulated phosphoprotein Ser157 and Ser239 and protein kinase C beta(2) phosphorylation, thromboxane B-2, cyclooxygenases 1 and 2, docking and molecular dynamics. Alibertia edulis leaf extract significantly inhibited (100-1000 mu g mL(-1)) platelet aggregation induced by different agonists. Arachidonic acid increased levels of calcium and thromboxane B-2, phosphorylation of vasodilator-stimulated phosphoprotein Ser157 and Ser239, and protein kinase C beta, which were significantly reduced by Alibertia edulis leaf extract, rutin, and caffeic acid as well mixtures of rutin/caffeic acid. Cyclooxygenase 1 activity was inhibited for Alibertia edulis leaf extract, rutin and caffeic acid. These inhibitions were firsrtly explored by specific stabilization of rutin and caffeic acid compared to diclofenac at the catalytic site from docking score and free-energy dissociation profiles. Then, simulations detailed the rutin interactions close to the heme group and Tyr385, responsible for catalyzing the conversion of arachidonic acid to its products. Our results reveal the antiplatelet aggregation properties of Alibertia edulis leaf extract, rutin and caffeic acid providing pharmacological information about its origin from cyclooxygenase 1 inhibition and its downstream pathway. (AU)

• FAPESP's process: 17/26687-3 - Pharmacological characterization of glyphlozins in isolated human platelets: in vitro, in vivo evaluation and molecular modeling
• Grantee: Caroline Honaiser Lescano
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/12121-0 - LIPID-BASED NANOCARRIERS FOR THE LOCAL ANESTHETIC TETRACAINE
• Grantee: Fernando Freitas de Lima
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/02201-4 - Study of the inhibition of the accumulation of cyclic nucleotide by pyridopyrimidine derivatives using molecular dynamics simulations
• Grantee: Ivan Pires de Oliveira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/01237-8 - Encapsulation of bioactive and probiotic components by combined method for the development of functional drinks based on fruits and whey
• Grantee: Fernando Freitas de Lima
• Support Opportunities: Scholarships in Brazil - Post-Doctoral