Research PaperAqueous extract from Brownea grandiceps flowers with effect on coagulation and fibrinolytic system
Graphical abstract
Introduction
The hemostatic system requires a balance between fibrin formation (coagulation) and fibrin dissolution (fibrinolysis) to prevent blood loss by sealing sites of injury and ensure perfusion through tissues (Riddel et al., 2007). Thrombin is the enzyme that transforms fibrinogen into fibrin, while plasmin is the main enzyme capable of degrading both fibrinogen and fibrin under physiological conditions (Monroe et al., 2002). Any disruption of this equilibrium may bring about thrombosis or hemorrhage, that is, on the one hand, excessive local or systemic activation of coagulation may wind up in the development of thrombi or consumption coagulopathy. On the other hand, excessive local or systemic fibrinolytic activity may very well evolve into heavy bleeding or clotting episodes (Rasche, 2001). These coagulation and fibrinolysis disorders cause serious medical problems, which have led to isolate anti- and pro-coagulant compounds as fibrinolytic and antifibrinolytic components, resorting to various sources such as snakes, caterpillars, scorpions and plants to name but a few, and are currently being investigated aiming to control these problems (Reis et al., 2001, Swenson and Markland, 2005, Shivaprasad et al., 2009, Brazón et al., 2008, Brazón et al., 2009, Brazón et al., 2013, Brazón et al., 2014).
In most developing countries, plant remedies are the most prevalent treatments, where recipes have been handed down from generation to generation and every culture has used decoctions or extracts of leaves, flowers, barks or roots to treat various medical problems (Agra et al., 2007). Several isolated plant components have a marked effect on the hemostasis. It is worth mentioning flavonoids with vasodilator effect (Victório et al., 2009), coumarins with antiaggregant platelet effects (Lee et al., 2003), phenolic compounds with inhibitory activity on platelets adhesion and secretion (Olas et al., 2005), proteases exhibiting coagulation factors-like activity or else showing fibrinolytic components-like activity (Shivaprasad et al., 2009) and inhibitors of thrombin activity (Francischetti et al., 1997).
Brownea genus belongs to the Fabaceae family, comprising evergreen small trees with capitate racemes axillary or terminal of red, yellow or white flowers which are found from the south of Mexico to Peru, including Antillean islands, Jamaica, Trinidad and Tobago (Stevermark and Huber, 1978). Species from this genus are used in the traditional medicine for treatment of hemorrhages (Otero et al., 2000, Márquez et al., 2005, Díaz and Ortega, 2006). In Colombia and Brazil, some plant species from this genus such as Brownea ariza Bentham and Brownea rosademonte are mostly employed in folk medicine as cicatrizant and to neutralize hemorrhages caused by snake venom (Otero et al., 2000). However, in Venezuela, flowers of Brownea grandiceps and other species of this genus (called mountain rose or rose-of-Venezuela) are used as decoctions in traditional medicine to reduce the bleeding in women with heavy menstrual blood loss (Díaz and Ortega, 2006). Nevertheless, the biological active components are yet to be identified.
Due to the scarce actual scientific information and our interest in the haemostatic activity compounds with great medical potential present in Brownea grandiceps, the very aim of this study was to evaluate in vitro the effects of aqueous extract from Brownea grandiceps flowers on the coagulation system and fibrinolysis in order to determine whether Brownea grandiceps flowers contain components that could aid in the reduction of heavy menstrual blood loss, because menorrhagia as a common clinical problem among reproductive age females, happens to have a severe impact on the impairment of their quality of life, not just by causing an iron deficiency anemia, but also altering their emotional, social and working life to a great degree (Shankar et al., 2008).
Section snippets
Collection of vegetal material and preparation of aqueous extracts
Brownea grandiceps flowers were collected from 3-m-tall wild trees, fertilizers free, from the areas surrounding the Posada Mocundo, Carabobo State, Venezuela (10°14′14′′N–68°15′44′′W). The identity of this plant, collected in March 2014, was confirmed by Reina Gonto, and a voucher specimen of it (number 5699) was deposited in the herbarium of the Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas, Venezuela.
An infusion using 116 g of Brownea grandiceps fresh flowers was
Phytochemical analyses
Phytochemical screening of the BGE is shown in Table 1. The qualitative analyses revealed the presence of saponins, tannins, alkaloids, flavonoids, glycosides, coumarins and carbohydrates. However, BGE did not present triterpenoids.
Anti- and pro-coagulant effects determined by PTT, PT and TT
BGE at concentrations ≤625 µg/mL had no effect whatsoever on PTT, though, 1250 µg/mL BGE produced a significant increase on PTT of 38.6 (38.35–39.7) s, with respect to control [32.6 (32.55–32.7) s]. This anti-coagulant effect was more pronounced with 25000 µg/mL BGE,
Discussion
In modern medicine, heavy menstrual blood loss (menorrhagia) in women is treated with the tranexamic acid antifibrinolytic agent, this drug has been shown to reduce menstrual bleeding by approximately 50% and in most studies it was administered from days 1 to 4 or 5 of menses in a dose of 4 g/day, during 3 consecutive menstrual cycles. However, nausea, vomiting, diarrhea, and some impaired color vision has been reported after the administration of tranexamic acid (Philipp., 2011).
On the other
Acknowledgments
The authors are indebted to the family Baasch Castrillo of Posada Mocundo, Carabobo State, Venezuela for the supply of Brownea grandiceps flowers. We greatly appreciated the technical assistance of Moises Sandoval, Crisol Osorio, Elaine Suárez and Genesis Rivera. This research was supported by grants from the Fondo Nacional de Ciencias, Técnología e Innovación-Programa Estímulo a la Innovación e Investigación (FONACIT-PEII) No. 2012001444 and IVIC No. 603.
References (49)
- et al.
Synopsis of the plants known as medicinal and poisonous in Northeast of Brazil
Revista Brasilera de Farmacognosia
(2007) - et al.
A Laboratory Manual of Blood Coagulation
(1975) - et al.
Organic Analysis: Qualitative and Quantitative
(1921) - et al.
Efecto del veneno de escorpión Tityus discrepans sobre las pruebas globales de la coagulación. Estudios preliminares
Investigación Clínica
(2008) - et al.
Discreplasminin, a plasmin inhibitor isolated from Tityus discrepans scorpion venom
Archive of Toxicology
(2009) - et al.
Anticoagulant and procoagulant activities of Tityus discrepans scorpion venom
Acta Toxicológica Argentina
(2013) - et al.
Presence of fibrin(ogen)olytic enzymes in Tityus discrepans scorpion venom
Comparative Biochemistry and Physiology
(2014) - et al.
Análisis fitoquímico preliminar de hojas, tallos y semillas de Cupatá (Strychnos schultesiana krukoff) stems and sedes
Colombia Forestal
(2009) Appendices
The Analysis Of Controlled Substances
(2003)Lectures on Biostatistics: An Introduction To Statistics With Applications In Biology And Medicine
(1971)
Natural occurring polyphenols as template for drug desing. Focus on serine proteases
Chemical Biology & Drug Design
Inventario de recursos botánicos útiles y potenciales de la cuenca del río Morón, Estado Carabobo, Venezuela
Ernstia
Colorimetric method for determination of sugars and related substances
Analytical Chemistry
Spot Test in Organic Analysis
Purification and biochemical characterization of Eumilin from Euphorbia milii var. hislopii latex
Phytochemistry
Identification of glycyrrizan as a thrombin inhibitor
Biochemical and Biophysical Research Communications
Activation of human prothrombin by the venom of Lonomia achelous (Cramer) caterpillars
Thrombosis Research
Phytochemical Methods
Non Parametric Statistical Procedures
Pharmacognosy and Pharmaco-Botechnology
Mangrove extracts prevent the blood coagulate
Indian Journal Biotechnology
Effect of antihemophilic factor on one-stage clotting tests. A presumptive test for hemophilia and a simple one-stage antihemophilic factor assay procedure
Journal of Laboratory and Clinical Medicine Sciences
Platelet anti-aggregatory effects of coumarins from the roots of Angelica genuflexa and Angelica gigas
Archives of Pharmacology Research
A disheartening story: aprotinin in cardiac surgery
Critical Care
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2021, South African Journal of BotanyCitation Excerpt :is a small tree widely used as an ornamental and in traditional medicine. It was reported that aqueous extract of B. grandiceps flowers (called mountain rose or rose-of-Venezuela) possess anti-fibrinolytic (Pereira and Brazón, 2015) and anti-plasmin activities (Pereira et al., 2017). Despite the traditional uses of Brownea, there is scarcity in published scientific data on this genus.
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2017, Journal of EthnopharmacologyCitation Excerpt :The inhibitory effect of Browplasminin, a condensed tannin of approximately 5 kDa, has showed to be higher than the reference compounds EACA (131 Da) and TA (157 Da) but similar in molecular mass and inhibitory effect to aprotinin (Table 2). This find could help explain how the (anti-plasmin) anti-fibrinolytic activity of Browplasminin could be related to the reduction of blood loss reported by women that practice the Venezuelan traditional medicine (Díaz and Ortega, 2006; Pereira and Brazón, 2015). This work is the first study that shows anti-plasmin activity in condensed tannins.
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