The efficacy of Ankaferd Blood Stopper in antithrombotic drug-induced primary and secondary hemostatic abnormalities of a rat-bleeding model

Objective: Ankaferd ® Blood Stopper (ABS) is an herbal extract that has historically been used as a hemostatic agent in traditional Turkish medicine. ABS is comprised of a standardized herbal mixture of T. vulgaris, G. glabra, V. vinifera, A. officinarum, and U. dioica. ABS's basic mechanism of action is the formation of an encapsulated protein web, which represents the focal point for vital erythrocyte masses. The hemostatic effects of ABS have been observed in vitro and in vivo. ABS was registered as a hemostatic agent for external hemorrhages and dental bleeding following phase I randomized, double-blind crossover placebo-controlled clinical research, and safety and efficacy reports. In terms of the potential use of ABS, transcription factors may be novel factors that play a role in the hemostatic and other pleiotropic effects of ABS. Materials and Methods: Hence, the present study aimed to investigate the effects of ABS on endothelium, and possible transcription factor changes in HUVEC (human umbilical vein endothelial cells) and the erythrocyte membrane profile. ABS (5 μL and 50 μL) was administered to HUVEC (in 75 cm 2 ; ~75% fullness) for 5 min and 15 min. Results: ABS caused significant increases in the level of activation of the following transcription factors; AP2, AR, CRE/ATF1, CREB, E2F1-5, E2F6, EGR, GATA, HNF-1, ISRE, Myc-Max, NF-1, NFkB, p53, PPAR, SMAD 2/3, SP1, TRE/AP1, and YY1. Following erythrocyte membrane isolation, protein complexes were undissolved, but denatured. The protein complex formed was resistant to heat and detergent. Trypsin and sonication were used in order to break this complex; the complex dissolved and erythrocyte membrane proteins were released in SDS-PAGE. Conclusion: ABS established a very fast and solid protein web, and increased the level of transcription factor activation. Therefore the cellular effects of ABS could be related to different intracellular biological pathways. (Turk J Hematol 2011; 28: 276-85)

Section: Discussionmentioning

confidence: 99%

The effects of Ankaferd Blood Stopper on transcription factors in HUVEC and erythrocyte protein profile

Yılmaz¹,

Güleç²,

Torun³

et al. 2011

“…Those preclinical results reflect a starting point to search any possible systemic confounding effect of ABS when applied to internal topical surfaces. Physiological cell-based coagulation could be clinically managed via topical ABS application to prevent and treat bleeding in many distinct clinicopathological states [7][8][9][10][11][12][13].…”

Section: Discussionmentioning

confidence: 99%

“…ABS has been approved for local topical applications in external post-surgical and post-dental surgery bleedings in Turkey (www.Ankaferd.com). Ankaferd has also been used topically for the management of hemorrhages uncontrolled by standard measures in a wide variety of difficult clinical conditions [7][8][9][10][11][12][13]. Ankaferd represents its unique local hemostatic effect by promoting the very rapid (<1 s) formation of a protein network, which acts as an anchor for vital physiological erythrocyte aggregation, covering the classical cascade model of the clotting system without independently acting on coagulation factors and platelets [1,12].…”

Section: Introductionmentioning

confidence: 99%

Functional proteomic analysis of Ankaferd® Blood Stopper

Demiralp¹,

Haznedaroğlu²,

Akar³

2010

Objective: Ankaferd® Blood Stopper (ABS) comprises a standardized mixture of the plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica. The basic mechanism of action for ABS is the formation of an encapsulated protein network that provides focal points for vital erythrocyte aggregation. ABSinduced protein network formation with blood cells, particularly erythrocytes, covers the primary and secondary hemostatic system without disturbing individual coagulation factors. Materials and Methods: To understand the effect mechanisms of ABS on hemostasis, a proteomic analysis using 2D gel electrophoresis and mass spectrometer was performed. Results: Proteins of plant origin in Ankaferd ® were NADP-dependent-malic enzyme, ribulose bisphosphatecarboxylase-large chain, maturase K, ATP synthase subunit-beta, ATP synthase subunit-alpha, chalcone-flavanone isomerase-1, chalcone-flavanone isomerase-2, and actin-depolymerizing factor. Furthermore, functional proteomic studies revealed that proteins resembling human peptides have been detected within Ankaferd ® , including ATP synthase, mucin-16 (CD164 sialomucin-like 2 protein), coiled-coil domain containing 141 hypothetical protein LOC283638 isoform 1, hypothetical protein LOC283638 isoform 2, dynactin 5, complex I intermediate-associated protein 30, mitochondrial, NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, TP synthase, H+ transporting, mitochondrial actin binding 1 isoform, LIM domain and actin binding 1 isoform a, LIM domain and actin binding 1 isoform b, spectrin alpha non erythrocytic 1, prolactin releasing hormone receptor, utrophin, tet oncogene family member 2 isoform b, protein phosphatase 1 regulatory subunit 12A, NIMA (never in mitosis gene a)-related kinase, ATP-binding cassette protein C12, Homo sapiens malic enzyme 1, mitochondrial NADP(+)-dependent malic enzyme 3, ME2 protein, nuclear factor 1 B-type, abhydrolase domain-containing protein 12B, E3 SUMO-protein ligase PIAS2, alpha-1, 2-glucosyltransferase ALG10-A, cofilin, non-muscle isoform, 18 kDa phosphoprotein, p18, actin-depolymerizing factor (ADF), twinfilin-1, ankyrin repeat and FYVE domain-containing protein 1, usherin precursor, urotensin II receptor, interleukin 4, and midkine. Conclusion: Proteomic analysis of Ankaferd ® represents a true basis for the upcoming Ankaferd ® studies focusing on its wound healing, hemostatic, anti-infective, antineoplastic, and preservative biological actions. (Turk J Hematol 2010; 27: 70-7)

“…Immediate enhanced expression of pro-hemostatic PAI-1 and down-regulation of anti-coagulant EPCR upon exposure to ABS are compatible with the sudden anti-hemorrhagic efficacy previously shown in experimental and clinical settings. The topical hemostatic efficacy of ABS has been previously tested in animals with normal and defective hemostasis [28,29]. Experimental studies have set the preclinical stage for the development of this hemostatic product.…”

Section: Discussionmentioning

confidence: 99%

Surgical and histopathological effects of topical ankaferd hemostat on major arterial vessel injury in relation to the enhanced intra-arterial blood pressure

Uluş¹,

Turan²,

Özyalçın³

et al. 2011

Self Cite

Objective: The aim of this study was to assess the surgical and histopathological hemostatic effects of topical Ankaferd blood stopper (ABS) on major arterial vessel injury related to elevated intra-arterial blood pressure in an experimental rabbit model. Materials and Methods: The study included 14 New Zealand rabbits. ABS was used to treat femoral artery puncture on 1 side in each animal and the other untreated side served as the control. Likewise, for abdominal aortic puncture, only 50% of the aortic injuries received topical liquid ABS and the others did not (control). The experiment was performed under conditions of normal arterial blood pressure and was repeated with a 50% increase in blood pressure. Histopathological analysis was performed in all of the studied animals. Results: Mean bleeding time in the control femoral arteries was 105.0±18.3 s, versus 51.4±9.8 s (p<0.05) in those treated with ABS. Mean blood loss from the punctured control femoral arteries was 5.0±1.5 mg and 1.6±0.4 mg from those treated with ABS (p<0.05). Histopathological examination of the damaged arterial structures showed that ABS induced red blood cell aggregates. Conclusion: ABS administered to experimental major arterial vessel injury reduced both bleeding time and blood loss under conditions of normal and elevated intra-arterial blood pressure. ABS-induced erythroid aggregation was prominent at the vascular tissue level. These findings will inform the design of future experimental and clinical studies on the anti-bleeding and vascular repairing effects of the novel hemostatic agent ABS. (Turk J Hematol 2011; 28: 206-12)