Hemostatic Role of a Folkloric Medicinal Plant Extract in a Rat Partial Nephrectomy Model: Controlled Experimental Trial

Hurі, Emre; Akgül, Turgay; Ayyıldız, Ali; Üstün, Hüseyin; Germíyanoğlu, Cankon

doi:10.1016/j.juro.2009.01.016

Cited by 41 publications

(44 citation statements)

References 16 publications

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“…Numerous studies reported the hemostatic effects of topical ABS in the animals with normal [10,12,14,[16][17][18] and defective hemostasis [15,24], and have set the preclinical stage for the development of this hemostatic product. The effects of ABS on hemostatic parameters have also been searched [2,6,25].…”

Section: Discussionmentioning

confidence: 99%

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

Yılmaz¹,

Güleç²,

Torun³

et al. 2011

Turk J Hematol

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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)

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Section: Discussionmentioning

confidence: 99%

“…The hemostatic effects of ABS have been observed in vitro and in vivo [12][13][14][15][16][17][18]. Use of ABS as a hemostatic agent in external hemorrhages and in dental treatment in humans provided the first data showing that ABS was safe and effective in humans [9].…”

Section: Introductionmentioning

confidence: 99%

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

Yılmaz¹,

Güleç²,

Torun³

et al. 2011

Turk J Hematol

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“…Topical hemostatic efficacy of ABS has been previously tested in animals with normal [2,5] and defective hemostasis [3,6]. Short-term hematological and biochemical safety of the oral systemic administration of Ankaferd to rabbits has been shown [20].…”

Section: Discussionmentioning

confidence: 99%

“…Topical safety of ABS in normal healthy human volunteers was shown in a randomized double-blind cross-over Phase I clinical trial after preclinical animal studies [2][3][4][5][6]. ABS has been approved for local topical applications in external post-surgical and post-dental surgery bleedings in Turkey (www.Ankaferd.com).…”

Section: Introductionmentioning

confidence: 99%

Functional proteomic analysis of Ankaferd® Blood Stopper

Demiralp¹,

Haznedaroğlu²,

Akar³

2010

Turk J Hematol

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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)

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“…Those findings are compatible with the previous studies by Huri et al testing topical ABS in the in the partial nephrectomy and renal trauma models. [18][19][20] Essential erythroid proteins (Ankrin recurrent and FYVE bundle containing protein 1, Spectrin alpha, Actin-depolimerisation factor, Actin-depolimerizing factor, LIM bundle and actine binding subunit 1 isoform a, LIM bundle and actine binding subunit 1 isoform b, NADP-dependent malic enzyme, NADH dehydrogenase (Ubiquinone) 1 alpha subcomplex, Mitochondrial NADP (+) dependent malic enzyme 3, Ribulose bisphosphatecarbocsilase large chain, Maturase K) and the required ATP bioenergy (ATP synthase, ATP synthase beta subunit, ATP synthase alpha subunit, ATP-binding protein C12, TP synthase H+ transporter protein, ADF, Alpha-1,2-glycosyltransferase ALG10-A) are included in the protein library of ABS. ABS also up-regulates GA-TA/FOG transcription system affecting erythroid functions and urotensin II.…”

Section: Discussionmentioning

confidence: 99%

Histopathological Alterations in the Kidney Tissue Following Topical Ankaferd Hemostat Application in a Rat Renal Injury Model

Karakoç¹,

Akar²,

Aksu³

et al. 2012

UHOD

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Ankaferd Blood Stopper (ABS) is a novel topical hemostatic agent. ABS has been approved in Turkey for clinical hemorrhages, when the conventional control of bleeding by ligature and/or conventional hemostatic measures is ineffective. ABS has many cellular effects and could modulate numerous hemostatic proteins at the tissue and blood. ABS-induced formation of the protein network with vital erythroid aggregation covers the entire physiological hemostatic process. The aim of this study was to assess histopathological alterations due to topical ABS administration at the renal tissue level. Thirty-six Wistar rats weighing 70 to 80 gm were included into the study. The rats were divided into two groups as "the ABS-applied group" (ABS−G) and "the control group" (C−G). The animals in both groups were then again divided into the three subgroups of "postoperative (Postop.) 60th minutes", "Postop. 48th hours", and "Postop. 15th day". Therefore, there were six rats in each of the subgroups at the end of the analyses. The standard renal injury sites in the rats of ABS−G were applied 2 ml. of topical ABS, whereas 2 ml. of topical saline was applied to the renal injury sites of the rats in the C−G group. We detected significant erythrocyte aggregation and the accumulation of siderophages in the kidney tissue just after 60 minutes of ABS application persisting over 15 days. Our results indicated red blood cell accumulation and siderophages following the use of ABS are compatible with the suggested 'mechanism-of-action' of ABS that ABS-induced formation of the protein network with vital erythroid aggregation covers the entire physiological hemostatic process. Further experimental search is needed to find out the molecules inside the ABS protein library leading to the ABS-induced aggregation at the renal tissue level.

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Hemostatic Role of a Folkloric Medicinal Plant Extract in a Rat Partial Nephrectomy Model: Controlled Experimental Trial

Abstract: Ankaferd BloodStopper decreases partial nephrectomy and warm ischemia times, and provides hemostasis. Erythrocyte aggregation confirmed the hemostatic action of the agent, while the absence of glomerular necrosis and calcification may have positive relevance.

Cited by 41 publications

References 16 publications

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

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

Functional proteomic analysis of Ankaferd® Blood Stopper

Histopathological Alterations in the Kidney Tissue Following Topical Ankaferd Hemostat Application in a Rat Renal Injury Model

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