Ankaferd hemostat (ABS) as a potential mucosal topical agent for the management of COVID-19 syndrome based on its PAR-1 inhibitory effect and oestrogen content.

COVID-19 due to the SARS-CoV-2 infection is a multi-systemic immune syndrome affecting mainly the lungs, oropharyngeal region, and other vascular endothelial beds. There are tremendous ongoing efforts for the aim of developing drugs against the COVID-19 syndrome-associated inflammation. However, currently no specific medicine is present for the absolute pharmacological cure of COVID-19 mucositis. The re-purposing/re-positioning of already existing drugs is a very important strategy for the management of ongoing pandemy since the development of a new drug needs decades. Apart from altering angiotensin signaling pathways, novel drug candidates for re-purposing comprise medications shall target COVID-19 pathobiology, including pharmaceutical formulations that antagonize proteinase-activated receptors (PARs), mainly PAR-1. Activation of the PAR-1, mediators and hormones impact on the hemostasis, endothelial activation, alveolar epithelial cells and mucosal inflammatory responses which are the essentials of the COVID-19 pathophysiology. In this context, Ankaferd hemostat (Ankaferd Blood Stopper, ABS) which is an already approved hemostatic agent affecting via vital erythroid aggregation and fibrinogen gamma could be a potential topical remedy for the mucosal management of COVID-19. ABS is a clinically safe and effective topical hemostatic agent of plant origin capable of exerting pleiotropic effects on the endothelial cells, angiogenesis, cell proliferation and vascular dynamics. ABS had been approved as a topically applied hemostatic agent for the management of post-surgical/dental bleedings and healing of infected inflammatory mucosal wounds. The anti-inflammatory and proteinase-activated receptor axis properties of ABS with a considerable amount of oestrogenic hormone presence highlight this unique topical hemostatic drug regarding the clinical re-positioning for COVID-19-associated mucositis. Topical ABS as a biological response modifier may lessen SARS-CoV-2 associated microthrombosis, endothelial dysfunction, oropharyngeal inflammation and mucosal lung damage. Moreover, PAR-1 inhibition ability of ABS might be helpful for reducing the initial virus propagation and mocasal spread of COVID-19.

Analysis of the Antiproliferative Effect of Ankaferd Hemostat on Caco-2 Colon Cancer Cells via LC/MS Shotgun Proteomics Approach.

Ankaferd hemostat (ABS), a traditional herbal extract, is a hemostatic agent used for wound healing and bleeding treatment. A standardized form of plants contains many biomolecules. In recent years, previous studies have demonstrated the antineoplastic effect of ABS. In the present work, we focused on the mechanism of its antineoplastic effect over Caco-2 colon cancer cells. The LC/MS-based proteomics method was used to understand the effect of ABS at the protein level. The results were evaluated with gene ontology, protein interaction, and pathway analysis. As shown by our results, ABS altered glucose, fatty acids, and protein metabolism. Moreover, ABS affects the cell cycle machinery. Moreover, we found that ABS induced critical cancer target and suppressor proteins such as carboxyl-terminal hydrolase 1, 60S ribosomal protein L5, Tumor protein D52-like2, karyopherin alpha 2, and protein deglycase DJ-1. In conclusion, the proteomics results indicated that ABS affects various cancer targets and suppressor proteins. Moreover ABS has systematical effect on cell metabolism and cell cycle in Caco-2 cells, suggesting that it could be used as an antineoplastic agent.

Effects of Ankaferd Hemostat on Helicobacter pylori strains and antibiotic resistance

Background/aim: Ankaferd hemostat (ABS; Ankaferd blood stopper, Istanbul, Turkey) is a folkloric medicinal plant extract. The aim of this study was to determine the effect of Ankaferd hemostat (ABS) on the fate of Helicobacter pylori strains. The study also aims to determine alterations in the antimicrobial resistance of three different H. pylori strains in response to ABS exposure. Materials and methods: H. pylori Strain 1 was obtained from the culture collection ATCC 43504 and passaged three times for viability. Strain 2 was isolated from a gastric ulcer patient and Strain 3 was isolated from a gastritis patient. 1% of ABS was added to all of the strains and antimicrobial susceptibility was observed on 30 and 60 min after application. Results: The efficacy of ABS solutions in achieving significant logarithmic reduction in foodborne pathogens of H. pylori was observed in this study. This study showed that ABS has antibacterial (Anti-H. pylori) effects. Conclusion: Our present study indicated, for the first time, that ABS could act against H. pylori. ABS is clinically used for the management of GI bleeding due to benign and malignant GI lesions. Thus, the possible anti-H. pylori effect of ABS shall expand the therapeutic spectrum of the drug in GI lesions in relation to H. pylori infection such as peptic ulser disease (PUD) and lymphoid tissue (MALT) lymphomagenesis.

Antibacterial Activities of Ankaferd Hemostat (ABS) on Shiga Toxin-Producing Escherichia coli and Other Pathogens Significant in Foodborne Diseases.

OBJECTIVE: Ankaferd hemostat (Ankaferd Blood Stopper®, ABS)-induced pharmacological modulation of essential erythroid proteins can cause vital erythroid aggregation via acting on fibrinogen gamma. Topical endoscopic ABS application is effective in the controlling of gastrointestinal (GI) system hemorrhages and/or infected GI wounds. Escherichia coli O157:H7, the predominant serotype of enterohemorrhagic E. coli, is a cause of both outbreaks and sporadic cases of hemorrhagic colitis. The aim of this study is to examine the effects of ABS on 6 different Shiga toxigenic E. coli serotypes including O26, O103, O104, O111, O145, and O157 and on other pathogens significant in foodborne diseases, such as Salmonella Typhimurium, Campylobacter jejuni, and Listeria monocytogenes, were also assessed. MATERIALS AND METHODS: All strains were applied with different amounts of ABS and antimicrobial effect was screened. S. Typhimurium groups were screened for survival using the fluorescence in situ hybridization technique. RESULTS: The relative efficacy of ABS solutions to achieve significant logarithmic reduction in foodborne pathogens E. coli O157:H7 and non-O157 serogroups and other emerging foodborne pathogens is demonstrated in this study. ABS has antibacterial effects. CONCLUSION: Our present study indicated for the first time that ABS may act against E. coli O157:H7, which is a cause of thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, and hemorrhagic colitis. The interrelationships between colitis, infection, and hemostasis within the context of ABS application should be further investigated in future studies.

Splenic artery embolization with Ankaferd blood stopper in a sheep model.

PURPOSE: Splenic artery embolization is a minimally invasive therapeutic procedure utilized in a number of disorders. Ankaferd blood stopper (ABS) is a novel hemostatic agent with a new mechanism of action independent of clotting factors. We aimed to investigate the safety and efficiency of ABS for splenic artery embolization in a sheep model. METHODS: Seven adult female sheep were included in the study. Selective celiac angiography was performed using a 5F diagnostic catheter and then a 2.7F hydrophilic coating microcatheter was advanced coaxially to the distal part of the main splenic artery. Under fluoroscopic guidance, 6 mL mixture composed of half-and-half ABS and contrast agent was slowly injected. Fluoroscopy was used to observe the deceleration and stagnation of the flow. Control celiac angiograms were obtained immediately after the embolization. After the procedure, the animals were observed for one day and then sacrificed with intravenous sodium thiopental. RESULTS: Technical success rate was 100%. None of the animals died or experienced a major systemic adverse event during the procedure. All of the spleens appeared dark on macroscopic examination due to excessive thrombosis. Microscopically, the majority of the splenic sinusoids (90%-95%) were necrotic. CONCLUSION: In our study, splenic artery embolization by ABS was found to be safe and effective in the short-term. Further studies are needed to better understand the embolizing potential of this novel hemostatic agent.

Qualitative/Chemical Analyses of Ankaferd Hemostat and Its Antioxidant Content in Synthetic Gastric Fluids.

INTRODUCTION: Ankaferd hemostat (ABS) is the first topical haemostatic agent involving the red blood cell-fibrinogen interactions. The antihemorrhagic efficacy of ABS has been tested in controlled clinical trials. The drug induces the formation of an encapsulated complex protein web with vital erythroid aggregation. The aim of this study is to detect the essential toxicity profile and the antioxidant molecules inside ABS. METHODS: The pesticides were analyzed by GC-MS and LC-MS. The determination by ICP-MS after pressure digestion was performed for the heavy metals. HPLC was used for the detection of mycotoxins. Dioxin Response Chemically Activated Luciferase Gene Expression method was used for the dioxin evaluation. TOF-MS and spectra data were evaluated to detect the antioxidants and other molecules. RESULTS: TOF-MS spectra revealed the presence of several antioxidant molecules (including tocotrienols, vitamin E, tryptophan, estriol, galangin, apigenin, oenin, 3,4-divanillyltetrahydrofuran, TBHQ, thymol, BHA, BHT, lycopene, glycyrrhetinic acid, and tomatine), which may have clinical implications in the pharmacobiological actions of ABS. CONCLUSION: The safety of ABS regarding the presence of heavy metals, pesticides, mycotoxins, GMO and dioxins, and PCBs was demonstrated. Thus the present toxicological results indicated the safety of ABS. The antioxidant content of ABS should be investigated in future studies.

Effective management of hemoptysis via endobronchial application of Ankaferd hemostat.

Hemoptysis is symptomatic of potentially serious and life-threatening chest disease and requires urgent evaluation and treatment. The aim of this study was to evaluate the hemostatic efficacy of endobronchial application of Ankaferd Blood Stopper(®) (ABS) solution in patients with hemoptysis. This retrospective study included 20 patients with hemoptysis in whom endobronchial ABS was applied in 25 bronchoscopic procedures. Endobronchial application of ABS was successful in 23 of the 25 bronchoscopic procedures. ABS application was repeated due to recurrent bleeding in 4 patients. This is the first case series demonstrating the endobronchial application of ABS, a novel hemostatic agent, effective in the management of bleeding, especially in local endobronchial malignant lesions. Bronchoscopic ABS application may be an alternative supportive therapeutic method in cases of uncontrolled hemoptysis.

Topical Ankaferd hemostat application for the management of oral cavity bleedings in children with hemorrhagic diathesis.

Ankaferd blood stopper (ABS) is a hemostatic agent used topically for controlling bleedings of skin or mucosal surfaces in Turkey. It is currently topically used in bleedings of body injuries, traumas, and minor or major surgical interventions. Here we have evaluated 12 pediatric patients with hemorrhagic diathesis on whom Ankaferd was used for oral bleedings. Topical Ankaferd was administered for hemorrhages of oral cavity during 15 bleeding attacks. ABS administrations successfully stopped the bleedings, except for one patient with oral hemorrhage who did not respond to ABS application. Ankaferd is effective for oral bleedings of children with bleeding diathesis especially when other measures have failed.

Prohemostatic and antithrombin activities of Ankaferd hemostat are linked to fibrinogen gamma chain and prothrombin by functional proteomic analyses.

Ankaferd blood stopper (ABS) is a novel topical hemostatic agent of plant origin registered for the management of external hemorrhages, in Turkey. The ABS-induced formation of the protein network with vital erythroid aggregation covers the whole physiological hemostatic process. The aim of this study is to assess prohemostatic and antithrombin effects of ABS on the basis of functional proteomic analyses performed in ABS-treated plasma and serum samples based on the previous hypotheses about ABS action. For this purpose, serum and plasma proteins were separated by 2-dimensional (2D) gel electrophoresis, and proteins were identified using reference plasma gel on Swiss-2DPAGE database. Our results indicated that fibrinogen gamma chain and prothrombin levels just initially decreased first and thereafter enhanced following the ABS exposure. Dual effects of ABS on those critical hemostatic molecules seem to be associated with prohemostatic and antithrombin activities of the hemostatic agent.

Pleiotropic cellular, hemostatic, and biological actions of Ankaferd hemostat.

Sustaining hemostasis in clinical hemorrhages is a challenging task and requires extensive effort to stabilize medically hard-to-treat traumatic injuries. Several hemostatic agents are preferred to control external and internal bleedings, yet commercially available products are not sufficiently effective or fast-acting to achieve hemostasis in extreme cases. Ankaferd Blood Stopper (ABS) is a herbal extract traditionally used as a hemostatic agent. Recent studies have shown that ABS could be utilized successfully as a hemostatic agent for the management of clinical hemorrhages when conventional methods were ineffective. This review serves as a basis to provide recent findings on several applications of ABS, specifically preclinical, biological, and clinical studies both in vitro and in vivo. Another section focuses on the ultrastructural morphology and protein network formation of ABS in an effort to understand the hemostatic mechanisms of this unique agent at tissue level.

Ankaferd hemostat in the management of gastrointestinal hemorrhages.

Gastrointestinal (GI) bleeding refers to any hemorrhage ascribed to the pathologies of the gastrointestinal tract, extending from the mouth to the anal canal. Despite the recent improvements in the endoscopic, hemostatic and adjuvant pharmacologic techniques, the reported mortality is still around 5%-10% for peptic ulcer bleeding and about 15%-20% for variceal hemorrhages. Although endoscopic management reduces the rates of re-bleeding, surgery, and mortality in active bleeding; early recurrence ratios still occur in around 20% of the cases even with effective initial hemostatic measures. In this quest for an alternative pro-hemostatic agent for the management of GI bleedings, Ankaferd blood stopper (ABS) offers a successful candidate, specifically for "difficult-to-manage" situations as evidenced by data presented in several studies. ABS is a standardized mixture of the plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica. It is effective in both bleeding individuals with normal hemostatic parameters and in patients with deficient primary and/or secondary hemostasis. ABS also modulates the cellular apoptotic responses to hemorrhagic stress, as well as hemostatic hemodynamic activity. Through its effects on the endothelium, blood cells, angiogenesis, cellular proliferation, vascular dynamics, and wound healing, ABS is now becoming an effective alternative hemostatic medicine for gastrointestinal bleedings that are resistant to conventional anti-hemorrhagic measurements. The aim of this review is to outline current literature experience suggesting the place of ABS in the management of GI bleeding, and potential future controlled trials in this complicated field.