scholarly journals Investigation of the effect of selected edible and medicinal plants on in-vitro blood coagulation profile

2021 ◽  
Author(s):  
Hoda M. Fathy ◽  
◽  
Rahma SR. Mahrous ◽  
Rasha M.Abu EL-Khair ◽  
Abdallah A. Omar ◽  
...  
Keyword(s):  
Medicinal Plants ◽  
Blood Coagulation ◽  
Anticoagulant Activity ◽  
Case Reports ◽  
Anticoagulation Therapy ◽  
Medication Regimen ◽  
Spontaneous Bleeding ◽  
Coagulation Profile ◽  
Treatment And Prevention

Anticoagulation therapy represents a mainstay of treatment and prevention of cardiovascular diseases which are the leading causes of mortality worldwide. In addition, several case reports of spontaneous bleeding occurred linking the consumption of many dietary supplements during treatment with anticoagulants or in postoperative patients. This prompted our study which is conducted on eleven well-known Egyptian medicinal plants to highlight their effect on blood coagulation profile using Prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests. Some of these plants showed interesting results that need more in-depth evaluation of their anticoagulant activity as Hibiscus sabdarifa calyx for its effect on PT. In addition, extracts of Trifolium alexandrinum aerial parts and Pimpinella anismum fruit were proved to affect aPTT. Post operative or cardiovascular patients using herbal supplements should be cautioned about food-drug or herb-drug interactions and to adjust their herbal medication regimen before surgery.

In Vitro Inhibition of Blood Coagulation by Tripeptide Aldehydes - A Retrospective Screening Study Focused on the Stable D-MePhe-Pro-Arg-H · H2SO4

1992 ◽  
Vol 67 (03) ◽  
pp. 325-330 ◽  
Author(s):  
Daniel Bágdy ◽  
Èva Barabás ◽  
Sándor Bajusz ◽  
Erzsébet Széll
Keyword(s):  
Blood Coagulation ◽  
Plasma Proteins ◽  
Anticoagulant Activity ◽  
Coagulation Factors ◽  
Inhibitory Effect ◽  
Inhibitory Potency ◽  
Peptide Aldehydes ◽  
Screening Study ◽  
Tissue Homogenates

SummaryA series of peptide aldehydes synthetized in our institute during the last 15 years were screened to detect their inhibitory effect on blood coagulation. Simple conventional clotting assays, platelet function tests and fibrinolytic methods were used to evaluate the inhibitory potency of the compounds in complex clotting systems as well as their supposed antifibrinolytic effect in vitro. Special attention was paid to the possible interactions with blood cells and plasma proteins, and to the functional stability of the inhibitors in several tissue homogenates. D-Phe-Pro-Arg-H (GYKI-14166, RGH-2958), Boc-D-Phe-Pro-Arg-H (GYKI-14451) and D-MePhe-Pro-Arg-H (GYKI-14766) were found to be the most potent inhibitors. The peptide aldehydes via formation of reversible complexes with thrombin impede the enzyme to react with the coagulation factors, platelet membrane and vessel wall. The compounds inhibit platelet aggregation induced by thrombin specifically without changing the sensitivity of platelets to other inducers. D-Phe-Pro-Arg-H and D-MePhe-Pro-Arg-H showed no antifibrinolytic effect. D-MePhe-Pro-Arg-H and Boc-D-Phe-Pro-Arg-H proved to be stable in dry state for years and in solution at room temperature for several days. The anticoagulant activity of the compounds was declared in NIH antithrombin units.

scholarly journals Platelet Aggregation Activities of Vietnamese Medicinal Plants: Anti-Thrombolytic Potentials?

2020 ◽  
Vol 36 (2) ◽  
Author(s):  
Luong Phu Hung ◽  
Nguyen Thi Van Anh ◽  
Do Tien Dung ◽  
Vu Thi Thom
Keyword(s):  
Platelet Aggregation ◽  
Medicinal Plants ◽  
Traditional Medicine ◽  
Anticoagulant Activity ◽  
Pharmaceutical Journal ◽  
Coagulation System ◽  
Academic Press ◽  
Fourth Edition ◽  
Medical Publisher

Blood coagulant, an important physiological process, underlines pathology of various diseases. Thrombosis caused by activated platelets in blood stream can lead to narrowing or blocking the blood flow, which results in stroke or ischemic conditions. The number of human deaths caused by coronary disease or stroke has been increasing rapidly over the last few years in Vietnam. Many anti-thrombosis and anti-platelet aggregation drugs have been discovered and applied in treatment. However, these drugs have many side effects such as bleeding, stomach lesion, etc. Vietnam is a tropical country with plenty of medicinal plants, from which a potential drug for anti-thrombolytic activities can be prepared. Therefore, an overview of Vietnamese medicinal plants with anti-platelet aggregation activities, such as Panax L., Canna, is highly needed for improving the quality of exploiting Vietnamese medicinal resources. Keywords Anti-thrombosis, Canna, Panax L., platelet aggregation, Vietnamese medicinal plants. References [1] P.T.M. Duc, Physiology, Vietnamese Medical Publisher, 2006 (in Vietnamese).[2] S. H. Yun, E.H. Sim, R.Y. Goh, J.I. Park, J.Y. Han, Platelet Activation: The Mechanisms and Potential Biomarkers, Biomed Res Int, 2016. https://doi.org/10.1155/2016/9060143.[3] E.K. Shin, H. Park, J.Y. Noh, K.M. Lim, J.H. Chung, Platelet Shape Changes and Cytoskeleton Dynamics as Novel Therapeutic Targets for Anti-Thrombotic Drugs, Biomol Ther (Seoul) 25 (2017) 223–230. https://doi.org/10.4062/biomolther.2016.138.[4] R. Flaumenhaft, A. Sharda, 19 - Platelet Secretion, in: A.D. Michelson (Ed.), Platelets (Fourth Edition), Academic Press, 2019, pp. 349–370. https://doi.org/10.1016/B978-0-12-813456-6.00019-9.[5] S.A. Smith, J.H. Morrissey, 21 - Interactions Between Platelets and the Coagulation System, in: A.D. Michelson (Ed.), Platelets (Fourth Edition), Academic Press, 2019, pp. 393–400. https://doi.org/10.1016/B978-0-12-813456-6.00021-7.[6] H.P. Rang, M.M. Dale, J.M. Ritter, R. Flower, G. Henderson, Rang & Dale’s Pharmacology, 7th Edition, Churchill Livingstone, 2011.[7] L. Luyen, V. Thom, L.T. Huong, D.L. Huong, N.V. Anh, Inhibitory effect on human platelet aggregation, antioxidant activity, and phytochemicals of Canna warszewiczii (A. Dietr) Nb. tanaka, Phcog Res. 12 (2020) 47. https://doi.org/10.4103/pr.pr_72_19.[8] B.G. Katzung, A.J. Trevor, Basic & Clinical Pharmacology, 13th ed., Lange, 2015.[9] T. Pham, N. Pham, T.V. Ta, K. Pham, T. Vu, L. Dinh, VKORC1 and CYP2C9*3 Polymorphisms and Their Impacts to Acenocoumarol Dosage in Vietnamese Heart Valve Replacement Patients †1, 2018.[10] J.D. McFadyen, M. Schaff, K. Peter, Current and future antiplatelet therapies: emphasis on preserving haemostasis, Nat Rev Cardiol. 15 (2018) 181–191. https://doi.org/10.1038/nrcardio.2017.206.[11] N.A. Trí, Clinical Coagulation, Vietnam Medical Publisher, 2008 (in Vietnamese).[12] C. Gachet, Antiplatelet drugs: which targets for which treatments?, Journal of Thrombosis and Haemostasis. 13 (2015) S313–S322. https://doi.org/10.1111/jth.12947.[13] V.T Thom, V.P. Thao, V.N. Trung, N.T.T. Mau, The relationship between platelet aggregation and CYP2C19*2, CYP2C19*3 genotypes with other factors in patients with unstable angina, VNU Journal of Science: Medical and Pharmaceutical Sciences 34 (2018) 74–81.[14] C. Patrono, J. Morais, C. Baigent, J.-P. Collet, D. Fitzgerald, S. Halvorsen, B. Rocca, A. Siegbahn, R.F. Storey, G. Vilahur, Antiplatelet Agents for the Treatment and Prevention of Coronary Atherothrombosis, J Am Coll Cardiol 70 (2017) 1760–1776. https://doi.org/10.1016/j.jacc.2017.08.037.[15] R. Teng, Ticagrelor: Pharmacokinetic, Pharmacodynamic and Pharmacogenetic Profile: An Update, Clin Pharmacokinet 54 (2015) 1125–1138. https://doi.org/10.1007/s40262-015-0290-2.[16] R.J. Gryka, L.F. Buckley, S.M. Anderson, Vorapaxar: The Current Role and Future Directions of a Novel Protease-Activated Receptor Antagonist for Risk Reduction in Atherosclerotic Disease, Drugs R D. 17 (2017) 65–72. https://doi.org/10.1007/s40268-016-0158-4.[17] V.D. Loi, T.T. Vung, L.T.T. Huong, Medicial Plants, VNU publisher, 2016.[18] N.V. Đạt, T.T.P. Anh, V.T. Chinh, P.K. Long, H.L.T. Anh, Panax L (Araliaceae) in Vietnam 2017, pp. 106–111 (in Vietnamese).[19] D.T, Lợi, Vietnamese medicinal plants and traditional medicine, Vietnam Medical Publisher, 2004 (in Vietnamese). [20] N.T.T. Trinh., L.T. Tam, V.T. Thom, Đ.Đ Long, D.T.L. Huong, Influence of various fractions extracted from Panax bipinnatifidus (Seem.) on the blood coagulation and platelet aggregation in vitro, Vietnam Pharmaceutical Journal 58 (2018) 06-11–11.[21] L.T.T. Hoa, N.T. Giang, D.T.L. Huong, V.T. Thom Study on the effects of saponin-enriched extracts of Panax bipinnatifidus Seem. and Panax stipuleanatus H.Tsai et K.M.Feng on anti-aggregation activities of platelet in vitro, Journal of Research in Traditional Medicine and Pharmacy 57(2018) 49-60.[22] N.Đ. Phuong, N.D. Nhu, N.D. Thuan, New medicinal plants in Vietnam - Canna warszewiczii A.Dietr, Vietnam Pharmaceutical Journal 476 (2015) 20–23 (in Vietnamese).[23] T.V.A. Nguyen, H.D.T. Ly, T.T. Vu, T.T. Nguyen, H.L. Le, Novel finding on anticoagulant activity of Canna warszewiczii extracts, Asian Journal of Pharmacognosy 2(2) (2018) 30-34.        

Effect of i. v. and Oral Administration of Heparinoids G31150, G31150-A and of Nitrilotriacetic Acid on Blood Coagulation

1971 ◽  
Vol 25 (01) ◽  
pp. 187-200 ◽  
Author(s):  
C. L Jarrett ◽  
L. B Jaques
Keyword(s):  
Absorption Spectrum ◽  
Oral Administration ◽  
Blood Coagulation ◽  
Intravenous Injection ◽  
Anticoagulant Activity ◽  
Chelating Agent ◽  
Nitrilotriacetic Acid ◽  
Clotting Time ◽  
Coagulation Time

SummaryThe heparinoid G31150-A and nitrilotriacetic acid (NTA) were compared with heparinoid G31150 and heparin. In vitro the anticoagulant activity of NTA was 1/20000, G31150-A 1/8th and G31150, 1/10th of heparin. On intravenous injection in dogs, the degree and duration of hypocoagulability was about the same for the two heparinoids but less than predicted from the effects in vitro. Injection of 25 mg NTA/kg caused a slight increase in coagulation time lasting over 4 hours. When heparinoid G31150-A and NTA were given orally, there was an increase in clotting time of blood and metachromatic activity appeared in the urine. The greatest amount of activity was excreted with the highest dose of NTA alone. Microelectrophoresis of the urinary concentrate indicated the excreted material after NTA was not heparin, but another mucopolysaccharide; after G31150, a heparinoid. These results were confirmed by the resulting absorption spectrum of the dye obtained with added urinary concentrate. It is suggested that the effects produced when a chelating agent is given with oral heparin and heparinoids may be due to the release of a mucopolysaccharide.

In vitro anticoagulant activity of selected medicinal plants: potential interactions with warfarin and development of new anticoagulants

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Paula Mendonça Leite ◽  
Aline Freitas ◽  
Juliana Amorim ◽  
Rita Carolina Duarte Figueiredo ◽  
Suzan Bertolucci ◽  
...  
Keyword(s):  
Medicinal Plants ◽  
Anticoagulant Activity ◽  
Cross Sectional Study ◽  
Clinical Value ◽  
Cross Sectional ◽  
New Anticoagulants ◽  
Chemical Profiles ◽  
Ethanol Extracts ◽  
Mentha Crispa

Abstract Objectives Warfarin is the most widely used anticoagulant in the world, but it has several limitations including its narrow therapeutic range, need for dose adjustment and high potential for interactions. The simultaneous use of other drugs or even medicinal plants and certain foods could interfere with its therapeutic activity. In this context, this study aims to investigate the in vitro anticoagulant potential and phytochemical constitution of 17 plants selected from a previous clinical cross-sectional study (2014), that investigated the habits of plant utilization among patients taking warfarin. Methods Ethanol extracts and essential oils were evaluated, in vitro, as to their effect in the prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests. Four species that presented aPTT >50 s were selected for phytochemical evaluation. Results Thirteen of the 17 plants selected demonstrated a significant anticoagulant effect in at least one of the evaluated parameters. Citrus sinensis (PT=14.75 and aPTT=53.15), Mentha crispa (aPTT=51.25), Mikania laevigata (PT=14.90 and aPTT=52.10), and Nasturtium officinale (aPTT=50.55) showed greater anticoagulant potential compared to normal plasma pool (PT=12.25 and aPTT=37.73). Chemical profiles of these four species were obtained, and certain compounds were identified: rosmarinic acid from M. crispa and isoorientin from N. officinale. Conclusions Thus, the results of this study could be a useful indicator for clinical practice towards the possibility of interaction between these plants and anticoagulants, although further clinical research is needed taking into consideration the limitations of in vitro studies. These findings also suggest that further research into the action of these plants could be of real clinical value in identifying potential alternative anticoagulant therapies.

A Novel Polymer Based Antidote for Reversing the Anticoagulation Effect of Clinically Used Heparins,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3359-3359
Author(s):  
Rajesh A Shenoi ◽  
Benjamin F L Lai ◽  
Dirk Lange ◽  
Donald E Brooks ◽  
Ben Chew ◽  
...  
Keyword(s):  
Blood Coagulation ◽  
Complement Activation ◽  
Conflicts Of Interest ◽  
Dose Range ◽  
Anticoagulation Therapy ◽  
The Body ◽  
Bleeding Complications ◽  
Clinical Practices

Abstract Abstract 3359 Introduction Anticoagulation is one of the most widely used and essential clinical practices in modern medicine. Heparins are universally used for the prevention of blood coagulation in surgical procedures and for the treatment of diseases such as venous thromboembolism (VTE). Unfractionated heparin (UFH), low and ultra-low molecular weight heparins (LMWHs&ULMWHs) and synthetic pentasaccharides such as fondaparinux and idraparinux are the most commonly used clinical anticoagulants. Heparin is the second most widely used drug after insulin. However, it is associated with bleeding complications and heparin induced thrombocytopenia. Hence a careful monitoring and neutralization of heparins is essential. Protamine is the only clinically approved antidote to UFH, but it has several side effects and is not effective against LMWHs and synthetic pentasaccharides. Hence there is an unmet clinical need to develop safer and more efficient antidotes for all these anticoagulants. Here, we report a novel polymer based antidote, heparin binding synthetic polyvalent cationic macromolecule (HBSPCM), that completely neutralizes UFH and LMWHs in vitro and in vivo and is highly biocompatible and non-toxic in the required therapeutic dose range. Experimental HBSPCMs were synthesized by the polymerization of glycidol and methoxy polyethylene glycol and functionalized with multifunctional tertiary amines as binding groups. Blood compatibility of HBSPCM was evaluated by activated partial thromboplastin time (APTT), prothrombin time (PT), thromboelastography (TEG), platelet and complement activation assays. Cell viability of HBSPCM was evaluated in human umbilical vein endothelial cells and fibroblast cells. Single dose tolerability in mice was studied by injecting escalating doses of HBSPCM and monitoring the body weights over a period of 29 days. HBSPCMs were tested for in vitro heparin neutralization by measuring the APTT in human plasma. An anti-fXa assay was used to study the in vivo neutralization of heparins by HBSPCM in a rat model. Pharmacokinetics and biodistribution of 3H-labeled HBSPCM was studied by bolus i.v. injection in female Balb/c mice and measuring the radioactivity in major organs at different time points. Results and Discussion The newly designed antidotes, HBSPCMs, alone do not show any adverse effect on blood coagulation, platelet and complement activation and cytotoxicity that reveal their excellent blood and cell compatibilities. When injected in mice, HBSPCMs were well-tolerated up to the maximum injected dose of 200 mg/kg, which is ten-fold higher than the maximum tolerated dose of protamine (20 mg/kg) (Figure 1). HBSPCMs were 20-times more efficient than protamine for neutralizing heparins in vitro, and unlike protamine they do not show anticoagulant effect at higher concentrations. In vivo studies in rats revealed complete neutralization of both UFH and LMWHs by HBSPCMs, and the neutralization activities for LMWHs were significantly higher than that of protamine (Figure 2). HBSPCMs and their heparin complexes showed rapid clearance through urine, without significant accumulation in major organs. Conclusions and Significance In order to overcome the challenges associated with heparin based anticoagulation therapy, there is an increasing demand to develop safer, stable, effective, economical and universal antidotes which could neutralize all the available heparin anticoagulants. The developed polymer based antidote, HBSPCM, represents a major breakthrough towards this goal and could be a potential replacement for protamine. This polymer based therapeutic agent opens the scope for the development of non-toxic antidotes for all heparin based drugs. Disclosures: No relevant conflicts of interest to declare.

A Comprehensive Review on Ethnomedicinal, Pharmacological and Phytochemical Basis of Anticancer Medicinal Plants of Pakistan

2019 ◽  
Vol 19 (2) ◽  
pp. 120-151 ◽  
Author(s):  
Muhammad Furqan Akhtar ◽  
Ammara Saleem ◽  
Alamgeer ◽  
Mohammad Saleem
Keyword(s):  
Medicinal Plants ◽  
Conservation Status ◽  
Chemotherapeutic Agents ◽  
Anticancer Activities ◽  
Toxicological Evaluation ◽  
Worldwide Distribution ◽  
Treatment And Prevention ◽  
Development Of Resistance

The widespread emergence of cancer and development of resistance to chemotherapeutic agents is increasing the interest of scientists in the use of ethnomedicinal preparations and isolated phytochemicals in the treatment and prevention of disease. Medicinal plants have been used in Pakistan since prehistoric times. </P><P> The present review was designed to identify anticancer plants of ethnomedicinal significance and to summarize the anticancer activities carried out on these medicinal plants to establish the pharmacological and phytochemical basis of their use. </P><P> Pakistani anticancer medicinal plants of ethnopharmacological significance were reviewed. Conservation status, worldwide distribution and ethno-botanical preparations of these medicinal plants were also tabulated. These medicinal plants and their isolated phytochemicals were also explored for their anticancer activities. </P><P> It was revealed that there were 108 anticancer medicinal plants used to treat different neoplastic conditions on the folklore basis throughout Pakistan. Among these anticancer plants, 64 plants were found to be investigated previously for anticancer activity through in vivo and in vitro methods. Several ethnomedicinal plants have been validated for their anticancer activities through in vitro and animal models. These medicinal plants and phytochemicals resulted in the inhibition of initiation, progression or metastasis of neoplasm. Some medicinal plants (10) are endangered species. </P><P> Half of folkloric Pakistani plants have been validated for use against various cancers through in vitro or in vivo methods. It is necessary to carry out further pharmacological and toxicological evaluation of these folkloric anticancer plants of Pakistan. It is also necessary to identify and isolate further potential phytochemicals so as to be evaluated in cancer patients.

In Vitro Anti-Infective Screening Of Selected West African Medicinal Plants

Planta Medica ◽  
2016 ◽  
Vol 82 (05) ◽  
Author(s):  
VO Imieje ◽  
PS Fasinu ◽  
KO Ogbeide ◽  
NO Egiebor ◽  
A Falodun
Keyword(s):  
Medicinal Plants ◽  
West African

Dermatan Sulfate and LMW Heparin Enhance the Anticoagulant Action of Activated Protein C

1999 ◽  
Vol 82 (11) ◽  
pp. 1462-1468 ◽  
Author(s):  
José Fernández ◽  
Jari Petäjä ◽  
John Griffin
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Protein C ◽  
Dermatan Sulfate ◽  
Anticoagulant Activity ◽  
Activated Protein C ◽  
Factor V ◽  
Factor Va ◽  
Anticoagulant Action

SummaryUnfractionated heparin potentiates the anticoagulant action of activated protein C (APC) through several mechanisms, including the recently described enhancement of proteolytic inactivation of factor V. Possible anticoagulant synergism between APC and physiologic glycosaminoglycans, pharmacologic low molecular weight heparins (LMWHs), and other heparin derivatives was studied. Dermatan sulfate showed potent APC-enhancing effect. Commercial LMWHs showed differing abilities to promote APC activity, and the molecular weight of LMWHs correlated with enhancement of APC activity. Degree of sulfation of the glycosaminoglycans influenced APC enhancement. However, because dextran sulfates did not potentiate APC action, the presence of sulfate groups per se on a polysaccharide is not sufficient for APC enhancement. As previously for unfractionated heparin, APC anticoagulant activity was enhanced by glycosaminoglycans when factor V but not factor Va was the substrate. Thus, dermatan sulfate and LMWHs exhibit APC enhancing activity in vitro that could be of physiologic and pharmacologic significance.

Assays for Phospholipid-Dependent Formation of Thrombin and Xa: A Potential Method for Quantifying Lupus Anticoagulant Activity

1991 ◽  
Vol 66 (04) ◽  
pp. 453-458 ◽  
Author(s):  
John T Brandt
Keyword(s):  
Specific Activity ◽  
Anticoagulant Activity ◽  
Factor Xa ◽  
Clinical Importance ◽  
Potential Method ◽  
Quantitative Expression ◽  
Increased Risk ◽  
Apparent Association

SummaryLupus anticoagulants (LAs) are antibodies which interfere with phospholipid-dependent procoagulant reactions. Their clinical importance is due to their apparent association with an increased risk of thrombo-embolic disease. To date there have been few assays for quantifying the specific activity of these antibodies in vitro and this has hampered attempts to purify and characterize these antibodies. Methods for determining phospholipid-dependent generation of thrombin and factor Xa are described. Isolated IgG fractions from 7 of 9 patients with LAs were found to reproducibly inhibit enzyme generation in these assay systems, permitting quantitative expression of inhibitor activity. Different patterns of inhibitory activity, based on the relative inhibition of thrombin and factor Xa generation, were found, further substantiating the known heterogeneity of these antibodies. These systems may prove helpful in further purification and characterization of LAs.

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