Author(s):
G.M. Abdullina, N.V. Kudashkina, S.R. Khasanova, S.E. Romanova
Email(s):
gmabdullina@mail.ru
DOI:
10.52711/0974-360X.2026.00201
Address:
G.M. Abdullina1, N.V. Kudashkina2, S.R. Khasanova2, S.E. Romanova3
1Department of Biochemistry, Bashkir State Medical University, Ufa, Russian Federation.
2Department of Pharmacognosy and Botany, Bashkir State Medical University, Ufa, Russian Federation.
3Department of Pharmacology with the course of Clinical Pharmacology, Bashkir State Medical University, Ufa, Russian Federation.
*Corresponding Author
Published In:
Volume - 19,
Issue - 3,
Year - 2026
ABSTRACT:
Objectives: To consider the specifics of the research methodology for the antithrombotic (anticoagulation and antiplatelet) activity of plant bioactive compounds, that represent a great potential in the development of novel drugs for the correction of hemostasis disorders. Materials and methods: analysis of research data obtained in the peer-reviewed bibliographic databases PubMed, Google Scholar for the search query "plant biologically active compounds", "anticoagulation activity", "antiplatelet activity", "hemostasis". Results: In vitro experiments predominate in the structure of studies of the effect of phytochemicals on the hemostasis system. To assess the effect on coagulation hemostasis, standard blood clotting tests (activated partial prothrombin time, prothrombin time, thrombin time) are most commonly used, antiplatelet activity is commonly assessed using the optical aggregometry method. In studies of the effect of plant bioactive compounds on the hemostasis system, two directions can be distinguished, in particular, the study of the effect of crude extracts - screening, aimed at finding promising plant sources of substances with antithrombotic activity. The second research strategy is to isolate, fractionate and identify a class of biologically active substances or individual compounds directly responsible for exerting anticoagulation and/or antiplatelet activity. Both crude phytoextracts and individual plant compounds can have a multidirectional effect on the hemostasis system, at the same time, a larger number of plant biologically active compounds exert their effect on hemostasis at the platelet level. Conclusions: In the number of classes of plant biologically active compounds with the most pronounced effect on the hemostatic system (antiplatelet effect), classes of phytochemicals such as phenolic compounds (curcuminoids, lignans, phenolic acids, flavonoid polyphenols, coumarins), alkaloids, saponins, iridoid glycosides, sesquiterpenes, and furan derivatives can be noted. The available data allow us to conclude that the main target for the action of plant origin bioactive compounds is the arachidonic acid cascade signaling pathway.
Cite this article:
G.M. Abdullina, N.V. Kudashkina, S.R. Khasanova, S.E. Romanova. Methodological Approaches to Assessing Influence of Plant Bioactive Substances on Hemostasis System. Research Journal Pharmacy and Technology. 2026;19(3):1395-2. doi: 10.52711/0974-360X.2026.00201
Cite(Electronic):
G.M. Abdullina, N.V. Kudashkina, S.R. Khasanova, S.E. Romanova. Methodological Approaches to Assessing Influence of Plant Bioactive Substances on Hemostasis System. Research Journal Pharmacy and Technology. 2026;19(3):1395-2. doi: 10.52711/0974-360X.2026.00201 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2026-19-3-62
REFERENCES:
1. Bochanova EN, Vajman EJe, Gackih EV, Goncharova PS, Demko IV, Zimnickaja OV et al. Pharmacogenetics of direct oral anticoagulants. SPb.: DEAN. 2022.
2. Myers K, Lyden A. A Review on the New and Old Anticoagulants. Orthop Nurs. 2019; 38(1): 43-52. doi:10.1097/NOR.0000000000000517
3. Kosarev VV, Babanov SA. Clinical pharmacology of modern antiplatelet agents and their place in the pharmacotherapy of coronary heart disease and associated conditions. Russian Medical Journal. 2013; 21(27): 1378-1383. doi: Not Available
4. Kuter DJ. Novel therapies for immune thrombocytopenia. Br. J. Haematol. 2022; 196(6): 1311- 1328. doi: 10.1111/bjh.17872
5. Iqbal AM, Lopez RA, Hai O. Antiplatelet medications. Treasure Island (FL): StatPearls Publishing; 2022. available on https://www.ncbi.nlm.nih.gov/books/NBK537062/ (access date: 22.02.2022).
6. Tanashyan MM, Raskurazhev AA, Kuznetsova PI. Aspirin: The legend continues. Preventive Medicine. 2018; 21(5): 124-129. doi. org/10.17116/profmed201821051124
7. Talik P, Krzek J, Ekiert RJ. Analytical techniques used for determination of methylxanthines and their analogues—Recent advances. Separation and Purification Reviews. 2012; 41(1): 1-61. doi: 10.1080/15422119.2011.569047
8. Matos MJ. Coumarin and its derivatives – Editorial. Molecules. 2021; 26(20): 6320. doi:10.3390/molecules26206320
9. Quindere ALG, Santos GRC, Oliveira S-NMCG, Glauser BF, Fontes BF, Queiroz INL. et al. Is the antithrombotic effect of sulfated galactans independent of serpin? J Thromb Haemost. 2014; 12: 43–53. doi:10.1111/jth.12448
10. Markwardt F. Hirudin as alternative anticoagulant--a historical review. Semin Thromb Hemost. 2002; 28(5): 405-414. doi:10.1055/s-2002-35292
11. Ponphaiboon J, Krongrawa W, Aung WW, Chinatangkul N, Limmatvapirat S, Limmatvapirat C. Advances in Natural Product Extraction Techniques, Electrospun Fiber Fabrication, and the Integration of Experimental Design: A Comprehensive Review. Molecules. 2023; 28(13): 5163. doi:10.3390/molecules28135163
12. Abubakar AR, Haque M. Preparation of medicinal plants: Basic extraction and fractionation procedures for experimental purposes. J Pharm Bioal Sci. 2020;12:1-10. doi:10.4103/jpbs.IPBS_175_19
13. Musifulina VM, Omarov MM. Comparative characteristics of extraction methods of plant raw materials. Bulletin of the Innovative Eurasian University. 2021; 4(84): 107-112. doi:10.37788/2021-4/107-112
14. Chamara MR, Thiripuranathar G. Assessment of Haemostatic Activity of Medicinal Plants Using In Vitro Methods: A Concise Review. Journal of Pharmacy and Biological Sciences. 2020: 15(1): 26-34. doi:10.9790/3008-1501022634
15. Ebrahimi F, Torbati M, Mahmoudi J, Valizadeh H. Medicinal Plants as Potential Hemostatic Agents. J Pharm Pharm Sci. 2020; 23(1): 10-23. doi:10.18433/jpps30446
16. Kamilov FKh., Timerkhanova GA, Samorodova AI, Khaliullin FA, Samorodov AV. The choice of a solvent for studying the effect of water-insoluble substances on the coagulation component of hemostasis in vitro at the preclinical stage. Problems of biological, Medical And Pharmaceutical Chemistry. 2014; 6: 11-15. doi: Not Available
17. Lee DH, Kwak HJ, Shin Y, Kim SJ, Lee GH, Park I-H. et al. Elucidation of Phytochemicals Affecting Platelet Responsiveness in Dangguisu-san: Active Ingredient Prediction and Experimental Research Using Network Pharmacology. Plants (Basel). 2023; 12(5): 1120. doi:10.3390/plants12051120
18. Levy JH, Szlam F, Wolberg AS,Winkler A. Clinical Use of the Activated Partial Thromboplastin Time and Prothrombin Time for Screening: a Review of the Literature and Current Guidelines for Testing. Clin. Lab. Med. 2014; 34: 453–477. doi:10.1016/j.cll.2014.06.005
19. Undas A. Determination of Fibrinogen and Thrombin Time (TT), In: Favaloro E. J., Lippi G. (eds.) Hemostasis And Thrombosis: Methods and Protocols. New York, NY: Springer New York); 2017. 105–110. doi:10.1007/978-1-4939-7196-1_8
20. Paniccia R, Priora R, Liotta AA, Abbate R. Platelet function tests: a comparative review. Vasc Health Risk Manag. 2015; 18(11): 133-48. doi: 10.2147/VHRM.S44469
21. Omar G, Abdullah L, Rahim AA, Othman R, Barakat A. Selected Wild Plants Ethanol Extracts Bioactivity on the Coagulation Cascade. J. Sci. Res. Reports. 2017; 13 (6): 1–10. doi: Not Available
22. Ambreen S, Tariq M, Masoud MS, Ali I, Qasim M, Mushtaq A. et al. Anticoagulant Potential and Total Phenolic Content of Six Species of the Genus Ficusfrom Azad Kashmir, Pakistan. Trop. J. Pharm. Res. 2019; 18 (6): 1245-1251. doi: 10.4314/tjpr.v18i6.14
23. Sarkar S, Bagchi A, Raha A, Mukherjee P, Paul M, Roy S. et al. In Vitro Anticoagulant Activity of Datura Stramonium Flower Extracts on Blood Plasma of Poultry Bird. Pharma Innov. J. 2019; 8 (4): 1146–1148. doi: Not Available
24. Shafee W, Yusof NY, Fauzi HM, Vuanghao L, Kamalaldin NA, Yahaya BH. Anti-Coagulation Activities of Malaysian Mikania Cordata Leaves. Int. J. Pept. Res.Ther. 2019; 25 (3): 941–949. doi: 10.1007/s10989-018-9742-5
25. Ramya D, Thirunavukkarasu P, Barathi AAS. In Vitro Anticoagulant Activity of Nelumbo Nucifera Leaf Extracts on NormalHealthy Blood Plasma. Int. J. Green Pharm. 2017; 11(3): 116–170. doi: Not Available
26. Abdullina GM, Kudashkina NV, Khasanova SR, Ganyev RZh, Samorodov AV, Ciduku N. et al. Anticoagulation and antiaggregation activity of medicinal plant phytoextracts: in vitro screening study. Avicenna Bulletin. 2024; 26(1): 67-75 ]doi:10.25005/2074-0581-2024-26-1-67-75
27. Pereira B, Brazón J, Rincón M, Vonasek E. Browplasminin, a Condensed Tannin with Anti-plasmin Activity Isolated from an Aqueous Extract of Brownea Grandiceps Jacq. Flowers. J. Ethnopharmacol. 2017; 198: 282–290. doi:10.1016/j.jep.2017.01.012
28. Bijak M, Ponczek MB, Nowak P. Polyphenol Compounds Belonging to Flavonoids Inhibit Activity of Coagulation Factor X. Int. J. Biol. Macromol. 2014; 65: 129–135. doi:10.1016/j.ijbiomac.2014.01.023
29. Marcinczyk N, Gromotowicz-Poplawska A, Tomczyk M, Chabielska E. Tannins as Hemostasis Modulators. Front. Pharmacol. 2022; 12: 806891. doi: 10.3389/fphar.2021.806991
30. Morozova JE, Gilmullina ZR, Voloshina AD, Amerhanova SK, Syakaev VV, Babaeva OB. et al. Calix[4]Resorcinarene Carboxybetaines and Carboxybetaine Esters: Synthesis, Investigation of In Vitro Toxicity, Anti-Platelet Effects, Anticoagulant Activity, and BSA Binding Affinities. Int J Mol Sci. 2022; 23(23): 15298. doi:10.3390/ijms232315298
31. Bogdanov AV, Voloshina AD, Sapunova AS, Kulik NV, Bukharov SV, Dobrynin AB. et al. Isatin-3-acylhydrazones with Enhanced Lipophilicity: Synthesis, Antimicrobial Activity Evaluation and the Influence on Hemostasis System. Chem Biodivers. 2022; 19(2): e202100496. doi:10.1002/cbdv.20210049
32. Bogdanov AV, Sirazieva AR, Voloshina AD, Abzalilov TA, Samorodov AV, Mirinov FV. Synthesis and Antimicrobial, Antiplatelet, and Anticoagulant Activities of New Isatin Derivatives Containing a Hetero-Fused Imidazole Fragment. Russian Journal of Organic Chemistry. 2022; 58 (3): 327-334. doi:10.1134/S1070428022030101.
33. Shaturnyj VI, Shahidzhanov SS, Sveshnikova AN, Panteleev MA. Activators, receptors, and intracellular signaling pathways in blood platelets. Biomed. chemistry. 2014; 60(2): 182-200. doi:10.18097/pbmc20146002182
34. Nasirov KJe, Nadzhimova Kh, Musaeva MK, Muhitdinov B. The effect of certain compounds on platelet aggregation in vitro. Universum: chemistry and biology. 2020; 5(71): 16-22. doi: Not Available№5
35. Ngo T, Kim K, Bian Y, Noh H, Lim KM, Chung JH, Bae ON. Antithrombotic Effects of Paeoniflorin from Paeonia suffruticosa by Selective Inhibition on Shear Stress-Induced Platelet Aggregation. Int. J. Mol. Sci. 2019; 20: 5040. doi:10.3390/ijms20205040
36. Qiu H, Zhang L, Zhu M, Zhang M, Chen J, Feng L. et al. Capture of anti-coagulant active ingredients from Moutan Cortex by platelet immobilized chromatography and evaluation of anticoagulant activity in rats. Biomed Pharmacother. 2017; 95: 235-244. doi: 10.1016/j.biopha.2017.08.051
37. Xie P, Cui L, Shan Y, Kang WY. Antithrombotic Effect and Mechanism of Radix Paeoniae Rubra. Biomed Res Int. 2017; 17: 1-9. doi:10.1155/2017/9475074
38. Lambert JD, Yennawar N, Gu Y, Elias RJ. Inhibition of Secreted Phospholipase A2 by Proanthocyanidins: a Comparative Enzymological and In Silico Modeling Study. J. Agric. Food Chem.2012; 60: 7417–7420. doi:10.1021/ jf302308k
39. Ksenofontov AA, Bocharov PS, Antina EV, Shevchenko OG, Samorodov AV, Gilfanov IR. et al. Thioterpenoids as Potential Antithrombotic Drugs: Molecular Docking, Antiaggregant, Anticoagulant and Antioxidant Activities. Biomolecules. 2022; 12(11): 1599. Published 2022 Oct 30. doi:10.3390/biom12111599
40. Rullyansyah S, Kusumawati I, Purwanto DA. Molecular Docking and Secondary Metabolite ADMET Studies from Curcuma longa Linn. as an Antithrombotic. Research Journal Pharmacy and Technology. 2025; 18(1): 152-8. doi: 10.52711/0974-360X.2025.00023
41. Sharma S, Kaur R., Gupta J, Devi N. Evaluation of Cardioprotective Activity of Magnolia officinalis Bark Extract against Doxorubicin Induced Toxicity in Mice. Research Journal Pharmacy and Technology. 2025; 18(8): 3572-8. doi:10.52711/0974-360X.2025.00514
42. Subramani B, Sathiyarajeswaran P. Current update on herbal sources of antithrombotic activity-a comprehensive review. Egypt J Intern Med. 2022; 34(1): 26. doi:10.1186/s43162-021-00090-9
43. Kubatka P, Mazurakova A, Koklesova L, Samec M, Sokol J, Samuel SM. et al. Antithrombotic and antiplatelet effects of plant-derived compounds: a great utility potential for primary, secondary, and tertiary care in the framework of 3P medicine. EPMA Journal. 2022; 13: 407–431. doi:10.1007/s13167-022—00293-2
44. Vazhappilly CG, Ansari SA, Al-Jaleeli R, Al-Azawi AV, Ramadan WS, Menon V. et al. Role of flavonoids in thrombotic, cardiovascular, and inflammatory diseases. Inflammopharmacol. 2019; 27: 863–9. doi:10.1007/s10787-019-00612-6
45. Vallance TM, Ravishankar D, Albadawi DAI, Osborn HMI, Vaiyapuri S. Synthetic flavonoids as novel modulators of platelet function and thrombosis. IJMS. 2019; 20: 3106. doi:10.3390/ijms20123106
46. Nam GS, Park HJ, Nam KS. The antithrombotic effect of caffeic acid is associated with a cAMP-dependent pathway and clot retraction in human platelets. Thromb Res. 2020;. 195: 87–94. Doi:10.1016/j.thromres.2020.07.024.
47. Fang H, Gao B, Zhao Y, Fang X, Bian M, Xia Q. Curdione inhibits thrombin-induced platelet aggregation via regulating the AMP-activated protein kinase-vinculin/talin-integrin αIIbβ3 sign pathway. Phytomedicine. 2019; 61: 152859. doi: 10.1016/j.phymed.2019.152859
48. Zhang R, Huang B., Du D., Guo X, Xin G, Xing Zh. et al. Anti-thrombosis effect of diosgenyl saponins in vitro and in vivo. Steroids. 2013; 78: 1064–70. doi: 10.1016/j.steroids.2013.07.003
49. Huang ChJ, Huang WCh, Lin WT, Shu LH, Sheu JR. Tran OT. et al. Rutaecarpine, an alkaloid from evodia rutaecarpa, can prevent platelet activation in humans and reduce microvascular thrombosis in mice: crucial role of the PI3K/Akt/GSK3β signal axis through a cyclic nucleotides/VASP—independent mechanism. IJMS. 2021;. 22: 11109. doi:10.3390/ijms222011109
50. Tamer F, Tullemans BME, Kuijpers MJE, Claushuis TAM, Heemskerk JWM. Nutrition Phytochemicals Affecting Platelet Signaling and Responsiveness: Implications for Thrombosis and Hemostasis. Thromb Haemost. 2022; 122(6): 879-894. doi:10.1055/a-1683-5599
51. Mattiello ., Trifirò E, Jotti GS, Pulcinelli FM. Effects of Pomegranate Juice and Extract Polyphenols on Platelet Function. J. Med. Food. 2009; 12: 334–339. doi:10.1089/jmf.2007.0640
52. Mayanglambam A, Dangelmaier CA, Thomas D, Damodar Reddy C, Daniel JL, Kunapuli SP. Curcumin inhibits GPVI-mediated platelet activation by interfering with the kinase activity of Syk and the subsequent activation of PLCgamma2. Platelets. 2010; 21(03): 211–220. doi: 10.3109/09537100903528269
53. Onselaer MB, Nagy M, Pallini C, Pike JA, Perella G, Quintanilla L.G. et al. Comparison of the GPVI inhibitors losartan and honokiol. Platelets. 2020; 31(02): 187–197. doi:10.1080/09537104.2019.1585526
54. Bijak M, Szelenberger R, Dziedzic A, Saluk-Bijak J. Inhibitory effect of flavonolignans on the P2Y12 pathway in blood platelets. Molecules. 2018; 23(02): 374. doi: 103390/molecules23020374
55. Bijak M, Szelenberger R, Saluk J, Nowak P. Flavonolignans inhibit ADP induced blood platelets activation and aggregation in whole blood. Int J Biol Macromol. 2017; 95: 682–688. doi: 10.1016/j.ijbiomac.2016.12.002
56. Fuentes E, Caballero J, Alarcón M, Rojas A, Palomo I. Chlorogenic acid inhibits human platelet activation and thrombus formation. PLoS One. 2014; 9(03): e90699. doi: 10.1371/journal.pone.0090699
57. Park JB. 5-Caffeoylquinic acid and caffeic acid orally administered suppress P-selectin expression on mouse platelets. J Nutr Biochem. 2009; 20(10): 800–805. doi: 10.1016/j.jnutbio.2008.07009
58. Ostertag LM, O’Kennedy, Horgan GW, Kroon PA, Duthie GG, de Roos B. In vitro anti-platelet effects of simple plant-derived phenolic compounds are only found at high, non-physiological concentrations. Mol. Nutr. Food Res. 2011; 55(11): 1624–1636. doi: 10.1002/mnfr.201100135
59. Nam GS, Park HJ, Nam KS. The antithrombotic effect of caffeic acid is associated with a cAMP-dependent pathway and clot retraction in human platelets. Thromb Res. 2020; 195: 87–94. doi: 10.1016/j.thromres.2020.07.024
60. Lee DH, Kim HH, Cho HJ, Bae JS, Yu YB, Park HJ. Antiplatelet effects of caffeic acid due to Ca(2þ) mobilizationinhibition via cAMP-dependent inositol-1, 4, 5-trisphosphate receptor phosphorylation. J Atheroscler Thromb. 2014; 21(01): 23–37. doi: 10.5551/jat.18994
61. Ravishankar D, Albadawi DAI, Chaggar V, Patra PH, Williams HF, Salamah M. et al. Isorhapontigenin, a resveratrol analogue selectively inhibits ADP-stimulated platelet activation. Eur J Pharmacol. 2019; 862: 172627. doi: 10.1016/j.ejphar.2019.172627
62. Wang Z, Huang Y, Zou J, Cao K, Xu Y, Wu JM. Effects of red wine and wine polyphenol resveratrol on platelet aggregation in vivo and in vitro. Int J Mol Med. 2002; 9(01): 77–79. doi: Not Available
63. Xu M, Xue W, Ma Zh, Bai J, Wu S. Resveratrol reduces the incidence of portal vein system thrombosis after splenectomy in a rat fibrosis model. Oxid Med Cell Longev. 2016; 2016: 1–7. doi:10.1155/2016/7453849
64. Krga I, Vidovic N, Milenkovic D, Konic-Ristic A, Stojanovic F, Morand C. et al. Effects of anthocyanins and their gut metabolites on adenosine diphosphate-induced platelet activation and their aggregation with monocytes and neutrophils. Arch Biochem Biophys. 2018; 645: 34–41. doi:10.1016/j.abb.2018.03.016
65. Yao Y, Chen Y, Adili R, McKeown T, Chen P, Zhu G. et al. Plant-based food cyanidin-3-glucoside modulates human platelet glycoprotein VI signaling and inhibits platelet activation and thrombus formation. J Nutr. 2017; 147(10): 1917–1925. doi:10.39945/jn.116.245944
66. Wright B, Moraes LA, Kemp CF, Mullen W, Crozier A, Lovegrove JA. et al. A structural basis for the inhibition of collagen-stimulated platelet function by quercetin and structurally related flavonoids. Br J Pharmacol. 2010; 159 (06): 1312–1325. doi: 10.1111/j.1476-5381.2009.00632.x
67. Iida Y, Doi T, Matsushima-Nishiwaki R, Tokuda H, Ogura Sh, Kozava O. et al. (-)-Epigallocatechin gallate selectively inhibits adenosine diphosphate–stimulated human platelet activation: suppression of heat shock protein 27phosphorylation via p38 mitogen–activated protein kinase. MolMed Rep. 2014; 10(03): 1383–1388. doi: 10.3892/mmr.2014.2389
68. Crescente M, Jessen G, Momi S, Holtje HD, Gresele P, Cerletti Ch. et al. Interactions of gallic acid, resveratrol, quercetin and aspirin at the platelet cyclooxygenase-1 level. Functional and modelling studies. Thromb Haemost. 2009; 102(02): 336–346. doi: 10.1160/TH09-01-0057
69. Stainer AR, Sasikumar P, Bye AP, Unsworth AJ, Holbrook LM, Tindall M. et al. The metabolites of the dietary flavonoid quercetin possess potent antithrombotic activity, and interact with aspirin to enhance antiplatelet effects. TH Open. 2019; 03: e24458. doi:10.1055/s-0039-1694028
70. Suzuki Y, Kondo K, Ikeda Y, Umemura K. Antithrombotic effect of geniposide and genipin in the mouse thrombosis model. Planta Med. 2001; 67: 807–10. doi:10.1055/s-2001-18842
71. Fang H, Gao B, Zhao Y, Fang X, Bian M, Xia Q. Curdione inhibits thrombin-induced platelet aggregation via regulating the AMP-activated protein kinase-vinculin/talin-integrin αIIbβ3 sign pathway. Phytomedicine. 2019; 61: 152859. doi:10.1016/j.phymed.2019.152859
72. Qi H, Huang Y, Yang Y, Dou G, Wan F, Zhang W. et al. Anti-platelet activity of panaxatriol saponins is mediated by suppression of intracellular calcium mobilization and ERK2/p38 activation. BMC Complement Altern Med. 2016; 16: 97. doi:10.1186/s12906-016-1160-7.
73. Hsia ChW, Lin KC, Lee TY, Hsia ChH, Chou DS, Jayakumar T. et al. Esculetin, a coumarin derivative, prevents thrombosis: inhibitory signaling on PLCγ2–PKC–AKT activation in human platelets. IJMS. 2019; 20: 2731. Doi:10.3390/ijms20112731.