Evaluation of the potential anticoagulant properties of medicinal plants’ extracts
Article Main
Abstract
Plant-derived phenolics are widely recognized for their therapeutic properties. Therefore, the present study aimed to evaluate medicinal plant extracts' anticoagulant activities to develop a safe and effective strategy for controlling thrombotic disorders. Total phenolic content (TPC) from 120 dried powders of different medicinal plants purchased from the local market of Pune, India, were extracted separately in 70% ethanol. Their contents were determined using the Folin-Ciocalteu assay. Anticoagulant activity was initially assessed using the clotting time (CT) assay. The highest phenolic content (8.3 mg/mL) was estimated in Woodfordia fruticosa flower. Out of 120 plant extracts, 47 exhibited anticoagulant activities with a significant prolongation of clotting time (CT) (More than control time i. e. 8 min). From these plant extracts, 36, 29 and 21 plants showed anticoagulant activities performed by activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) tests, respectively. The plant extracts from W. fruticosa flower, Terminalia chebula fruit, Punica granatum peel, Tecoma undulata bark, Tedrminalia bellirica fruit, Zingiber officinale rhizome, and Curcuma zedoaria rhizome exhibited prominent anticoagulant activities with a significant prolongation of CT, APTT, PT and TT tests. Linear regression revealed a weak positive correlation between plant phenolic concentrations and anticoagulant activities, as evaluated by CT, APTT, PT and TT tests. ANOVA test showed significant differences (P < 0.05) in the anticoagulant activities of the plant phenolics. The plant extracts showing very high anticoagulant activity could be useful for preparing herbal drugs to control thrombotic disorders.
Article Details
Article Details
Keywords
Anticoagulant activity, Punica granatum, Terminalia chebula, Total phenolics, Woodfordia fruticosa
References
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Behl, T., Bungau, S., Kumar, K., Zengin, G., Khan, F., Kumar, A., Kaur, R., Venkatachalam, T., Tit, D. M., Vesa, C. M., & Barsan G. (2020). Pleotropic effects of polyphenols in cardiovascular system. Biomed & Pharmacother, 1(130),1107-1114. https://doi.org/10.1016/j.biopha.2020.11 0714
Dapper, D.V., Achinike, P.N. & Gwotmut, M.D. (2007). The effects of Aloe vera [gel] on clotting time, prothrombin time and plasma fibrinogen concentration in albino Wistar rats. Port. Harcourt. Med. J, 2, 56-60. DOI:10.4314/phmedj.v2i1.38894
Das, P. K., Goswami, S., Chinniah, A., Panda, N., Banerjee, S., Sahu, N. P. & Achari, B. (2007). Woodfordia fruticosa: Traditional uses and recent findings. Journal of Ethnopharmacol, 110(2), 189-199. https://doi.org/10.1016/j.jep.2006.12.029
Duffy, S. J., Vita, J. A., Holbrook, M., Swerdloff, P. L. & Keaney Jr, J.F. (2001). Effect of acute and chronic tea consumption on platelet aggregation in patients with coronary artery disease. Arterioscler. Thromb. Vasc. Biol, 21(6), 1084-1089. DOI: 10.1161/01.atv.21.6.1084
Fan, W., Fan, L., Wang, Z., Mei, Y., Liu, L., Li, L., Yang, L. & Wang, Z. (2024). Rare ginsenosides: a unique perspective of ginseng research. J. Adv. Res, 66, 303-328. https://doi.org/10.1016/j.jare.2024.01.003
Feigin, V. L., Stark, B. A., Johnson, C. O., Roth, G.A. , Bisignano, C., Abady, G. G., Abbasifard, M., Abbasi-Kangevari, M., Abd-Allah, F., Abedi, V. & Abualhasan, A. (2021). Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet, Neurol, 20(10), 795-820. DOI: 10.1016/S1474-4422(21)00252-0
Furie, B. & Furie, B. C. (2008). Mechanisms of thrombus formation. N, Engl, J, Med, 359(9), 938-949. DOI: 10.1056/NEJMra0801082
García-Lafuente, A., Guillamón, E., Villares, A., Rostagno, M. A. & Martínez, J. A. (2009). Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease. Inflamm. res, 58(9), 537-552. DOI: 10.1007/s00011-009-0037-3
Heit, J. A., Cohen, A. T. & Anderson Jr, F.A. (2005). Estimated annual number of incident and recurrent, non-fatal and fatal venous thromboembolism (VTE) events in the US. Blood, 106(11), 910. https://doi.org/10.1182/blood.V106.11.910.910
Hubbard, G. P., Wolffram, S., Lovegrove, J. A. & Gibbins, J. M. (2004). Ingestion of quercetin inhibits platelet aggregation and essential components of the collagen‐stimulated platelet activation pathway in humans. Journal of Thrombosis and Haemostasis, 2(12), 2138-2145. https://doi.org/10.1111/j.1538-7836.2004.01067.x
Koch, E. & Biber, A. (2007). Treatment of rats with the Pelargonium sidoides extract has no effect on blood coagulation parameters or on the pharmacokinetics of warfarin. Phytomedicine, 14, .40-45. https://doi.org/10.1016/j.phymed.2006.11.026
Kolodziejczyk-Czepas, J. & Czepas, J. (2023). Plant-Derived Compounds and Extracts as Modulators of Plasmin Activity—A Review. Molecules, 28(4), 1677.
Kumar, D. R., Hanlin, E., Glurich, I., Mazza, J. J. & Yale, S. H. (2010). Virchow's contribution to the understanding of thrombosis and cellular biology. Clin. Med. res, 8(3-4), 168-172. doi: 10.3121/cmr.2009.866
Kuriakose, D. & Xiao, Z. (2020). Pathophysiology and treatment of stroke: present status and future perspectives. Int. J. mol. Sci, 21(20), 7609. doi: 10.3390/ijms21207609
Lichota, A., Szewczyk, E. M. & Gwozdzinski, K. (2020). Factors affecting the formation and treatment of thrombosis by natural and synthetic compounds. Int. J. Mol. Sci, 21(21), 7975. doi: 10.3390/ijms21217975
Lutsey, P. L. & Zakai, N. A. (2023). Epidemiology and prevention of venous thromboembolism. Nat. Rev. Cardiol, 20(4), 248-262. doi: 10.1038/s41569-022-00787-6.
Middleton, E., Kandaswami, C. & Theoharides, T.C. (2000). The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol. rev, 52(4), 673-751. https://pubmed.ncbi.nlm.nih.gov/11121513/
Mozaffarian, D., Benjamin, E. J., Go, A. S., Arnett, D. K., Blaha, M. J., Cushman, M., Das, S. R., De Ferranti, S., Després, J. P., Fullerton, H. J. & Howard, V. J. (2016). Heart disease and stroke statistics—2016 update: a report from the American Heart Association. circ, 133(4), 338-360. https://doi.org/10.1161/CIR.0000000000000350
Nicholson, M., Chan, N., Bhagirath, V. & Ginsberg, J. (2020). Prevention of venous thromboembolism in 2020 and beyond. J, clin, med, 9(8), 2467. https://doi.org/10.3390/jcm9082467
Pandey, K. B. & Rizvi, S. I. (2009). Plant polyphenols as dietary antioxidants in human health and disease. Oxid. Med. Cell. Longev, 2(5), 270-278. DOI:10.4161/oxim.2.5.9498
Pawlaczyk, I., Czerchawski, L., Kuliczkowski, W., Karolko, B., Pilecki, W., Witkiewicz, W. & Gancarz, R. (2011). Anticoagulant and anti-platelet activity of polyphenolic-polysaccharide preparation isolated from the medicinal plant Erigeron canadensis L. Thromb. Res, 127(4), 328-340. DOI: 10.1016/j.thromres.2010.11.031
Ramachandraiah, C., Nandish, S.M., Kengaiah, J., Srinivas, C., Shiviah, A., Hanumegowda, S. M. & Sannaningaiah, D. (2019). Anticoagulant, antiplatelet and fibrinogenolytic activity of serine protease from Cicer arietinumseed extract. Int J Pharm Biol Sci, 9(2), pp.863-878.
Reddy, L. A. L. I. N. I., Odhav, B. & Bhoola, K. D. (2003). Natural products for cancer prevention: a global perspective. Pharma. therap, 99(1), 1-13. DOI: 10.1016/s0163-7258(03)00042-1
Reshma, B. V., Manohar, R. N. & Anaha, V .I. (2018). A review on Laccifer lacca. World J. Pharm. Res, 7(10), 206-218. DOI:10.20959/wjpr201810-12282
Rohilla, R. & Garg, M. (2014). Phytochemistry and pharmacology of Tecomella undulata. Int. J. of Green Pharm, 8(1). DOI:10.4103/0973-8258.126811
Rosenberg, R.D. & Aird, W.C. (1999). Vascular-bed–specific hemostasis and hypercoagulable states. N. Engl. J. Med, 340(20), 1555-1564. DOI: 10.1056/NEJM199905203402007
Sharifi-Rad, J., Quispe, C., Zam, W., Kumar, M., Cardoso, S.M., Pereira, O.R., Ademiluyi, A.O., Adeleke, O., Moreira, A.C., Živković, J. & Noriega, F. (2021). Phenolic bioactives as antiplatelet aggregation factors: The pivotal ingredients in maintaining cardiovascular health. Oxid. Med. Cell. Longev, (1), 2195902. doi: 10.1155/202 1/2195902
Simon, J. M. & Jeffrey, S. G. (2005) New Anticoagulants for the Prevention and Treatment of Venous Thromboembolism. Vasc. Health. Risk. Manag. 1(1): 41–53.doi: 10.2147/vhrm.1.1.41.58936
Singleton, V. L. & Rossi, J. A. (1965). Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents. Am. J. Enol. Vitic, 16(3), 144-158. DOI: 10.5344/ajev.1965.16.3.144
Srivastava, K. C., Bordia, A. & Verma, S. K. (1995). Curcumin, a major component of food spice turmeric (Curcuma longa) inhibits aggregation and alters eicosanoid metabolism in human blood platelets. Prostaglandins. Leukot. Essent. Fat. Acids, 52(4), 223-227. https://doi.org/10.1016/0952-3278(95)90040-3
Tewari, R., Gupta, M., Ahmad, F., Rout, P.K., Misra, L., Patwardhan, A. & Vasudeva, R. (2017). Extraction, quantification and antioxidant activities of flavonoids, polyphenols and pinitol from wild and cultivated Saraca asoca bark using RP-HPLC-PDA-RI method. Ind. Crops Prod, 103, 73-80. https://doi.org/10.1016/j.indcrop.2017.03.036
Waterhouse, A.L. (2002). Determination of total phenolics. Current Protocols in Food Analytical Chemistry, 6(1), 1-1 https://doi.org/10.1002/0471142913.fai0101s06
Bachheti, R. K., Worku, L. A., Gonfa, Y. H., Zebeaman, M. D., Pandey, D. P. and Bachheti, A. (2022). Prevention and treatment of cardiovascular diseases with plant phytochemicals: A Review. J. Evid.-based Complement. Altern. Med., (1), 01-21. doi: 10.1155/2022/5741198
Behl, T., Bungau, S., Kumar, K., Zengin, G., Khan, F., Kumar, A., Kaur, R., Venkatachalam, T., Tit, D. M., Vesa, C. M., & Barsan G. (2020). Pleotropic effects of polyphenols in cardiovascular system. Biomed & Pharmacother, 1(130),1107-1114. https://doi.org/10.1016/j.biopha.2020.11 0714
Dapper, D.V., Achinike, P.N. & Gwotmut, M.D. (2007). The effects of Aloe vera [gel] on clotting time, prothrombin time and plasma fibrinogen concentration in albino Wistar rats. Port. Harcourt. Med. J, 2, 56-60. DOI:10.4314/phmedj.v2i1.38894
Das, P. K., Goswami, S., Chinniah, A., Panda, N., Banerjee, S., Sahu, N. P. & Achari, B. (2007). Woodfordia fruticosa: Traditional uses and recent findings. Journal of Ethnopharmacol, 110(2), 189-199. https://doi.org/10.1016/j.jep.2006.12.029
Duffy, S. J., Vita, J. A., Holbrook, M., Swerdloff, P. L. & Keaney Jr, J.F. (2001). Effect of acute and chronic tea consumption on platelet aggregation in patients with coronary artery disease. Arterioscler. Thromb. Vasc. Biol, 21(6), 1084-1089. DOI: 10.1161/01.atv.21.6.1084
Fan, W., Fan, L., Wang, Z., Mei, Y., Liu, L., Li, L., Yang, L. & Wang, Z. (2024). Rare ginsenosides: a unique perspective of ginseng research. J. Adv. Res, 66, 303-328. https://doi.org/10.1016/j.jare.2024.01.003
Feigin, V. L., Stark, B. A., Johnson, C. O., Roth, G.A. , Bisignano, C., Abady, G. G., Abbasifard, M., Abbasi-Kangevari, M., Abd-Allah, F., Abedi, V. & Abualhasan, A. (2021). Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet, Neurol, 20(10), 795-820. DOI: 10.1016/S1474-4422(21)00252-0
Furie, B. & Furie, B. C. (2008). Mechanisms of thrombus formation. N, Engl, J, Med, 359(9), 938-949. DOI: 10.1056/NEJMra0801082
García-Lafuente, A., Guillamón, E., Villares, A., Rostagno, M. A. & Martínez, J. A. (2009). Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease. Inflamm. res, 58(9), 537-552. DOI: 10.1007/s00011-009-0037-3
Heit, J. A., Cohen, A. T. & Anderson Jr, F.A. (2005). Estimated annual number of incident and recurrent, non-fatal and fatal venous thromboembolism (VTE) events in the US. Blood, 106(11), 910. https://doi.org/10.1182/blood.V106.11.910.910
Hubbard, G. P., Wolffram, S., Lovegrove, J. A. & Gibbins, J. M. (2004). Ingestion of quercetin inhibits platelet aggregation and essential components of the collagen‐stimulated platelet activation pathway in humans. Journal of Thrombosis and Haemostasis, 2(12), 2138-2145. https://doi.org/10.1111/j.1538-7836.2004.01067.x
Koch, E. & Biber, A. (2007). Treatment of rats with the Pelargonium sidoides extract has no effect on blood coagulation parameters or on the pharmacokinetics of warfarin. Phytomedicine, 14, .40-45. https://doi.org/10.1016/j.phymed.2006.11.026
Kolodziejczyk-Czepas, J. & Czepas, J. (2023). Plant-Derived Compounds and Extracts as Modulators of Plasmin Activity—A Review. Molecules, 28(4), 1677.
Kumar, D. R., Hanlin, E., Glurich, I., Mazza, J. J. & Yale, S. H. (2010). Virchow's contribution to the understanding of thrombosis and cellular biology. Clin. Med. res, 8(3-4), 168-172. doi: 10.3121/cmr.2009.866
Kuriakose, D. & Xiao, Z. (2020). Pathophysiology and treatment of stroke: present status and future perspectives. Int. J. mol. Sci, 21(20), 7609. doi: 10.3390/ijms21207609
Lichota, A., Szewczyk, E. M. & Gwozdzinski, K. (2020). Factors affecting the formation and treatment of thrombosis by natural and synthetic compounds. Int. J. Mol. Sci, 21(21), 7975. doi: 10.3390/ijms21217975
Lutsey, P. L. & Zakai, N. A. (2023). Epidemiology and prevention of venous thromboembolism. Nat. Rev. Cardiol, 20(4), 248-262. doi: 10.1038/s41569-022-00787-6.
Middleton, E., Kandaswami, C. & Theoharides, T.C. (2000). The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol. rev, 52(4), 673-751. https://pubmed.ncbi.nlm.nih.gov/11121513/
Mozaffarian, D., Benjamin, E. J., Go, A. S., Arnett, D. K., Blaha, M. J., Cushman, M., Das, S. R., De Ferranti, S., Després, J. P., Fullerton, H. J. & Howard, V. J. (2016). Heart disease and stroke statistics—2016 update: a report from the American Heart Association. circ, 133(4), 338-360. https://doi.org/10.1161/CIR.0000000000000350
Nicholson, M., Chan, N., Bhagirath, V. & Ginsberg, J. (2020). Prevention of venous thromboembolism in 2020 and beyond. J, clin, med, 9(8), 2467. https://doi.org/10.3390/jcm9082467
Pandey, K. B. & Rizvi, S. I. (2009). Plant polyphenols as dietary antioxidants in human health and disease. Oxid. Med. Cell. Longev, 2(5), 270-278. DOI:10.4161/oxim.2.5.9498
Pawlaczyk, I., Czerchawski, L., Kuliczkowski, W., Karolko, B., Pilecki, W., Witkiewicz, W. & Gancarz, R. (2011). Anticoagulant and anti-platelet activity of polyphenolic-polysaccharide preparation isolated from the medicinal plant Erigeron canadensis L. Thromb. Res, 127(4), 328-340. DOI: 10.1016/j.thromres.2010.11.031
Ramachandraiah, C., Nandish, S.M., Kengaiah, J., Srinivas, C., Shiviah, A., Hanumegowda, S. M. & Sannaningaiah, D. (2019). Anticoagulant, antiplatelet and fibrinogenolytic activity of serine protease from Cicer arietinumseed extract. Int J Pharm Biol Sci, 9(2), pp.863-878.
Reddy, L. A. L. I. N. I., Odhav, B. & Bhoola, K. D. (2003). Natural products for cancer prevention: a global perspective. Pharma. therap, 99(1), 1-13. DOI: 10.1016/s0163-7258(03)00042-1
Reshma, B. V., Manohar, R. N. & Anaha, V .I. (2018). A review on Laccifer lacca. World J. Pharm. Res, 7(10), 206-218. DOI:10.20959/wjpr201810-12282
Rohilla, R. & Garg, M. (2014). Phytochemistry and pharmacology of Tecomella undulata. Int. J. of Green Pharm, 8(1). DOI:10.4103/0973-8258.126811
Rosenberg, R.D. & Aird, W.C. (1999). Vascular-bed–specific hemostasis and hypercoagulable states. N. Engl. J. Med, 340(20), 1555-1564. DOI: 10.1056/NEJM199905203402007
Sharifi-Rad, J., Quispe, C., Zam, W., Kumar, M., Cardoso, S.M., Pereira, O.R., Ademiluyi, A.O., Adeleke, O., Moreira, A.C., Živković, J. & Noriega, F. (2021). Phenolic bioactives as antiplatelet aggregation factors: The pivotal ingredients in maintaining cardiovascular health. Oxid. Med. Cell. Longev, (1), 2195902. doi: 10.1155/202 1/2195902
Simon, J. M. & Jeffrey, S. G. (2005) New Anticoagulants for the Prevention and Treatment of Venous Thromboembolism. Vasc. Health. Risk. Manag. 1(1): 41–53.doi: 10.2147/vhrm.1.1.41.58936
Singleton, V. L. & Rossi, J. A. (1965). Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents. Am. J. Enol. Vitic, 16(3), 144-158. DOI: 10.5344/ajev.1965.16.3.144
Srivastava, K. C., Bordia, A. & Verma, S. K. (1995). Curcumin, a major component of food spice turmeric (Curcuma longa) inhibits aggregation and alters eicosanoid metabolism in human blood platelets. Prostaglandins. Leukot. Essent. Fat. Acids, 52(4), 223-227. https://doi.org/10.1016/0952-3278(95)90040-3
Tewari, R., Gupta, M., Ahmad, F., Rout, P.K., Misra, L., Patwardhan, A. & Vasudeva, R. (2017). Extraction, quantification and antioxidant activities of flavonoids, polyphenols and pinitol from wild and cultivated Saraca asoca bark using RP-HPLC-PDA-RI method. Ind. Crops Prod, 103, 73-80. https://doi.org/10.1016/j.indcrop.2017.03.036
Waterhouse, A.L. (2002). Determination of total phenolics. Current Protocols in Food Analytical Chemistry, 6(1), 1-1 https://doi.org/10.1002/0471142913.fai0101s06
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Evaluation of the potential anticoagulant properties of medicinal plants’ extracts. (2025). Journal of Applied and Natural Science, 17(1), 244-252. https://doi.org/10.31018/jans.v17i1.6240
