Inhibitory effect of various Thai natural plants ethanolic extracts on platelet aggregation and blood coagulation in vitro
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Published:
Jan 1, 2016
Keywords:
Thai natural plants antiplatelet drug blood coagulation platelet aggregation
Main Article Content
Abstract
Introduction: Platelets and blood coagulation play critical roles in haemostasis and also mediate pathologic thrombosis, responsible for cardiovascular diseases (CVD). Surgery and anti-platelet drugs has been used for the therapeutic purposes. However, some side effects are concerned such as bleeding, thrombocytopenia, etc. Therefore, natural herbal extracts may be a good candidate to counteract hemostatic disturbs with little or less side effects.
Objective: To investigate antiplatelet and anticoagulant effects of 14 different Thai natural plant ethanolic extracts. They were the extracts from Phyllanthus amarus, Tagetes erecta, Tinospora crispa, Angelica sinensis, Acorus calamus, Atractylodes lancea, Curcuma latifolia, Ligusticum sinense, Homalomena noboguine-ensis, Butea monosperma, Cissus quadrangularis, Artemisia annua, Pachyrrhizus erosus, and Curcuma zedoaria.
Materials and methods: Platelet aggregation using light transmission platelet aggregometer and platelet viability determined by microculture tetrazolium (MTT) assay were studied. Effect of the extracts on blood coagulation was studied by prothrombin time (PT) and activated partial thromboplastin time (aPTT). These assays were monitored before and after treated with the extracts.
Results: Curcuma zedoaria extract significantly interfered platelet aggregation with 50% inhibitory concentration (IC50) of 4.8 mg/ml at p<0.05 when compared with control. However, it did not show any toxicity to platelet viability. Moreover, it did not inhibit blood coagulation. Other herbal extracts did not have any effect platelet aggregation or blood coagulation.
Conclusion: Curcuma zedoaria has inhibitory effect on platelet aggregation. It was still unclear in its mechanism. So, mechanism of action of Curcuma zedoaria extract on platelet aggregation inhibition should be further on studied. This would be a candidate for potential antithrombotic and antiplatelet drug which can be a new approach for management and treatment of patients with cardiovascular diseases.
Bull Chiang Mai Assoc Med Sci 2016; 49(1): 77-89. Doi: 10.14456/jams.2016.9
Article Details
How to Cite
Duangmano, S., Wonkngam, S., Ladchantha, P., Palanan, W., & Wongtagan, O. (2016). Inhibitory effect of various Thai natural plants ethanolic extracts on platelet aggregation and blood coagulation in vitro. Journal of Associated Medical Sciences, 49(1), 77. Retrieved from https://he01.tci-thaijo.org/index.php/bulletinAMS/article/view/59929
Section
Research Articles
Personal views expressed by the contributors in their articles are not necessarily those of the Journal of Associated Medical Sciences, Faculty of Associated Medical Sciences, Chiang Mai University.
References
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7. Shah BH, Nawaz Z, Pertani SA, Roomi A, Mahmood H, Saeed SA, et al. Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonicacidmediated platelet aggregation through inhibition of thromboxane formation and Ca2+signaling. Biochem Pharmacol 1999; 58(7): 1167–72.
8. Srivastava KC, Bordia A, Verma SK. Curcumin, a major component of food spice turmeric (Curcuma longa) inhibits aggregation and alters eicosanoid metabolism in human blood platelets. Prostaglandins Leukot Essent Fatty Acids 1995; 52(4): 223–7.
9. Shih CY, Chou TC. The antiplatelet activity of magnolol is mediated by PPAR-beta/gamma. Biochem Pharmacol 2012; 84(6): 793–803.
10. Shin DW, Kim SN, Lee SM, Lee W, Song MJ, Park SM, et al. (-)-Catechin promotes adipocyte differentiation in human bone marrow mesenchymal stem cells through PPAR gamma transactivation. Biochem Pharmacol 2009; 77(1): 125–33.
11. Son DJ, Cho MR, Jin YR, Kim SY, Park YH, Lee SH, et al. Antiplatelet effect of green tea catechins: a possible mechanism through arachidonic acid pathway. Prostaglandins Leukot Essent Fatty Acids. 2004 Jul; 71(1): 25-31.
12. Hollman PC, van Trijp JM, Mengelers MJ, de Vries JH, Katan MB. Bioavailability of the dietary antioxidant flavonol quercetin in man. Cancer Lett. 1997; 114(1–2): 139-40.
13. Fang XK, Gao J, Zhu DN. Kaempferol and quercetin isolated from Euonymus alatus improve glucose uptake of 3T3-L1 cells without adipogenesis activity. Life Sci 2008; 82(11–12): 615–22.
14. Oh WJ, Endale M, Park SC, Cho JY, Rhee MH. Dual Roles of Quercetin in Platelets: Phosphoinositide-3-Kinase and MAP Kinases Inhibition, and cAMP-Dependent Vasodilator Stimulated Phosphoprotein Stimulation. Evid Based Complement Alternat Med. 2012; 2012: 485262. doi: 10.1155/2012/485262. Epub 2012 Dec 17.
15. Ibrahim D, Hong LS, Kuppan N. Antimicrobial activity of crude methanolic extract from Phyllanthus niruri. Nat Prod Commun. 2013; 8(4): 493-6.
16. Freitas AM, Schor N, Boim MA. The effect of Phyllanthus niruri on urinary inhibitors of calcium oxalate crystallization and other factors associated with renal stone formation. BJU Int. 2002; 89(9): 829-34.
17. Manjrekar AP, Jisha V, Bag PP, Adhikary B, Pai MM, Hegde A, et al. Effect of Phyllanthus niruri Linn. treatment on liver, kidney and testes in CCl4 induced hepatotoxic rats. Indian J Exp Biol. 2008; 46(7): 514-20.
18. Matic IZ, Juranic Z, Savikin K, Zdunic G, Nadvinski N, Godevac D. Chamomile and Marigold Tea: Chemical Characterization and Evaluation of Anticancer Activity. Phytother Res. 2013; 27(6): 852-8.
19. Lokman FE, Gu HF, Wan Mohamud WN, Yusoff MM, Chia KL, Ostenson CG. Antidiabetic Effect of Oral Borapetol B Compound, Isolated from the Plant Tinospora crispa, by Stimulating Insulin Release. Evid Based Complement Alternat Med. 2013; 2013: 727602. doi: 10.1155/2013/727602. Epub 2013 Nov 10.
20. Yusoff M, Hamid H, Houghton P. Anticholinesterase Inhibitory Activity of Quaternary Alkaloids from Tinospora crispa. Molecules. 2014; 19(1): 1201-11.
21. Rungruang T, Boonmars T. In vivo antiparasitic activity of the Thai traditional medicine plant, Tinospora crispa against Plasmodium yoelii. Southeast Asian J Trop Med Public Health. 2009; 40(5): 898-900.
22. Kumar SN, Aravind SR, Sreelekha TT, Jacob J, Kumar BS. Asarones from Acorus calamus in Combination with Azoles and Amphotericin B: A Novel Synergistic Combination to Compete Against Human Pathogenic Candida Species In Vitro. Appl Bioc Biotechnol. 2015; 175(8): 3683-95.
23. Ponrasu T, Madhukumar KN, Ganeshkumar M, Iyappan K, Sangeethapriya V, Gayathri VS, et al. Efficacy of Acorus calamus on collagen maturation on full thickness cutaneous wounds in rats. Pharmacog Mag. 2014; 10(Suppl 2): S299-305.
24. Shi GB, Wang B, Wu Q, Wang TC, Wang CL, Sun XH, et al. Evaluation of the wound-healing activity and anti-inflammatory activity of aqueous extracts from Acorus calamus L. Pak J Pharm Sci. 2014; 27(1): 91-5.
25. Kim D-Y, Lee S-H, Kim W-J, Jiang J, Kim M-K, Shin Y-K, et al. Inhibitory effects of Acorus calamus extracts on mast cell-dependent anaphylactic reactions using mast cell and mouse model. J Ethnopharmacol. 2012; 141(1): 526-9.
26. Lai P, Liu Y. Angelica sinensis polysaccharides inhibit endothelial progenitor cell senescence through the reduction of oxidative stress and activation of the Akt/hTERT pathway. Pharm Biol. 2015; 53(12): 1842-9. 1-8.
27. Champakaew D, Junkum A, Chaithong U, Jitpakdi A, Riyong D, Sanghong R, et al. Angelica sinensis (Umbelliferae) with proven repellent properties against Aedes aegypti, the primary dengue fever vector in Thailand. Parasitol Res. 2015; 114(6): 2187-98.
28. Jing Q, Wu GT, Du LD, Liu WZ, Li YD, Ren Y. Therapeutic effects of ethanol extracts of Angelica sinensis and Astragalus mongholicus in diabetic gastroparesis rats. Zhong Yao Cai. 2014; 37(8): 1415-20.
29. Bunel V, Antoine M-H, Nortier J, Duez P, Stévigny C. Nephroprotective effects of ferulic acid, Z-ligustilide and E-ligustilide isolated from Angelica sinensis against cisplatin toxicity in vitro. Toxicol In Vitro. 2015; 29(3): 458-67.
30. Makchuchit S, Itharat A. Tewtrakul S. Antioxidant and Nitric Oxide Inhibition Activities of Thai Medicinal Plants. J Med Assoc Thai. 2010; 93. Suppl 7: S227-35.
31. Gao XF, Li QL, Li HL, Zhang HY, Su JY, Wang B, et al. Extracts from Curcuma zedoaria Inhibit Proliferation of Human Breast Cancer Cell MDA-MB-231 In Vitro. Evid based Complement Alternat Med. 2014; 2014: 730678. doi: 10.1155/2014/730678. Epub 2014 May 5
32. Lobo R, Prabhu KS, Shirwaikar A, Shirwaikar A. Curcuma zedoaria Rosc. (white turmeric): a review of its chemical, pharmacological and ethnomedicinal properties. J Pharm Pharmacol. 2009; 61(1): 13-21.
33. Wilson B, Abraham G, Manju VS, Mathew M, Vimala B, Sundaresan S, et al. Antimicrobial activity of Curcuma zedoaria and Curcuma malabarica tubers. J Ethnopharmacol. 2005; 99(1): 147-51.
34. Koonrungsesomboon N, Na-Bangchang K, Karbwang J. Therapeutic potential and pharmacological activities of Atractylodes lancea (Thunb.) DC. Asian Pac J Trop Med. 2014; 7(6): 421-8.
35. Wang XM, Yang B, Ren CG, Wang HW, Wang JY, Dai CC. Involvement of abscisic acid and salicylic acid in signal cascade regulating bacterial endophyte-induced volatile oil biosynthesis in plantlets of Atractylodes lancea. Physiol Plant. 2015; 153(1): 30-42.
36. Kimura Y, Sumiyoshi M. Effects of an Atractylodes lancea rhizome extract and a volatile component β-eudesmol on gastrointestinal motility in mice. J Ethnopharmacol. 2012; 141(1): 530-6.
37. Muthuswamy R, Senthamarai R. Anatomical investigation of flower of Butea monosperma Lam. Anc Sci Life. 2014; 34(2): 73-9.
38. Krolikiewicz-Renimel I, Michel T, Destandau E, Reddy M, Andre P, Elfakir C, et al. Protective effect of a Butea monosperma (Lam.) Taub. flowers extract against skin inflammation: antioxidant, anti-inflammatory and matrix metalloproteinases inhibitory activities. J Ethnopharmacol. 2013; 148(2): 537-43.
39. Song X, Wang J, Wu F, Li X, Teng M, Gong W. cDNA cloning, functional expression and antifungal activities of a dimeric plant defensin SPE10 from Pachyrrhizus erosus seeds. Plant Mol Biol. 2005; 57(1): 13-20.
40. Abid M, Hrishikeshavan HJ, Asad M. Pharmacological evaluation of Pachyrrhizus erosus (L) seeds for central nervous system depressant activity. Indian J Physiol Pharmacol. 2006; 50(2): 143-51.
41. Singh N, Singh V, Singh RK, Pant AB, Pal US, Malkunje LR, et al. Osteogenic potential of Cissus qudrangularis assessed with osteopontin expression. Natl J Maxillofac Surg. 2013; 4(1): 52-6.
42. Nie TW, Shukkoor MS, Nair RS, Amiruddin FK, Ramasamy S. Involvement of opioidergic and serotonergic systems in the analgesic activity of Cissus quadrangularis L. stem extract in mice. J Basic Clin Physiol Pharmacol. 2015; 26(1): 35-41.
43. Kang JW, Min BS, Lee JH. Anti-platelet activity of erythro-(7S,8R)-7-acetoxy-3,4,3’,5’-tetramethoxy-8-O-4’-neolignan from Myristica fragrans. Phytother Res. 2013; 27(11): 1694-9.
44. Samuels N. Herbal remedies and anticoagulant therapy. Thromb haemost. 2005; 93(1): 3-7.
45. Nurtjahja-Tjendraputra E, Ammit AJ, Roufogalis BD, Tran VH, Duke CC. Effective anti-platelet and COX-1 enzyme inhibitors from pungent constituents of ginger. Thromb Res. 2003; 111(4-5): 259-65.
46. Lee SH. Antiplatelet property of Curcuma longa L. rhizome-derived ar-turmerone. Bioresour Technol. 2006; 97(12): 1372-6.
47. Paramapojn S, Gritsanapan W. Free radical scavenging activity determination and quantitative analysis of curcuminoids in Curcuma zedoaria rhizome extracts by HPLC method. Current science. 2009; 97(7): 1069-73.
48. Azam G, Noman S, Al-Amin M. Phytochemical Screening and Antipyretic Effect of Curcuma zedoaria Rosc. (Zingiberaceae) Rhizome. British Journal of Pharmaceutical Research. 2014; 4(5): 569-75.
2. Marder VJ, Aird WC, Bennett JS, Schulman S, White GC, editors. Hemostasis and thombosis: basic principles and clinical practice. 6th Edition. Philadelphia, Lippincott Williams & Wilkins; 2012
3. Bloom AL, Forbes CD, Thomas DP, Tuddenham EGD, editors. Haemostasis and thrombosis. 3rd Edition. Edinburgh: Churchill Livingstone; 1994.
4. Bick RL. Disorders of thrombosis and hemostasis: clinical and laboratory practice. In: Bick RL, editors. ASCP Press, Chicago; 1992:239 [chapter 12]
5. Collins B, Hollidge C. Antithrombotic drug market. Nat Rev Drug Discov 2003; 2(1): 11–2.
6. Raju NC, Eikelboom JW. The aspirin controversy in primary prevention. Curr Opin Cardiol 2012; 27(5): 499-507.
7. Shah BH, Nawaz Z, Pertani SA, Roomi A, Mahmood H, Saeed SA, et al. Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonicacidmediated platelet aggregation through inhibition of thromboxane formation and Ca2+signaling. Biochem Pharmacol 1999; 58(7): 1167–72.
8. Srivastava KC, Bordia A, Verma SK. Curcumin, a major component of food spice turmeric (Curcuma longa) inhibits aggregation and alters eicosanoid metabolism in human blood platelets. Prostaglandins Leukot Essent Fatty Acids 1995; 52(4): 223–7.
9. Shih CY, Chou TC. The antiplatelet activity of magnolol is mediated by PPAR-beta/gamma. Biochem Pharmacol 2012; 84(6): 793–803.
10. Shin DW, Kim SN, Lee SM, Lee W, Song MJ, Park SM, et al. (-)-Catechin promotes adipocyte differentiation in human bone marrow mesenchymal stem cells through PPAR gamma transactivation. Biochem Pharmacol 2009; 77(1): 125–33.
11. Son DJ, Cho MR, Jin YR, Kim SY, Park YH, Lee SH, et al. Antiplatelet effect of green tea catechins: a possible mechanism through arachidonic acid pathway. Prostaglandins Leukot Essent Fatty Acids. 2004 Jul; 71(1): 25-31.
12. Hollman PC, van Trijp JM, Mengelers MJ, de Vries JH, Katan MB. Bioavailability of the dietary antioxidant flavonol quercetin in man. Cancer Lett. 1997; 114(1–2): 139-40.
13. Fang XK, Gao J, Zhu DN. Kaempferol and quercetin isolated from Euonymus alatus improve glucose uptake of 3T3-L1 cells without adipogenesis activity. Life Sci 2008; 82(11–12): 615–22.
14. Oh WJ, Endale M, Park SC, Cho JY, Rhee MH. Dual Roles of Quercetin in Platelets: Phosphoinositide-3-Kinase and MAP Kinases Inhibition, and cAMP-Dependent Vasodilator Stimulated Phosphoprotein Stimulation. Evid Based Complement Alternat Med. 2012; 2012: 485262. doi: 10.1155/2012/485262. Epub 2012 Dec 17.
15. Ibrahim D, Hong LS, Kuppan N. Antimicrobial activity of crude methanolic extract from Phyllanthus niruri. Nat Prod Commun. 2013; 8(4): 493-6.
16. Freitas AM, Schor N, Boim MA. The effect of Phyllanthus niruri on urinary inhibitors of calcium oxalate crystallization and other factors associated with renal stone formation. BJU Int. 2002; 89(9): 829-34.
17. Manjrekar AP, Jisha V, Bag PP, Adhikary B, Pai MM, Hegde A, et al. Effect of Phyllanthus niruri Linn. treatment on liver, kidney and testes in CCl4 induced hepatotoxic rats. Indian J Exp Biol. 2008; 46(7): 514-20.
18. Matic IZ, Juranic Z, Savikin K, Zdunic G, Nadvinski N, Godevac D. Chamomile and Marigold Tea: Chemical Characterization and Evaluation of Anticancer Activity. Phytother Res. 2013; 27(6): 852-8.
19. Lokman FE, Gu HF, Wan Mohamud WN, Yusoff MM, Chia KL, Ostenson CG. Antidiabetic Effect of Oral Borapetol B Compound, Isolated from the Plant Tinospora crispa, by Stimulating Insulin Release. Evid Based Complement Alternat Med. 2013; 2013: 727602. doi: 10.1155/2013/727602. Epub 2013 Nov 10.
20. Yusoff M, Hamid H, Houghton P. Anticholinesterase Inhibitory Activity of Quaternary Alkaloids from Tinospora crispa. Molecules. 2014; 19(1): 1201-11.
21. Rungruang T, Boonmars T. In vivo antiparasitic activity of the Thai traditional medicine plant, Tinospora crispa against Plasmodium yoelii. Southeast Asian J Trop Med Public Health. 2009; 40(5): 898-900.
22. Kumar SN, Aravind SR, Sreelekha TT, Jacob J, Kumar BS. Asarones from Acorus calamus in Combination with Azoles and Amphotericin B: A Novel Synergistic Combination to Compete Against Human Pathogenic Candida Species In Vitro. Appl Bioc Biotechnol. 2015; 175(8): 3683-95.
23. Ponrasu T, Madhukumar KN, Ganeshkumar M, Iyappan K, Sangeethapriya V, Gayathri VS, et al. Efficacy of Acorus calamus on collagen maturation on full thickness cutaneous wounds in rats. Pharmacog Mag. 2014; 10(Suppl 2): S299-305.
24. Shi GB, Wang B, Wu Q, Wang TC, Wang CL, Sun XH, et al. Evaluation of the wound-healing activity and anti-inflammatory activity of aqueous extracts from Acorus calamus L. Pak J Pharm Sci. 2014; 27(1): 91-5.
25. Kim D-Y, Lee S-H, Kim W-J, Jiang J, Kim M-K, Shin Y-K, et al. Inhibitory effects of Acorus calamus extracts on mast cell-dependent anaphylactic reactions using mast cell and mouse model. J Ethnopharmacol. 2012; 141(1): 526-9.
26. Lai P, Liu Y. Angelica sinensis polysaccharides inhibit endothelial progenitor cell senescence through the reduction of oxidative stress and activation of the Akt/hTERT pathway. Pharm Biol. 2015; 53(12): 1842-9. 1-8.
27. Champakaew D, Junkum A, Chaithong U, Jitpakdi A, Riyong D, Sanghong R, et al. Angelica sinensis (Umbelliferae) with proven repellent properties against Aedes aegypti, the primary dengue fever vector in Thailand. Parasitol Res. 2015; 114(6): 2187-98.
28. Jing Q, Wu GT, Du LD, Liu WZ, Li YD, Ren Y. Therapeutic effects of ethanol extracts of Angelica sinensis and Astragalus mongholicus in diabetic gastroparesis rats. Zhong Yao Cai. 2014; 37(8): 1415-20.
29. Bunel V, Antoine M-H, Nortier J, Duez P, Stévigny C. Nephroprotective effects of ferulic acid, Z-ligustilide and E-ligustilide isolated from Angelica sinensis against cisplatin toxicity in vitro. Toxicol In Vitro. 2015; 29(3): 458-67.
30. Makchuchit S, Itharat A. Tewtrakul S. Antioxidant and Nitric Oxide Inhibition Activities of Thai Medicinal Plants. J Med Assoc Thai. 2010; 93. Suppl 7: S227-35.
31. Gao XF, Li QL, Li HL, Zhang HY, Su JY, Wang B, et al. Extracts from Curcuma zedoaria Inhibit Proliferation of Human Breast Cancer Cell MDA-MB-231 In Vitro. Evid based Complement Alternat Med. 2014; 2014: 730678. doi: 10.1155/2014/730678. Epub 2014 May 5
32. Lobo R, Prabhu KS, Shirwaikar A, Shirwaikar A. Curcuma zedoaria Rosc. (white turmeric): a review of its chemical, pharmacological and ethnomedicinal properties. J Pharm Pharmacol. 2009; 61(1): 13-21.
33. Wilson B, Abraham G, Manju VS, Mathew M, Vimala B, Sundaresan S, et al. Antimicrobial activity of Curcuma zedoaria and Curcuma malabarica tubers. J Ethnopharmacol. 2005; 99(1): 147-51.
34. Koonrungsesomboon N, Na-Bangchang K, Karbwang J. Therapeutic potential and pharmacological activities of Atractylodes lancea (Thunb.) DC. Asian Pac J Trop Med. 2014; 7(6): 421-8.
35. Wang XM, Yang B, Ren CG, Wang HW, Wang JY, Dai CC. Involvement of abscisic acid and salicylic acid in signal cascade regulating bacterial endophyte-induced volatile oil biosynthesis in plantlets of Atractylodes lancea. Physiol Plant. 2015; 153(1): 30-42.
36. Kimura Y, Sumiyoshi M. Effects of an Atractylodes lancea rhizome extract and a volatile component β-eudesmol on gastrointestinal motility in mice. J Ethnopharmacol. 2012; 141(1): 530-6.
37. Muthuswamy R, Senthamarai R. Anatomical investigation of flower of Butea monosperma Lam. Anc Sci Life. 2014; 34(2): 73-9.
38. Krolikiewicz-Renimel I, Michel T, Destandau E, Reddy M, Andre P, Elfakir C, et al. Protective effect of a Butea monosperma (Lam.) Taub. flowers extract against skin inflammation: antioxidant, anti-inflammatory and matrix metalloproteinases inhibitory activities. J Ethnopharmacol. 2013; 148(2): 537-43.
39. Song X, Wang J, Wu F, Li X, Teng M, Gong W. cDNA cloning, functional expression and antifungal activities of a dimeric plant defensin SPE10 from Pachyrrhizus erosus seeds. Plant Mol Biol. 2005; 57(1): 13-20.
40. Abid M, Hrishikeshavan HJ, Asad M. Pharmacological evaluation of Pachyrrhizus erosus (L) seeds for central nervous system depressant activity. Indian J Physiol Pharmacol. 2006; 50(2): 143-51.
41. Singh N, Singh V, Singh RK, Pant AB, Pal US, Malkunje LR, et al. Osteogenic potential of Cissus qudrangularis assessed with osteopontin expression. Natl J Maxillofac Surg. 2013; 4(1): 52-6.
42. Nie TW, Shukkoor MS, Nair RS, Amiruddin FK, Ramasamy S. Involvement of opioidergic and serotonergic systems in the analgesic activity of Cissus quadrangularis L. stem extract in mice. J Basic Clin Physiol Pharmacol. 2015; 26(1): 35-41.
43. Kang JW, Min BS, Lee JH. Anti-platelet activity of erythro-(7S,8R)-7-acetoxy-3,4,3’,5’-tetramethoxy-8-O-4’-neolignan from Myristica fragrans. Phytother Res. 2013; 27(11): 1694-9.
44. Samuels N. Herbal remedies and anticoagulant therapy. Thromb haemost. 2005; 93(1): 3-7.
45. Nurtjahja-Tjendraputra E, Ammit AJ, Roufogalis BD, Tran VH, Duke CC. Effective anti-platelet and COX-1 enzyme inhibitors from pungent constituents of ginger. Thromb Res. 2003; 111(4-5): 259-65.
46. Lee SH. Antiplatelet property of Curcuma longa L. rhizome-derived ar-turmerone. Bioresour Technol. 2006; 97(12): 1372-6.
47. Paramapojn S, Gritsanapan W. Free radical scavenging activity determination and quantitative analysis of curcuminoids in Curcuma zedoaria rhizome extracts by HPLC method. Current science. 2009; 97(7): 1069-73.
48. Azam G, Noman S, Al-Amin M. Phytochemical Screening and Antipyretic Effect of Curcuma zedoaria Rosc. (Zingiberaceae) Rhizome. British Journal of Pharmaceutical Research. 2014; 4(5): 569-75.