Content uploaded by Kartheek Chegu
Author content
All content in this area was uploaded by Kartheek Chegu on May 14, 2019
Content may be subject to copyright.
www.wjpps.com Vol 7, Issue 5, 2018.
904
Chegu et al. World Journal of Pharmacy and Pharmaceutical Sciences
IN VITRO STUDY OF THE ANTICOAGULANT ACTIVITY OF SOME
PLANT EXTRACTS
Kartheek Chegu*, K. Mounika, M. Rajeswari, N. Vanibala, P. Sujatha, P. Sridurga,
D. R. Brahma Reddy
Nalanda Institute of Pharmaceutical Sciences, Kantepudi, Sattenapalli, Guntur (Dt.),
Andhra Pradesh, 522403.
ABSTARCT
Hemostasis is the process of formation of clots within the walls of
damaged blood vessels. To prevent abnormal bleeding and to maintain
intravascular blood in a fluid state, in this study we aimed to evaluate
the possible anticoagulant effect of aqueous extracts of Ginger, Garlic,
Green tea and Clove. The aqueous extracts of Ginger, Garlic, Green tea
and Clove were tested for in vitro prothrombin time (PT) test. The in
vitro anticoagulant effects examined by using plasma, collected from
blood samples of normal individuals by measuring PT.
Ethylenediaminetetraacetic acid (EDTA) and saline in distilled water
were used as a negative and positive control, respectively. The extract
plasma was subjected to anticoagulation activity and was compared
with EDTA-plasma and saline plasma. The observed prolonged prothrombin activity could be
due to the presence of certain phytochemical constituents in the crude extract. The crude
extracts and further, the active principles could be isolated and evaluated for clinical or
physiological purposes. In vitro, anticoagulant activity studies results demonstrated that the
all four aqueous extracts possess pharmacologically active anticoagulant components which
could be helpful in preventing blood clot.
KEYWORDS: Anticoagulant, Hemostasis, Prothrombin time, Ethylenediaminetetraacetic
acid (EDTA).
INTRODUCTION
Hemostasis is an interaction process between coagulation and anticoagulants that retains the
blood within the injured vascular system during periods of injury.[1] Hemostasis comprises a
WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
SJIF Impact Factor 7.421
Volume 7, Issue 5, 904-913 Research Article ISSN 2278 – 4357
Article Received on
04 March 2018,
Revised on 25 March 2018,
Accepted on 18 April 2018
DOI: 10.20959/wjpps20185-11492
*Corresponding Author
Kartheek Chegu
Nalanda Institute of
Pharmaceutical Sciences,
Kantepudi, Sattenapalli,
Guntur (Dt.),
Andhra Pradesh-522403.
www.wjpps.com Vol 7, Issue 5, 2018.
905
Chegu et al. World Journal of Pharmacy and Pharmaceutical Sciences
complex mechanism that contains three major steps: (1) Vasoconstriction, (2) temporary
blockage of a break by a platelet plug, and (3) blood coagulation, or formation of a fibrin clot.
Anticoagulant drugs are needed for the short-term treatment of arterial and venous thrombotic
disorders and for the long-term prevention of recurrences.[3] Although heparin has been the
mainstay of anticoagulant treatment for acute thrombotic disorders for decades, this drug
presents some limitations related to its clinical application, such as inefficacy in antithrombin
deficient patients, bleeding complications, potential for the development of heparin-induced
thrombocytopenia, immunosuppression and osteoporotic effect with long-term application as
side effects.[3,4] So, the search for new substances with anticoagulant and antithrombotic
activities is relevant.[3,4,5] Medicinal plants have historically been the first source of
anticoagulant and antithrombotic molecules.[5]
Therefore, it is necessity and demand of time to explore alternative anticoagulants. The plants
are safer source of medicines hence, we undertook the anticoagulation study of aqueous
extracts selected medicinal plants such as Allium sativum (Garlic), Zingiber officinale
(Ginger), Syzygium aromaticum (Clove), Camellia Sinensis(Green Tea).
MATERIALS AND METHODS
Materials: Centrifuge, EDTA (Ethylene Diamine Tetra acetic Acid), Sodium Chloride,
Calcium Chloride, Test tubes, Capillary tubes, Glass Slides, Syringes(5ml), Needles, Sprit,
Cotton, Filter paper, Micropipettes, Ginger, Garlic, Clove, Green Tea.
Preparation of Plant Extracts
Aqueous extract of Allium sativum (Garlic): Garlic (Allium sativum) species were
purchased from local market. 10g of peeled garlic was weighed and washed with sterile
distilled water by soaking for 5 minutes and then it was soaked in 95%ethanol for 3 minutes
to make the species sterile. Then the garlic was dried for 10 minutes to evaporate the ethanol.
Then the dried garlic was crushed in sterile mortar and pestle by adding 0.5ml of distilled
water. After mashing the garlic will be in a paste form, it is filtered using Whatman no. 1
filter paper and the extract collected was 15 ml. This extract was considered to be 100% was
used.
Aqueous extract of Zingiber officinale (Ginger): Dried Ginger (Zingiber officinale)
rhizomes were purchased from the local vegetable market. The dry rhizomes ground into a
fine powder and ten grams of the powder were weighed using sensitive balance and then
www.wjpps.com Vol 7, Issue 5, 2018.
906
Chegu et al. World Journal of Pharmacy and Pharmaceutical Sciences
suspended in 100 ml of distilled water in a conical flask with continues shaking for twenty
four hours. The supernatant of Zingiber officinale extract filtrated using filter paper size 42
mm. The final aqueous extract (10%) of Zingiber officinale was used for an in vitro testing of
its possible anticoagulant activity in blood samples.
Aqueous extract of Syzygium aromaticum (Clove)
Clove flower bud aqueous Extract preparation Dried flower buds of clove were collected
from local market and powdered (2 mm mesh size). 10 g crude powder was mixed in 100 ml
of double distilled water, and the mixture was left over night. The mixture was then filtered;
centrifuged and supernatant extract was stored at 4°C till further use.[23]
Aqueous extract of Camellia Sinensis(Green Tea)
Dried leaves of green tea (Camellia sinensis L.) were purchased from a Local Market s For
extraction, 10 g of ground leaves of each tea sample was extracted with 100 ml of distilled
water (DW) at constant temperature of 95 °C under continuous Stirring. The supernatant was
Subsequently filtered through Whatman No. 1 filter paper to remove rough particles and then
centrifuged at 3,000 rpm for 10 min. The supernatant, called green tea crude extracts (GTE)
was stored at 2–4 °C until analyzed.
Phytochemical Screening: Aqueous extracts are subjected for the presence of different
phytoconstituents like alkaloid, steroid, flavonoids, tannin, glycoside etc.
Blood Collection and Plasma Sample Preparation
Blood samples were drawn via vein puncture healthy volunteer donor (age 18-35 years old).
The blood placed separately in containers containing EDTA to prevent the clotting process.
Centrifugation (15 minutes at rate 3000 rpm) was carried out to separate the blood cells from
plasma in order to obtain pure platelet plasma (ppp) for prothrombin time test.
Anticoagulation Assay
Collection of Blood and Plasma Re-Calcification: 0.2 ml plasma, 0.1 ml of aqueous extract
of different concentration and different volume of CaCl2 (25 mM) were added together in a
clean fusion tube and incubated at 370C in water bath. For control experiment extract solution
was replaced by same volume of 0.9% saline water. The clotting time was recorded with
stopwatch by tilting the test tubes every 5 seconds. This time is called the prothrombin time.
www.wjpps.com Vol 7, Issue 5, 2018.
907
Chegu et al. World Journal of Pharmacy and Pharmaceutical Sciences
Determination of Coagulation Time
In the present study we taken as total groups are following
Groups
Name of Plant Extract
Amount of Plasma
Amount of Extract
Cacl2 Solution
Group I
Control
0.2ml
0.1ml
0.3ml
Group II
Aqueous extract of Ginger
0.2ml
0.1ml
0.3ml
Group III
Aqueous extract of Garlic
0.2ml
0.1ml
0.3ml
Group IV
Aqueous extract of Clove
0.2ml
0.1ml
0.3ml
Group V
Aqueous extract of Green Tea
0.2ml
0.1ml
0.3ml
Group VI
Aqueous extract of Ginger
plus Garlic
0.2ml
0.5ml +0.5ml
0.3ml
Group VII
Aqueous extract of Clove plus
Green Tea
0.2ml
0.5ml+0.5ml
0.3ml
Group VIII
Aqueous extract of Ginger +
Garlic+ Clove+ Green Tea
0.2ml
0.25ml+0.25ml+0.2
5ml+0.25ml
0.3ml
RESULTS AND DISCUSSION
This study was carried out to evaluate the effect of Allium sativum (Garlic), Zingiber
officinale (Ginger), Syzygium aromaticum (Clove), Camellia Sinensis(Green Tea) as an
anticoagulant in blood samples of normal individuals by using principles of coagulation time.
Coagulation Assay
Groups
Name of Plant Extract
Amount of
Plasma
Amount of Extract
Cacl2
Solution
Time of
Coagulation
Group I
Control
0.2ml
0.1ml
0.3ml
1.45min
Group II
Aqueous extract of
Ginger
0.2ml
0.1ml
0.3ml
4.15min
Group III
Aqueous extract of
Garlic
0.2ml
0.1ml
0.3ml
5.30min
Group IV
Aqueous extract of Clove
0.2ml
0.1ml
0.3ml
4.45min
Group V
Aqueous extract of Green
Tea
0.2ml
0.1ml
0.3ml
6.30min
Group VI
Aqueous extract of
Ginger plus Garlic
0.2ml
0.5ml +0.5ml
0.3ml
7.30min
Group VII
Aqueous extract of Clove
plus Green Tea
0.2ml
0.5ml+0.5ml
0.3ml
8.30min
Group VIII
Aqueous extract of
Ginger + Garlic+ Clove+
Green Tea
0.2ml
0.25ml+0.25ml+0.25
ml+0.25ml
0.3ml
12.30min
From the above table all extracts are shown significant anticoagulant activity. Its activity due
to the following chemical constituents present in the sample which showed the activity.
Ginger inhibits platelet aggregation in healthy individuals and patients with coronary artery
disease. The concurrent use of ginger and anticoagulants may result in an increased risk of
bleeding. In Ayurvedic science, ginger has been described as an excellent tonic for the heart.
www.wjpps.com Vol 7, Issue 5, 2018.
908
Chegu et al. World Journal of Pharmacy and Pharmaceutical Sciences
It helps prevent various heart diseases by reducing blood clotting that can lead to plaque
formation or thrombosis. It can also open the blockage in the blood vessels, thus decreasing
peripheral vascular resistance and hence blood pressure. Ginger may also help to lower high
cholesterol, making the heart healthy. Srivastava et al. found that aqueous extracts of ginger
inhibited platelet aggregation induced by ADP, epinephrine, collagen, and arachidonic acid in
vitro. The antiplatelet action of 6-gingerol was also mainly because of the inhibition of
thromboxane formation.
Green Tea: Tea from Camellia sinensis is one of the most ancient drinks and the second
most widely consumed beverage in the world. Tea can be classified into three types: green,
oolong, and black. Green tea, which is non-fermented and derived directly from drying and
steaming fresh tea leaves, contains polyphenolic compounds. The catechins in green tea
account for 16%–30% of its dry weight. Epigallocatechin-3-gallate (EGCG), the most
predominant catechin in green tea, is responsible for much of the biological activity mediated
by green tea.
In an early in vitro and in vivo study, both green tea and EGCG significantly prolonged
mouse tail bleeding time in conscious mice. They inhibited adenosine diphosphate- and
collagen-induced rat platelet aggregation in a dose-dependent manner. The antiplatelet
activity may result from the inhibition of thromboxane A2 formation. Because ATP release
from a dense granule is inhibited by catechins in washed platelets, thromboxane A2
formation may have been inhibited by preventing arachidonic acid liberation and
thromboxane A2 synthase. Regarding a possible adverse effect of green tea on platelets, one
case report showed that after a patient consumed a weight-loss product containing green tea,
thrombotic thrombocytopenic purpura developed. Since green tea contains vitamin K,
drinking green tea may antagonize the anticoagulant effects of warfarin.
In a randomized, double-blind, placebo-controlled study, eight subjects received oral EGCG
in a single dose of 50–1600 mg. In each dosage group, the kinetic profile revealed rapid
absorption with a one-peak plasma concentration versus time course, followed by a
multiphasic decrease consisting of a distribution phase and an elimination phase. The mean
half-life values observed were between 1.9 h and 4.6 h. In another pilot clinical study, after
five healthy subjects took tea extract orally, the concentration of EGCG in plasma was
determined; the half-life of EGCG was between 2.2 h and 3.4 h.[25,26,27]
www.wjpps.com Vol 7, Issue 5, 2018.
909
Chegu et al. World Journal of Pharmacy and Pharmaceutical Sciences
Garlic: Garlic (Allium sativum) has the potential to modify the risk of developing
atherosclerosis by reducing blood pressure, thrombus formation, and serum lipid and
cholesterol levels.[33] These effects are primarily attributed to the sulfur-containing
compounds, particularly allicin and its transformation products. Commercial garlic
preparations may be standardized to a fixed alliin and allicin content.[34]
Garlic inhibits platelet aggregation in vivo in a dose-dependent fashion.[35] The effect of one
of its constituents, ajoene, appears to be irreversible and may potentiate the effect of other
platelet inhibitors such as prostacyclin, forskolin, indomethacin, and dipyridamole 36.
Although these effects have not been consistently demonstrated in clinical trials[35], there are
several cases in the literature on excessive dietary garlic intake or use of garlic as a medicine
associated with coagulation alterations. One case report showed an interaction between garlic
and warfarin, resulting in an increased INR. In addition to bleeding concerns, garlic has the
potential to decrease systemic and pulmonary vascular resistance in laboratory animals, an
effect that was observed in clinical studies as well.
In an early study in rats, alliin was absorbed quickly after oral administration and eliminated
after 6 h. Allicin was absorbed slowly after oral administration, and its plasma peak level
appeared between 0.5 h and 2 h. Even four days later, allicin could still be detected in the
rats. Although in one clinical study garlic oil selectively inhibited CYP2E1 activity, it is still
difficult to predict drug interactions with garlic.[33-45]
Clove
Anticoagulants and antiplatelets: Clove has been associated with inhibiting platelet
aggregation (increasing INR, and report of disseminated intravascular coagulation.
Polysaccharides isolated from clove may have antithrombic effects in vitro. Therefore, use
with other anticoagulants or antiplatelet agents may result in additive effects and increased
bleeding risk Clove oil contains a chemical called eugenol that seems to slow blood clotting.
There is a concern that taking clove oil might cause bleeding in people with bleeding
disorders.[46] From all the above discussion all four aqueous extracts are showed significant
anticoagulant properties due to presence of their chemical constituents in it.
CONCLUSION
The anticoagulant activities of all four aqueous extracts are shown significant anticoagulant
properties was reported. Hence, further identification and characterization of active molecules
www.wjpps.com Vol 7, Issue 5, 2018.
910
Chegu et al. World Journal of Pharmacy and Pharmaceutical Sciences
responsible for activity was to be found out in future. The daily intake of these aqueous plant
extracts may help full to prevent the cardiovascular diseases. It requires further investigation
to find out active molecules and their Pharmacological properties and other effects.
REFERENCES
1. Sirridge MS, Shannon R. Hematology Principles and Procedures. 6th Ed. Philadelphia,
PA: Lea and Febiger, 1993; 202-78.
2. Hoffbrand, A. V. Essential Haematology. Oxford: Blackwell Science, 2002; 241–243.
3. Pallister CJ, Watson MS. Haematology. Scion Publishing, 2010; 336–347.
4. Long, Andrew T.; Kenne, Ellinor; Jung, Roman; Fuchs, Tobias A.; Renné, Thomas.
"Contact System Revisited: An Interface Between Inflammation, Coagulation, And Innate
Immunity". Journal of Thrombosis and Haemostasis, 2015; 14: 427-437.
5. Moll S, Roberts HR. Overview of Anticoagulant Drugs for the Future. Semin
Hematol, 2002; 39: 145–157.
6. Lapikova ES, Drozd NN, Tolstenkov AS, Makarov VA, Zvyagintseva TN, Shevchenko
NM, Bakunina IU, Besednova NN, Kuznetsova TA. Inhibition Of Thrombin And Factor
Xa By Fucus Evanescens Fucoidan And Its Modified Analogs. Bull Exp Biol Med., 2008;
146: 328-333.
7. Chaves DSA, Costa SS, Almeida AP, Frattani F, Assafim M, Zingali RB. Metabólitos
Secundários De Origem Vegetal: Uma Fonte Potencial De Fármacos
Antitrombóticos. Quim Nova, 2010; 33: 172-180.
8. Olaniyan O.T1*, Meraiyebu A.B1, Arogbonlo A1, Dare J.B2, Shekins O3, Shafe
M.O1.Effects Of Aqueous Extract Of Garlic (Allium Sativum) On Blood Parameters In
Adult Wistar Rats (Rattus Novergicus) International Journal Of Pharmaceutical Science
Invention ISSN (Online): 2319 – 6718, ISSN (Print): 2319 – 670X Www.Ijpsi.Org.,
March 2013; 2(3): 42-45.
9. Song CS, Kim JH, Kim ES, Lee PH. A Blood Anticoagulant Substance From Garlic
(Allium Sativum): I. Its Preparation And Studies On Its Anticoagulant Effect. Yonsei
Med J. Dec., 1963; 4(1): 17-20.
10. Narjis Hadi Mansoor Al-Saadi In Vitro Study Of The Anticoagulant Activity Of Some
Plant Extracts Indian Journal Of Applied Research, July 2013; III(VII).
11. Chan KC, Yin MC, Chao WJ. Effect Of Diallyl Trisulfide-Rich Garlic Oil On Blood
Coagulation And Plasma Activity Of Anticoagulation Factors In Rats. Food And
Chemical Toxicology, Mar 1 2007; 45(3): 502-7.
www.wjpps.com Vol 7, Issue 5, 2018.
911
Chegu et al. World Journal of Pharmacy and Pharmaceutical Sciences
12. Neutraceutical Potential Of Organosulfur Compounds In Fresh Garlic And Garlic
Preparations Katare Charu*1, Shrivastava Yogita1 And Saxena Sonali2 1govtkamla Raja
Girls Pg Autonomous College, Gwalior Madhya Pradesh 2 Schools Of Studies In
Biochemistry, Jiwaji University, Gwalior, Madhya Pradesh.
13. Thomson M, Ali M. Garlic Allium Sativum: A Review of Its Potential Use As An Anti-
Cancer Agent. Curr Cancer Drug Targets 2003; 3: 67-81.
14. Bergès R, Siess MH, Arnault I, Auger J, Kahane R, Pinnert MF, Et Al. Comparison Of
The Chemopreventive Efficacies Of Garlic Powders With Different Alliin Contents
Against Aflatoxin B1 Carcinogenicity In Rats. Carcinogenesis, 2004; 25: 1953-9.
15. Taj Eldin IM, MA Elmutalib, Hiba A., Hiba F., Thowiba S., Elnazeer I. Hamedelniel. An
In Vitro Anticoagulant Effect Of Aqueous Extract Of Ginger (Zingiber Officinale)
Rhizomes In Blood Samples Of Normal Individuals. American Journal Of Research
Communication, 2016, 4(1): 113-121
16. Pharmacological Activity Of Zingiber Officinale Rajesh Kumar Mishra٭, Anil Kumar
And Ashok Kumar Pharmacy College, Itaura, Chandeshwar, Azamgarh, Uttar Pradesh,
India, 1422-1428
17. Study Of Some Biological Activities Of Aqueous Extract Of Ginger (Zingiber Officinale)
Helal Mohamed MI, Osman Mona Y, Ghobashy Madeha OI, Helmy Wafaa A Year:
2014; 13(2): 144-150.
18. Marx, Wolfgang Et Al. “The Effect Of Ginger (Zingiber Officinale) On Platelet
Aggregation: A Systematic Literature Review.” Ed. Kathleen Freson. Plos ONE 10.10
(2015): E0141119. PMC. Web. 25 Mar. 2018
19. Dacie V John Sir, Lewis M S. Practical Haematology, ELBS. 8th Edition 1995; 297-349.
20. Saeed SA, Gilani AH. Antithrombotic Activity of Clove Oil. J Pak Med Assoc, 1994;
44(5): 112-5.
21. Rasheed A, Laekeman G, Totte J, Vlietinck A J, Herman A G. Eugenol And
Prostaglandin Biosynthesis. N Engl J Med., 1984; 310: 50-1.
22. Srivastava KC. Antiplatelet Principles From A Food Spice Clove (Syzygium Aromaticum
L). J Prostaglandins Leukot Essent Fatty Acids, 1993; 48: 363-72.
23. Ahmad T, Shinkafi TS, Routray I, Mahmood A, Ali S. Aqueous Extract Of Dried Flower
Buds Of Syzygium Aromaticum Inhibits Inflammation And Oxidative Stress. J Basic Clin
Pharm, 2012; 3(3): 323-327.
24. Stote K.S., Baer D.J. Tea Consumption May Improve Biomarkers Of Insulin Sensitivity
And Risk Factors For Diabetes. J. Nutr, 2008; 138: 1584S-1588S.
www.wjpps.com Vol 7, Issue 5, 2018.
912
Chegu et al. World Journal of Pharmacy and Pharmaceutical Sciences
25. Wang C.Z., Mehendale S.R., Yuan C.S. Commonly Used Antioxidant Botanicals: Active
Constituents And Their Potential Role In Cardiovascular Illness. Am. J. Chin.
Med., 2007; 35: 543–558. Doi: 10.1142/S0192415X07005053.
26. Kang W.S., Lim I.H., Yuk D.Y., Chung K.H., Park J.B., Yoo H.S., Yun Y.P.
Antithrombotic Activities of Green Tea Catechins And (−)-Epigallocatechin
Gallate. Thromb. Res., 1999; 96: 229-237.
27. Son D.J., Cho M.R., Jin Y.R., Kim S.Y., Park Y.H., Lee S.H., Akiba S., Sato T., Yun
Y.P. Antiplatelet Effect Of Green Tea Catechins: A Possible Mechanism Through
Arachidonic Acid Pathway. Prostaglandins Leukot. Essent. Fatty Acids, 2004; 71: 25-31.
28. Jin Y.R., Im J.H., Park E.S., Cho M.R., Han X.H., Lee J.J., Lim Y., Kim T.J., Yun Y.P.
Antiplatelet Activity Of Epigallocatechin Gallate Is Mediated By The Inhibition Of
Plcgamma2 Phosphorylation, Elevation Of PGD2 Production, And Maintaining Calcium-
Atpase Activity. J. Cardiovasc. Pharmacol, 2008; 51: 45–54.
29. Liatsos G.D., Moulakakis A., Ketikoglou I., Klonari S. Possible Green Tea-Induced
Thrombotic Thrombocytopenic Purpura. Am. J. Health Syst. Pharm, 2010; 67: 531–534.
30. Taylor J.R., Wilt V.M. Probable Antagonism Of Warfarin By Green Tea. Ann.
Pharmacother, 1999; 33: 426-428.
31. Ullmann U., Haller J., Decourt J.P., Girault N., Girault J., Richard-Caudron A.S., Pineau
B., Weber P. A Single Ascending Dose Study Of Epigallocatechin Gallate In Healthy
Volunteers. J. Int. Med. Res., 2003; 31: 88-101.
32. Gawande S., Kale A., Kotwal S. Effect Of Nutrient Mixture And Black Grapes On The
Pharmacokinetics Of Orally Administered (−) Epigallocatechin-3-Gallate From Green
Tea Extract: A Human Study. Phytother. Res., 2008; 22: 802–808.
33. Stevinson C., Pittler M.H., Ernst E. Garlic for Treating Hypercholesterolemia. A Meta-
Analysis of Randomized Clinical Trials. Ann. Intern. Med., 2000; 133: 420–429.
34. Rybak M.E., Calvey E.M., Harnly J.M. Quantitative Determination Of Allicin In Garlic:
Supercritical Fluid Extraction And Standard Addition Of Alliin. J. Agric. Food
Chem, 2004; 52: 682–687.
35. Chan K.C., Yin M.C., Chao W.J. Effect Of Diallyl Trisulfide-Rich Garlic Oil On Blood
Coagulation And Plasma Activity Of Anticoagulation Factors In Rats. Food Chem.
Toxicol, 2007; 45: 502–507. Fukao H., Yoshida H., Tazawa Y., Hada T. Antithrombotic
Effects Of Odorless Garlic Powder Both In Vitro And In Vivo. Biosci. Biotechnol.
Biochem, 2007; 71: 84–90.
www.wjpps.com Vol 7, Issue 5, 2018.
913
Chegu et al. World Journal of Pharmacy and Pharmaceutical Sciences
36. Rahman K. Effects of Garlic on Platelet Biochemistry And Physiology. Mol. Nutr. Food
Res., 2007; 51: 1335–1344.
37. Scharbert G., Kalb Madeleine L., Duris M., Marschalek C., Kozek-Langenecker Sibylle
A. Garlic At Dietary Doses Does Not Impair Platelet Function. Anesth. Analg, 2007; 105:
1214-1218.
38. Borrelli F., Capasso R., Izzo A.A. Garlic (Allium Sativum L.): Adverse Effects And
Drug Interactions In Humans. Mol. Nutr. Food Res., 2007; 51: 1386–1397.
39. Sunter W.H. Warfarin and Garlic. Pharm. J. 1991; 246: 722.
40. Reinhart K.M., Coleman C.I., Teevan C., Vachhani P., White C.M. Effects Of Garlic On
Blood Pressure In Patients With And Without Systolic Hypertension: A Meta-
Analysis. Ann. Pharmacother, 2008; 42: 1766–1771.
41. Lachmann G., Lorenz D., Radeck W., Steiper M. The Pharmacokinetics Of The S35
Labeled Labeled Garlic Constituents Alliin, Allicin And Vinyldithiine. Arzneim.
Forsch, 1994; 44: 734–743.
42. Gurley B.J., Gardner S.F., Hubbard M.A., Williams D.K., Gentry W.B., Cui Y., Ang
C.Y. Cytochrome P450 Phenotypic Ratios For Predicting Herb-Drug Interactions In
Humans. Clin. Pharmacol. Ther, 2002; 72: 276–287.
43. Shi S., Klotz U. Drug Interactions with Herbal Medicines. Clin. Pharmacokinet, 2012;
51: 77-104.
44. Berginc K., Kristl A. The Effect of Garlic Supplements and Phytochemicals on the
ADMET Properties Of Drugs. Expert Opin. Drug Metab. Toxicol, 2012; 8: 295–310.
45. Srivastava KC, Justesen U. Inhibition of Platelet Aggregation and Reduced Formation of
Thromboxane and Lipoxygenase Products In Platelets By Oil of Cloves. Prostaglandins
Leukot Med., 1987 Sep; 29(1): 11-8.
