Clove

Scientific Name(s): Syzygium aromaticum (L.) Merr. and L.M. Perry. Family: Myrtaceae (Myrtle).

Common Name(s): Clove , caryophyllus

Uses

Clove has historically been used for its antiseptic and analgesic effects. Clove and clove oils are used safely in foods, beverages, and toothpastes. Clove oil cream has been used in the treatment of anal fissures and an extract has exhibited aphrodisiac action in rats; however, there are limited studies supporting clinical applications for clove oil.

Dosing

There are limited studies to support therapeutic dosing for clove oil.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Contact dermatitis has been noted.

Toxicology

Toxicity has been observed following ingestion of the oil, but is rare and poorly documented.

Botany

The clove plant grows in warm climates and is cultivated commercially in Tanzania, Sumatra, the Maluku (Molucca) Islands, and South America. The tall evergreen plant grows up to 20 m and has leathery leaves. The strongly aromatic clove spice is the dried flower bud; essential oils are obtained from the buds, stems, and leaves. The dark brown buds are 12 to 22 mm in length and have 4 projecting calyx lobes. The 4 petals above the lobes fold over to form a hood, which hides numerous stamens. 1 , 2 Synonyms are Eugenia caryophyllata , Eugenia caryophyllus , and Caryophyllus aromaticus .

History

Clove has a long history of culinary and medicinal use. The oil has been used as an expectorant and antiemetic with inconsistent clinical results. Clove tea was used to relieve nausea. Use of the oil in dentistry as an analgesic and local antiseptic continues today. It also has been used topically as a counterirritant. 3

Chemistry

Clove buds yield approximately 15% to 20% of a volatile oil that is responsible for the characteristic aroma and flavor. The stems yield approximately 5% of the oil, and the leaves yield approximately 2%. In addition, the bud contains a tannin complex, gum and resin, and a number of glucosides of sterols.

The principal constituents of distilled clove bud oil (60% to 90%) are the phenylpropanoids, including primarily eugenol (4-allyl-2-methoxyphenol) and carvacrol, thymol, and cinnamaldehyde. The oil also contains approximately 10% acetyleugenol and small quantities of gallic acid, sesquiterpenes, furfural, vanillin, and methyl-n-amyl ketone. Other constituents include flavonoids, carbohydrates, lipids, oleanolic acid, rhamnetin, and vitamins. 3 , 4 , 5 , 6 , 7 Essential oil of the leaf has also been described, similarly containing eugenol, caryophyllene, humulene, and eugenyl acetate. 8 Flavonoid triglycosides have been identified in the seeds, and rapid high-performance chromatographic techniques have been developed for determining phenolic acid content. 9 , 10

Uses and Pharmacology

Anesthetic

Eugenol has been used extensively in dentistry for its anesthetic and antianaerobic bacteria activity. 3 , 11 The short duration of effect has been used in anesthesia of fish, such as the rainbow trout, channel catfish, and zebra fish. 3 , 12

Clinical data

Clove oil gel (2:3 vol/vol with glycerin) performed as well as benzocaine gel in an experiment evaluating effect on induced pain in the buccal mucosa. 13

Antimicrobial

In vitro studies demonstrate activity of clove oil against gram-positive and gram-negative bacteria pathogenic to humans, including multiresistant strains. 3 , 14 , 15 , 16 Activity against listeria in pasteurized milk has been demonstrated, 17 as well as antifungal action in vitro against Candida , Aspergillus , and Trichophyton species. 15 , 16 , 18 , 19 Antiviral activity against herpes simplex and hepatitis C virus has also occurred. 3

Animal data

Mice with induced pneumonia showed a decrease in bacterial colonization when fed clove oil for 15 days. 20 Clove oil has been proposed for use in cat and dog ear infections based on in vitro studies. 21

Clinical data

In vitro studies have shown antibacterial action against gram-negative anaerobes responsible for acne. 22

Cancer

Sesquiterpenes from cloves reveal anticarcinogenic potential. 23 Similarly, eugenol present in clove oil may ameliorate effects of environmental food mutagens. 24

Animal data

Whole cloves were chemoprotective against liver and bone marrow toxicity in mice. 25 In mice with induced lung cancer, an oral aqueous preparation of whole clove decreased cell proliferation and increased apoptosis. 26

Clinical data

There are no clinical evaluations of clove; however, activity against human cancer cell lines has been demonstrated. 3

Other uses
Anal fissure

The use of 1% clove oil cream resulted in significantly greater healing rates than 5% lignocaine in a small study of anal fissures. 27

Antioxidant

Clove oil possesses free radical scavenging and iron chelating properties and inhibits lipid peroxidation to a greater extent than eugenol alone. 3 , 8 , 28 , 29 Clinical applications are lacking.

Aphrodisiac

A 50% ethanolic extract of clove enhanced the sexual activity of male rats without any adverse or overt toxicological events. 30 , 31

Other

Clove oil possesses mosquito repellant and other insecticidal activity. 3 , 32 Eugenol possesses marked antipyretic activity in animals, similar to that of acetaminophen. Enhanced transdermal delivery of ibuprofen by clove oil has been demonstrated in rabbits. 33 Anti-inflammatory activity has been demonstrated in macrophages of mice fed aqueous clove extract. 34 , 35

Dosage

There are limited studies supporting clinical applications for clove oil.

A 1% clove oil cream has been used in the treatment of anal fissures. 27 Clove oil gel (2:3 vol/vol with glycerin) has been used on induced buccal mucosa pain. 13

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. In a toxicological experiment, clove added to the diet of pregnant mice for 2 weeks resulted in increases in cell death. No effects on pregnant adult mice were noted. 36

Interactions

Clove has been reported to have antiplatelet effects; however, case reports are lacking. 37 , 38 , 39

Adverse Reactions

Clove oil can be a skin and mucous membrane irritant and sensitizer; contact dermatitis has been noted. 7 , 40 A woman 24 years of age reported permanent local anesthesia and anhidrosis following clove oil spillage onto the facial area. 41

Toxicology

Clove and clove oils are used safely in foods, beverages, and toothpastes. In general, the level of clove used in foods does not exceed 0.24%; the oil is not used in amounts greater than 0.06%. Toxicity has been observed following ingestion of the oil but is rare and poorly documented. 42 , 43 There is no documentation of toxicity in the bud, leaf, or stem of the plant. 7

In rats, the oral median lethal dose (LD 50 ) of eugenol is 2,680 mg/kg; however, the toxicity of the compound increases almost 200-fold when administered intratracheally (LD 50 11 mg/kg). 44

Increased toxicity by the pulmonary route has been reported among people who have smoked clove cigarettes. Clove cigarettes, called “kreteks,” generally contain about 60% tobacco and 40% ground cloves. 45 , 46

Bibliography

1. Syzygium aromaticum . USDA, NRCS. 2010. The PLANTS Database ( http://plants.usda.gov , February 2011). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.
2. Bisset NG , trans-ed. Herbal Drugs and Phytopharmaceuticals . Boca Raton, FL: CRC Press; 1994:130-131.
3. Chaieb K, Hajlaoui H, Zmantar T, et al. The chemical composition and biological activity of clove essential oil, Eugenia caryophyllata ( Syzigium aromaticum L. Myrtaceae): a short review. Phytother Res . 2007;21(6):501-506.
4. Kramer RE. J Am Oil Chem Soc . 1985;62:111.
5. Narayanan CS, et al. Indian Perfum . 1985;29:15.
6. Windholz M, Budavari S, Blumetti RF, Otterbein ES, eds. The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals . 10th ed. Rahway, NJ: Merck & Co; 1983.
7. Newall CA, Anderson LA, Phillipson JD, et al. Herbal Medicines: A Guide for Health-Care Professionals . London: Pharmaceutical Press; 1996:79.
8. Jirovetz L, Buchbauer G, Stoilova I, Stoyanova A, Krastanov A, Schmidt E. Chemical composition and antioxidant properties of clove leaf essential oil. J Agric Food Chem . 2006;54(17):6303-6307.
9. Nassar MI. Flavonoid triglycosides from the seeds of Syzygium aromaticum . Carbohydr Res . 2006;341(1):160-163.
10. Rastogi S, Pandey MM, Rawat AK. High-performance thin-layer chromatography densitometric method for the simultaneous determination of three phenolic acids in Syzygium aromaticum (L.) Merr. & Perry. J AOAC Int . 2008;91(5):1169-1173.
11. Kumar P, Ansari SH, Ali J. Herbal remedies for the treatment of periodontal disease—a patent review. Recent Pat Drug Deliv Formul . 2009;3(3):221-228.
12. Grush J, Noakes DL, Moccia RD. The efficacy of clove oil as an anesthetic for the zebrafish, Danio rerio (Hamilton). Zebrafish . 2004;1(1):46-53.
13. Alqareer A, Alyahya A, Andersson L. The effect of clove and benzocaine versus placebo as topical anesthetics. J Dent . 2006;34(10):747-750.
14. Khan R, Islam B, Akram M, et al. Antimicrobial activity of five herbal extracts against multi drug resistant (MDR) strains of bacteria and fungus of clinical origin. Molecules . 2009;14(2):586-597.
15. Kalemba D, Kunicka A. Antibacterial and antifungal properties of essential oils. Curr Med Chem . 2003(10):813-829.
16. Fu Y, Zu Y, Chen L, et al. Antimicrobial activity of clove and rosemary essential oils alone and in combination. Phytother Res . 2007;21(10):989-994.
17. Cava R, Nowak E, Taboada A, Marin-Iniesta F. Antimicrobial activity of clove and cinnamon essential oils against Listeria monocytogenes in pasteurized milk. J Food Prot . 2007;70(12):2757-2763.
18. Inouye S, Nishiyama Y, Uchida K, Hasumi Y, Yamaguchi H, Abe S. The vapor activity of oregano, perilla, tea tree, lavender, clove, and geranium oils against a Trichophyton mentagrophytes in a closed box. J Infect Chemother . 2006;12(6):349-354.
19. Pinto E, Vale-Silva L, Cavaleiro C, Salgueiro L. Antifungal activity of the clove essential oil from Syzygium aromaticum on Candida , Aspergillus and dermatophyte species. J Med Microbiol . 2009;58(pt 11):1454-1462.
20. Saini A, Sharma S, Chhibber S. Induction of resistance to respiratory tract infection with Klebsiella pneumoniae in mice fed on a diet supplemented with tulsi ( Ocimum sanctum ) and clove ( Syzgium aromaticum ) oils. J Microbiol Immunol Infect . 2009;42(2):107-113.
21. Lans C, Turner N, Khan T. Medicinal plant treatments for fleas and ear problems of cats and dogs in British Columbia, Canada. Parasitol Res . 2008;103(4):889-898.
22. Fu Y, Chen L, Zu Y, et al. The antibacterial activity of clove essential oil against Propionibacterium acnes and its mechanism of action. Arch Dermatol . 2009;145(1):86-88.
23. Zheng GQ, Kenney PM, Lam LK. Sesquiterpenes from clove ( Eugenia caryophyllata ) as potential anticarcinogenic agents. J Nat Prod . 1992;55(7):999-1003.
24. Soudamini KK, Unnikrishnan MC, Sukumaran K, Kuttan R. Mutagenicity and anti-mutagenicity of selected spices. Indian J Physiol Pharmacol . 1995;39(4):347-353.
25. Kumari MV. Modulatory influences of clove ( Caryophyllus aromaticus , L) on hepatic detoxification systems and bone marrow genotoxicity in male Swiss albino mice. Cancer Lett . 1991;60(1):67-73.
26. Banerjee S, Panda CK, Das S. Clove ( Syzygium aromaticum L.), a potential chemopreventive agent for lung cancer. Carcinogenesis . 2006;27(8):1645-1654.
27. Elwakeel HA, Moneim HA, Farid M, Gohar AA. Clove oil cream: a new effective treatment for chronic anal fissure. Colorectal Dis . 2007;9(6):549-552.
28. Saito K, Kohno M, Yoshizaki F, Niwano Y. Extensive screening for edible herbal extracts with potent scavenging activity against superoxide anions. Plant Foods Hum Nutr . 2008;63(2):65-70.
29. Yadav AS, Bhatnagar D. Free radical scavenging activity, metal chelation and antioxidant power of some of the Indian spices. Biofactors . 2007;31(3-4):219-227.
30. Tajuddin, Ahmad S, Latif A, Qasmi IA. Aphrodisiac activity of 50% ethanolic extracts of Myristica fragrans Houtt. (nutmeg) and Syzygium aromaticum (L) Merr. & Perry. (clove) in male mice: a comparative study. BMC Complement Altern Med . 2003;3:6.
31. Tajuddin, Ahmad S, Latif A, Qasmi IA. Effect of 50% ethanolic extract of Syzygium aromaticum (L.) Merr. & Perry. (clove) on sexual behaviour of normal male rats. BMC Complement Altern Med . 2004;4:17.
32. Trongtokit Y, Rongsriyam Y, Komalamisra N, Apiwathnasorn C. Comparative repellency of 38 essential oils against mosquito bites. Phytother Res . 2005;19(4):303-309.
33. Shen Q, Li W, Li W. The effect of clove oil on the transdermal delivery of ibuprofen in the rabbit by in vitro and in vivo methods. Drug Dev Ind Pharm . 2007;33(12):1369-1374.
34. Rodrigues TG, Fernandes A Jr, Sousa JP, et al. In vitro and in vivo effects of clove on pro-inflammatory cytokines production by macrophages. Nat Prod Res . 2009;23(4):319-326.
35. Joe B, Lokesh BR. Role of capsaicin, curcumin and dietary n-3 fatty acids in lowering the generation of reactive oxygen species in rat peritoneal macrophages. Biochim Biophys Acta . 1994;1224(2):255-263.
36. Domaracký M, Rehák P, Juhás S, Koppel J. Effects of selected plant essential oils on the growth and development of mouse preimplantation embryos in vivo. Physiol Res . 2007;56(1):97-104.
37. Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm . 2000;57(13):1221-1227.
38. Srivastava KC. Antiplatelet principles from a food spice clove ( Syzygium aromaticum L). Prostaglandins Leukot Essent Fatty Acids . 1993;48(5):363-372.
39. Saeed SA, Gilani AH. Antithrombotic activity of clove oil. J Pak Med Assoc . 1994;44(5):112-115.
40. Larsen W, Nakayama H, Fischer T, et al. Fragrance contact dermatitis—a worldwide multicenter investigation (Part III). Contact Dermatitis . 2002;46(3):141-144.
41. Isaacs G. Permanent local anaesthesia and anhidrosis after clove oil spillage. Lancet . 1983;1(8329):882.
42. Brown SA, Biggerstaff J, Savidge GF. Disseminated intravascular coagulation and hepatocellular necrosis due to clove oil. Blood Coagul Fibrinolysis . 1992;3(5):665-668.
43. Lane BW, Ellenhorn MJ, Hulbert TV, McCarron M. Clove oil ingestion in an infant. Hum Exp Toxicol . 1991;10(4):291-294.
44. LaVoie EJ, Adams JD, Reinhardt J, Rivenson A, Hoffmann D. Toxicity studies on clove cigarette smoke and constituents of clove: determination of the LD50 of eugenol by intratracheal instillation in rats and hamsters. Arch Toxicol . 1986;59(2):78-81.
45. Centers for Disease Control (CDC). Illnesses possibly associated with smoking clove cigarettes. MMWR Morb Mortal Wkly Rep . 1985;34(21):297-299.
46. Hackett PH, Rodriguez G, Roach RC. Clove cigarettes and high-altitude pulmonary edema. JAMA . 1985;253(24):3551-3552.

Copyright © 2009 Wolters Kluwer Health

Hide
(web4)