Eugenia caryophyllata

Synonyms

Caryophyllus aromaticus Linn., Myrtus caryophyllus Spreng., Eugenia aromaticus (L.) Baill., Eugenia caryophyllus (Spreng.), Jambosa caryophyllus (Spr.), Syzygium aromaticum (Linn.) [4]

Vernacular Names:

Malaysia: Cengkeh
English:  Clove
Chinese: 

Ding Xiang, Ding Heung (Cantonese), Ting Hsiang (Mandarin)

Indonesia:  Cengkeh (Jawa, Sunda); Wunga Lawang (Bali); Cangkih (Lampung); Sake (Nias); Bungeu   Lawang (Gayo); Cengke (Bugis); Sinke (Flores); Canke (Ujung Pandang); Gomode (Halmahera, Tidore); Bunga Lawang (Batak); Singhe (Karo); Bunga Lasang (Toba); Bunga Cengkeh (Mjnangkabau); Cangke (Dayak Ngaju, Bima,Makasar); Bunga Rawan (Sangir); Pungo Lawan (Gorontalo); Bwungo Laango (Buol); Poirawane (Seram); Buglawa (Buru); Balawala (Ternate); Chanque (Muluku)
Vietnam:  Dinh Hương
India:  Lavang (Hindi,Gujerati, Marathi), Karambu (Tamil), Karayanpu (Malayalam), Lavanga (Bengali)
Sri Lanka:  Karabu Neti
Japan:  Choji
Korea:  Jeong-hyang
Africa: 

Karanfal (Arabic); Benefundi (Bambara); Kanumfari, Karanho, Kade (Hausa); Osaragbogo-eze (Igbo); Karafwu (Swahili); Konofuru (Yoruba)

French:  Clou, Giroflier, Clou de Girofle, Le Giroflier
German:  Gewurznelke
Italian:  Garofano, Il Garfano Aromatico
Spanish:  Raja, Il Clavo Aromatico
Russian:  Givosditschka [4]

General Information

Description

Eugenia caryophylata is a member of the Myrtaceae family. It is a very handsome tree with trunk reaching up to 5-10m high, measures 30cm in diameter and divided into branches 1-2m above the ground. The leaves are opposite, persisent, coriaceous about 10cm long with a stong midrib, and parallel lateral nerves. They are ovate-lanceolate, quite entire, smooth on both sides, reddish and rather shining above, paler underneath, sprinkled with minute resinous dots, and tapering at the base into a slender petiole, measures nearly 5cm long. The petiole is the most aromatic part of the plant. The flowers are odorous, from nine to fifteen or more in a branch, in short terminal panicles, trichotomously divided, and jointed at every division. The calyx consists of four ovate, concave, spreading segments, at first green, but afterwards becoming red. The petals are four, ovate, concave, yellowish-red, larger than the calyx, coherent by their edges, and forming a calyptra which is caducous. In the center of the calyx, and occupying the top of the gemen, is a quadrangular elevated line, into which the stamens are inserted, surrounding the base of the of the short obtusely subulate style. The filaments are numerous, much longer than the petals, bearing small yellow ovate-cordate anthers. The germen is inferior, oblong, 2-celled, with twenty ovules in each cell; all of which become abortive, or one or two prove fertile. The fruit is a large elliptic purple berry with only 1 or 2 seeds. [1]

Plant Part Used

Flowerbud (Clove) and fruit [1][5]

Chemical Constituents

a-cubebene; a-pinene; a-terpinene; a-terpineol; a-caryophyllene; a-copaene; a-humulene; asarone; (E,E)-a-farnesene; a-ylangene; anethole; (E)-a-bergamotene; allo-aromadendrene; a-selinene; b-caryophyllene; b-caryophyllene oxide; b-pinene; b-terpineol; benzaldehyde; (E)-b-ocimene;benzyl alcohol;1,8-cineol; p-cymene; carvone; chavicol; 2-heptanol; 2-hexanone; humulene oxide II; hexadecyl acetate humulene epoxide I; humulene epoxide II; 2-nonanol; (E)-nerolidol; nerol; n-octane; n-butyl benzoate; d-cadinene; g-cadinene; t-cadinol; cadalene; calamenene; isoeugenol; eugenol acetate; eugenol; eugenly acetate; farnesol; vanillin; linalool; linalyl acetate; terpinen-4-ol; methyl benzoate; m-methyl acetophenone; methyl salicylate; methyl eugenol; germacrene D; t- cadinol; t-muurolol; epi-a-cadinol; a-cadinol; n-heptadecane; benzyl n-octanate; myristic acid; iso-propyl myristate; oleic acid; oleanolic acid; maslinic acid; 2a-hydroxyoleanolic acid; sitosterol; stigmasterol; campesterol; isobiflorin; biflorin; eugenone; eugenine; eugenitin; isoeugenitol; gallotannic acid; eugeniin; ellagitannin; syzyginin A; syzyginin B; apigenin; kaempferol; rhamnetin. [3]

Traditional Used:

Clove is one of the most stimulating herbs used in medicine. They are used principally as an adjuvant in any compound medicine in particular with other bitters and vegetative cathartics. [1] 

Most traditional systems consider E. caryophylata as a drug acting mainly in the digestive system with properties like carminative, antidiarrhoeic, antiemetic, antinauseant, antispasmodic, digestive and vermifuge. It has been used effectively to treat cases of flatulance, diarrhoea and cholera. [2] Due to its multiple action on the digestive tract one can see the relevance of its used in cooking. It has been proven to stimulate gastric secretion in particular the pepsin component. [3] This results in increase digestion and helps in dispelling wind. [1] It is also a potent ascaricide at a dose of 0.1 to 1.0g/kg of the alcohol based extract or the essential oil. It is prescribed as a remedy for hiccough and vomiting. [3] In Africa clove and clove oil is used to treat toothache and halithosis in the form of mouthwash. 

Many societies had made used of E. caryophylata to treat toothache in recognition of its analgesic property. In Malaysia it is also used to treat headache and made used of in compound medicine for the treatment of various forms of pain like lumbago, rheumatism. [4][5] The oil makes good addition to a heating liniment, however it is irritating to the skin and mucous membrane so care must be taken when applying the liniment. [6] 

E. caryophylata is included in the remedy for cough, cold, flu and bronchial congestion. 

E. caryophylata is considered as an aphrodisiac and is recognized thus by many physicians of the past. In the Middle east, India, Pakistan it is included in the remedy for sexual asthenia in both male and female to stimulate libido. The Chinese made used of it to treat impotency with lassitude in the loin and knees believed to be caused by deficiency of kidney yang. For this they combined it with radix aconiti lateralis preparata, radix morindae officinalis and cortex cinnamomi. [7] In Malaysia the fruits are considered as an aphrodisiac. The buds are used to stimulate and ease mentrual flow and also forms part of the pot herb being given to women after delivery. [5] 

The essential oil of E. caryophylata had been used to treat parasitic lesions of the skin from scabies to ringworm. It had been recognized to have good antimicribial properties as evidenced by its extensive and worldwide use in the treatment of various microbial infections of the skin like tinea versicolor, athele’s foot, ring worm, wound infection, ulcers. In Africa the plant is used as an antiseptic wash for wounds. 

In small doses E. caryophylata oil is considered a central nervous system stimulant, helping to overcome nervousness, mental fatigue and poor memory. However, in high doses it can cause supression to the extent of coma as cited below under case reports of poisoning. [7] 

Pre-Clinical Data

Pharmacology


Most of the pharmacological activities of Eugenia caryophyllata is attributed to the high content of eugenol in the oil or extracts of the flower buds or clove. 

Antimicrobial activity 

Antiviral

The extracts of E. caryophylata had been found effectively inhibit a number of virus including human cytomegalovirus, murine cytomegalocvirus, herpes simplex virus and hepatitis C virus. 

An earlier study on the anitviral activity of E. caryophylata extract showed inhibition of replication of human cytomegalovirus and murine cytomegalovirus. The antiviral activity was reported that there was significant suppression of MCMV yields in lungs of immunosuppressed mice. [8][9] Kurokawa et. al found that when extracts of E. caryophylata was combined with acyclovir there was a significant limitation of development of skin lesion due to HSV-1 infection and prolonged mean survival times of infected mice as compared to individual acyclovir or clove extract. The combination were found to also reduced yields in brain and skin more strongly with those of the brain more than the skin. [10] In subsequent studies A study was conducted in isolating and characterising the essential element responsible for the anti-herpesvirus activity. Eugenin was found to inhibit the growth of acyclovir-phosphonoacetic acid resistant HSV-1, thymidine kinase-deficient HSV-1 and wild HSV type 2. This effect is due to its ability to inhibit viral DNA and late viral protein syntheses in their infected Vero cells. [11] In a screening test for antiviral activities against Hepatitis C virus, it was reported that extracts of E. caryophylata has amongst the most potent activity. [12] 

Antibacterial

The use of clove as an analgesic and a breath fresherners had directed researchers to see its effects on the populations of oral pathogens. a crude methanol extract of E. caryophylata exhibited preferential growth-inhibitory activity against Gram-negative anaerobic periodontal oral pathogens, including Porphyromonas gingivaslis and Prevotella intermedia. Amongst the compounds isolated from the extract, they found the flavones, kaempferol and myricetin had the most potent growth inhibitory against these pathogens. [13] The feeding rats with clove oil could significantly reduce bacterial colonization of Klebsiella pneumoniae and thus could protect against bacterial colonization of the lungs. [14] 

Multi-drug resistant (MDR) strains of bacteria and fungi pose a great challenge to doctor to treat in clinical practice today. The effects of crude ethanolic extracts of five plants against MDR stains of Escherichia coli, Klebsiella pneumoniae and Candida albicans. ATCC strains of Streptococcus mutans, Staphylococcus aureus, Enterococcus faecalis, Streptococcus bovis, Pseudimonas aeruginosa, Salmonella typhimurium, Escherichia coli, Klebsiella pneumoniae and Candida albicans were tested. It was reported that the MDR strains were sensitive to the antimicrobial activity of E. caryophylata and it could be used against MDR microbes causing nosocomial and community acquired infections. [15] The essential oil of E. caryophylata show quorum sensing inhibitory activity which could explain its usefulness in the treatment of MDR microbial strains. 

Antifungal

The essential oil of E. caryophylata was used traditionally to treat many form of fungal dermatoses including the commonly occurring tinea versicolor and ringworm. The major component of this essential oil had been found to be eugenol. Determination of the effectiveness of the essential oil as an antifungal reported that it not only inhibit the growth of Apergillus, Candida and dermatophyte clinical and American type culture collection strains but also the fluconazole-resistant strains. [16] 

Antiparasites

Petroleum ether extracts of E. caryophylata had been found to be effective in the control of house-dust mites (Dermatophagoides farinae) and renders it useful as an additive is bio-degradable insecticide. [17] The effect of E. caryophylata oil on head lice and their eggs was studied and reported that the oil in a vapour form was effective in killing female lice and deactivating the eggs. [18] The essential oil of E. caryophylata was found to have inhibitory effects on Gardia lamblia. [19] 

Antiplatelet activity 

Two components of the essential oil of E. caryophylata had been found to have antiplatelet activity which are eugenol and acetyleugenol. The compounds inhibit arachidonate-, adrenaline- and collagen-induced platelet aggregation, and are more potent in inhibiting the first two agonist. Their antiaggregatory activity is due to inhibition of platelet thromboxane formation, and increased formation of 12-lipoxygenase products. The inhibitory effect was reversible and the presence of plasma proteins was seen to reduce the effective concentrantion of these susbstances due to binding. This is probably due to the fact that the increase in formation of 12-lipocygenase products facilitated by albumin acts as a conduit to divert frees arachidonic acid from the platelet cyclo-oxygenase to the lipoxygenase pathway. Both eugenol and acetyl eugenol were found to be more potent than aspirin and when used in combination was found to be more effective than when alone and also produced additive effect. [20][21] 

The antithrombotic activities in two polysaccharides isolated from E. caryophylata was studied. One is relatively high molecular weight while the other was low molecular weight polysaccharides. The LMW polysaccharide was mainly composed of Rha, Gal, GalA and Ara (molar %: 24.1, 18.9, 18.0 and 17.9, respectively) with 10.8% of sulfate and 18.2% of protein. The HMW fraction consisted of Ara, Gal, Glc and Rha (molar %: 26.0, 23.7, 17.5 and 12.4, respectively) with 15.4% of sulfate and 8.0% of protein. Both polysaccharides had the backbone of type I rhamnogalacturonan and the side chain of arabinan. Comparatively, the LMW polysaccharide displayed a slightly lower activity and did not show acute toxicity, while the acute LD50 of the HMW fraction was approximately 2-fold lower than that of heparin. [22] 

Local anaesthetic activity 

Beta-caryophyllene is one of the main components of clove oil obtained from dried flower-buds of E. caryophylata. Studies on the local anaesthetic acitivity of this compound and found that the local anaesthetic activity of beta-caryophyllene is dose dependent and is strictly dependent on its chemical structure. [23] 

Gastrointestinal activity 

E. caryophylata had been used traditionally to treat constipation. The possible effects of E. caryophylata extract on the intestinal propulsion as well as its suspected gastrointestinal protective properties was studied and reported that the extract was able to increase gut muscle propulsion via cholinergic mechanism. A decoction of clove was found to reduce the number of ulcer and ulcer area in ethanol induced ulcers in rats. [24] 

Transderma permeability enhancement activity 

Evaluation of the skin permeation ehnhancement effects of essential oil of E. caryophylata and reported that it significantly enhances permeation. The eugenol and acetyleugenol were the main component of the oil that might contribute to this effect both in vitro and in vivo. [25] 

COX-2 inhibition activity 

Inducible cyclo-oxygenase (COX-2) had been implicated in the processes of inflammation and carcinogenesis. Thus, COX-2 inhibitors would have anti-inflammatory and cancer chemoprotective propertiesStudies on 170 methanolic extracts of natural products including Korean herbal medicines for the inhibition of prostaglandin e(2) production and nitric oxide formation in lipopolysaccharide-induced mouse macrophages RAW264.7 cells. In this sutdy they found that amongst other the extract of E. caryophylata prove to have significant inhinbitory activity. [26] 

Further studies on the COX-2 inhibitory activity in methanolic extract of the bark of E. caryophylata reported to inhibit the prostaglandin E(2) production in lipopolysaccharide-activated mouse macrophages RFAW264.7 cells. It was further found that the hexane soluble layer was the most active portion. The main component of this fraction was found to be eugenol. It not only inhibit PGE(2) production but it also suppressed the cyclo-oxygenase-2 gene expression in LPS-stimulated mouse macrophage cells. The eugenol was also able to inhibit proliferation of HT-29 cells (human colon cancer cells) and the mRNA expression of COX-2, but not COX-1.  [27] 

Immunomodulatory activity 

E. caryophylata aqueous extract was found to have inhibitive effects on local immunoglobulin E (IgE)-mediated passive cutaneous anaphylactic reaction. Pretreatment with the aqueous extract reduced the serum histamine levels in a dose-dependent manner. The result indicates that the extract inhibits immediate hypersensitivity by inhibition of histamine release from the mast cells both in vivo and in vitro. [28] 

Essential oil of E. caryophylata was reported to increase the total white cell count and enhance the delayed-type hypersensitivity response in mice. It was able to restore the cellular and humoral immune responses in in immunosuppressed mice. The immunostimulatory activity of essential oil of E. caryophylata found in mice was due to improvement in humour- and cell-mediated immune response mechanism. [29] 

Chemoprotective and chemopreventive activity 

Antimutagenic activity was seen in various extracts of E. caryophylata as shown in their ability to suppressed furylfuramide-induced SOS response in umu test. The following compounds responsible includes trans-eugenol, eugenol, dihydrodieugenol and trans-coniferyl aldehyde. [30][31] 

The chemoprotective and chemopreventive activity of aqueous extracts of E. caryophylata had been reported as it was seen in mice when on administration of the extract there was a delay in the formation of papiloma and a reduction of the incidence of the same. [32] The E. caryophylata infusion was found to have chemopreventive potential in view of its apoptogenic and antiploriferative activities. [33] E. caryophylata oil was found to be highly cytotoxic at concentration as low as 0.03 % with 73% of the activity attributable to eugenol. [34] 

Aphrodisiac activity 

E. caryophylata had been advocated in the treatment of various sexual disorders from impotency to sexual stimulants (aphrodisiacs). Studies on the effects of hexane extracts of E. caryophylata on the testicular function and found that the treatment did not induce toxicity at the doses tested. It was also found that at the lower dose of 15mg of the extracts increased the activities of Delta(5) 3 beta-HSD and 17 beta-HSD, and serum level of testosterone. At higher doses it ihibited these parameters and induced non-uniform degenerative changes in the seminiferous tubules associated with decrease in daily sperm production and depletion of 1C (round and elongated spermatids) population. 50% ethanolic extract of E. caryophylata extract significantly increased the Mounting Frequency, Intromission Frequency; Intromission Latency, Erections; Quick Flips, Long Flips as well as aggregate of penile reflexes and caused significant reduction in the Mounting Latency and Post Ejaculatory Interval. It was devoid of any conspicous general short term toxicity. [35][36] 

Antidiabetic activity 

E. caryophylata extract acts like insulin in hepatocytes and hepatoma cells by reducing phosphoenolpyruvate carboxykinase and glucose-6-phosphatase gene expression. This suppression is reversed by PI3K inhibitors and N-acetylcysteine. [37] 

Toxicities

No documentation

Clinical Data

Clinical Trials

No documentation

Adverse Effects in Human:

It is a dermal and mucous membrane irritant in high concentrations and it is not advisable to apply any of the clove oils neat because of the high content of eugenol. There have been cases reported of permanent local anaesthesia and anhidrosis after accidental neat spillage on the skin. [38] 

Inhaling clove cigarette smoke has been associated with severe lung injury in a few susceptible individuals with prodromal respiratory infection. Some individuals with normal respiratory tracts have apparently suffered aspiration pneumonitis as the result of a diminished gag reflex induced by a local anesthetic action of eugenol (the active component of cloves), which is volatilized into the smoke. [39] These conditions had been cited in the United States of America amongst the caucasian population. However, no such reports had been recorded to happen amongst keretek smokers in Malaysia and Indonesia. 

Used in Certain Conditions

Pregnancy / Breastfeeding

Cloves stimulatory effect on menstrual flow can possibly induce abortion too. It use during pregnancy should be with great caution. [5]

Age Limitations

Neonates / Adolescents

Use with caution in children because of the rapid absorbability and the toxicity to the brain as cited below. [40] 

Geriatrics

No documentation

Chronic Disease Conditions

No documentation

Interactions

Interactions with drugs

Caution should be exercised when taking clove extracts with anti-diabetic drugs as its insulino-mimetic activity can further supress blood sugar levels. [37]

Interactions with Other Herbs / Herbal Constituents

No documentation

Contraindications

Contraindications

No documentation

Case Reports

A number of cases of adverse reaction due to exposure to Clove oil had been reported in various journals since 1983: 

A case of a 24-year-old woman reports permanent local anesthesia and anhidrosis following clove oil spillage into the facial area. [40]

A 7 month old child developed Central nervous system depression, urinary abnormalities and a large anion-gap acidosis following accidental administration of clove oil. The patient fully recovered following gastric lavage and supportive care. [41] 

A 2-year old child developed disseminated intravascular coagulopathy with hepatocellular necrosis following ingestion of clove oil. Rapid treatment with heparin and fresh frozen plasma followed by specific haemostasis assay and administration of appropriate coagulation factor and inhibitor concentrates were successful in saving the child. [42]

Read More

  1)  Malaysian Herbal Plants

References

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