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Phytochemical evaluation and pharmacological activity of syzygium

aromaticum: A comprehensive review

Article  in  International Journal of Pharmacy and Pharmaceutical Sciences · January 2014

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 Innovare International Journal of Pharmacy and Pharmaceutical Sciences
Academic Sciences
ISSN- 0975-1491 Vol 6, Issue 8, 2014

Review Article

PHYTOCHEMICAL EVALUATION AND PHARMACOLOGICAL ACTIVITY OF SYZYGIUM

AROMATICUM: A COMPREHENSIVE REVIEW

MONIKA MITTAL, NOMITA GUPTA, PALAK PARASHAR, VARSHA MEHRA, MANISHA KHATRI*
Shaheed Rajguru College of Applied Sciences for Women, University of Delhi, Delhi, India.
Email: [email protected]
Received: 16 Jul 2014 Revised and Accepted: 15 Aug 2014
ABSTRACT
Medicinal plants are generating an ever-increasing amount of interest due to the effectiveness, low cost and minimal side-effects associated with
drugs derived from them. Clove (Syzygium aromaticum (L.) (Family Myrtaceae) is one of the most important herbs in traditional medicine, having a
wide spectrum of biological activity. Phytoconstituents of clove comprise of various classes and groups of chemical compounds such as
monoterpenes, sesquiterpenes, phenolics and hydrocarbon compounds. The major phytochemicals found in clove oil is mainly eugenol (70-85%)
followed by eugenyl acetate (15%) and β-caryophyllene (5–12%). Their derivatives result in biological benefits such as antibacterial, antifungal,
insecticidal, antioxidant, anticarcinogenic capacities. In addition to clove oil’s worldwide use as a food flavoring agent, it has also been employed for
centuries as a topical analgesic in dentistry. This review presents an overview and details of the phytochemical and pharmacological investigations
on the S. aromaticum.
Keywords: Clove, Syzygium aromaticum, Phytoconstituents, Pharmacological activity.

INTRODUCTION PHYTOCHEMICAL CONSTITUENTS OF CLOVE

Medicinal plants have been the mainstay of traditional herbal Various studies have been carried out to find various constituents of
medicine amongst rural dwellers worldwide since antiquity to date. S. aromaticum [10-12]. Clove buds contain 15–20% essential oil,
Natural products have been an integral part of the ancient which is dominated by eugenol (70–85%), eugenyl acetate (15%)
traditional medicine systems like Ayurveda, Chinese and Egyptian. It and β-caryophyllene (5–12%). Other essential oil ingredients of
is estimated that 40% of the world population depends directly on clove oil are vanillin, crategolic acid, tannins, gallotannic acid, methyl
plant based medicine for their health care. India has rich medicinal salicylate, flavonoids eugenin, kaempferol, rhamnetin, eugenitin and
plant flora of some 25,000 species, out of which 150 species are triterpenoids like oleanolic acid. The constituents of the oil also include
commercially used for extracting medicines or drug formulation. methyl amyl ketone, methyl salicylate, α and β-humulene, benzaldehyde,
Over the last few years, researchers have aimed at identifying and β-ylangene and chavicol. The minor constituents like methyl amyl
validating plants derived substances for the treatment of various ketone, methyl salicylate etc., are responsible for the characteristic
diseases. Interestingly, it is estimated that more than 25% of pleasant odour of cloves. Gopalakrishnan et al. (1984) characterized six
modern medicines are directly or indirectly derived from plants. In sesquiterpenes, namely: α-cubebene (1.3%), α-copaene (0.4%), β-
this context, it is worth mentioning that Indian plants are considered humulene (9.1%), β- caryophyllene (64.5%), γ-cadinene (2.6%) and δ-
as vast source of several pharmacologically active principles and cadinene (2.6%) in the hydrocarbon fraction of the freshly distilled
compounds, which are commonly used in home remedies against Indian clove bud oil [13]. The pharmacological activities of different
multiple ailments. The focus of this review is to provide information phytoconstituents of S. aromaticum are presented in Table 1.
on the phytochemicals, ethno medicinal uses and pharmacological PHARMACOLOGICAL ACTIVITY OF CLOVE
activities of Syzygium aromaticum commonly known as clove.
Antibacterial activity
Clove (Syzygium aromaticum (L.) Merril. & Perry, syn. Eugenia
aromaticum or E. caryophyllata) is one of the most ancient and Several studies have demonstrated potent antibacterial effects of
valuable spices of the Orient. It is a member of the family Myrtaceae. clove [47,48]. The inhibitory activity of clove is due to the presence
The clove of commerce is its dried unopened flower buds. Whole of several constituents, mainly eugenol, eugenyl acetate, β-
and ground cloves are used to enhance the flavor of meat and rice dishes caryophyllene, 2-heptanone, [6] acetyl-eugenol, α-humulene, methyl
and used widely in curry powders and masalas. They are highly valued salicylate, iso-eugenol, methyl-eugenol, [9] phenyl propanoides,
in medicine as a carminative and stimulant and are said to be a natural dehydrodieugenol, trans-confireryl aldehyde, biflorin, kaempferol,
anthelmintic. It is used throughout Europe and Asia and is smoked in a rhamnetin, myricetin, gallic acid, ellagic acid and oleanolic acid [49].
type of cigarette, known locally as kretek in Indonesia and in occasional These compounds can denature proteins and react with cell
coffee bars in the West, mixed with marijuana to create marijuana spliffs. membrane phospholipids, changing their permeability. Burst and
In the last several years, it has been recognized as an effective anesthetic Reinders 2003, found clove oil effective against non-toxigenic strains
for sedating fish for a number of invasive and noninvasive fisheries of E. coli O157:H7 [50]. Similarly in another study clove oil was
management and research procedures [1,2]. Oil of clove is used found to be active against food borne gram positive bacteria (S.
extensively for flavoring all kinds of food products, such as meats, aureus, B. cereus, E. faecalis, L. monocytogenes) and gram negative
sausages, baked goods, confectionery, candies, table sauces, pickles, etc. bacteria ( E. coli, Y. enterocolitica, S. choleraesuis, P. aerugenosa) [47].
It is used in medicine for its antibacterial, antiseptic and antibiotic Demirpek et al, 2009 showed that aqueous and ethanolic extracts of
properties. It has also been successfully used for asthma and various clove buds inhibit growth of methicillin resistant clinical isolates at
allergic disorders by oral administration [3]. Sesquiterpenes, found in 1000 and 500mg/ml concentration [51]. The isolates were multi
clove were also investigated as potential anti-carcinogenic agents [4]. drug resistant, mostly against beta-lactams, aminoglycosides,
The oil has many industrial applications and is used extensively in tetracyclines, floroquinolones and macrolide antibiotics. In another
perfumes, soaps and as a clearing agent in histological work. In addition, study eugenol at 2μg/mL inhibited growth of 31 strains of
the cloves are anti-mutagenic, [5] anti-inflammatory, [3] antioxidant, [6] Helicobacter pylori, after 9 hours of incubation, which is being more
antiviral, [7] anti-thrombotic [8] and anti-parasitic [9]. potent than amoxicillin and doesn’t develop resistance [52].
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Int J Pharm Pharm Sci, Vol 6, Issue 8, 67-72

Table 1: Pharmacological activities of different phytochemicals isolated from S. aromaticum

S. Name of Structure of Phytoconstituent Biological Activity Reference
No. Phytoconstituent
Antimicrobial, Analgesic,
1 Eugenol Antioxidant, Anticancer, Anthelmintic, Antiulcer, [14]
Anti-inflammatory, Anti-depressant, Bone preserving,
antipyretic, Antithrombotic

Antitumor, anti-apoptotic [15]

2 β-caryophyllene Anesthetic [16]
Anti-lishmanial [17]
Anti-inflammatory [18]
Antioxidant, antibiotic [19]

Antimicrobial [20]
3 Vanillin Antioxidant [21]
Antidepressant [22]

4 Crategolic acid Antitumor [23]

(Maslinic acid)

Antimicrobial, Antioxidant [24]

5 Kaempferol Anti-inflammatory [25]
Anticancer [26]

Anti-inflammatory, Antioxidant [27]

6 Rhamnetin Cardio protective [28]
Antifungal [29]

7 Eugenitin Antifungal [30]

8 Eugenin No activity reported

Antimicrobial, Antioxidant [31]

9 Gallic acid Anti-inflammatory [32]

HO O CH3 Antibacterial [33]

10 Biflorin HO O Antioxidant, Anticancer [34]
OH O
HO OH
OH
Antimicrobial [35]
11 Myricetin Antioxidant, Anticancer [36]
Anti-inflammatory [37]

Antibacterial [38]
12 Campesterol Antinociceptive [39]
Anti-carcinogenic [40]

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Int J Pharm Pharm Sci, Vol 6, Issue 8, 67-72

Antimicrobial [38]
13 Stigmasterol Antitumor [41]
Acaricidal [42]
Block cartilage degradation [43]

Anti-diabetic [44]
14 Oleanolic acid Antimicrobial [45]
Anticancer [46]

15 Bicornin No activity reported

Antifungal activity chemo preventive role of clove oil, particularly in cases of lung, skin
and digestive cancers [64]. Ethyl acetate extract of clove inhibits
Many studies have reported antifungal activity for clove oil and tumor growth and promotes cell cycle arrest and apoptosis.
eugenol against yeasts and filamentous fungi, such as several food- Oleanolic acid one of the components of ethyl acetate extract of clove
borne fungal species [53] and human pathogenic fungi [54]. Clove oil was found to be responsible for its antitumor activity. Its mechanism
and eugenol have also been tested as antifungal agents in animal was attributed to the promotion of Go/G1 cell cycle arrest and
models [55]. The phenolic components of clove, carvacrol and induction of apoptosis in a dose-dependent manner [65]. Eugenol
eugenol, are known to possess fungicidal characteristics [56] acts as a potential molecule that can interfere with several cell-
including activity against fungi isolated from onychomycosis. Rana signaling pathways, specifically the NF-κB. In an another study,
et al. determined antifungal activity of clove oil in different strains eugenol was found to suppress growth of malignant melanoma
and reported following scale of sensibility- Mucor sp.> Microsporum WM1205Lu of both anchorage-dependent and anchorage
gypseum> Fusarium monoliforme NCIM 1100> Trichophytum independent growth, decreased size of tumors and inhibited
rubrum> Aspergillus sp.> Fusarium oxysporum [57]. In melanoma invasion and metastasis by the inhibition of two
chromatographic analysis eugenol was found to be the main transition factors of the E2F family [66]. Hussain et al. studied the
compound responsible for the antifungal activity, due to lysis of the effect of eugenol combined with gemcitabine on cervical carcinoma
spores and micelles. A similar mechanism of action of membrane and found that the combination of eugenol and gemcitabine can
disruption and deformation of macromolecules produced by eugenol inhibit cancer cell growth, even in low concentrations [67]. Studies
was also reported by Devi et al [58]. The large spectrum of fungicidal on related gene also found that eugenol can reduce the possibility of
activity of clove oil and eugenol was reported on Candida, apoptosis of B-cell lymphoma-2 (Bcl-2), Cyclooxygenase-2 (COX-2),
Aspergillus and dermatophytes and the mechanism of action was and interleukin-1β (IL-1β), reduce inflammation, and increase the
attributed to the lesions of the cytoplasmic membrane [53]. Burt treatment efficacy of gemcitabine. Moreover, Eugenol showed better
proposed that different modes of action can be involved in the curative effects in skin cancer and melanoma.
antifungal activity of essential oils. The activity may in part be due to
their hydrophobicity, which is responsible for their partition into the Analgesic activity
lipid bilayer of the cell membrane, leading to an alteration of
permeability and a consequent leakage of cell contents [50]. Eugenol is a routine analgesic agent widely used in dental clinics due
to its ability to alleviate tooth pain. Its anesthetic effects in dental
Antioxidant/Free radical scavenging activity pain as well as analgesic and anti-inflammatory effects in animal
models have been well documented [68]. The effects have been
Clove essential oil has the highest antioxidant capability and perhaps attributed to its capability to suppress prostaglandins and other
one of the best known oil for food or supplement. For this reason, it inflammatory mediators such as leukotriene. It is also believed to
has been included in some longevity formulae. Clove and eugenol depress the sensory receptors involved in pain perception, [69]
possess strong antioxidant activity, which is comparable to the inhibits the conduction of action potential in sciatic nerves [70] and
activities of the synthetic antioxidants, BHA and pyrogallol [59]. N-methyl-D-aspartate (NMDA) receptors but potentiates ionotropic
Clove oil inhibited 97.3% lipid peroxidation of linoleic acid emulsion γ-aminobutyric acid (GABA A ) receptors, which are both involved in
at 15 µg/mL concentration. The essential oil demonstrated pain sensitivity [71].
scavenging activity against the 2,2-diphenyl-1-picryl hydrazyl
(DPPH) radical at concentrations lower than the concentrations of Anti-inflammatory activity
eugenol, butylated hydroxytoluene (BHT), and butylated hydroxyl
Clove oil clear respiratory passages, acting as an expectorant for
anisole (BHA) [60]. Abojid et al observed enhanced liver functions,
treating many upper-respiratory conditions including colds, eye
kidney functions, and antioxidant status in clove treated rats and sties, bronchitis, sinus conditions, cough and asthma. One of the
showed that its protective role against H 2 O 2 induced cell damages studies showed that the essential oil possess significant anti-
might be due to the effect of active compounds found in essential oil inflammatory effect at doses of 0.05 ml/kg (90.15% inhibition) and
and plant extract [61]. A recent study by Calleja et al reported that β- 0.200 ml/kg (82.78% inhibition) [72]. Clove has been used in
caryophyllene isolated from clove essential oil protects rat liver traditional public medicine to relieve nasal obstruction and
from carbon tetrachloride induced fibrosis by inhibiting hepatic musculoskeletal pain which implies its anti-inflammatory activity
stellate cell activation [19]. and the activity is due to COX-2 inhibition [73]. The aromatic oil,
Anticarcinogenic activity when inhaled, can help relieve certain respiratory conditions like
coughs, colds, asthma, bronchitis and sinusitis. Clove also contains a
Clove essential oil has also been reported to show anticarcinogenic variety of flavonoids including kaempferol, rhamnetin and β-
[4] and antimutagenic potential because of its strong free radical caryophyllene which also contributed to its anti-inflammatory and
scavenging activity [63]. Several Preliminary studies suggested antioxidant properties [16]. It has an anti-inflammatory effect

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Int J Pharm Pharm Sci, Vol 6, Issue 8, 67-72

matching to that of etodolac at 0.025 and 0.1 ml/kg and to that of as safe. The World Health Organization (WHO) Expert Committee on
indomethacin at 0.05 and 0.2 ml/kg doses. Eugenol (200 and 400 Food additives has established the acceptable daily human intake of
mg/kg) was also found to reduce the volume of pleural exudates clove oil at 2.5 mg/kg body weight for humans. The major
without changing the total blood leukocyte count indicating its anti- pharmacological activities of clove are antimicrobial, anti-
inflammatory potential [74]. inflammatory, anesthetic, analgesic, antioxidant and anticancer.
Some other activities are aphrodisiac, mosquito repellant,
Antithrombotic activity insecticidal and antipyretic. All the major activities of clove are
Clove oil inhibited human platelet aggregation induced by explained and appreciable results have been reported regarding the
arachidonic acid (AA), platelet-activating factor (PAF) or collagen. It various activities discussed in the review. Furthermore considering
was a more effective inhibitor for aggregation induced by AA and its versatile medicinal uses, there is an ample scope for future
PAF (IC50: 4 and 6 µM respectively) than collagen (IC50: 132 µM). research.
The in vivo experiments in rabbits showed that clove oil (50-100 CONFLICTS OF INTEREST
mg/kg) afforded 100% protection against PAF (11 mg/kg, i.v.) and
70% protection against AA (2.0 mg/kg, i.v.) induced thrombosis and All authors have none to declare.
shock due to pulmonary platelet thrombosis. It also inhibited
thromboxane-A2 and 12-HETE production by human platelets ACKNOWLEDGEMENT
incubated with [C[14]] AA [75]. Eugenol inhibits prostaglandin Authors are thankful to University of Delhi for providing the funds
biosynthesis, the formation of thromboxane B2, and arachidonic under Innovative Project (SRCA-204). First three authors are
acid-induced platelet aggregation in vitro [76]. Eugenol and acetyl undergraduate students and equally contributed in this review
eugenol are found to be more potent than aspirin in inhibiting article.
platelet aggregation induced by arachidonate, adrenaline and
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