Clove Bud Essential Oil

Clove Oil (Syzigium aromaticumor Eugenia caryophyllata). This oil comes from the distillation of dried buds of the clove tree, which is cultivated worldwide. Extensively used as a spice, clove buds have been used in traditional medicine systems for conditions ranging from bronchitis to digestive problems to hernias (Lawless, 1992). Clove bud oil typically consists of around 89% of the phenylpropene eugenol 6% eugenyl acetate, 1.5% β-caryophyllene, and many other trace compounds (Chaieb et al., 2007). 

       
Clove buds before and after drying.

Antimicrobial Properties of Clove Bud Oil

A range of potential properties has been the subject of research into clove bud oil, the most extensive of which is its antimicrobial potential

Bacteria

Clove bud oil was found to possess antimicrobial activity against a wide range of bacteria, including the notable pathogens Staphylococcus aureusand Escherichia coliat concentrations as low as 0.25% (Hammer, Carson and Riley, 1999), Staphylococcus epidermidisand the acne-causing bacteria Propionibacterium acnes (Owen, Price and Laird, 2014) as well as the antibiotic resistant pathogen methicillin-resistant Staphylococcus aureus(Owen, 2014).

Oral Bacteria

Moon, Kim and Cha (2011) investigated the antimicrobial activity of clove oil against bacteria known to cause dental caries and periodontitis such as Streptococcus mutans.Clove possessed strong bactericidal activity against all tested species at concentrations as low as 0.1mg/ml. It was also found to work synergistically with the antibiotic ampicillin, decreasing by 4-8 fold the concentration needed to inhibit or kill the bacteria. This suggests that clove oil could be used as a preventative for dental caries and periodontitis, or as a treatment either alone or in combination with antibiotics.

Fungi

In a study of common fungal species including Candida albicans, Aspergillus flavus, and Aspergillus nigerand fungal skin infection-causing species (dermatophytes), clove bud oil successfully inhibited all strains tested, thus demonstrating its broad spectrum antifungal activity. The dermatophytes were most susceptible, with the minimum concentration needed to inhibit them being 0.16 microliters/ml (0.00016 ml per ml of medium!). This data therefore suggests that clove bud oil may be useful as an alternative treatment to antifungal agents for the treatment of fungal skin infections such as candidiasis (Pinto et al., 2009).

Parasites

Clove oil effectively inhibited the growth of the intestinal parasite Giardia lamblia,a pathogen that is a significant problem in developing countries, especially in children. After 3 hours of exposure to clove oil, adherence of the parasite to substrates, which is important in infection as it adheres to the intestinal wall, was significantly reduced. As such it may be a potential novel anti-giardial therapy or preventative (Machado et al., 2011), and due to clove oils cheapness compared to anti-parasitics this could be valuable for developing countries. 

Clove oil was also found to inhibit the growth of Trypansoma cruzi,the parasite that causes Chaga’s disease. Clove was found to successfully inhibit T. cruzi,with 50% of cells inhibited at 57.5 micrograms/ml (Santoro et al., 2007).

Viruses

One study found that clove extract was highly active at inhibiting replication of the hepatitis C virus (≥90% inhibition at 100 µg/mL) and another isolated and identified an anti-herpes simlex virus 1 compound, eugenin from clove oil (Chaieb et al., 2007).

Anti-inflammatory Activity

In rats, injections of eugenol significantly reduced carrageenan-induced paw oedema (swelling) compared to controls that were not treated with eugenol, suggesting that it possesses anti-inflammatory activity (Daniel et al., 2009).

Anti-allergic Activity

Clove oil was found to inhibit artificially-induced systemic anaphylaxis and IgE antibody-mediated passive cutaneous anaphylaxis reactions, and significantly reduced the levels of histamine in the blood, by inhibiting the release of histamine from mast cells (Kim et al., 1998). This suggests that clove has significant anti-allergic activity, so it may be useful for disorders such as hayfever or asthma . In another study, clove and eugenol were both found to possess significant relaxant activity upon tracheal smooth muscle, which contracts in allergic reactions such as asthma (Reiter and Brandt, 1985), further highlighting clove oil as a potential candidate for anti-allergic treatment. 

Immunostimulant Activity

Carrasco et al. (2010) investigated the effects of oral administration of clove, ginger and sage oils upon the white blood cells of healthy and immunosuppressed mice. It was found that after seven days, the total white blood cell count of both non- and immunosuppressed mice had increased in a dose-dependent manner. For example, 200mg/kg of clove oil increased the white blood cell count in non-immunosuppressed mice by an average of 71.1% in seven days. Ginger and sage oils did not have a significant effect on total white blood cell count. Clove essential oil was found to stimulate a cell-mediated response as it caused an increase in delayed-type hypersensitivity reactions. Cell-mediated responses are important for defending against viruses and intracellular bacteria, and fungi, suggesting clove could help activate this response to protect against these, however further research into the mechanisms behind this response and trials in humans are needed to confirm if it would be a useful immunostimulant.

Analgesic

Clove and eugenol have both been used extensively as a relief for toothache and as an anaesthetic for fish, and some research has been conducted into whether clove oil possesses significant analgesic activity. In mice, 10mg/kg injections of 10% clove oil exerted significant analgesic activity, when exposed to painful thermal stimuli, compared to controls. The authors suggest an inhibition of prostaglandins and other inflammatory mediators such as leukotrienes as the mechanisms of analgesic action (Hosseini, Asl and Rakhshandeh, 2011). It was also suggested that eugenol blocks pain receptors, thus preventing the brain from receiving pain signals (Hosseini, Asl and Rakhshandeh, 2011). These results support the traditional uses of clove oil for the relief of toothache.  

In 73 humans, a topical clove gel was compared to a traditional topical anaesthetic, benzocaine, used to numb the pain of needle insertion in dental surgery. 73 adult volunteers. After 5 min of material application in a randomized, subject-blinded manner, each participant received two needle sticks. Pain response was registered using a visual analogue pain scale. Both clove and benzocaine gels had significantly lower mean pain scores than placebos, and no significant difference was observed between clove and benzocaine regarding pain scores. This suggests that clove is as efficacious as benzocaine and might possess a potential to replace benzocaine as a topical agent before needle insertion (Alqareer, Alyahya and Andersson, 2006)

Antidepressant

Acute oral administration of 200mg/kg clove oil to mice exerted significant anti-depressant effects in the forced swimming and tail suspension tests (used to test anti-depressant drugs). Long-term administration of 50-200mg/kg clove oil orally to mice exposed to chronic unpredictable mild stress also significantly elevated the protein levels of hippocampal p-ERK, p-CREB, and brain-derived neurotrophic factor, which are usually decreased in depression (Liu et al., 2015). Eugenol was also found to induce brain-derived neurotropic factor in mice, suggesting that this may be responsible for clove oils antidepressant activity. Eugenol’s activity was comparable to imipramine, an antidepressant drug (Irie et al., 2004). These results suggest that clove oil or eugenol alone may be potential alternatives to antidepressant drugs for treating depression.

Learning and Memory

In order to evaluate the beneficial effect of clove on learning and memory, an experimental study was conducted in normal male mice. A Shuttle Box device, where mild electric shocks are given to the feet if the mice do not move into another compartment in response to visual and auditory stimuli, was used to evaluate the active avoidance learning and memory in mice. 100, 200 and 400 mg/kg of an ethanolic extract of clove were injected intraperitoneally to animals in the test groups; those in control groups received saline.The learning procedure (mean numbers of free shock trials) in the test groups were increased compared with the control group but the difference was only significant with the 100 mg/kg dose. In the short- and long-term memory assessments the animals in the test groups received less shocks than the control group and the differences were significant in the case of the 100 and 200 mg/kg clove extract. This indicates that acute administrations of ethanolic extracts of clove enhance the learning and memory recall ability in mice. The author suggested that the higher doses of 400mg/kg did not exert this effect due to its hypnotic and analgesic effects (Dashti-R and Mordeshi, 2009). As such, at lower doses clove oil could help with cognition and memory however at high doses this would not be seen.

Gastroprotective (Anti-ulcer) Activity

One study used several methods to investigate the ability of clove oil and eugenol to protect from induced ulcers in rats. Both clove bud oil and eugenol displayed gastroprotective properties (significantly reduced incidence of ulcers than controls) in the rats. Studies focusing on the possible mechanisms of gastroprotection were also undertaken. The results show that there was no significant effect on the volume of gastric juice and total acidity. However, the quantification of free gastric mucus showed that the clove oil and eugenol were capable of significantly enhancing mucus production. As such, the authors concluded that clove bud oil and eugenol exert antiulcer activity in rats through their ability to stimulate the synthesis of mucus, an important gastroprotective factor. Therefore, these may be potential candidates for novel anti-ulcer therapies in the future (Santin et al., 2011). 

Clove oil has also been found to inhibit the bacterium Helicobacter pylori in vitro,which infects the stomach and is correlated with gastric ulcers and gastric cancer. By inhibiting H. pylori,this further increases the gastroprotective effect of clove bud oil.

Anticarcinogenic

Clove essential oil has been reported to show anti-carcinogenic and antimutagenic potential (inhibits cancerous cells and mutations), and eugenol was shown to induce apoptosis (cell death) of human cancer cells, with the major antimutagenic compound being identified as dehydrodieugenol (Chaieb et al., 2007). Another study investigated the protective effect of cloveon skin papillomas in mice, finding that both topical and oral administration delayed the development and reduced the incidence of papillomas, with oral administration of 100 microliters/day to be the most effective (Banjeree and Das, 2005). These studies suggests that clove oil could have chemopreventative effects, however, this would need to be studied in greater detail.

For more information on Antimicrobial, check out our blog on Winter Immunity and our Antimicrobial Protection Range.

References

Alqareer, A., Alyahya, A. and Andersson, L. (2006) The effect of clove and benzocaine versus placebo as topical anesthetics. Journal of Dentistry, 34 (10), pp. 747-750.

Banjeree and Das, (2005) Anticarcinogenic Effects of an Aqueous Infusion of Cloves on Skin Carcinogenesis. Asian Pacific Journal of Cancer Prevention,6,pp. 304-308. 

Carrasco, F.R. et al. (2009) Immunomodulatory activity of Zingiber officinale Roscoe, Salvia officinalis L. and Syzygium aromaticum L. essential oils: evidence for humor- and cell-mediated responses. Journal of Pharmacy and Pharmacology, 61 (7), pp. 961-967.

Chaieb, K. et al. (2007) The Chemical Composition and Biological Activity of Clove Essential Oil, Eugenia caryophyllata (Syzigium aromaticum L. Myrtaceae): A Short Review. Phytotherapy Research,21, pp. 501-506. 

Daniel, A.N. et al. (2009) Anti-inflammatory and antinociceptive activities A of eugenol essential oil in experimental animal models. Revista Brasileira de Farmacognosia,19 (1). 

Dashti-R, M.H. and Mordeshi, A. (2009) The effects of Syzygium aromaticum (clove) on learning and memory in mice. Asian Journal of Traditional Medicines,4 (4), pp. 128-133.  

Hammer, K.A., Carson, C.F. and Riley, T.V. (1999) Antimicrobial activity of essential oils and other plant extracts. Journal of Applied Microbiology, 86 (6), pp. 985-990.

Hosseini, M., Asl, M.K. and Rakhshandeh H. (2011) Analgesic effect of clove essential oil in mice. Avicenna Journal of Phytomedicine,1 (1), pp. 1-6. 

Hosseini, M., Asl, M.K. and Rakhshandeh H. (2013) Analgesic effect of the aqueous and ethanolic extracts of clove. Avicenna Journal of Phytomedicine, 3(2), pp.186–192.

Irie, Y. et al. (2004) Eugenol exhibits antidepressant-like activity in mice and induces expression of metallothionein-III in the hippocampus. Brain Research, 1011 (2), pp. 243-246.

KIM, M.H. et al. (1998) Effect of Syzygium aromaticum extract on immediate hypersensitivity in rats. Journal of Ethnopharmacology, 60 (2), pp. 125-131.

Liu, B.B. et al. (2015) Essential Oil of Syzygium aromaticum Reverses the Deficits of Stress-Induced Behaviors and Hippocampal p-ERK/p-CREB/Brain-Derived Neurotrophic Factor Expression. Planta Medica,81(3), pp. 185-192. 

Machado, M. et al. (2011) Anti-Giardia activity of Syzygium aromaticum essential oil and eugenol: Effects on growth, viability, adherence and ultrastructure. Experimental Parasitology, 127 (4), pp. 732-739.

Moon, S.E., Kim, H.Y. and Cha, J.D. (2011) Synergistic effect between clove oil and its major compounds and antibiotics against oral bacteria. Archives of Oral Biology,56 (9), pp. 907-916. 

Owen, L. (2014) Determination of the Antimicrobial Efficacy of Tea Tree, Clove Bud, Lemon and Orange Essential Oils and their Vapours Against E. coli, S. aureus and Multi-Drug Resistant S. aureus.BSc (Hons), University of the West of England. 

Owen, L., Price, P. and Laird, K. (2014)An Investigation of the Double and Triple Synergistic Antimicrobial Interactions Between Litsea, Rosewood and Clove Essential Oils Against Acne-Associated Bacteria Propionibacterium acnesand Staphylococcus epidermidis.[Poster] Antibiotic Alternatives for the New Millennium, London. 

Pinto, E. et al. (2009) Antifungal activity of the clove essential oil from Syzygium aromaticumon Candida, Aspergillus and dermatophyte species. Journal of Medical Microbiology,58 (11), pp. 1454-1462.

Reiter, M. and Brandt, W. (1985) Relaxant effects on tracheal and ileal smooth muscles of the guinea pig. Arzneimittel-Forschung, 35 (1), pp. 408-414. 

Santin, J.R. et al.(2011) Gastroprotective activity of essential oil of the Syzygium aromaticum and its major component eugenol in different animal models. Naunyn-Schmiedeberg's Archives of Pharmacology, 383 (2), pp. 149-158.

Santoro, G.F. et al. (2007) Trypanosoma cruzi: Activity of essential oils from Achillea millefolium L., Syzygium aromaticum L. and Ocimum basilicum L. on epimastigotes and trypomastigotes. Experimental Parasitology, 116 (3), pp. 283-290.

                         

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