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Synergy Between Essential Oil Components and Antibiotics a Review

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Open access peer-reviewed chapter

Essential Oils: Partnering with Antibiotics

Mariam Aljaafari, Maryam Sultan Alhosani, Aisha Abushelaibi, Kok-Song Lai and Swee-Hua Erin Lim

Submitted: November 20th, 2018 Reviewed: April 29th, 2019 Published: June 5th, 2019

DOI: x.5772/intechopen.86575

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Abstract

Essential oils (EO) are volatile, non-lipid-based oils produced as a constitute defense mechanism. Studies from our grouping have validated the potential usefulness of EOs to synergistically and additively work with antibiotics. In this book chapter, we aim to outline some background on the EOs and their uses and applications, to hash out the different mechanisms of action in partnering with antibiotics, and, finally, to explore their potential use confronting multidrug-resistant leaner. Applications of EO in therapy will enable the revival of previously sidelined antibiotics and enhance the development of new drug regimens to better mitigate what may be the biggest health claiming by year 2050.

Keywords

  • lavander oil
  • cinnamon bark oil
  • peppermint oil
  • multidrug-resistant bacteria
  • synergistic interaction
  • antimicrobial

1. Introduction

Essential oil (EO) is a concentrated mixture of organic compounds. EOs are produced by plants equally a course of defense in improver to existence an attractant to insects for dispersion of pollens and seeds [1, 2]. These oils are formed by the glandular trichomes and specialized secretory construction like secretory hairs, ducts, cavities, and glands; they then lengthened to the surface organs of plant such as leaves and flowers [3, 4]. The process of EOs formation involves three pathways which are the methyl-D-erythritol-4-phosphate (MEP), mevalonate, and malonic acid pathways [5]. The MEP and mevalonate pathways contribute in the biosynthesis of isoprenoids, whereas the malonic acrid pathway will grade the phenolic compounds [6, 7].

EOs have been used for many years for dissimilar purposes, such equally to preserve raw and candy nutrient considering information technology can inhibit the growth of microorganisms like leaner, viruses, and fungi [1, 8, ix]. Also food, EO was also utilized in the area of perfumery for many years specially for ancient civilizations of India, Hellenic republic, Egypt, and Rome [10, eleven].

In addition, EOs also serve as an alternative medicine that is important for local populations to treat astringent burns to accelerate healing [11] and also for diseases such every bit leishmaniasis, schistosomiasis, and malaria [12, 13]. To date, approximately ten% of all EOs have been analyzed and commercially used as an insect repellent, attributed past its low toxicity to mammalian cells and the environment [x, fourteen]. Even so, certain EOs may crusade toxicity or allergies which results in health and rubber problems. Hence, national and international organizations have set up standards to control the use of EOs [15].

EOs tin can be found in various plants species, in particular those that vest to the Coniferae, Myrtaceae, Rutaceae, Labiatae, Umbelliferae, Alliaceae, and Zingiberaceae families [16, 17]. EOs are derived from different plant parts, such as flowers, leaves, wood, roots, seeds, rhizomes, and fruits [18]. See Tabular array one for examples of EOs constitute in each of the plant parts.

Part Name of essential oil References
Flowers Lavender, jasmine [18]
Leaves Mint, lemongrass [19, 20]
Forest Sandal, cedarwood [21, 22]
Roots Sassafras, valerian [23, 24]
Seeds Fennel, nutmeg [25, 26]
Rhizomes Ginger, orris [27, 28]
Fruits Orange, juniper [18, 29]

Table 1.

EOs extracted from constitute parts.

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2. Classification of essential oils

In general, EOs can be classified based on their chemical limerick, aroma created past the oil, evaporation speed, taxonomy or the families they vest to, their therapeutic uses, consistency, their origin, and the alphabetical order [sixteen, 30]. Classification based on consistency, for example, tin be divided into essences, balms, and resins [16, 31]. See Table 2 for definition and examples of each.

Based on consistency Definition Examples
Essences Volatile liquid at room temperature [16] Lavender, jasmine, geranium, rose [32, 33]
Balsams Thick very volatile natural extract from tree or bush-league [16] Copaiba balsam, Peruvian balsam, Canada balsam, Tolu balsam, Cabreuva balsam, Bangui balsam [sixteen, 34]
Resins Solid or semisolid products that comprise of derivates and abietic acid [16] Patchouli, sandalwood, frankincense [33]

Tabular array two.

Classification of EOs based on consistencies.

Furthermore, there are three classifications of EOs based on their origin which are natural, bogus, and synthetic [16]. The natural EOs are taken from the plant without concrete or chemic modifications, while the artificial oils are obtained by enriching the essence with extra components (can exist one or more than). The synthetic EOs, however, are obtained by combining many chemical substances together [16]. Come across Table 3 for comparison between natural and synthetic EOs.

Types of essential oil Disadvantages Advantages
Natural Expensive, need a lot of natural sources to create, can crusade burns if non diluted [15, 35, 36] Great smell, helpful for concrete and mental wellness [36]
Synthetic No therapeutic properties, damaging the pare and respiratory organization [36] Cheap, commonly used as fragrance and gustation enhancers, long lasting [15, 36]

Tabular array 3.

Classification of EOs based on their origin.

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three. Essential oil extraction

V one thousand years ago, the ancient civilizations accept already incorporated the use of machines for EO extraction [11]. Yet, at that place has been an expansion of the dissimilar extraction methods today. One of the of import methods is the hydro-distillation which is divided into water distillation, water-steam distillation, and steam distillation [37, 38]. Hydro-distillation method involves hydro-improvidence, hydrolysis, and decomposition by oestrus [xviii]. In improver, steam distillation is performed by using the Clevenger organisation to excerpt oil from both fresh and dried plants, and information technology takes nigh 3 h [1, 11]. Another method is the expression method which utilizes the machines to compress the EO out of the institute [9, 11]. Additionally, solvent extraction and ultrasonic extraction methods are also routinely used [17].

Throughout the distillation procedure, water is separated by gravity, and at the terminate it leaves the volatile liquid behind; this liquid is the EO [sixteen, 39]. EOs that are extracted by the use of chemical solvents cannot be chosen true EOs according to the National Cancer Constitute, considering they tin cause changes in the clarity, scent, and fragrance of the oil [xl]. The four criteria that affect the amount of essential oils produced are (i) time of distillation, (ii) temperature, (3) force per unit area, and (four) plant quality.

three.1 Hydro-distillation

Hydro-distillation is the well-nigh commonly used method of extraction of EOs in which the establish is boiled in water [41, 42]. This method takes 1 h of distillation for fresh samples and 1 h and 15 min for dried samples. In the hydro-distillation method, a round-bottomed flask is used to place the establish material in with distilled h2o; if the plant textile is dry, yard ml of distilled water should be used for 75 chiliad of plant fabric, and if it is fresh material, 400 ml of distilled water should be used with 200 g of institute fabric; if the sample of plant is smaller, nevertheless, they can adjust the amount of h2o using this ratio: 13.3 ml of distilled h2o for each gram of dry plant. For water distillation, the modified Clevenger trap should exist used to extract EO, and at the end the volume of the oil should be determined, and the EO should exist analyzed immediately [43, 44, 45]. An advanced distillation method which is the microwave-assisted hydro-distillation tin be used to shorten extraction time [46, 47].

3.2 Steam distillation

Steam distillation is the traditional method of extraction of EOs from plants [37]. The fundamental principle of steam distillation is that the mixture is allowed to be distilled at a temperature that is lower than the boiling bespeak of the component; EO substances have a high boiling indicate that can accomplish 200°C; nevertheless, these substances will be volatile when steam or boiling h2o is present which is in 100°C; then the hot gas mixture will exist condensed to form oil if it passes through a cooling system [48]. In steam distillation, the steam is first passed into a flask that contains the plant material; after that the condensate at the lesser of the flask should be nerveless which will be the h2o and oil; then the extract is condensated 3 times with ethyl ether to ensure that the essential oil is fully extracted; then the moisture should be removed by adding sodium sulfate to the ethyl ether, followed by rotary evaporation to remove ethyl ether; and finally the volume of the EO is determined [43]. The advantages of this method of extraction are that it is rapid and can be controlled past the operator and it gives an acceptable quality than EOs extracted with other methods [48].

three.3 Solvent extraction

Solvent extraction method or liquid-liquid method is done past separating compounds based on their role solubility [49]. The bones principle of the solvent extraction method is that between 2 immiscible solvents, the solute distributes itself in a fixed ratio, whereby one is unremarkably water and the other is an organic solvent [l]. In this method, the plant fabric will exist grinded in a mortar that contains anhydrous hexane NatwoSO4, followed by four rounds of extraction with hexane to obtain the yellow excerpt, then this is followed by adding a sufficient amount of Norite A charcoal for all extracts to remove the yellow color after low-speed centrifugation, and eventually the solution volition be full-bodied under air stream at room temperature [37, 43, 49]. A newer method of solvent extraction, chosen the microwave-assisted simultaneous distillation-solvent extraction (MW-SDE), is faster and simpler and uses fewer solvents to determine volatile compounds than conventional methods [51].

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iv. Composition of essential oils

4.1 Physical backdrop of EOs

EOs are volatile and become liquid at room temperature; they might be colorless or slightly yellowish in color when extracted. Moreover EOs are lower in density than water, except for sassafras and clove essences [xvi]. EOs can exist either liposoluble or soluble in alcohol and organic solvents, but they are only slightly soluble in water [4, 16, 32].

four.2. Chemical backdrop of EOs

Plants metabolites are divided into primary and secondary metabolites. The chief metabolites include proteins, Deoxyribonucleic acid, and compounds that are important for cellular part. Secondary metabolites are produced past plants as a response of stress to deter herbivores or animals that would feed on them [52, 53]. Of the secondary metabolites, establish terpenes are the most numerous and diverse natural products of plant secondary metabolites which can be found in EOs [53]. They are plant in monoterpene and diterpene oils and may be aliphatic, cyclic, or aromatic depending on the functional group [sixteen]. According to the functional grouping, they can exist alcohols, esters, ethers, hydrocarbon, and aldehydes [16].

The composition varies due to the place of origin, harvesting moment, extraction method, planting time, mineral fertilization, and climate [v, 16, 54]. For example, in warm places in that location will be more EOs than the cold or hot areas [16]. The concentration of EOs is extremely high due to the extraction methods used [23]. The simplest unit of EOs is the isoprene units that are equanimous of five carbons which can be assembled to form terpenes [xvi, 52]. EOs are composed of hydrocarbon molecules. Terpenes, for instance, are hydrocarbon molecules that comprise of ten, fifteen, twenty, and xxx carbon atoms and are made out of five-carbon isoprene units [55, 56].

EOs' main components are divided into terpenoid and non-terpenoid groups nowadays in different concentrations [4]. The non-terpenoid group contains short-chain aliphatic, aromatic, nitrogenated, and sulfated substances [16, 57]. The terpenoid grouping contains a unlike composition of hydrocarbon terpenes, terpenoids, and sesquiterpenes which is responsible for the special aroma [5, 58]. In general, the not-terpenoid group is less important than the terpenoid in terms of applications [53].

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5. Use of essential oils against multidrug-resistant bacteria

Antibiotics are effective drugs that play an of import part in treating infections and decreasing morbidity and mortality rates [59, sixty]. In general, antibiotics impale multidrug-resistant (MDR) bacteria through various mechanisms. Examples include the β-lactam antibiotics that inhibit the bacterial cell wall synthesis, fluoroquinolones that inhibit Dna synthesis, tetracycline which is an inhibitor of poly peptide synthesis, sulfonamides as a metabolic pathway or folic acid synthesis inhibitor, and polymyxin B which interferes with cell membrane integrity [60, 61, 62, 63]. Antibiotic resistance develops naturally only is accelerated when the antibiotics are misused in both human and animals; the leaner volition evolve and develop resistance toward antibiotics, preventing the antibiotic from killing the bacteria [59, 64]. The bacteria afterward go resistant by many mechanisms depending on the selective pressure incurred by the antibody used; for example, if the penicillin is used, the bacteria will become resistant to information technology by producing enzymes that will deed against the antibody which is in this situation penicillinase enzyme [39]. For example, a report conducted in 173 hospitals in Europe showed that loftier antibiotic consumption hospitals have a higher number of methicillin-resistant Staphylococcus aureus (MRSA) [65].

Antibiotic resistance in microorganisms is increasing at a worrisome rate [66]. Hence, over the years, researchers are exploring possible alternative sources that will be helpful to mitigate MDR bacteria. Of all the potential sources, EO was identified as one of the good alternative sources, considering of their effectiveness in folk medicine [67]. Bacteria can be divided into two chief types: the gram-positive and the gram-negative. The gram-positive accept a thicker peptidoglycan layer than the gram-negative bacteria [68]. Likewise that, the gram-negative leaner also have an outer membrane that is absent-minded in the gram-positive bacteria (Figure 1).

Figure 1.

Schematic of different gram-positive (at the top) and gram-negative (at the bottom) cell walls.

Generally, the gram-positive leaner are less resistant to EOs than gram-negative leaner [69, 70]. In gram-positive bacteria, hydrophobic molecules are able to penetrate the cell and act on the jail cell wall and cytoplasm. This is exemplified by the phenolic compounds in EOs confronting gram-positive bacteria [66]. In the gram-negative bacteria, a thin layer of peptidoglycans is present with an outer membrane that contains LPS. LPS consists of lipid A, core LPS, and O-side chain, which makes the gram-negative bacteria more than resistant to EOs than gram-positive bacteria [66, 71]. Pocket-size hydrophilic solutes will make use of the porin proteins in the gram-negative bacteria to pass through the outer membrane; it is this porin selectivity that also makes the gram-negative bacteria less susceptible to hydrophobic antibiotics [66, 72, 73].

EOs via their different components have dissimilar targets against microorganisms such equally the membrane and the cytoplasm [viii]. Scientists have also found that the solubility of EO in h2o allowed them to decipher how EOs penetrated the cell wall of microbes; in other words EOs, being soluble in the jail cell membrane phospholipid bilayer, diffuse through the membrane [74]. A written report done using the EO of Melaleuca alternifolia (tea tree) against MDR gram-negative bacteria (eastward.g., Escherichia coli and carbapenem-resistant Thou. pneumoniae ) and methicillin-resistant South. aureus (MRSA) showed that in that location is a bactericidal effect of tea tree EO on these microorganisms [75]. This indicated that the EO tin be used to impale resistant bacteria [74]. Moreover, EO phenolic compounds' consequence is concentration-dependent, whereby at low concentrations the phenolic chemical compound volition work with enzymes to produce free energy, while at high concentration it will denature proteins [66, 76].

five.1 Determination of MIC of EOs for bacteria

Minimal inhibitory concentration (MIC) is the lowest concentration of a specific drug to inhibit the growth of microorganisms such as bacteria [1, 77]. After knowing that a particular EO has bactericidal, viricidal, and antiparasitic effects, the lowest concentration of EO to inhibit microbial growth should be measured [57, 78]. There are many assays to evaluate and screen for antimicrobial activity such every bit the disk diffusion test, microdilution (resazurin) or broth method, and agar dilution method [79, 80]. The agar disk diffusion examination is commonly used to determine the antibacterial activeness of the EO, but this method works merely for EO with known components. This is because, for the EOs with unknown components, the antimicrobial effect may give rise to false or negative result caused by the unknown components [81]. Previously, in a study performed using the deejay diffusion test to examine the antimicrobial action of Eucalyptus globulus leaves, EO showed that there was a bacterial inhibitory effect on E. coli and S. aureus [82].

The commonly used culling method to decide antimicrobial activity is the dilution method through a serial dilution of the EO in several tubes, and then determining the MIC after adding the test microorganism, turbidity is measured every bit a betoken for growth [81]. In this method, the EO is commencement diluted; so it volition be added to the medium that contains the broth culture, followed by incubation for 18 h in 37°C [69]. After the incubation menses, the tube with the everyman concentration that showed no sign of growth is the MIC of the EO [69, 83]. However, this method requires a large quantity of the plant extract [81]. A report using the redox dye resazurin for the new modified microdilution method has been carried out to determine the MIC for tea tree EO ( Melaleuca alternifolia ) against the gram-positive and gram-negative bacteria. The results showed that the resazurin method is accurate to determine the MIC and is higher in sensitivity than the results obtained from the agar dilution analysis [80].

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6. Mechanisms of actions with antibiotic

EOs' machinery of action is poorly understood, but in full general it depends on their chemic composition [8, 66, 84]. Every bit antimicrobial resistance to antibiotics is increasing, scientists are currently exploring the power of the plant extract to modify bacterial resistance against drugs [39]. The three main types of interactions that occur between the combination of antibody and EO are synergism, additivity, and antagonism [85]. Synergistic interaction is when the effect of the combined chemicals is greater than the effect of a chemic alone; condiment interaction is when the sum of two chemicals is equal to the sum of chemical result alone, while animosity is when the whole effect of the two chemicals is less than the sum of effect of a unmarried chemical lone [86]. In a report performed using the tea tree EO confronting the MDR leaner, when a combination of tea tree EO with antibiotic (e.yard., oxacillin) was tested on the leaner, in particular the MRSA, a high synergistic index in the sub-inhibitory concentration was recorded [75]. This indicates that the EO can exist used to overcome bacterial resistance to antibiotic. The synergism level increases when the combined upshot is higher than the private effect in the combination therapy [39].

Combination therapy is a new method that combines antibiotics and EO to kill resistant bacteria, via enhancement of the antimicrobial activity [39, 87]. Moreover, EOs take more than components possessing different mechanisms of actions for many targets than antibiotics that have only one target. Combination therapy would be useful and able to provide a new treatment option for resistance leaner [39].

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vii. Application of essential oils in therapy

Daily, the homo trunk comes into contact with EOs through various sources such as herbs, spices, orange, spearmint, lemongrass, etc., merely but limited information near the amount of EO uptake is known [four, 88]. Effects of EO begin to appear after it penetrates the human torso in several ways such as by ingestion, by absorbing the EO or diffusion, and by inhalation [4, 89]. EOs tin can exist taken by inhalation through the lungs and distributed into the blood considering of their volatility [90, 91, 92]. Moreover, consumption of EO by ingestion should be taken with care because EOs may cause probable toxicity [iv]. EOs are used in folk medicine to treat many health problems and can also be used equally food preservatives past giving antimicrobial, antioxidant, and anti-inflammation properties [93, 94].

Many studies investigated the efficiency of EOs in combination with antibiotics to gainsay bacterial resistance; EOs with its compounds and secondary metabolites have shown promising synergistic interaction equally an indication that they would be helpful to treat and decrease bacterial resistance to antibiotics [39, 95]. The advantages that make the EOs preferable are that they volition decrease adverse reactions, too beingness comparatively more toll-effective, with more public acceptance due to traditional usage, and beingness renewable with better biodegradability backdrop [39, 96].

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8. Synergistic activity of essential oil

The synergistic effects between the EOs and antibiotics against the MDR bacteria accept been investigated [97]. The synergistic effect can be divers as the ability of EO components to act together with the antibiotic component to increase the activity of the EO against MDR bacteria [98]. This is important because it volition aid to reduce the utilize of antibiotics and decrease the rates of antibody resistance [97]. Some studies take been done to assess the combinatory activities of lavender, cinnamon bark, peppermint, and other EOs confronting bacteria, and the results show there is a synergistic effect [97]. Some of these EOs will exist discussed in the post-obit sections.

8.1 Lavender essential oil

The lavander EO is used in traditional medicine as well equally in corrective products; this oil is believed to have sedative, anti-inflammatory, and antimicrobial effects [99]. Lavender EO shows a synergistic effect when combined with piperacillin antibiotic against beta-lactamase-producing Escherichia coli under study with partial inhibitory concentration (FIC) alphabetize between 0.26 and 0.v [97]. This finding shows that it'due south possible to utilise the lavender EO every bit an agent in modifying the antibiotic resistance [97]. Some other study which aimed to compare the antimicrobial efficacy of four types of lavender oil on MSSA and MSRA shows that by direct contact the oil inhibits the growth of these microbes [100]. Fusidic acrid is ane of the compounds inside this oil which gives it the antimicrobial activity, the mechanism of which is to cause bacterial cell impairment by reducing synthesis of proteins [101].

8.2 Cinnamon bawl essential oil

The cinnamon bark EO can be obtained from different parts of the tropical evergreen tree, which is important for man health and agriculture uses [102]. Previously, a study reported that a combination of cinnamon bawl EO with piperacillin resulted in a synergistic human relationship with FIC ≤ 0.v, and this result indicates the possibility of using cinnamon bark EO every bit a resistance-modifying agent against MDR bacteria [97, 103]. Cinnamon bark oil contains cinnamaldehyde which is one of the compounds that inhibit the activity of amino acid decarboxylase; this compound with others within the oil gives this oil the ability to inhibit some pathogenic bacteria [104].

8.3 Peppermint essential oil

Peppermint EO is meaning in inhibiting the microbial growth and increasing the shelf-life of food past preventing nutrient spoilage [105]. Combination of piperacillin and peppermint EOs with FIC in the range 0.26–0.5 was found showing a synergistic issue that is absent-minded in 31 other combination pairs that were studied, indicating a promising alternative to reduce the use of antibiotic and achieve the reverse beta-lactam antibiotic resistance [91]. The antibacterial action for this oil is associated with menthol and ethyl acetate in high concentrations [106].

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9. Time to come perspectives

Research about the reversal antibody resistance is important to preserve the healthy microbial ecosystem in the human host. It is imperative to understand the cause of antimicrobial resistance and to find solutions to alleviate the present situation. As discussed above, combination therapy between EOs and antibiotic provides a promising alternative to mitigate MDR bacteria, peradventure by disrupting the bacterial cell wall. Although EOs accept been proven to be useful for mitigating MDR bacteria spread, in that location is nonetheless much to exist done in terms of the combination stability, selectivity, definite machinery of action, chemical nature, availability of these products in homo body, optimal dose, and adverse reactions as a handling. These gaps need to be taken into consideration earlier applying EOs for clinical usage. In add-on, at that place is also a demand for animal report and human trials in the future, if one intends to employ EOs as a therapeutic option in medical settings.

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Acknowledgments

The authors would like to give thanks the HCT Research Grants from the Higher Colleges of Engineering science, UAE for supporting this work.

Conflict of interest

The authors declare they accept no competing interests.

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Mariam Aljaafari, Maryam Sultan Alhosani, Aisha Abushelaibi, Kok-Vocal Lai and Swee-Hua Erin Lim

Submitted: Nov 20th, 2018 Reviewed: April 29th, 2019 Published: June 5th, 2019

© 2019 The Author(due south). Licensee IntechOpen. This affiliate is distributed nether the terms of the Creative Commons Attribution 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original piece of work is properly cited.

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