Eucalyptus

Rodrigues, Mayara & Mazzafera, Paulo, 2025, Essential oils from Eucalyptus species: a review of their activities, applications, and the Brazilian market, Acta Botanica Brasilica (e 20240111) 39, pp. 1-21 : 4-16

Biological activities of eucalyptus essential oils

Essential oils are increasingly recognized and utilized for numerous purposes across different sectors. Their lipophilic nature allows interactions with the cell plasma membrane, making it permeable. Moreover, they can depolarize the mitochondrial membrane, rendering it permeable and potentially leading to toxicity ( Gautam et al., 2014; Abdoul-Latif et al., 2023). Another relevant point is that terpenes can easily traverse cell membranes due to their low molecular weight, thereby inducing biological activities such as antimicrobial and antioxidant effects ( Al-Radadi, 2022). Defining the modes and mechanisms of action determining the efficacy of essential oils is challenging due to their complex and variable composition, requiring further studies.

Many studies focus on the use of EOs as potential antimicrobials because conventional chemicals typically lose their efficacy due to misuse, the development of microbial resistance, or the emergence of microorganisms that require new means of control. In addition to the resistance mechanisms developed by microorganisms, there is the risk of the resistance factor being transmitted to pathogenic descendants ( Salem et al., 2018).

The increased use of EOs in agricultural pest management is also justified by changes in pesticide market regulations in the European Union (EU) (Directive 2009/128/EC), which mandate the implementation of Integrated Pest Management (IPM) and the sustainable use of pesticides, especially non-synthetic ones, for weed control ( Verdeguer et al., 2020b). A comprehensive review of the bioherbicidal potential of EOs from various weed species was conducted by Verdeguer et al. (2020b). These authors highlighted two challenges for evaluating EOs in vivo: they must be mixed with emulsifiers and not with water, making the type of emulsifier another factor to be tested, and rapid volatilization requires appropriate formulations, with microencapsulation and nanoemulsion being the most commonly used for EOs ( Vinceković et al., 2017).

Tab. 2 shows the biological activities of eucalyptus EOs published in the literature. The eucalyptus oils have a large range of bioactivity probably because of their diverse composition. The bioactivities cover from agriculture applications to the control of human pathogens. Other eucalyptus species from which essential oil is extracted for medicinal use include E. maidenii F. Muell , E. bicostata Maiden, Blakely & Simmond , E. sideroxylon A. Cunn. ex Woolls , E. cinerea F. Muell. ex Benth. , E. leucoxylon F. Muell. , and E. tereticornis Sm. ( Mieres-Castro et al., 2021) .

Formulations that yield satisfactory results have to meet environmental and safety concerns. Pant et al. (2014) prepared a nanoemulsion using aqueous filtrates of Pongamia glabra Vent. and Jatropha curcas L. left after biodiesel oil extraction to enhance the activity of Eucalyptus globulus Labill. oil in controlling Tribolium castaneum (Herbst) , a pest of stored grains. The product was effective in control, with karanjin, phorbol esters, and eucalyptol being the main constituents responsible for the observed insecticidal effect. It is worth noting that such products improve the performance of EOs and can be used on food grains, not polluting the environment and expanding the range of pesticide products, reducing resistance risks.

Eucalyptus essential oil was trapped within the micro-nanostructures of a polydimethylsiloxane (PDMS) substrate, which increased significantly the hydrophobicity ( Hidouri et al., 2024). The authors demonstrated the antibacterial ability of these superhydrophobic surfaces to inhibit the growth of Escherichia coli (Migula) Castellani & Chalmers and Bacillus cereus Frankland & Frankland bacterial colonies and biofilms.

Due to the complexity of EOs composition, relating observed effects to only one constituent is still a challenging task, as additive, synergistic, or antagonistic effects may occur with their combinations ( Yap et al., 2014; Filomeno et al., 2020; Verdeguer et al., 2020b). While some researchers associate the fumigant effect of eucalyptus EOs against grain pests with its eucalyptol content ( Aref et al., 2015; Hamdi et al., 2015), Filomeno et al. (2020) found that eucalyptus EOs with approximately 70% eucalyptol showed intermediate mortality, suggesting that other constituents may promote antagonistic effects. When evaluating the antibacterial efficacy of eucalyptus EOs compared to eucalyptol, its dominant constituent, Hendry et al. (2009) found better results with the oil, suggesting that other minor constituents also contribute to the final objective. A similar situation was observed in other studies when testing the effect of Eucalyptus resinifera EO and its main active ingredients against the pests Rhyzopertha dominica Frabricius ( Filomeno et al., 2020) and Hypothenemus hampei Ferrari ( Reyes et al., 2019) .

It has been suggested a possible synergistic effect between eucalyptol and p-cymene in increasing the antibacterial activity of EOs, additive and synergistic effects between eucalyptol and aromadendrene against methicillin-resistant Staphylococcus aureus ( Salem et al., 2018) , and additive effects between eucalyptol and p-cymene against Rhyzopertha dominica ( Filomeno et al., 2020) . A wide range of binary mixtures of components present in EOs was tested to assess the effect (antagonism, synergism, or no effect) against larvae of Spodoptera littoralis ( Pavela, 2014) .

EOs are used in the composition of commercial products, such as some herbicides available in the North American market, such as Matratec (50% clove oil), WeedZap (45% clove oil + 45% cinnamon oil), and GreenMatch EX (50% lemongrass oil) ( Verdeguer et al., 2020b). They can also be combined to develop new products, as demonstrated by Golestani et al. (2015), who formulated two phytomedicines from different concentrations of four EOs ( Eucalyptus globulus , Dianthus caryophyllus L., Mentha piperita L., and Thymus vulgaris L.) against Escherichia coli O157:H7. These formulations were tested, showing superior antibacterial effects compared to a commercially available phytomedicine with Thymus vulgaris essential oil. Another possibility is the combination of EOs with existing products to enhance results, as mentioned by Luís et al. (2016) when observing a synergistic effect between commercial antibiotics and Eucalyptus globulus EO against Acinetobacter baumannii Bouvet and Grimont , a multi-resistant opportunistic pathogen typically associated with hospital infections. Knezevic et al. (2016) also reported in vitro synergistic effects of antibiotics ciprofloxacin, gentamicin, and polymyxin B with essential oils of Eucalyptus camaldulensis against multi-resistant A. baumannii .

The application method of EOs and their active compounds can also lead to distinct results, as Filomeno et al. (2020) mentioned. When they applied eucalyptol alone against Rhyzopertha dominica Fabricius adults, they obtained a better response as a fumigant (97.5% mortality) than when applied topically (32.5% mortality).

There are numerous applications for EOs, such as potential plant biostimulants ( Steffen et al., 2010; Praça, 2019). However, these effects are directly related to the constituents present in the oils. In other words, the results will also vary if there is variation in the necessary active compound within the same species. Knezevic et al. (2016) tested the antibacterial activity of two oils from E. camaldulensis produced in different regions of Montenegro against Acinetobacter baumannii and observed that one of the oils showed slightly higher activity than the other.

This knowledge about the activity of constituents and their different modes of action also allows an EO to be used for numerous purposes. Tab. 3 shows the activities of the components of eucalyptus EOs. It is interesting to observe that some components have several activities, while others have very little. This may be partly related to the number of studies focused on a component. For example, eucalyptol has several activities described in several reports, while only one is described for spathulenol. On the other hand, α-terpineol has several activities but is described in much fewer reports than eucalyptol. The number of studies on a component may also be related to the activity’s potency and the component’s abundance in the eucalyptus oil.

Various oils can be used for the same purpose as long as the necessary active compounds are present in the ideal proportion to perform these functions. For example, Lucia et al. (2012) studied the validation of models to estimate the fumigant and larvicidal activity of eucalyptus EOs against Aedes aegypti Linnaeus. They concluded that the larvicidal effect can be estimated based on the relative concentration of p-cymene and eucalyptol, while insecticidal activity typically occurs due to a large amount of eucalyptol. Additionally, the authors noted that an oil with a high insecticidal effect usually promotes lower larvicidal activity.

Results obtained over a long period showed that the use of eucalyptol allowed for a 36% reduction in the use of steroids in severe asthmatic patients. Other studies also highlight the efficacy of eucalyptol in improving patients with chronic respiratory conditions, demonstrating its anti-inflammatory activity ( Asif et al., 2020), in addition to mucolytic and bronchodilator properties ( Juergens et al., 2020), which explains the presence of eucalyptol in Vick VapoRub™, a widely used commercial product as a nasal decongestant ( Asif et al., 2020). Other commercial medications based on eucalyptol and other constituents of eucalyptus essential oil are also available on the market and have garnered attention for their respiratory system benefits. Examples include Myrtol® (a 300 mg capsule containing at least 75 mg of eucalyptol, 75 mg of limonene, and 20 mg of α-pinene), which is sold commercially as GeloMyrtol® and GeloMyrtol forte® ( Chandorkar et al., 2021).

The use of eucalyptus oil, both in its complete form and isolated constituents, has shown potential in antiviral therapies ( Schnitzler, 2019; Reichling, 2021), with positive impacts on the treatment of colds, asthma, and bronchiolitis through vapour inhalation ( Kim, 2021; Panikar et al., 2021).

Recent research has also been conducted using eucalyptus essential oils and constituents such as eucalyptol and jensenone in studies related to the treatment of COVID-19, with exciting and promising preliminary results ( Asif et al., 2020; Sharma & Kaur, 2020; Panyod et al., 2020; Abbass, 2020; Panikar et al., 2021). A significant interaction was observed between bioactive constituents found in eucalyptus essential oil and the Mpro protease enzyme of SARS-CoV-2. This enzyme is crucial for viral replication and transcription, and the results suggest that eucalyptus essential oil or certain monoterpenes like eucalyptol may have an inhibitory effect on the coronavirus ( Silva et al., 2020; Fitriani et al., unpub. data; Panikar et al., 2021).

Mieres-Castro et al. (2021) suggest that the virucidal effect of essential oil and its constituents is related to modifications in the viral envelope and associated structures, such as glycoproteins, which are essential for viral adsorption and entry into host cells. Furthermore, they emphasize that some studies support this mechanism by demonstrating the inhibition of critical viral enzymes.

Although many benefits have been reported from the mixture of oils and their constituents, antagonistic effects can also be observed and should be equally documented.According to Gibbs (2019), EOs containing pinene and linalool can cause respiratory complications, such as rhinitis and seasonal asthma, in allergic individuals. Verdeguer et al. (2020b) added that allergic individuals or those sensitive to a constituent may experience reactions such as contact dermatitis after contact with the EOs. The use of essential oils and their constituents for specific situations still provides preliminary information and should be evaluated on a case-by-case basis through detailed research to establish their efficacy, active ingredients, and safe doses for each purpose, particularly concerning human health.

The Brazilian essential oil market

There are several ISO standards related to the technical specifications of essential oils for each botanical species, analysis methods, and labelling for commercialization. These technical specifications aim to standardize products within tolerance ranges ( Bizzo & Rezende, 2022). However, when searching for information on the essential oils market, it is expected to find other aromatic extracts obtained by solvents or any other product that does not fit into the category, making analysis and comparison of information challenging ( Bizzo & Rezende, 2022).

In Brazil, the classification of oils is done through a set of numerical codes originating from three nomenclatures: global product nomenclatures (Harmonized System – HS), Mercosur (Common Nomenclature of Mercosur – NCM), which complements the first, and Brazil (National Classification of Economic Activities – CNAE), which complements the previous ones and classifies oils into three categories (Orange Essential Oils, Essential Oils of other citruses except orange, and other Essential Oils), making it difficult to collect specific information about eucalyptus EO production ( Bizzo & Rezende, 2022).

According to 2021 International Trade Centre Map (ITC) data, Brazil was at the top of the ranking when it comes to the export of essential oils (quantity) in the international market, followed by India, the United States, China, and the United Kingdom. The main destinations for Brazilian oils are the United States, the Netherlands, Germany, China, and India. But in general, the countries that lead world imports in volume are the United States, Burkina Faso, Germany, the United Kingdom, and France. Regarding export values, China rises to the first position, and Brazil falls to the fifth, which can be explained by the variation in the prices of oils from the botanical species each country trades (ITC Trade Map, 2023).

The ITC Trade Map (2023) data includes, in addition to essential oils, all aromatic materials classified in position 3301 of the HS, which considers “essential oils (terpeneless or not), including so-called ‘concretes’ or ‘absolutes’; resinoids; oleoresins of extraction; concentrated solutions of essential oils in fats, fixed oils, waxes or similar materials, obtained by treating flowers with fatty substances or by maceration; terpene residues resulting from the terpeneless of essential oils; aromatic distilled waters and aqueous solutions of essential oils.” Thus, it is noted that the detailed study of the international market is complex because, in addition to the available information, including products not considered essential oils, i.e., not falling under ISO 9235, many documents from specific agencies are not freely available.

Despite this complexity regarding the classification and obtaining of accurate and unified information from the global essential oils market, there was growth in this market after the pandemic ( Pascuta & Vodnar, 2022), driven by increased consumer awareness of its benefits, leading manufacturers from various sectors to replace synthetic ingredients with natural ones, following the demand. It is a market with a forecasted growth of 8.6% (2023-2027). However, it is still well-segmented, represented mainly by companies such as KATO Flavors & Fragrances (KFF), Herbal Family, Robertet, Food Base Kft, Biolandes, A. Fakhry & Co., Lebermuth Inc., Givaudan SA, Sydney Essentials, Phoenix Aromas & Essential Oils LLC, Doterra Holdings LLC ( Mordor Intelligence, 2023).

In Brazil, among the most exported essential oils, orange essential oil stands out due to the orange juice industry’s strong production and export market, followed by citrus essential oils (except orange) and eucalyptus essential oil. Specifications about imported essential oils are more restricted due to the significant number of species within the “other essential oils” classification, but the most relevant essential oil is Japanese mint oil ( Mentha arvensis ), with others like eucalyptus, lemon, orange, and lavender also being significant. Much of this information can be obtained from the portal for free access to Brazil’s foreign trade statistics – Comex Stat - https://comexstat.mdic. gov.br/pt/home.

By filtering only the essential oils data (HS code 3301.11.00 to 3301.29.90) in the “general export and import” category, it is possible to track transactions from 1997 to the present. Analyzing Fig. 2 A-B, the quantities of essential oils exported in this period averaged 28 thousand tons, with the maximum reached in 2020 (36 thousand tons) and the minimum in 2000 (18 thousand tons). The received values increased until 2018, with declines in 2019, 2020, and 2021, reaching a peak in 2022 (USD 323 million). The average of imported essential oils in the same period was two thousand tons, with the smallest quantities and the highest values recorded in the last decade. The price of essential oils varies significantly according to the botanical species, quantitative and qualitative composition, availability in each country, and market dynamics.

Analyzing specifically eucalyptus EO (HS code 3301.29.19) ( Fig. 3 A-B), it is noted that after a decline in exports in 2012 and 2013, these numbers increased in the following period until reaching around 560 tons exported and eight million dollars in 2020, which was maintained with slight variation until 2022. As for importation, in the last decade, it has remained around 200 tons.

For EOs and their constituents to be used and commercialized in natura or incorporated into any formulation, they must comply with the current legislation of each country. If these products are exported, the regulations of the destination country must also be checked.

In Brazil, there is still no well-consolidated regulation regarding the use of EOs, and they must follow specific norms according to their established use, such as food additives, phytotherapies, medicines, and cosmetics; these norms should always be consulted as they may be updated ( Bizzo & Rezende, 2022).

In general terms, the market for EOs is economically relevant, with the potential for production expansion in both quantity and explored species. This requires monitoring market advances and demands, structuring the production chain, and always complying with legal requirements.

Future Perspectives and Final Considerations

The data from the “Vegetal Extraction and Forestry Production – PEVS 2021” of IBGE show that the eucalyptus area for commercial purposes in Brazil is 7.3 million hectares, with 45.4% of these areas located in the southeastern region ( IBGE, 2021). The germplasms currently being used, according to the Brazilian Agricultural Research Corporation (EMBRAPA), are: E. benthamii , E. dunni , E. grandis , E. saligna , E. urophylla , Corymbia citriodora , hybrids of E. grandis x E. urophylla , and other interspecific hybrids; these materials are chosen based on the characteristics of their wood, economic importance, adaptability, and resistance to pests and diseases ( Embrapa, 2022).

Eucalyptus globulus is also very interesting for the EOs market, mainly due to its eucalyptol content, but also for being a species adapted to colder regions and cultivated only in southern Brazil. However, analyzing the collected data in the literature, it is noticed that other eucalyptus species besides E. globulus have presented EOs with eucalyptol percentages exceeding 60%, such as E. camaldulensis in Egypt ( Salem et al., 2016), E. dunnii in Argentina ( Santadino et al., 2017), E. exserta in Tunisia ( Elaissi et al., 2011), E. saligna in China ( Lu et al., 2014), and E. urophylla in Brazil ( Filomeno et al., 2016). In two E. saligna EO from leaves collected in Brazil ( Filomeno et al., 2016) and Argentina ( Toloza et al., 2006), percentages of 92% and 93% eucalyptol were recorded, respectively. In other words, in addition to scientifically unexplored species, there is potential to expand the EOs market by adding more value to species already cultivated for timber purposes.

Considering all the variables that interfere with EO chemotypes, more advanced chemical, biological, and data analysis techniques must be applied to study and map the biotic and abiotic conditions that define specific oil compositions and the mechanisms and modes of action involved. Due to the already discussed complexity of these products, many researchers evaluate the effect and mode of action of isolated actives (usually the most representative in EOs); these studies should be encouraged and continued, but evaluations of combined actives are also necessary to test possible additive, synergistic, or antagonistic effects that may still be unknown.

It is essential to emphasize that in addition to the comprehensive number of factors to be controlled, there are also numerous eucalypt species and possibilities for the application of EOs and their actives. The lack of study of some species because they are already considered for a particular purpose may prevent the discovery of effective products for other purposes. All these points generate an infinity of possibilities for studies, which should always document all plant characteristics, location, collection, extraction, and oil analysis whenever possible.

Although many studies present benefits and the responsible and safe use of EOs, possible negative or undesired impacts can also be obtained; this type of response is found less frequently in the literature but should be equally documented when obtained.

With more consolidated data related to raw materials and efficacy, another challenge is to make viable the use of these products through formulations that provide EO stability and are suitable for each application and objective, since one of their main characteristics is high volatility.

Economic aspects should also be addressed to stimulate the entire previously mentioned process. The production and marketing of EOs have the potential for expansion and must be organized to ensure the quality and reliability of the products, as it is a market that supplies other countries with specific requirements and diverse uses. Even for internal use, oils need to meet certain standards to be used, and considering this economic context, in addition to specific constituents, another factor to be considered is the oil yield of the selected eucalyptus species.

A quick way to assess interest in EOs is by surveying published works on the topic. Searching for the terms “essential oil” and “ Eucalyptus ” as topics in the Web of Science yielded 1945 works (publications between 1900 and 2023). When limiting this search to the last ten years, 1265 publications are found, showing that it is a topic that has been more studied in recent years.

Solutions to problems faced today may be present in elements available in nature, such as EOs, which can be an alternative source for the development of natural medicines and more sustainable bio-inputs. Companies are increasingly interested in these products that can act through different mechanisms against microorganisms already resistant to traditional agents or generate new solutions. Thus, the more information and solutions obtained, the more viable this market will be, including financially.

Figures

Figure 2. Quantities and values of exported essential oils (A) and imported essential oils (B) in Brazil. FOB: “Free On Board,” total price of the goods at the point of shipment, excluding transportation and insurance costs after that point. Source: Comex Stat

Figure 3. Quantities and values of eucalyptus essential oils (EOs) exported (A) and imported (B) in Brazil. FOB: “Free On Board,” total price of the goods at the point of shipment, excluding transportation and insurance costs after that point. Source: Comex Stat