Therapeutic Potential of Artemisia campestris Essential Oil: A Comprehensive Review of Its Bioactive Properties and Pharmacological Applications

Morphological Characteristics of Artemisia campestris

Artemisia campestris L., commonly known as field wormwood, is a herbaceous or semi-woody perennial plant belonging to the Asteraceae family. It typically grows between 20-100 cm in height and displays a highly branched, erect stem, which can be glabrous or slightly pubescent. The leaves are alternately arranged, finely divided, and covered with silvery hair, giving the plant a greyish-green appearance. Basal leaves are longer and more deeply lobed than those on the stem. The inflorescences are terminal panicles composed of small, yellowish to reddish capitula (flower heads), each surrounded by involucral bracts. Flowering generally occurs from July to October, depending on the geographic region.^[27]

Taxonomic Classification

Artemisia campestris L. belongs to the large and diverse genus Artemisia, which is part of the Asteraceae family, one of the largest families of flowering plants. The genus includes more than 500 species, many of which are renowned for their medicinal, aromatic, and ecological importance.^[28] Within this genus, A. campestris is a polymorphic species, displaying substantial variation across its geographic range. This diversity is reflected in the existence of multiple subspecies and varieties, which differ in morphological features, habitat preferences, and chemical composition. These differences are often driven by local environmental pressures, leading to adaptations that enhance survival in arid or semi-arid ecosystems. The formal taxonomic classification of A. campestris has been presented in the table 1.

This taxonomic placement aligns A. campestris with a group of plants that have adapted to thrive in diverse climates, from temperate to arid zones. Understanding the taxonomy of A. campestris is not only important for botanical classification but also for guiding research into its phytochemistry and pharmacological potential, as taxonomic differences often correlate with variations in essential oil composition and bioactivity.

Natural Habitats and Global Distribution

A. campestris is widely distributed across the Northern Hemisphere, especially in Europe, North Africa, and temperate regions of Asia. It is also found in parts of North America. This species typically grows in dry, sandy, and rocky soils, including coastal dunes, grasslands, steppes, and degraded lands. It thrives in open, sun-exposed areas and is tolerant of arid to semi-arid climates [Table 2].^[29]

Chemotypes and Ecological Factors Influencing Composition

The phytochemical composition of A. campestris is highly variable and influenced by ecological, climatic, and geographical factors. Several chemotypes have been identified across different regions, distinguished by variations in major constituents of the EO, such as camphor, 1,8-cineole, myrcene, borneol, and spathulenol. For example:

• In Algeria, A. campestris EO is often rich in camphor and 1,8-cineole.^[30]

• In Tunisia, the plant shows higher levels of α-thujone and borneol.^[31]

• In Central Asia, chemotypes are dominated by sesquiterpenes such as caryophyllene oxide.^[32]

Common Extraction Techniques

The EOs of Artemisia campestris are primarily extracted from the aerial parts of the plant using several methods, with hydrodistillation being the most widely employed technique. This method involves immersing plant material in water and boiling it to release volatile compounds, which are then condensed and collected. It is the traditional method recommended by the European Pharmacopoeia and widely used due to its simplicity and effectiveness in preserving thermolabile components [Table 3].^[33]

Other techniques include:

• Steam distillation: Similar to hydrodistillation, but uses steam passed through plant material. It is more energy-efficient and preferred for industrial-scale production.

• Solvent extraction: Uses organic solvents (e.g., hexane, ethanol) to extract EOs, especially when targeting less volatile or heat-sensitive compounds. This method often yields concrete or absolute forms.^[34]

• Supercritical fluid extraction (SFE): Utilizes supercritical CO₂ for a high-purity extract with minimal degradation. Though more expensive, SFE is gaining popularity for sensitive phytochemical profiles.^[35]

Factors Effecting Yield and Composition

The yield and chemical composition of A. campestris EO are influenced by a combination of intrinsic and extrinsic factors:

• Plant part used: Leaves generally yield more oil and a richer profile than stems or flowers.

• Developmental stage: Harvesting during the flowering stage often results in higher oil content and a broader spectrum of bioactive compounds.^[29]

• Geographical origin and climate: Altitude, temperature, and precipitation directly impact secondary metabolite biosynthesis. For instance, plants in arid zones show higher concentrations of oxygenated monoterpenes like camphor and 1,8-cineole.^[30]

• Extraction parameters: Time, temperature, and distillation method significantly affect both yield and quality.

Major Chemical Constituents

The EO of Artemisia campestris, a species in the Asteraceae family, is known for its complex chemical composition. Major constituents identified include monoterpenes, sesquiterpenes, and oxygenated compounds [Table 4]. The most prominent chemical components of A. campestris EO include:

• Camphor: A bicyclic ketone with a characteristic odor, camphor is one of the most abundant constituents in A. campestris oil. It has antimicrobial, anti-inflammatory, and analgesic properties.^[36]

• 1,8-Cineole: Also known as eucalyptol, it is a monoterpene oxide with a cooling, minty aroma. It has antiseptic and bronchodilatory properties.^[37]

• Borneol: A bicyclic alcohol that contributes to the oil’s cooling, minty aroma. It has antifungal and anti-inflammatory properties.^[36]

• Thujone: A ketone found in many Artemisia species, thujone has potential neurotoxic effects but also displays antimicrobial and insecticidal properties.^[37]

• α-Pinene: A monoterpene that is found in many EOs, α-pinene has a fresh pine-like aroma and exhibits anti-inflammatory and antimicrobial activities.^[36]

• β-Pinene: Another monoterpene that contributes to the fragrance profile of the oil and has been shown to possess anti-inflammatory properties.^[37]

• Linalool: A terpenoid alcohol with a floral lavender-like scent, linalool has calming, anti-anxiety, and sedative effects.^[36]

Variation in Composition Based on Geography, Climate, and Harvest Time

The chemical composition of A. campestris EO can vary significantly depending on several environmental and seasonal factors:

• Geographical Variation: Studies have shown that A. campestris from different regions exhibit variations in the levels of major constituents. For example, plants grown in Mediterranean climates tend to have higher concentrations of camphor and 1,8-cineole, while those from temperate regions may show increased levels of borneol and thujone.^[37]

• Climate Conditions: Temperature, humidity, and rainfall during the growing season can influence the biosynthesis of EO constituents. Dry climates may lead to higher concentrations of monoterpenes, whereas more humid conditions can result in higher levels of oxygenated compounds like camphor and borneol.

• Harvest Time: The timing of the harvest can also affect the oil’s composition. EOs extracted from plants harvested during peak flowering or early fruiting periods may contain higher levels of certain volatile compounds. For instance, the concentration of 1,8-cineole can vary significantly depending on whether the plant is harvested in the early morning or late afternoon.^[36]

Chemometric Analysis and Cluster Grouping

Chemometric methods, such as principal component analysis (PCA), hierarchical clustering, and multivariate analysis, have been widely used to study the variation in the chemical composition of EOs. These techniques help identify patterns in the data that may be associated with geographic location, harvest time, and climatic factors.

• Cluster Analysis: Through chemometric analysis, researchers can group EOs into clusters based on their chemical similarity. This allows for the identification of patterns that correlate with specific environmental conditions.^[36]

• Principal Component Analysis (PCA): PCA can be used to reduce the dimensionality of large datasets, helping to visualize the differences and similarities in the chemical composition of EOs from different regions and harvest times.^[36]

Such analyses have revealed that A. campestris EOs from plants grown in similar climates often exhibit closely related chemical profiles, while oils from geographically distant populations show distinct compositional differences.^[37]

Anticancer and Cytotoxic Effects

Artemisia campestris EO has shown promising anticancer and cytotoxic properties in various in vitro and in vivo studies. The oil has been reported to inhibit the growth of several cancer cell lines and demonstrates selective cytotoxicity.^[39]

Other Biological Activities

Apart from its anticancer and cytotoxic properties, Artemisia campestris essential oil has demonstrated several other beneficial biological activities:

Use in food preservation and flavoring

Artemisia campestris EO is recognized for its antimicrobial and antioxidant properties, making it a valuable ingredient in food preservation and flavoring. The oil’s ability to inhibit microbial growth and prevent spoilage has led to its exploration as a natural preservative in food products. It is especially useful in extending the shelf life of perishable goods such as meat, dairy, and baked products.

• Preservative Properties: The EOs antimicrobial properties, particularly against bacteria and fungi, make it suitable for use in food products to prevent contamination and extend freshness.^[36] The oil’s active compounds, such as camphor and 1,8-cineole, are effective against a wide range of spoilage microorganisms.

• Flavoring Agent: The distinctive aroma of A. campestris EO, which is a blend of herbal, camphorous, and minty notes, has been utilized as a natural flavoring agent in food products. It is particularly popular in beverages, confectionery, and sauces, where its unique flavor profile can enhance the taste.

Applications in Cosmetics and Personal Care Products

The EO of Artemisia campestris has found multiple uses in the cosmetics and personal care industries due to its beneficial properties for skin and hair. Its antimicrobial, anti-inflammatory, and antioxidant effects make it an excellent addition to formulations aimed at promoting skin health and addressing common cosmetic concerns.

• Skin Care: The oil’s antimicrobial properties help in treating acne, fungal infections, and skin irritations. Its anti-inflammatory effects make it a suitable ingredient for soothing and calming the skin.^[37] Additionally, its antioxidant activity protects the skin from oxidative stress, which is a major contributor to premature aging.

• Hair Care: A. campestris EO has been used in hair care products to promote scalp health, reduce dandruff, and improve hair growth. Its antifungal properties help combat scalp conditions caused by fungal infections, while its antimicrobial effects prevent bacterial growth.^[36]

• Perfume and Fragrance: Due to its unique aroma, A. campestris EO is also utilized in the perfume industry to create distinctive fragrances. The oil’s refreshing scent, which combines herbal and minty notes, is incorporated into both men’s and women’s fragrances.

Potential as a Bio-Pesticide or Eco-Friendly Agent

With the increasing demand for environmentally friendly agricultural practices, Artemisia campestris EO has emerged as a potential bio-pesticide. Its insecticidal, larvicidal, and repellent properties make it an effective and eco-friendly alternative to chemical pesticides [Table 7].

• Insecticidal and Larvicidal Effects: As mentioned previously, A. campestris EO has been shown to effectively kill insect larvae and act as a repellent. These properties have been utilized in the development of bio-pesticide formulations to control pests in crops.

• Eco-friendly Pesticide: The oil’s low toxicity to humans and animals, along with its biodegradable nature, makes it an attractive alternative to synthetic chemical pesticides. Unlike conventional pesticides, A. campestris essential oil breaks down naturally in the environment, posing minimal risk of pollution and ecosystem disruption.^[37]

• Plant Protection: Additionally, its application as a plant protectant helps control fungal diseases in crops, reducing the need for chemical fungicides. This is especially beneficial in organic farming practices, where the use of synthetic chemicals is restricted.

Acute and chronic toxicity data

Acute toxicity studies assess the immediate harmful effects of a substance after a single dose or exposure. Research on Artemisia campestris EO suggests that, while the oil exhibits beneficial effects, it can be toxic at high concentrations. In animal studies, oral administration of the essential oil has resulted in mild to moderate toxicity symptoms, including gastrointestinal irritation, lethargy, and, in severe cases, death at extremely high doses.^[37] A study by Rashed et al.,^[36] in rats showed that a single high dose (greater than 500 mg/kg body weight) of A. campestris essential oil led to toxic signs like excessive salivation and respiratory distress. However, lower doses (below 200 mg/kg body weight) did not produce any significant adverse effects.

Chronic toxicity refers to the long-term effects of repeated exposure to a substance. Long-term exposure to A. campestris EO, particularly at doses exceeding the recommended therapeutic levels, has been associated with liver damage and kidney dysfunction in some animal models. However, the oil appears to be relatively safe when used in low concentrations and in short-term applications, such as in cosmetic formulations and food products.

Cytotoxicity and Genotoxicity Assessments

Cytotoxicity refers to the potential of a substance to damage or kill cells. Several in vitro studies have assessed the cytotoxic effects of A. campestris EO on human cell lines. While the EO exhibits anticancer activity, it has also shown cytotoxic effects on non-cancerous cells at higher concentrations. Studies using human fibroblast and liver cells (HepG2) indicated that A. campestris oil can induce cell death, but these effects were generally dose-dependent.^[40] At therapeutic doses, the oil demonstrated selective toxicity towards cancer cells, making it a promising anticancer agent.

Genotoxicity refers to the ability of a substance to cause genetic damage, leading to mutations or cancer. Few studies have directly assessed the genotoxicity of A. campestris essential oil. However, in some preliminary studies, the oil’s major constituents, such as camphor and 1,8-cineole, have been shown to possess genotoxic potential at high concentrations, particularly in bacterial mutagenesis assays.^[40] While the oil does not exhibit significant genotoxicity at typical exposure levels, caution should be exercised when using it in high doses or over prolonged periods.

Safe Dosage Ranges and Regulatory Considerations

Gaps in Current Research

While Artemisia campestris EO has demonstrated promising biological and pharmacological activities, there are significant gaps in our understanding of its full therapeutic potential and mechanisms of action. Some of the key research gaps include:

Standardization and Quality Control Issues

One of the major challenges in the use of Artemisia campestris EO is the lack of standardization and quality control in its production and application. EOs are highly susceptible to variations in composition based on factors such as geographic origin, climatic conditions, and harvesting methods. These variations can result in inconsistent therapeutic effects and efficacy.

Need for Clinical Validation and Formulation Development

While the antimicrobial, anticancer, and antioxidant properties of A. campestris EO have been supported by in vitro and animal studies,^[43] clinical trials are essential to validate its efficacy and safety in human populations. Some key areas requiring further research include.^[44]

Sustainable Harvesting and Cultivation Practices

As the demand for Artemisia campestris EO grows, ensuring the sustainability of its production is crucial to prevent overharvesting and protect biodiversity.^[45] Several factors need to be addressed to ensure that the cultivation and harvesting of A. campestris are environmentally sustainable [Table 9].