Exploring the chemical composition and anti-cancer potential of Matricaria recutita L. essential oil

1 Introduction

Matricaria recutita L. (syn. Matricaria chamomilla L., Chamomilla recutita L. Rauschert) commonly known as true chamomile or German chamomile, is indigenous to Central and Southern European regions but has spread to other continents like America, Africa, and Australia. This aromatic plant yields an essential oil renowned for its distinctive properties [1], [2], [3]. German chamomile is a medicinal herb renowned for its therapeutic benefits, particularly in the form of essential oil. Extracted from the flowers of this plant, chamomile essential oil possesses a diverse array of pharmacological properties, protective activities, and therapeutic uses that have been recognized and utilized across various medical and wellness practices.

The essential oil (MEO), a dense blue liquid with a potent aroma and a bitter-aromatic taste, undergoes a fascinating transformation in colder temperatures, solidifying into a mass reminiscent of a basement. The blue hue of the oil owes itself to chamazulene, a compound derived from the dehydrogenation of proazulenes present in the raw material. Chamazulene typically constitutes 1 %–18 % of the oil, occasionally reaching up to 24 % [1], 2], [4], [5], [6], [7], [8], [9], [10].

Scientific research has validated the biological efficacy of chamomile essential oil, showcasing its antimicrobial, antioxidant, and anti-inflammatory characteristics [4], 5], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18]. As a result, it finds widespread application in medicine, cosmetics, and the food industry [1], [2], [3], [9], 14].

Medicinal plants have long been utilized for treating various types of cancer complications, and their use has gradually increased due to the side effects associated with chemical medications [19], 20]. According to the World Health Organization (WHO), nearly 65 % of the global population relies on traditional medicine for primary healthcare [21], 22].

The aim of the present study is to determine chemical composition and anticancer activity of Matricaria recutita L. using different cancer cell lines.

2 Materials and methods

3 Results

Table 1 presents the chemical composition of the essential oil extracted from flowers, revealing a total of 47 constituents that collectively account for 99.86 % of the oil’s content. Among these constituents, several prominent compounds stand out, each comprising over 3 % of the oil’s composition. The primary constituents include (Z)-β-farnesene, constituting 33.90 % of the oil, followed by α-bisabolol oxide B at 11.60 %, (E,E)-α-farnesene at 11.00 %, α-bisabolol oxide A at 6.79 %, germacrene D at 5.96 %, chamazulene at 5.04 %, α-bisabolone oxide A at 4.18 %, and cis-Spiroether at 3.16 %. Additionally, Table 1 outlines the distribution of major aroma substance groups within the oils. Sesquiterpene hydrocarbons emerge as the dominant group, constituting 64.05 % of the chamomile oil. Following closely are oxygenated sesquiterpenes at 28.79 %, aliphatic hydrocarbons at 3.17 %, monoterpene hydrocarbons at 3.08 %, oxygenated aliphatics at 0.40 %, phenyl propanoids at 0.22 %, oxygenated monoterpenes at 0.21 %, and furans at 0.08 %.

MTT assay was performed as three separate experiments to examine the cytotoxicity and the growth inhibitory potential of chamomile essential oil. The IC₅₀ values of tested concentrations of chamomile essential oil are summarized in Table 2. It is clearly shown that essential oil showed nearly same cytotoxicity to all cancer cell lines.

Cytotoxic activity of chamomile essential oil in L929 cell lines is illustrated in Figure 1. All tested concentrations show reduced cell survival when compared with solvent control. This decrease was generally shown in 72 h exposure of 3.9, 7.81 and 15.62 μg/mL concentrations and all exposure times of 62.50 μg/mL and higher concentrations (Figure 1).

Figure 1:

Cytotoxic effects of German chamomile essential oil in L929 cell lines.

Figure 2 shows anti-proliferative activity of chamomile essential oil against human lung adenocarcinoma epithelial (A549) cell lines. All concentrations decreased the proliferation when compared with solvent control but the decrease was only found statistically significant levels at 72 h exposure of 31.25 μg/mL and all tested concentrations and exposure times of highest ones. The highest three concentrations showed nearly 100 % reduction in cell survival.

Figure 2:

Cytotoxic effects of German chamomile essential oil in A549 cell lines.

Chamomile essential oil decreased cell survival of human breast adenocarcinoma cells (MDA-MB-231) at all concentrations tested. The reduction was found statistically significant levels at especially over 7.81 μg/mL concentrations. The highest decrease was observed at 250, 500 and 1,000 μg/mL concentrations (Figure 3).

Figure 3:

Cytotoxic effects of German chamomile essential oil in MDA-MB-231 cell lines.

Concentrations of chamomile essential oil significantly reduced cell survival of human hepatocellular carcinoma cells (HepG2) at 72 h exposure of 15.62 and 31.25 μg/mL and all exposure time of 62.5 μg/mL and over concentrations (Figure 4).

Figure 4:

Cytotoxic effects of German chamomile essential oil in HepG2 cell lines.

4 Discussion

Based on its chemical composition, the studied chamomile essential oil can be classified as the β-farnesene chemotype, which distinguishes it from data in the literature. In our opinion, this difference may be attributed to soil and climatic conditions, as well as the various chemotypes of chamomile that grow in different regions of Europe [1].

Chamomile essential oil is rich in bioactive compounds that contribute to its pharmacological effects. One of its notable properties is its anti-inflammatory activity, attributed to constituents such as bisabolol oxide A and B. These compounds inhibit inflammatory pathways and reduce swelling, making chamomile oil effective in treating inflammatory conditions such as arthritis, dermatitis, and gastrointestinal inflammation. In this study, we determined chemical composition of chamomile essential oil and tried to figure out anti-carcinogenic profile using human lung adenocarcinoma epithelial cells (A549), human hepatocellular carcinoma cells (HepG2), mouse fibroblast cells (L929), and human breast adenocarcinoma cells (MDA-MB-231). Our results clearly show that CEO has strong anti-proliferative capacity to all used cell lines especially at higher concentrations and treatment period.

The potential beneficial effects of chamomile essential oil were also noted in several studies. The essential oil demonstrated a dose-dependent reduction in cell viability, with an IC₅₀ of approximately 300 μg/mL. Furthermore, it significantly inhibited the levels of important angiogenesis markers in both HepG2 cells and ex vivo, as reported by [24]. Sak et al. [25] investigated the potential anticancer effects of extracts from German chamomile on human melanoma and epidermoid carcinoma cells. Methanolic extracts from chamomile flowers were evaluated using the sulforhodamine B assay to measure cytotoxic activity. The IC₅₀ value of chamomile flower extract against melanoma cells (40.7 μg/mL) was approximately twofold higher than that against epidermoid carcinoma cells (71.4 μg/mL).

Shaaban et al. [26] have shown that the (Z)-β-farnesene component in M. chamomilla extracts has significant anticancer potential, inhibiting Caco-2 colon cancer cell migration. The (Z)-β-farnesene component in essential oil obtained from the leaves of Cedrelopsis grevei, an aromatic and medicinal plant from Madagascar, has shown a significant correlation with anticancer activity (on human breast cancer cells MCF-7) [27]. The anticancer effects and mechanisms of α-bisabolol in numerous types of cancer including, pancreatic, endometrial, breast and liver have been demonstrated in many experimental studies [28], 29]. Additionally, upregulating the expression of bcl-2 and suppression of bax, P53, APAF-1, caspase-3 and caspase-9 activity indicates the anti-apoptotic effects of α-bisabolol [28]. The molecular mechanisms underlying anti-apoptotic effects of α-bisabolol were proven in different study models. Based on those research studies, upregulating the expression anti-apoptotic bcl-2 expressions and suppression of the bax, P53, APAF-1, caspase-3 and caspase-9 activity indicates the anti-apoptotic effect α-bisabolol. It is noteworthy that, two probable molecular mechanisms for anticancer effects of α-bisabolol appear to be through NF-κB and PI3K/PDK1/Akt signaling pathways [29].

Santos et al. [30] evaluated the effects of combining the antineoplastic drug 5-fluorouracil (5-FU) with Matricaria recutita flower extract (MRFE) in treating mice transplanted with sarcoma 180. They assessed tumor inhibition, variations in body and visceral mass, as well as biochemical, hematological, and histopathological parameters. The study found that both isolated 5-FU and combinations of 5-FU with MRFE at doses of 100 mg/kg/day and 200 mg/kg/day reduced tumor growth. Notably, the 5-FU + MRFE at 200 mg/kg/day demonstrated a more significant reduction in tumor size compared to 5-FU alone. These findings suggest that the combination of 5-FU with MRFE at 200 mg/kg/day may enhance antitumor activity while reducing chemotherapy-induced loss of body mass and minimizing toxicity.

5 Conclusions

In this study, we explored the chemical composition and anti-cancer potential of Matricaria recutita L. essential oil from Southern Bulgaria. The detailed analysis revealed that the essential oil primarily belongs to the β-farnesene chemotype, a distinction influenced by the specific soil and climatic conditions of the region. This chemotype variation emphasizes the importance of geographic and environmental factors in defining the chemical profiles of essential oils. Our investigation into the anti-cancer properties demonstrated promising results, particularly against select cancer cell lines. The bioactive compounds identified within the oil, including chamazulene, α-bisabolol, and apigenin, have shown significant cytotoxic effects, supporting the potential of chamomile essential oil as a complementary approach in cancer treatment. These findings contribute to the growing body of evidence suggesting that natural products, particularly those derived from Matricaria recutita L., could play a valuable role in cancer treatment.