Skip to main content
NCBI home page
Molecules logoLink to Molecules
. 2021 Feb 19;26(4):1110. doi: 10.3390/molecules26041110

Chemical Composition and Cytotoxic Activity of the Fractionated Trunk Bark Essential Oil from Tetraclinis articulata (Vahl) Mast. Growing in Tunisia

Salma Jlizi 1, Aida Lahmar 2, Afifa Zardi-Bergaoui 1, Roberta Ascrizzi 3, Guido Flamini 3,4, Abdel Halim Harrath 5, Leila Chekir-Ghedira 2, Hichem Ben Jannet 1,*
Editor: Peter Karuso
PMCID: PMC7922514  PMID: 33669825

Abstract

The aim of the present research was to determine the chemical composition and the cytotoxic effects of Tetraclinis articulata trunk bark essential oil (HEE) obtained by steam distillation and five fractions obtained by normal phase silica chromatographic separation. Chemical analysis allowed the identification of 54 known compounds. Relatively high amounts of oxygenated sesquiterpenes (44.4–70.2%) were detected, mainly consisting of caryophyllene oxide (13.1–26.6%), carotol (9.2–21.2%),14-hydroxy-9-epi-(E)-caryophyllene (3.2–15.5%) and humulene epoxide II (2.6–7.2%). The cytotoxic activity against human mammary carcinoma cell lines (MDA-MB-231) and colorectal carcinoma cell lines (SW620) of the essential oil and its fractions were assessed. All the samples displayed moderate to weak activity compared to 5-fluorouracil. The colorectal carcinoma cell line was relatively more sensitive to the essential oil and its fractions compared to the breast cancer cell line, showing IC50 values from 25.7 to 96.5 μg/mL. In addition, the essential oil and its fraction E.2 revealed a cytotoxic activity against colorectal carcinoma cell line, with IC50 values lower than 30 μg/mL. This is the first report on the chemical composition and cytotoxic activity of the trunk bark essential oil of T. articulata.

Keywords: Tetraclinis articulata, trunk bark, essential oil, fractionation, chemical composition, cytotoxic activity

1. Introduction

Medicinal and aromatic plants (MAPs), in their entirety or their separated parts, are used as they are or can be further processed by extraction of essential oils and are considered an important resource in various fields, such as pharmaceutical, flavor and fragrance, perfumery, and cosmetic industries [1]. Essential oils from medicinal and aromatic plants are a very interesting source of secondary metabolites because of their many different biological properties, such as cytotoxic [2], anti-inflammatory [3], antioxidant [4], insecticidal [5], antifungal [6] and antimicrobial [7,8,9], many of which are of increasing interest in the field of human and animal health. In recent years, the development of antibiotic resistance represents the major issue in medical microbiology and the search for new weapons against antibiotic resistances has led to the search of new sources of potential antimicrobials. Among them, the plant kingdom offers a wide range of biodiversity with a great value for the pharmaceutical industry. In Tunisia and in other North African countries, MAPs in human and veterinary medicine are mainly used for respiratory and intestinal infections in children, and in the treatment of gastric pains, diabetes, hypertension, diarrhea and rheumatism [10,11,12,13]. The genus Tetraclinis is part of the Cupressaceae family and unspecific, consisting of only Tetraclinis articulata (Vahl) Masters (synonyms: Thuja articulata Vahl, Callitris quadrivalvis Vent), commonly known as “Barbary thuja”. This species is widespread across the North African region. In Tunisia, this coniferous tree is located in the northeastern region of the country [14]. Previous studies on this species indicated its use as an antibacterial and antifungal [13,15,16], cytotoxic [17], antioxidant and anti-inflammatory agent [18]. The essential oils isolated from some Tetraclinis articulata organs (nonwoody branches, wood branches, wood, cones, roots, leaves, fruits and seeds) so far have exhibited wide variability in their major compounds, the most commonly encountered ones being monoterpene hydrocarbons, such as α-pinene in leaves, fruits and cones (Algeria and Tunisia) [19,20,21] and camphene in wood branches and roots (Tunisia) [22], followed by oxygenated monoterpenes such as camphor and bornyl acetate in roots, leaves, nonwoody branches and wood branches (Malta, Algeria and Tunisia) [16,23,24].To date, no reports have been published on the chemical and cytotoxic activity of the trunk bark essential oil of T. articulata (HEE). Our aim was thus to isolate the essential oils of HEE from northeast Tunisia by steam distillation, and fractionate these by normal phase silica chromatography and assess the fractions for cytotoxic activity [25].

2. Results and Discussion

2.1. Chemical Composition of the Trunk Bark Essential Oil (HEE) and Its Fractions (E.1–E.5)

The steam distillation of the trunk bark of T. articulata yielded 0.05% (w/w) of a pale-yellow colored oil. The full chemical profiles were determined by Gas Chromatography coupled to Mass Spectrometry (GC/MS) and are presented in Table 1. Overall, 54 compounds were identified, representing from 90.8% up to 96.0% of the total compositions. Terpenes (in the form of both mono- and sesquiterpenes) were detected as the main chemical group of compounds, with relative concentrations ranging from 88.2% to 95.8%. Oxygenated sesquiterpenes were the most abundant chemical class of compounds in all samples. Among them, caryophyllene oxide (40) was detected as the major constituent in all samples, ranging from a minimum of 13.1% in HEE, up to 26.6% in E.2, carotol (45) and 14-hydroxy-9-epi-(E)-caryophyllene (52) followed, with relative percentages varying from a minimum of 9.2% in HEE to a maximum of 21.2% in E.4, and between 2.7% in E.1 and 15.5% in E.5. Oxygenated monoterpenes were the second most abundant chemical class in HEE and E.1; α-terpineol (0.3–10.4%; 12), borneol (0.3–4.1%; 9), and geranyl 2-methylbutyrate (0.2–4.9%; 41) were the most represented. In all other samples, sesquiterpene hydrocarbons followed as the second most abundant chemical group, among which α-muurolene (30, from 5.5% in HEE, up to 12.5% in E.5) and β-caryophyllene (24, not detected in E.5, up to 5.5% in HEE) showed the highest relative presence. Caryophyllene oxide, β-caryophyllene and carotol (Figure 1) have all been described as potent medicinal compounds with various activities, such as analgesic [26] and cytotoxic [27]. To the best of our knowledge, this is the first report on the itemized chemical characterization of the trunk bark essential oil of T. articulata. In spite of the many investigations into the chemical composition of essential oils from the different organs of the same species, the trunk bark essential oil of T. articulata presented a totally distinct chemical profile. In Tunisia, Tekaya-Karoui et al. [16,22] demonstrated that the main components in the nonwoody branches oil was Z-muurolene (29.0%) and 4,6-dimethyl-octane-3,5-dione (22.4%). In the cone oil, the most important compounds found were p-cymene-8-ol (10.4%) and β-phellandrene (8.1%). The major constituent in the oils of the roots and the woody branches was found to be camphene (70.2 and 43.2%, respectively). Nonan-1-ol was the main constituent present in the fraction of the essential oil from woody terminal branches (75.2%).In the fraction of the essential oil from roots, the major compound detected was bornyl acetate (16.6%).The results reported by Barrero et al. [12], from Morocco, have shown that the leaf essential oil was rich in bornyl acetate (16.5%), camphor (19.1%) and borneol (9.6%), and that the essential oil from the wood was rich in cedrol (28.2%) and 1,7-di-epi-cedrol (17.9%).

Table 1.

Constituents of T. articulata trunk bark essential oil (HEE) and its fractions (E.1–E.5) identified by GC/MS.

Compound LRI a Composition (%) m/z c
HEE E.1 E.2 E.3 E.4 E.5
1 2-Nonanol 1100 0.1 0.2 - b - - - 45, 69, 144
2 Fenchol 1113 0.2 0.4 - - - - 81, 80, 154
3 α-Campholenal 1126 0.2 0.3 - - - - 108, 93, 152
4 trans-Pinocarveol 1141 0.3 0.9 - - - - 92, 70, 152
5 cis-Verbenol 1142 0.1 0.2 - - - - 94, 109, 152
6 trans-Verbenol 1143 0.4 1.2 - - - - 91, 109, 152
7 Camphene hydrate 1150 0.1 0.4 - - - - 71, 43, 154
8 Isoborneol 1156 0.1 0.4 - - - - 95, 41, 154
9 Borneol 1168 2.4 4.1 0.3 - - 0.6 95, 110, 154
10 4-Terpineol 1179 0.2 0.6 - - - - 71, 111, 154
11 p-Cymen-8-ol 1185 1.2 1.4 0.7 0.4 0.4 0.8 43, 135, 150
12 α-Terpineol 1191 7.5 10.4 1.3 0.4 0.3 0.9 59, 93, 154
13 Myrtenol 1193 1.2 2.5 0.3 - - 0.2 79, 91, 152
14 Verbenone 1205 1.3 1.3 0.7 0.6 0.4 1.1 107, 135, 150
15 trans-Carveol 1220 0.9 1.2 0.4 - - 0.3 109, 84, 152
16 cis-Myrtanol 1251 0.4 0.7 - - - - 41, 69, 154
17 trans-Myrtanol 1258 0.7 0.9 0.4 - - - 42, 69, 154
18 Bornyl acetate 1286 0.5 1.1 - - - - 95, 43, 196
19 Carvacrol 1298 0.1 0.4 - - - - 135, 91, 150
20 Cyclosativene 1369 - - 0.3 - - 0.3 161, 105, 204
21 Longicyclene 1371 - - 0.3 - - 0.5 94, 105, 204
22 α-Copaene 1377 0.2 0.6 0.7 0.8 0.5 0.7 161, 119, 204
23 Longifolene 1404 1.2 1.4 1.7 1.8 1.1 1.2 161, 94, 204
24 β-Caryophyllene 1419 5.5 5.2 2.6 2.9 0.6 - 93, 133, 204
25 α-Humulene 1455 1.4 1.6 1.0 1.0 0.3 - 98, 80, 204
26 γ-Muurolene 1478 0.2 0.5 0.9 0.9 1.1 1.3 161, 105, 204
27 8,9-Dehydrothymol isobutyrate 1480 0.6 - - - - - 148, 133, 218
28 Thymylisobutyrate 1481 3.4 0.1 - 0.3 - - 135, 150, 220
29 Nerylisobutyrate 1489 1.8 0.1 - - - - 69, 93, 208
30 α-Muurolene 1499 5.5 6.7 9.1 11.6 11.2 12.5 105, 161, 204
31 Modhephen-8-β-ol 1508 6.6 0.2 - - - - 189, 119, 204
32 trans-γ-Cadinene 1514 - - - 0.3 0.3 0.4 161, 105, 204
33 cis-Calamenene 1523 - - 0.7 - 0.7 0.8 159, 160, 202
34 δ-Cadinene 1524 0.9 1.0 - 1.1 - - 161, 134, 204
35 α-Calacorene 1543 - - - 0.3 - - 157, 142, 200
36 Elemol 1550 0.8 1.4 1.3 0.8 0.6 0.5 59, 93, 222
37 Dodecanoicacid 1567 - - - - - 2.7 73, 60, 200
38 Palustrol 1569 - - 0.8 0.7 - 0.5 41, 55, 222
39 Neryl 2-methylbutyrate 1575 2.5 0.1 - - - - 69, 41, 238
40 Caryophyllene oxide 1581 13.1 25.2 26.6 20.5 20.2 21.9 43, 41, 220
41 Geranyl 2-methylbutyrate 1586 4.9 0.2 - - - - 69, 41, 238
42 1-Hexadecene 1592 1.8 - - - - - 43, 55, 224
43 cis-Arteannuicacid 1593 4.1 - 1.2 - - - 121, 119, 234
44 n-Hexadecane 1600 - - - - 0.6 - 57, 43, 226
45 Carotol 1602 9.2 12.0 20.3 20.7 21.2 15.1 161, 204, 222
46 Humulene epoxide II 1607 2.6 4.0 7.2 6.1 6.2 5.4 109, 67, 220
47 1-epi-Cubenol 1629 - - - 0.8 0.6 - 119, 41, 222
48 γ-Eudesmol 1631 - - - 0.7 0.8 - 189, 204, 222
49 Caryophylla-4(14),8(15)-dien-5-ol 1637 1.6 1.2 2.0 2.0 1.8 1.4 136, 91, 220
50 T-Cadinol 1641 1.5 1.1 2.1 1.9 2.2 1.3 161, 43, 222
51 T-Muurolol 1642 1.7 0.9 1.9 2.3 2.7 1.8 95, 121, 222
52 14-Hydroxy-9-epi-(E)-caryophyllene 1665 3.2 2.7 6.8 9.6 13.1 15.5 91, 93, 220
53 Cadalene 1673 1.3 1.2 2.5 3.4 3.9 3.2 183, 168, 198
54 1-Octadecene 1793 1.7 - - - - - 43, 41, 252
Oxygenated monoterpenes 31.0 28.9 4.1 1.7 1.1 3.9
Sesquiterpene hydrocarbons 16.2 18.2 19.8 24.1 19.7 20.9
Oxygenated sesquiterpenes 44.4 48.7 70.2 66.1 69.4 63.4
Nonterpene derivatives 3.6 0.2 0.0 0.0 0.6 2.7
Total identified 95.2 96.0 94.1 91.9 90.8 90.9
Open in a new tab

a Linear retention indices calculated on a DB5 capillary column; b not detected; c two main peaks and the molecular one.

Figure 1.

Figure 1

Open in a new tab

Chemical structures of some major compounds identified in Tetraclinis articulata trunk bark essential oil (HEE) and its fractions (E.1–E.5).

2.2. Cytotoxic Activity

To determine whether T. articulata trunk bark essential oil and its fractions could exert a cytotoxic action, we exposed MDA-MB-231 breast cancer cells and SW620 colon cancer cells to increasing amounts of tested agents (0 to 100 µg/mL) for 48 h, prior to a cell viability assay (Table 2, Figure 2). A dose-dependent cytotoxic activity was shown against both cell lines with the SW620 cells being more sensitive to all tested fractions. Several reports highlighted the expression of multidrug resistance proteins in MDA-MB-231 cell line [28,29]. The complete essential oil of T. articulata displayed the highest inhibitory activity against SW620 and MDA-MB-231 cells with IC50 values of 25.7 and 83.0 µg/mL, respectively. Interestingly, fraction E.2 was most active against SW620 cells and E.3 was most active against MDA cells. The essential oil of T. articulata trunk bark, and its fractions, showed low cytotoxicity towards both cell lines, compared to the positive control used. According to American National Cancer Institute, however, extracts with IC50 values below 30 μg/mL against experimental cancer cell lines may represent promising anticancer agents for further drug development [30].

Table 2.

IC50 (µg/mL) values for T. articulata trunk bark complete essential oil (HEE) and its fractions (E.1–E.5) towards MDA-MB-231 and SW620 cell lines.

IC50 5-FU HEE E.1 E.2 E.3 E.4 E.5
MDA-MB-231 2.2 83.0 96.5 90.7 85.9 91.8 100.0
SW620 0.3 25.7 37.8 26.2 43.1 57.2 96.5
Open in a new tab

Figure 2.

Figure 2

Open in a new tab

Inhibitory effects on MDA-MB-231 and SW620 cell proliferation with increasing concentrations (0–100 mg/mL) for 48 h of (A) T. articulata trunk bark complete essential oil (HEE); (B) Fraction E.1; (C) Fraction E.2; (D) Fraction E.3; (E) Fraction E.4; (F) Fraction E.5; (G) 5-fluorouracil. The percentage of cell viability was determined using crystal violet assay. Results are expressed as mean percentage of control growth ± SD of three independent experiments.

The cytotoxic activity of the essential oil of T. articulata trunk bark and its fractions may be attributed to specific components of the oils. In previous works [27,31,32,33], it has been shown that caryophyllene oxide (HEE: 13.1%, E.1: 25.2%, E.2: 26.6%, E.3: 20.5%, E.4: 20.2% and E.5: 21.9%; 40) and carotol (HEE: 9.2%, E.1: 12.0%, E.2: 20.3%, E.3: 20.5%, E.4: 21.2% and E.5: 15.1%; 45) (Table 1), which are predominant in the essential oil and its fractions, could be responsible for the cytotoxic activity. It has been reported that caryophyllene oxide inhibited cell growth, in a dose-dependent and cell-specific manner, against different types of cell lines, e.g., HepG2, AGS, HeLa, SNU-1 and SNU-16 cells, with IC50 values ranging from 3.9 to 27.4 µM [34]. Therefore, the cytotoxicity of the crude essential oil and its fractions could be due to these sesquiterpenes, as already reported for the cytotoxic activity of Myrica gale L. essential oil [35]. In addition, minor components could also contribute to cytotoxic activity of the oils, acting in synergy with the other quantitatively predominant compounds [36,37].

3. Material and Methods

3.1. Plant Material

The trunk bark of T. articulata was collected from the region of Mornag, Governorate of Ben Arous (northeast Tunisia), in January 2019. The plant material identification was accomplished by Professor F. Harzallah-skhiri (Higher Institute of Biotechnology of Monastir, University of Monastir, Tunisia). A voucher specimen (TA-19) was deposited at the Laboratory of Heterocyclic Chemistry, Natural Products and Reactivity (LR11ES39), Faculty of Sciences of Monastir, Tunisia, for further reference.

3.2. Isolation and Fractionation of the Essential Oil

Trunk bark of T. articulata (750 g) was cut into little pieces and subjected to steam distillation over 4 h using a Clevenger-type system. The essential oil (HEE) obtained was decanted, dried over anhydrous Na2SO4 and stored in sealed glass vials at 4–5 °C until chemical and biological analysis. The essential oil (300 mg) was fractionated on a column of silica gel using a hexane/ethyl acetate step gradient (95:5; 90:10; 80:20; 70:30) to afford five fractions (E.1–E.5): fraction E.1 (137 mg, 45.7% of oil); fraction E.2 (37 mg, 12.4% of oil); fraction E.3 (28 mg, 9.4% of oil); fraction E.4 (22 mg, 7.4% of oil); fraction E.5 (46 mg, 15.4% of oil). These fractions (E.1–E.5) were also submitted to gas chromatography coupled with mass spectrometry.

3.3. Gas Chromatography–Mass Spectrometry Analyses and Peak Identification

The composition of HEE and its five fractions was determined by Gas Chromatography/Electron Ionization-Mass Spectrometry (GC-EI-MS). Analyses were carried out with a Varian CP-3800 gas chromatograph (Varian Inc., Palo Alto, CA, USA) fitted with an HP-5 capillary column (30 m, 0.25 mm, 0.25 μm film thickness) coupled with a Varian Saturn (Varian Inc., Palo Alto, CA, USA) 2000 ion-trap mass detector. Operating conditions were as follows: injector temperature, 220 °C; transfer line temperature, 240 °C; oven temperature, 60 to 240 °C (set to a 3 °C/min increment), carrier gas: helium at a 1 mL/min flow. After dilution (5%) in HPLC-grade n-hexane, 1 µL was injected in the GC (split ratio 1:30). The acquisition was performed with the following parameters: full scan, with a scan range of 35–300 m/z; scan time: 1.0 s; threshold: 1 count. The identification of the constituents was based on the comparison of their retention times (tR) with those of pure reference samples and of their linear retention indices (LRIs), which were determined relative to the tR of a series of n-alkanes (C9–C25). The mass spectra detected were compared with those listed in the commercial libraries NIST 14 and ADAMS, and in a homemade mass-spectral library, built from pure substances and components of essential oils of known composition and MS literature data [38,39].

3.4. Cell Lines

Human mammary carcinoma cell line (MDA-MB-231) and colorectal carcinoma cell line (SW620) were obtained from the American Tissue Culture Collection (ATCC, Molsheim, France). Cells were maintained in a 5% CO2 humidified atmosphere at 37 °C and cultured in Roswell Park Memorial Institute (RPMI) medium 1640 supplemented with 10% (v/v) fetal calf serum (Dutscher, Brumath, France).

3.5. Determination of Cell Viability

Cells were seeded into a 96-well plate 5 × 103–1 × 104 cells per well. The next day, cells were challenged for 48 h with increasing concentrations of the essential oil and its fractions for 48 h. After the indicated times, cells were washed with PBS and then stained with crystal violet (0.5% w/v) for 5 min and then rinsed three times with water. Absorbance was read at 540 nm after extraction of the dye with 0.1 M sodium citrate in 50% ethanol. The inhibitory concentrations of 50% (IC50) were calculated using a four-parameter nonlinear regression with GraphPad Prism version 6 software (GraphPad Software, La Jolla, CA, USA). The chemotherapeutical drug 5-fluorouracil was used as positive control [40].

4. Conclusions

The chemical composition of T. articulata trunk bark complete essential oil (HEE) and its fractions (E.1–E.5) is dominated by oxygenated sesquiterpenes (44.4–70.2%). Caryophyllene oxide, carotol and 14-hydroxy-epi-(E)-caryophyllene were determined as the major components. HEE and its fractions (E.1–E.5) did not exhibit substantial cytotoxic activity against human cell line MDA-MB-231 and SW640.The increasing content of oxygenated sesquiterpenes correlated with an increase of the cytotoxicity.

Acknowledgments

The authors are grateful to the Ministry of Higher Education and Scientific Research of Tunisia for financial support (LR11ES39) and to Fethia Harzallah-Skhiri (Higher Institute of Biotechnology of Monastir, Tunisia) for the botanical identification. In addition, the authors are grateful to Researchers Supporting Project number (RSP-2021/17) at King Saud University, Riyadh, Saudi Arabia.

Author Contributions

Conceptualization, S.J., A.Z.-B., A.L. and H.B.J.; data curation and formal analysis, S.J., A.L., A.H.H., R.A., G.F., L.C.-G. and H.B.J.; investigation, S.J., A.Z.-B. and A.L.; resources, S.J. and H.B.J.; writing of the first draft, S.J., A.Z.-B., A.L., R.A. and G.F.; writing—review and editing, S.J., A.Z.-B., A.L., A.H.H., L.C.-G. and H.B.J.; supervision, L.C.-G. and H.B.J. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by the LR11ES39 Grant from Ministry of High Education and Scientific Research, Tunisia.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

Footnotes

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

  • 1.Swamy M.K., Sinniah U.R. A comprehensive review on the phytochemical constituents and pharmacological activities of Pogostemon cablin Benth.: An aromatic medicinal plant of industrial importance. Molecules. 2015;20:8521–8547. doi: 10.3390/molecules20058521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.El Ayeb-Zakhama A., Ben Salem S., Sakka-Rouis L., Flamini G., Ben Jannet H., Harzallah-Skhiri F. Chemical Composition and Phytotoxic Effects of Essential Oils Obtained from Ailanthus altissima (Mill.) Swingle Cultivated in Tunisia. Chem. Biodivers. 2014;11:1216–1227. doi: 10.1002/cbdv.201300409. [DOI] [PubMed] [Google Scholar]
  • 3.Woguem V., Fogang H.P., Maggi F., Tapondjou L.A., Womeni H.M., Quassinti L., Bramucci M., Vitali L.A., Petrelli D., Lupidi G., et al. Volatile oil from striped African pepper (Xylopia parviflora, Annonaceae) possesses notable chemopreventive, anti-inflammatory and antimicrobial potential. Food Chem. 2014;149:183–189. doi: 10.1016/j.foodchem.2013.10.093. [DOI] [PubMed] [Google Scholar]
  • 4.Zardi-Bergaoui A., Ben Nejma A., Harzallah-Skhiri F., Flamini G., Ascrizzi R., Ben Jannet H. Chemical Composition and Biological Studies of the Essantial Oil from Aerial Parts of Beta vulgaris subsp. maritima (L.) ARCANG. Growing in Tunisia. Chem. Biodivers. 2017;14:e1700234. doi: 10.1002/cbdv.201700234. [DOI] [PubMed] [Google Scholar]
  • 5.Baccari W., Znati M., Zardi-Bergaoui A., Chaieb I., Flamini G., Ascrizzi R., Ben Jannet H. Composition and insecticide potential against Tribolium castaneum of the fractionated essential oil from the flowers of the Tunisian endemic plant Ferula tunetana Pomel ex Batt. Ind. Crops Prod. 2020;143:111888. doi: 10.1016/j.indcrop.2019.111888. [DOI] [Google Scholar]
  • 6.Zardi-Bergaoui A., Jelizi S., Flamini G., Ascrizzi R., Ben Jannet H. Comparative study of the chemical composition and bioactivities of essential oils of fresh and dry seeds from Myoporum insulare R. Br. Ind. Crops Prod. 2018;111:232–237. doi: 10.1016/j.indcrop.2017.10.019. [DOI] [Google Scholar]
  • 7.Wińska K., Mączka W., Łyczko J., Grabarczyk M., Czubaszek A., Szumny A. Essential Oils as Antimicrobial Agents—Myth or Real Alternative? Molecules. 2019;24:2130. doi: 10.3390/molecules24112130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Rabib H., Elagdi C., Hsaine M., Fougrach H., Koussa T., Badri W. Antioxidant and Antibacterial Activities of the Essential Oil of Moroccan Tetraclinis articulata (Vahl) Masters. Biochem. Res. Int. 2020;2020:1–6. doi: 10.1155/2020/9638548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Le N.T., Donadu M.G., Ho D.V., Doan T.Q., Le A.T., Raal A., Usai D., Sanna G., Marchetti M., Usai M., et al. Biological activities of essential oil extracted from leaves of Atalantia Sessiflora Guillauminin Vietnam. J. Infect. Dev. Ctries. 2020;14:1054–1064. doi: 10.3855/jidc.12469. [DOI] [PubMed] [Google Scholar]
  • 10.Bellakhdar J., Honda G., Miki W. Herb–Drugs and Herbalists in the Maghrib. Institute of the Study of Languages and Cultures of Asia and Africa; Tokyo, Japan: 1982. [Google Scholar]
  • 11.Ait Igri M., Holeman M., Ilidrissi A., Berrada M. Contribution to the chemical study of branches and wood essential oils of Tetraclinis articulata (Vahl) Masters. Plant Med. Phytother. 1990;24:36–43. [Google Scholar]
  • 12.Barrero A.F., Herrador M.M., Arteaga P., Quilez J., Akssira M., Mellouki F., Akkad S. Chemical Composition of the Essential Oils of Leaves and Wood of Tetraclinis articulata (Vahl) Masters. J. Essent. Oil. Res. 2005;17:166–168. doi: 10.1080/10412905.2005.9698865. [DOI] [Google Scholar]
  • 13.Bourkhiss M., Hnach M., Lakhlifi T., Bourkhiss B., Ouhssine M., Satrani B. Production et Caractérisation de l’huile essntielle de la scuire de bois de Tetraclinis articulata (Vahl) Masters. Bull. Soc. R. Sci. Liège. 2010;79:4–11. [Google Scholar]
  • 14.Pottier-Alapetite G. Flore de la Tunisie: Angiospermes-Dicotylédones, Apétales Dialypétales. Publications Scientifiques Tunisiennes; Tunis, Tunisia: 1981. pp. 36–37. [Google Scholar]
  • 15.Abi-Ayad F.Z., Abi-Ayad M., Lazzouni H.A., Rebiahi S.A., Bessiere Antibacterial activity of essential oil extracted from leaves of Tetraclinis articulata (Vahl) Masters from Algeria flora. J. Microbiol. Biotechnol. Res. 2011;1:1–6. [Google Scholar]
  • 16.Tekaya-Karoui A., Boughalle N., Hammami S., Ben Jannet H., Mighri Z. Chemical composition and antifungal activity of volatile components from woody terminal branches and roots of Tetraclinis articulata (Vahl) Masters growing in Tunisia. Afr. J. Plant Sci. 2011;5:115–122. [Google Scholar]
  • 17.Buhagiar J.A., Podesta M.T., Wilson A.P., Micallef M.J., Ali S. The induction of apoptosis in human melanoma, breast and ovarian cancer cell lines using an essential oil extract from the conifer Tetraclinis articulata. Anticancer Res. 1999;19:5435–5443. [PubMed] [Google Scholar]
  • 18.Djouahri A., Boudarene L. Antioxidant and anti-inflammatory activity of methanolic, chloroform and ethyl acetate extracts of leaves Tetraclinis articulata (Vahl) Masters Algerian. Int. J. Res. Phytochem. Pharm. 2012;2:7–11. [Google Scholar]
  • 19.Chikhoune A., Hazzit M., Kerbouche L., Baaliouamer A., Aissat K. Tetraclinis articulata (Vahl.) Masters essentials: Chemical composition and biological activities. J. Essent. Oil. Res. 2013;25:300–307. doi: 10.1080/10412905.2013.774625. [DOI] [Google Scholar]
  • 20.Ghnaya A.B., Amri I., Hanana M., Gargouri S., Jamoussi B., Romane A., Hamrouni L. Tetraclinis articulata (Vahl.) Masters essential oil from Tunisia: Chemical characterization and herbicidal and antifungal activities assessment. Ind. Crops Prod. 2016;83:113–117. doi: 10.1016/j.indcrop.2015.12.026. [DOI] [Google Scholar]
  • 21.Rguez S., Ben Slimene I., Abid G., Hammemi M., Kefi A., Elkahoui S., Ksouri R., Hamrouni Sellami I., Djebali N. Tetraclinis articulata essential oil reduces Botrytis cinerea infections on tomato. Sci. Hortic. 2020;266:109291. doi: 10.1016/j.scienta.2020.109291. [DOI] [Google Scholar]
  • 22.Tekaya-Karoui A., Ben Jannet H., Mighri Z. Essential oil composition of terminal branches, cones and roots of Tetraclinis articulata from Tunisia. Pak. J. Biol. 2007;10:2495–2499. doi: 10.3923/pjbs.2007.2495.2499. [DOI] [PubMed] [Google Scholar]
  • 23.Larabi F., Benhassaini H., Bennaoum Z. Phytochemical Screening of Non Woody Terminal Branches of Tetraclinis articulata from the North-western Region of Algeria. TEOP. 2016;19:1816–1820. [Google Scholar]
  • 24.Buhagiar J., Camilleri Podestà M.T., Cioni P.L., Flamini G., Morelli I. Essential oil composition of different parts of Tetraclinis articulata. J. Essent. Oil Res. 2000;12:29–32. doi: 10.1080/10412905.2000.9712034. [DOI] [Google Scholar]
  • 25.Jlizi S., Zardi-Bergaoui A., Znati M., Flamini G., Ascrizzi R., Ben Jannet H. Chemical composition and biological evaluation of the resin from Tetraclinis articulata (Vahl.) Masters: A promising source of bioactive secondary metabolites. Ind. Crops Prod. 2018;124:74–83. doi: 10.1016/j.indcrop.2018.07.055. [DOI] [Google Scholar]
  • 26.Fidyt K., Fiedorowicz A., Strządała L., Szumny A. β-caryophyllene and β-caryophyllene oxide—natural compounds of anticancer and analgesic properties. Cancer Med. 2016;5:3007–3017. doi: 10.1002/cam4.816. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Sieniawska E., Swiatek Ł., Rajtar B., Kozioł E., Polz-Dacewicz M., Skalicka-Wozniak K. Carrot seed essential oil—Source of carotol and cytotoxicity study. Ind. Crops Prod. 2016;92:109–115. doi: 10.1016/j.indcrop.2016.08.001. [DOI] [Google Scholar]
  • 28.Alidadiyani N., Salehi R., Ghaderi S., Samadi N., Davaran S. Synergistic antiproliferative effects of methotrexate-loaded smart silica nanocomposites in MDA-MB-231 breast cancer cells. Artif. Cells Nanomed. Biotechnol. 2016;44:603–609. doi: 10.3109/21691401.2014.975235. [DOI] [PubMed] [Google Scholar]
  • 29.Guan X., Guan Y. Artemisinin induces selective and potent anticancer effects in drug-resistant breast cancer cells by inducing cellular apoptosis and autophagy and G2/M cell cycle arrest. JBUON. 2020;25:1330–1336. [PubMed] [Google Scholar]
  • 30.Oliveira P.F., Morais Alves J., Lopes Damasceno J., Oliveira R.A.M., Júnior Dias H., Eduardo Miller Crotti A., Crispim Tavares D. Cytotoxicity screening of essential oils in cancer cell lines. Rev. Bras. Farm. 2015;25:183–188. doi: 10.1016/j.bjp.2015.02.009. [DOI] [Google Scholar]
  • 31.Pan Z., Wang S.-K., Cheng X.-L., Tian X.-W., Wang J. Caryophyllene oxide exhibits anti-cancer effects in MG-63 human os-teosarcoma cells via the inhibition of cell migration, generation of reactive oxygen species and induction of apoptosis. Bangla-desh J. Pharmacol. 2016;11:817–823. doi: 10.3329/bjp.v11i4.27517. [DOI] [Google Scholar]
  • 32.Di Giacomo S., Di Sotto A., Mazzanti G., Wink M. Chemosensitizing Properties of β-Caryophyllene and β-Caryophyllene Oxide in Combination with Doxorubicin in Human Cancer Cells. Anticancer Res. 2017;37:1191–1196. doi: 10.21873/anticanres.11433. [DOI] [PubMed] [Google Scholar]
  • 33.Lin J., Cai Q.-Y., Xu W., Lin J.-M., Peng J. Chemical Composition, Anticancer, Anti-neuroinflammatory, and Antioxidant Activities of the Essential Oil of Patrinia scabiosaefolia. Chin. J. Integr. Med. 2018;24:207–212. doi: 10.1007/s11655-016-2459-4. [DOI] [PubMed] [Google Scholar]
  • 34.Jun N.J., Mosaddik A., Moon J.Y., Jang K.-C., Lee D.-S., Ahn K.S., Cho S.K. Cytotoxic Activity of β-Caryophyllene Oxide Isolated from Jeju Guava (Psidium cattleianum Sabine) Leaf. Rec. Nat. Prod. 2011;5:242–246. [Google Scholar]
  • 35.Sylvestre M., Legault J., Dufour D., Pichette A. Chemical composition and anticancer activity of leaf essential oil of Myrica gale L. Phytomedicine. 2005;12:299–304. doi: 10.1016/j.phymed.2003.12.004. [DOI] [PubMed] [Google Scholar]
  • 36.Lattaoui N., Tantaoui-Elaraki A. Individual and combined oils. Rivista Italiana EPPOS. 1994;13:13–19. [Google Scholar]
  • 37.Yu J.Q., Lei J.Q., Yu H.D., Cai X., Zou G.L. Chemical composition and antimicrobial activity of essential oil of Scutellaria barbata. Phytochemistry. 2004;65:881–884. doi: 10.1016/j.phytochem.2004.02.005. [DOI] [PubMed] [Google Scholar]
  • 38.National Institute of Standards and Technology . NIST/EPA/NIH Mass Spectral Library. The NIST Mass Spectrometry Data Center; Gaithersburg, MD, USA: 2014. [Google Scholar]
  • 39.Adams R.P. Identification of Essential Oil Components by Gas Chromatography/Mass Spectroscopy. 4th ed. Allured Pub. Corp.; Carol Stream, IL, USA: 2007. [Google Scholar]
  • 40.Scagliarini A., Mathey A., Aires V., Delmas D. Xanthohumol, a Prenylated Flavonoid from Hops, Induces DNA Damages in Colorectal Cancer Cells and Sensitizes SW480 Cells to the SN38 Chemotherapeutic Agent. Cells. 2020;9:932. doi: 10.3390/cells9040932. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

Not applicable.

Articles from Molecules are provided here courtesy of Multidisciplinary Digital Publishing Institute (MDPI)

RESOURCES