Cytotoxicity of the Essential Oil of Fennel (Foeniculum vulgare) from Tajikistan

Farukh Sharopov, Abdujabbor Valiev, Prabodh Satyal, Isomiddin Gulmurodov, Salomudin Yusufi, William N Setzer, Michael Wink, Farukh Sharopov, Abdujabbor Valiev, Prabodh Satyal, Isomiddin Gulmurodov, Salomudin Yusufi, William N Setzer, Michael Wink

Abstract

The essential oil of fennel (Foeniculum vulgare) is rich in lipophilic secondary metabolites, which can easily cross cell membranes by free diffusion. Several constituents of the oil carry reactive carbonyl groups in their ring structures. Carbonyl groups can react with amino groups of amino acid residues in proteins or in nucleotides of DNA to form Schiff's bases. Fennel essential oil is rich in anise aldehyde, which should interfere with molecular targets in cells. The aim of the present study was to investigate the chemical composition of the essential oil of fennel growing in Tajikistan. Gas chromatographic-mass spectrometric analysis revealed that the main components of F. vulgare oil were trans-anethole (36.8%); α-ethyl-p-methoxy-benzyl alcohol (9.1%); p-anisaldehyde (7.7%); carvone (4.9%); 1-phenyl-penta-2,4-diyne (4.8%) and fenchyl butanoate (4.2%). The oil exhibited moderate antioxidant activities. The potential cytotoxic activity was studied against HeLa (human cervical cancer), Caco-2 (human colorectal adenocarcinoma), MCF-7 (human breast adenocarcinoma), CCRF-CEM (human T lymphoblast leukaemia) and CEM/ADR5000 (adriamycin resistant leukaemia) cancer cell lines; IC50 values were between 30-210 mg L-1 and thus exhibited low cytotoxicity as compared to cytotoxic reference compounds.

Keywords: Foeniculum vulgare; anise aldehyde; cluster analysis; cytotoxicity; essential oil; trans-anethole.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Structures of main components of the essential oil Foeniculum vulgare.
Figure 1
Figure 1
Dendrogram obtained from the agglomerative hierarchical cluster analysis of 68 Foeniculum vulgare essential oil compositions. (CT1) anethole-rich chemotype, (CT1a) anethole chemotype, (CT1b) anethole/limonene chemotype, (CT1c) anethole/camphor chemotype, (CT2) estragole chemotype, (CT3) estragole/α-phellandrene chemotype, (CT4) anethole/estragole/α-pinene chemotype, (CT5) α-phellandrene chemotype, and (CT6) limonene/β-pinene/myrcene chemotype.
Figure 2
Figure 2
The images of untreated (a) and treated (b) CCRF cells with essential oil of Foeniculum vulgare.

References

    1. Mimica-Dukic N., Kujundyic S., Sokovic M., Couladis M. Essential oil composition and antifungal activity of Foeniculum vulgare Mill. Obtained by different distillation conditions. Phytother. Res. 2003;17:368–371. doi: 10.1002/ptr.1159.
    1. Rather M.A., Dar B.A., Sofi S.N., Bhat B.A., Qurishi M.A. Foeniculum vulgare: A comprehensive review of its traditional use, phytochemistry, pharmacology, and safety. Arab. J. Chem. 2012;9:S1574–S1583. doi: 10.1016/j.arabjc.2012.04.011.
    1. Diao W.R., Hu Q.P., Zhang H., Xu J.G. Chemical composition, antibacterial activity and mechanism of action of essential oil from seeds of fennel (Foeniculum vulgare Mill.) Food Control. 2014;35:109–116. doi: 10.1016/j.foodcont.2013.06.056.
    1. Van Wyk B.E., Wink M. Medicinal Plants of the World. Briza; Pretoria, Africa: 2004.
    1. Roby M.H., Sarhan M.A., Selim K.A., Khalel K.I. Antioxidant and antimicrobial activities of essential oil and extracts of fennel (Foeniculum vulgare L.) and chamomile (Matricaria chamomilla L.) Ind. Crops Prod. 2013;44:437–445. doi: 10.1016/j.indcrop.2012.10.012.
    1. Ouariachi E.E., Lahhit N., Bouyanzer A., Hammouti B., Paolini J., Majidi L., Desjobert J.M., Costa J. Chemical composition and antioxidant activity of essential oils and solvent extracts of Foeniculum vulgare Mill. from Morocco. J. Chem. Pharm. Res. 2014;6:743–748.
    1. Shahat A.A., Ibrahim A.Y., Hendawy S.F., Omer E.A., Hammouda F.M., Abdel-Rahman F.H., Saleh M.A. Chemical composition, antimicrobial and antioxidant activities of essential oils from organically cultivated fennel cultivars. Molecules. 2011:1366–1377. doi: 10.3390/molecules16021366.
    1. Ghanem I., Audeh A., Alnaser A., Tayoub G. Chemical constituents and insecticidal activity of the essential oil from fruits of Foeniculum vulgare Miller on larvae of khapra beetle (Trogoderma granarium Everts) Herba Polonica. 2013;59:86–96. doi: 10.2478/hepo-2013-0026.
    1. Tognolini M., Ballabeni V., Bertoni S., Bruni R., Impicciatore M., Barocelli E. Protective effect of Foeniculum vulgare essential oil and anethole in an experimental model of thrombosis. Pharmacol. Res. 2007;56:254–260. doi: 10.1016/j.phrs.2007.07.002.
    1. Villarini M., Pagiotti R., Dominici L., Fatigoni C., Vannini S., Levorato S., Moretti M. Investigation of the cytotoxic, genotoxic, and apoptosis-inducing effects of estragole isolated from fennel (Foeniculum vulgare) J. Nat. Prod. 2014;77:773–778. doi: 10.1021/np400653p.
    1. Bhardwaj P., Alok U., Khanna A. In vitro cytotoxicity of essensial oils: A review. Int. J. Res. Pharm. Chem. 2013;3:675–681.
    1. Heydarzade A., Moravvej G. Contact toxicity and persistence of essential oils from Foeniculum vulgare, Teucrium polium and Satureja hortensis against Callosobruchus maculatus (Fabricius) (Coleoptera: Bruchidae) adults. Turk. J. Entomol. 2012;36:507–518.
    1. Wink M. Evolutionary advantage and molecular modes of action of multi-component mixtures used in phytomedicine. Curr. Drug Metab. 2008;9:996–1009. doi: 10.2174/138920008786927794.
    1. Bassi A.M., Penco S., Canuto R.A., Muzioa G., Ferro M. Comparative evaluation of cytotoxicity and metabolism of four aldehydes in two hepatoma cell lines. Drug Chem. Toxicol. 1997;20:173–187. doi: 10.3109/01480549709003877.
    1. Sonboli A., Esmaeili M.A., Gholipour A., Kanani M.R. Composition, cytotoxicity and antioxidant activity of the essential oil of Dracocephalum surmandinum from Iran. Nat. Prod. Commun. 2010;5:341–344.
    1. Sharopov F.S., Wink M., Khalifaev D.R., Zhang H., Dosoky N.S., Setzer W.N. Chemical composition and antiproliferative activity of the essential oil of Galagania fragrantissima Lipsky (Apiaceae) Am. J. Essent. Oils Nat. Prod. 2013;1:11–13.
    1. Esterbauer H., Schaur R.J., Zollner H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic. Biol. Med. 1991;11:81–128. doi: 10.1016/0891-5849(91)90192-6.
    1. Zellagui A., Gherraf N., Elkhateeb A., Hegazy M.F., Mohamed T.A., Touil A., Shahat A., Rhouati S. Chemical constitutents from Algerian Foeniculum vulgare aerial parts and evaluation of antimicrobial activity. J. Chil. Chem. Soc. 2011;56:759–763. doi: 10.4067/S0717-97072011000300008.
    1. Chowdhury J.U., Mobarak H., Bhuiyan N.I., Nandi N.C. Constituents of essential oils from leaves and seeds of Foeniculum vulgare Mill. cultivated in Bangladesh. Bangladesh J. Bot. 2009;38:181–183. doi: 10.3329/bjb.v38i2.5144.
    1. Dadaliogylu I., Evrendilek G.A. Chemical compositions and antibacterial effects of essential oils of Turkish oregano (Origanum minutiflorum), bay laurel (Laurus nobilis), Spanish lavender (Lavandula stoechas L.), and fennel (Foeniculum vulgare) on common foodborne pathogens. J. Agric. Food Chem. 2004;52:8255–8260. doi: 10.1021/jf049033e.
    1. Aprotosoaie A.C., Spac A., Hancianu M., Miron A., Tanasescu V.F., Dorneanu V., Stanescu U. The chemical profile of essensial oils obtained from fennel fruits (Foeniculum vulgare Mill.) Farmacia. 2010;58:46–53.
    1. Radulovic N.S., Blagojevic P.D. A note on the volatile secondary metabolites of Foeniculum vulgare Mill. (Apiaceae) Facta Univ. 2010;8:25–37. doi: 10.2298/FUPCT1001025R.
    1. Stefanini M.B., Ming L.C., Marques M.O., Facanali R., Meireles M.A., Moura L.S., Marchese J.A., Sousa L.A. Essential oil constituents of different organs of fennel (Foeniculum vulgare var. vulgare) Braz. J. Med. Plants. 2006;8:193–198.
    1. Adams R.P. Identification of Essential Oil Components by Gas Chromatography/Mass Spectrometry. 4th ed. Allured Publishing Co. Carol Stream; Carol Stream, IL, USA: 2007.
    1. Sharopov F.S., Wink M., Setzer W.N. Radical scavenging and antioxidant activities of essential oil components—An experimental and computational investigation. Nat. Prod. Commun. 2015;10:153–156.
    1. Sharopov F.S. Ph.D. Thesis. Ruperto-Carola University of Heidelberg; Heidelberg, Germany: 2015. Phytochemistry and Bioactivities of Selected Plant Species with Volatile Secondary Metabolites.
    1. Sharopov F., Valiev A., Satyal P., Setzer W.N., Wink M. Chemical composition and anti-proliferative activity of the essential oil of Coriandrum sativum L. Am. J. Essent. Oils Nat. Prod. 2017;5:11–15.
    1. Zoubiri S., Baaliouamer A. Chemical composition and insecticidal properties of some aromatic herbs essential oils from Algeria. Food Chem. 2011;129:179–182. doi: 10.1016/j.foodchem.2011.04.033.
    1. Embong M.B., Hadziyev D., Molnar S. Essential oils from spices grown in Alberta. Fennel oil (Foeniculum vulgare var. dulce) Can. J. Plant Sci. 1977;57:829–837. doi: 10.4141/cjps77-120.
    1. De Oliveira P.F., Alves J.M., Damasceno J.L., Oliveira R.M., Dias H.J., Crotti A.M., Tavares D.C. Cytotoxicity screening of essential oils in cancer cell lines. Rev. Bras. Farmacogn. 2015;25:183–188. doi: 10.1016/j.bjp.2015.02.009.
    1. Zhao N.N., Zhou L., Liu Z.L., Du S.S., Deng Z.W. Evaluation of the toxicity of the essential oils of some common Chinese spices against Liposcelis bostrychophila. Food Control. 2012;26:486–490. doi: 10.1016/j.foodcont.2012.02.021.
    1. Zeng H., Chen X., Liang J. In vitro antifungal activity and mechanism of essential oil from fennel (Foeniculum vulgare l.) on dermatophyte species. J. Med. Microbiol. 2015;64:93–103. doi: 10.1099/jmm.0.077768-0.
    1. Pavela R., Zabka M., Bednar J., Tríska J., Vrchotova N. New knowledge for yield, composition and insecticidal activity of essential oils obtained from the aerial parts or seeds of fennel (Foeniculum vulgare Mill.) Ind. Crops Prod. 2016;83:275–282. doi: 10.1016/j.indcrop.2015.11.090.
    1. Muckensturm B., Foechterlen D., Reduron J.P., Dantont T.P., Hildenbrand M. Phytochemical and chemotaxonomic studies of Foeniculum vulgare. Biochem. Syst. Ecol. 1997;25:353–358. doi: 10.1016/S0305-1978(96)00106-8.
    1. Hashmi N., Khan M.M., Moinuddin, Idrees M., Khan Z.H., Ali A., Varshney L. Depolymerized carrageenan ameliorates growth, physiological attributes, essential oil yield and active constituents of Foeniculum vulgare Mill. Carbohydr. Polym. 2012;90:407–412. doi: 10.1016/j.carbpol.2012.05.058.
    1. Rahimmalek M., Maghsoudi H., Sabzalian M.R., Ghasemi Pirbalouti A. Variability of essential oil content and composition of different Iranian fennel (Foeniculum vulgare Mill.) accessions in relation to some morphological and climatic factors. J. Agric. Sci. Technol. 2014;16:1365–1374.
    1. Senatore F., Oliviero F., Scandolera E., Taglialatela-Scafati O., Roscigno G., Zaccardelli M., Falco E.D. Chemical composition, antimicrobial and antioxidant activities of anethole-rich oil from leaves of selected varieties of fennel [Foeniculum vulgare Mill. ssp. vulgare var. azoricum (Mill.) Thell] Fitoterapia. 2013;90:214–219.
    1. Han A.Y., Lee H.S., Seol G.H. Foeniculum vulgare Mill. Increases cytosolic Ca2+ concentration and inhibits store-operated Ca2+ entry in vascular endothelial cells. Biomed. Pharmacother. 2016;84:800–805. doi: 10.1016/j.biopha.2016.10.013.
    1. Lahhit N., Bouyanzer A., Desjobert J.M., Hammouti B., Salghi R., Costa J., Jama C., Bentiss F., Majidi L. Fennel (Foeniculum vulgare) essential oil as green corrosion inhibitor of carbon steel in hydrochloric acid solution. Port. Electrochim. Acta. 2011;29:127–138. doi: 10.4152/pea.201102127.
    1. Sousa R.M., Rosa J.S., Oliveira L., Cunha A., Fernandes-Ferreira M. Activities of Apiaceae essential oils and volatile compounds on hatchability, development, reproduction and nutrition of Pseudaletia unipuncta (Lepidoptera: Noctuidae) Ind. Crops Prod. 2015;63:226–237. doi: 10.1016/j.indcrop.2014.09.052.
    1. Cioanca O., Hancianu M., Mircea C., Trifan A., Hritcu L. Essential oils from Apiaceae as valuable resources in neurologicaldisorders: Foeniculi vulgare aetheroleum. Ind. Crops Prod. 2016;88:51–57. doi: 10.1016/j.indcrop.2016.02.064.
    1. Gorbunova E.V. Ph.D. Thesis. Michurinsk State Agricultural University; Michurinsk, Russia: 2015. Obosnovanie Osnovnich Elementov Technologii Kompleksnoy Pererabotki Sirya Fenchelya Obiknovennogo (Foeniculum vulgare Mill.)
    1. Oezcan M.M., Chalchat J.C., Arslan D., Ateş A., Uenver A. Comparative essential oil composition and antifungal effect of bitter fennel (Foeniculum vulgare ssp. piperitum) fruit oils obtained during different vegetation. J. Med. Food. 2006;9:552–561.
    1. Telci I., Demirtas I., Sahin A. Variation in plant properties and essential oil composition of sweet fennel (Foeniculum vulgare Mill.) fruits during stages of maturity. Ind. Crops Prod. 2009;30:126–130. doi: 10.1016/j.indcrop.2009.02.010.
    1. Timasheva L.A., Gorbunova E.V. A promising trend in the processing of fennel (Foeniculum vulgare Mill.) whole plants. Foods Raw Mater. 2014;2:51–57. doi: 10.12737/4134.
    1. Singh G., Maurya S., Lampasona M.P., Catalan C. Chemical constituents, antifungal and antioxidative potential of Foeniculum vulgare volatile oil and its acetone extract. Food Control. 2006;17:745–752. doi: 10.1016/j.foodcont.2005.03.010.
    1. Barazani O., Cohen Y., Fait A., Diminshtein S., Dudai N., Ravid U., Putievsky E., Friedman J. Chemotypic differentiation in indigenous populations of Foeniculum vulgare var. vulgare in israel. Biochem. Syst. Ecol. 2002;30:721–731. doi: 10.1016/S0305-1978(02)00019-4.
    1. Gross M., Friedman J., Dudai N., Larkov O., Cohen Y., Bar E., Ravid U., Putievsky E., Lewinsohn E. Biosynthesis of estragole and t-anethole in bitter fennel (Foeniculum vulgare Mill. var. vulgare) chemotypes. Changes in sam: Phenylpropene o-methyltransferase activities during development. Plant Sci. 2002;163:1047–1053.
    1. Franz C., Novak J. Sources of essential oils. In: Baser K.H.C., Buchbauer G., editors. Handbook of Essential Oils: Science, Technology, and Applications. CRC Press; Boca Raton, FL, USA: London, UK: New York, NY, USA: 2010. p. 994.
    1. Amorati R., Foti M.C., Valgimigli L. Antioxidant activity of essential oils. J. Agric. Food Chem. 2013;61:10835–10847. doi: 10.1021/jf403496k.
    1. Ettorre A., Frosali S., Andreassi M., Stefano A.D. Lycopene phytocomplex, but not pure lycopene, is able to trigger apoptosis and improve the efficacy of photodynamic therapy in HL60 human leukemia cells. Exp. Biol. Med. 2010;235:1114–1125. doi: 10.1258/ebm.2010.009386.
    1. Giovannini D., Gismondi A., Basso A., Canuti L., Braglia R., Canini A., Mariani F., Cappelli G. Lavandula angustifolia Mill. essential oil exerts antibacterial and anti-inflammatory effect in macrophage mediated immune response to Staphylococcus aureus. Immunol. Investig. 2016;45:11–28.
    1. Kulbacka J., Daczewska M., Dubińska-Magiera M., Choromańska A., Rembiałkowska N., Surowiak P., Kulbacki M., Kotulska M., Saczko J. Doxorubicin delivery enhanced by electroporation to gastrointestinal adenocarcinoma cells with P-gp overexpression. Bioelectrochemistry. 2014;100:96–104. doi: 10.1016/j.bioelechem.2014.03.013.
    1. Eid S.Y., El-Readi Z.M., Wink M. Carotenoids reverse multidrug resistance in cancer cells by interfering with abc-transporters. Phytomedicine. 2012;19:977–987. doi: 10.1016/j.phymed.2012.05.010.
    1. Russo R., Corasaniti M.T., Bagetta G., Morrone L.A. Exploitation of cytotoxicity of some essential oils for translation in cancer therapy. Evid. Based Complement. Altern. Med. 2015;2015 doi: 10.1155/2015/397821.
    1. Astani A., Reichling J., Schnitzler P. Screening for antiviral activities of isolated compounds from essential oils. Evid. Based Complement. Altern. Med. 2011;2011 doi: 10.1093/ecam/nep187.
    1. Nakagawa Y.T.S. Cytotoxic and xenoestrogenic effects via biotransformation of trans-anethole on isolated rat hepatocytes and cultured mcf-7 human breast cancer cells. Biochem. Pharmacol. 2003;66:63–73. doi: 10.1016/S0006-2952(03)00208-9.
    1. Muthukumari D., Padma P.R., Sumathi S. In vitro analysis of anethole as an anticancerous agent for triple negative breast cancer. Int. J. Pharm. Sci. Rev. Res. 2013;23:314–318.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe