Trans-Anethole: A Key Compound in Bogma Raki

Anethole [1-methoxy-4-(1-propenyl)benzene] is a natural flavor commonly used for covering unpleasant odors and in certain food materials and especially in alcohol- ic drinks. Alcoholic beverages like raki, absinth, mastika include anethole as flavor- ing agent. Anethole levels are 747-1547 mg/L in nationally certified brands of raki and 441.46-2098.10 mg/L or 0.01-2.6% in bogma raki (illegaly homemade raki) in Turkey. Toxicity and systemic effects of trans-anethole will be discussed in this presentation. Trans-anethole, especially its epoxide metabolite induces the liver cytochrome p450 enzyme. Decreased weight gain, low body weight, anorexia, lethargy, reduction in ad- iposity, elevated alanine transaminase, aspartate transaminase, gama-glutamyltrans- ferase, and alkaline phosphatase levels, hepatocellular dysmorphology were among effects of trans-anethole observed in animal studies. Inhibition of platelet aggre- gation as potently as aspirin and antithrombotic activity was revealed in literature. Trans-anethole inhibits pregnancy in a dose-dependent manner because of impaired hormonal balance. Additionally, it was suggested that trans-anethole consumption should be avoided in pregnancy, in breastfeeding mothers or in patients with estro- gen-sensitive cancers or endometriosis. It is suggested that pregnant women, breastfeeding mothers, patients with endome- triosis and estrogen-dependent cancers should avoid consumption; furthermore, pa- tients with bleeding disorder, hemophilia, major surgery, and diabetes mellitus should be informed and warned about its toxicity.

Kaynakça

Newberne P, Smith R, Doull J, et al. The FEMA GRAS assessment of trans-anethole used as a flavouring substance. Food and Chemical Toxicology 1999; 37: 789-811.

Marinov V, Valcheva-Kuzmanova S. Review on the pharmacolog- ical activities of anethole. Scripta Scientifica Pharmaceutica 2015; 2:

Avcı A, Giachino R, Ibraliu A, et al. Turkish anise (Pimpinella ani- sum L.). In: editor (eds). Proceedings of the Eighth Conference on Medicinal and Aromatic Plants of Southeast European Countries (8th CMAPSEEC) 19-22 May 2014, Durrës, Albania.; 2014; Association for Medicinal and Aromatic Plants of Southeast European Countries (AMAPSEEC); Year: 140-145.

Shojaii A, Abdollahi Fard M. Review of pharmacological proper- ties and chemical constituents of Pimpinella anisum. ISRN phar- maceutics 2012; 2012:

Ramazan A, Aykut L. Trans-anethole concentrations in bogma raki. Human & Experimental Toxicology 2016; 36: 203-204.

Gueven A. Chemical fingerprints of Raki: a traditional distilled al- coholic beverage. Journal of the Institute of Brewing 2013; 119: 126-132.

Bulur A, Research On The Fundamental Volatile Components Of Turkish Rakies. Place; PublishedUniversity Of Çukurova, AcademicDepartment; 2010.

Arslan MM, Zeren C, Aydin Z, et al. Analysis of methanol and its derivatives in illegally produced alcoholic beverages. Journal of forensic and legal medicine 2015; 33: 56-60.

Gökce H, Akcan R, Celikel A, et al. Hepatotoxicity of illegal home- made alcohols. Journal of Forensic and Legal Medicine 2016; 43: 85-89.

Wright J. Essential oils. In: P. R. Ashurst, editor. Food Flavorings. Boston, MA: Springer US; 1991. p. 25-57.

Rocha L, Fernandes CP. Aniseed (Pimpinella anisum, Apiaceae) Oils. In: V. R. Preedy, editor. Essential Oils in Food Preservation, Flavor and Safety. San Diego: Academic Press; 2016. p. 209-213.

Tisserand R, Young R. Constituent profiles. Essential Oil Safety (Second Edition). St. Louis: Churchill Livingstone; 2014. p. 483-647.

Sangster SA, Caldwell J, Hutt AJ, et al. The metabolic disposition of [methoxy-14C]-labelled trans-anethole, estragole and p-pro- pylanisole in human volunteers. Xenobiotica 1987; 17: Marshall A, Caldwell J. Influence of modulators of e1223-1232.

Marshall A, Caldwell J. Influence of modulators of epoxide me- tabolism on the cytotoxicity of trans-anethole in freshly isolat- ed rat hepatocytes. Food and Chemical Toxicology 1992; 30: 467-473.

Rompelberg CJM, Verhagen H, van Bladeren PJ. Effects of the naturally occurring alkenylbenzenes eugenol and trans-aneth- ole on drug-metabolizing enzymes in the rat liver. Food and Chemical Toxicology 1993; 31: 637-645.

Reed P, Caldwell J. Induction of hepatic cytochrome P450 and re- lated activities following dietary administration of trans-anethole in SD-CD rats. Human and Experimental Toxicology 1992; 11: 580-581.

Hazleton C. CHV Project No. 2595-103. Protocol. 90-day sub- chronic dietary toxicity study of trans-anethole in mice. RJ Reynolds1996.

Truhaut R, Le Bourhis B, Attia M, et al.Chronic toxicity/carcinoge- nicity study of trans-anethole in rats. Food and chemical toxicol- ogy 1989; 27: 11-20.

Nakagawa Y, Suzuki T. Cytotoxic and xenoestrogenic effects via biotransformation of trans-anethole on isolated rat hepatocytes and cultured MCF-7 human breast cancer cells. Biochemical pharmacology 2003; 66: 63-73.

Soares PMG, Lima RF, de Freitas Pires A, et al. Effects of anethole and structural analogues on the contractility of rat isolated aorta: Involvement of voltage-dependent Ca2+-channels. Life Sciences 2007; 81: 1085-1093.

Tognolini M, Ballabeni V, Bertoni S, et al. Protective effect of Foeniculum vulgare essential oil and anethole in an experimen- tal model of thrombosis. Pharmacological Research 2007; 56: 254-260.

Tognolini M, Barocelli E, Ballabeni V, et al. Comparative screening of plant essential oils: phenylpropanoid moiety as basic core for antiplatelet activity. Life sciences 2006; 78: 1419-1432.

Kreydiyyeh SI, Usta J, Knio K, et al. Aniseed oil increases glucose absorption and reduces urine output in the rat. Life Sciences 2003; 74: 663-673.

Javadi S, Ilkhnipour M, Heidari R, et al. The effect Foeniculum vul- gare Mill (fennel) essential oil on blood glucose in rats. Plant Sci Res 2008; 1: 47-49.

Sheikh BA, Pari L, Rathinam A, et al. Trans-anethole, a terpenoid ameliorates hyperglycemia by regulating key enzymes of car- bohydrate metabolism in streptozotocin induced diabetic rats. Biochimie 2015; 112: 57-65.

Zondek B, Bergmann E. Phenol methyl ethers as oestrogenic agents. Biochemical Journal 1938; 32: 641.

Albert-Puleo M. Fennel and anise as estrogenic agents. Journal of Ethnopharmacology 1980; 2: 337-344.

Tabanca N, Khan SI, Bedir E, et al. Estrogenic activity of isolated compounds and essential oils of Pimpinella species from Turkey, evaluated using a recombinant yeast screen. Planta medica 2004; 70: 728-735.

Howes MJ, Houghton P, Barlow D, et al. Assessment of estrogen- ic activity in some common essential oil constituents. Journal of pharmacy and pharmacology 2002; 54: 1521-1528.

Dhar S. Anti-fertility activity and hormonal profile of trans-aneth- ole in rats. Indian journal of physiology and pharmacology 1995; 39: 63-63.

Le Bourhis B. Proprietes biologiques de l’anethole; principe aro- matique des plantes anisees. Pref. du professeur Rene Truhaut. PlacePublished; Maloine, 1973:

Reproductive and developmental toxicity screening test of (trans-anethole) administered orally via gavage to Crl:CD BR VAF/ Plus female rats. Final Report. Argus Research Laboratories, Inc.; 1992.

Ostad SN, Khakinegad B, Sabzevari O. Evaluation of the teratoge- nicity of fennel essential oil (FEO) on the rat embryo limb buds culture. Toxicology in Vitro 2004; 18: 623-627.

Ostad SN, Soodi M, Shariffzadeh M, et al. The effect of fen- nel essential oil on uterine contraction as a model for dys- menorrhea, pharmacology and toxicology study. Journal of Ethnopharmacology 2001; 76: 299-304.

Hausner H, Bredie WLP, Mølgaard C, et al. Differential transfer of dietary flavour compounds into human breast milk. Physiology & Behavior 2008; 95: 118-124.

Skalli S, Bencheikh RS. Epileptic seizure induced by fennel essen- tial oil. Epileptic Disorders 2011; 13: 345-347.

Karimzadeh F, Hosseini M, Mangeng D, et al. Anticonvulsant and neuroprotective effects of Pimpinella anisum in rat brain. BMC complementary and alternative medicine 2012; 12: 76.

Abdul-Ghani A-S, El-Lati S, Sacaan A, et al.Anticonvulsant effects of some Arab medicinal plants. International Journal of Crude Drug Research 1987; 25: 39-43.

Pourgholami M, Majzoob S, Javadi M, et al. The fruit essential oil of Pimpinella anisum exerts anticonvulsant effects in mice. Journal of ethnopharmacology 1999; 66: 211-215.

Ryu S, Seol GH, Park H, et al. Trans-anethole protects cortical neu- ronal cells against oxygen–glucose deprivation/reoxygenation. Neurological Sciences 2014; 35: 1541-1547.

Bhadra S, Mukherjee PK, Kumar NS, et al. Anticholinesterase ac- tivity of standardized extract of Illicium verum Hook. f. fruits. Fitoterapia 2011; 82: 342-346.

Swanson AB, Chambliss DD, Blomquist JC, et al. The mutagenic- ities of safrole, estragole, eugenol, trans-anethole, and some of their known or possible metabolites for Salmonella typhimuri- um mutants. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 1979; 60: 143-153.

Sekizawa J, Shibamoto T. Genotoxicity of safrole-related chem- icals in microbial test systems. Mutation Research/Genetic Toxicology 1982; 101: 127-140.

Marcus C, Lichtenstein EP. Interactions of naturally occurring food plant components with insecticides and pentobarbital in rats and mice. Journal of agricultural and food chemistry 1982; 30: 563-568.

Hsia MS, Adamovics JA, Kreamer BL. Microbial mutagenicity studies of insect growth regulators and other potential insec- ticidal compounds in Salmonellatyphimurium. Chemosphere 1979; 8: 521-529.

Heck J, Vollmuth T, Cifone M, et al. An evaluation of food flavoring ingredients in a genetic toxicity screening battery. Toxicologist 1989; 9: 257-272.

Gorelick N. Genotoxicity of trans-anethole in vitro. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 1995; 326: 199-209.

Müller L, Kasper P, Müller-Tegethoff K, et al. The genotoxic poten- tial in vitro and in vivo of the allyl benzene etheric oils estrago- le, basil oil and trans-anethole. Mutation Research Letters 1994; 325: 129-136. © 2018 Acta Medica. All rights reserved. Akcan et al.

Nestmann ER, Lee EG-H. Mutagenicity of constituents of pulp and paper mill effluent in growing cells of Saccharomyces cerevi- siae. Mutation Research Letters 1983; 119: 273-280.

Nestmann ER, Lee EG, Matula TI, et al. Mutagenicity of con- stituents identified in pulp and paper mill effluents using the Salmonella/mammalian-microsome assay. Mutation Research/ Genetic Toxicology 1980; 79: 203-212.

Mortelmans K, Haworth S, Lawlor T, et al.Salmonella muta- genicity tests: II. Results from the testing of 270 chemicals. Environmental mutagenesis 1986; 8: 56-119.

Marshall A, Caldwell J. Lack of influence of modulators of epoxide metabolism on the genotoxicity of tans-anethole in freshly iso- lated rat hepatocytes assessed with the unscheduled DNA syn- thesis assay. Food and chemical toxicology 1996; 34: 337-345.

Caldwell J, Chan V, Marshall A, et al. Hydroxylation is the only metabolic pathway of simple alkenylbenzenes involved in their genotoxicity. Toxicologist 1992; 12: 56.

Al-Harbi M, Qureshi S, Raza M, et al. Influence of anethole treat- ment on the tumour induced by Ehrlich ascites carcinoma cells in paw of Swiss albino mice. European Journal of Cancer Prevention 1995; 4: 307-318.

Abraham S. Anti-genotoxic effects in mice after the interaction between coffee and dietary constituents. Food and chemical toxicology 1996; 34: 15-20.

Kim S, Liem A, Stewart B, et al. New studies on trans-anethole ox- ide and trans-asarone oxide. Carcinogenesis 1999; 20: 1303-1307.

Miller EC, Swanson AB, Phillips DH, et al. Structure-activity stud- ies of the carcinogenicities in the mouse and rat of some natural- ly occurring and synthetic alkenylbenzene derivatives related to safrole and estragole. Cancer Research 1983; 43: 1124-1134.

Newberne P, Carlton W, Brown W. Histopathological evaluation of proliferative liver lesions in rats fed trans-anethole in chronic studies. Food and chemical toxicology 1989; 27: 21-26.

Auerbach SS, Shah RR, Mav D, et al. Predicting the hepatocar- cinogenic potential of alkenylbenzene flavoring agents using toxicogenomics and machine learning. Toxicology and applied pharmacology 2010; 243: 300-314.

Taylor JM, Jenner PM, Jones WI. A comparison of the toxici- ty of some allyl, propenyl, and propyl compounds in the rat. Toxicology and applied pharmacology 1964; 6: 378-387.

Minnema DJ. CHV Project No. 2595-103. Protocol. 90-Day Subchronic Dietary Toxicity Study of Trans-Anethole in Mice. RJ Reynolds 1996.

JECFA.trans-Anethole(addendum). 1999. http://www.inchem. org/documents/jecfa/jecmono/v042je02.htm.

Rudzki E, Grzywa Z. Sensitizing and irritating properties of star anise oil. Contact Dermatitis 1976; 2: 305-308.

Poon TSC, Freeman S. Cheilitis caused by contact allergy to anethole in spearmint flavoured toothpaste. Australasian Journal of Dermatology 2006; 47: 300-301.

Garcia-Bravo B, Bernal AP, Garcia-Hernandez MJ, et al. Occupational contact dermatitis from anethole in food handlers. Contact Dermatitis 1997; 37: 38-38.

JECFA. Summary of Evaluations Performed by the Joint FAO/ WHO Expert Committee on Food Additives. http://www.inchem. org/documents/jecfa/jeceval/jec_137.htm.

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