Chemistry of spices: bornyl 4-methoxybenzoate from Ferula ovina (Boiss.) Boiss. (Apiaceae) induces hyperalgesia in mice† Niko S. Radulovi´ c, * a Dragan B. Zlatkovi´ c, a Pavle J. Randjelovi´ c, b Nikola M. Stojanovi´ c, c Slađana B. Novakovi´ c d and Hashem Akhlaghi e Ferula ovina (Boiss.) Boiss. is a traditional Iranian flavoring agent used as an ingredient of spices and condiments. Methods and results: GC–MS analyses of F. ovina aerial parts' essential oil revealed the presence of a number of rare aromatic esters of monoterpenic alcohols. The structures of these esters were corroborated by synthesis, and one of them, bornyl 4-methoxybenzoate, turned out to be a new natural compound. The antinociceptive activities of the oil and the new ester were assessed in mice using several different laboratory models. The oil exerted strong peripheral and moderate central analgesic activities. Surprisingly, mice treated with bornyl 4-methoxybenzoate had an increased sensitivity to the noxious stimulus compared to that of the control group. A dynamic hot plate test was used to demonstrate that bornyl 4-methoxybenzoate induces hyperalgesia and not allodynia. Conclusion: Essential oil constituents impart this spice with both antinociceptive and hyperalgesic potentially flavor-related properties. 1 Introduction Ferula L. is a genus of about 170 species of umbelliferous owering plants native to the Mediterranean region and east to central Asia. Many species of this genus have been historically used for culinary and medical purposes. Asafoetida, an oleogum resin obtained from the rhizome of F. asa-foetida and several other Ferula species, has been commonly used in Nepal as a avoring agent in many curry recipes. 1 Galbanum, a gum exudate collected from F. galbaniua and F. rubricaulis, is used as a candy additive, 2 and it has also been used for the treatment of intestinal disorders. 3 Bulgarian researchers have recently shown that Ferula spp. represent a new plant source of propolis in Malta. 4 Ferula orientalis is used in Turkey for avoring pickles. 5 Herbal products based on F. hermonis are sold as an aphrodisiac dietary supplement in the United States. 6 The Iranian ora comprises 30 species of this genus, one of them being F. ovina (Boiss.) Boiss. The resin obtained by cuts on the stem is a traditional avoring agent and is used as an ingredient of spices and condiments. 7 This plant is also very appreciated for its medicinal use. The aqueous extract of F. ovina was found to possess antispasmodic, anticholinergic and smooth muscle relaxant activities. 8 Although the essential oil composition of F. ovina was previously reported, 9,10 the potential pharmacological activity of this oil remains unknown up to date. Since a meticulous knowledge of the properties, both bene- cial and adverse, of each and every food ingredient is of vital importance, F. ovina deserves a more detailed investigation of its chemical and pharmacological prole. Having this and the ethnopharmacological use of this plant species in mind, we decided to perform detailed chemical composition analysis of the essential oil of aerial parts of F. ovina collected in Iran. An important motivation for this study was also the fact that plants from this genus are known to synthesize esters of substituted benzoic acids (vanillic, p-hydroxybenzoic and p-methoxybenzoic acids), e.g. ferutinin (ferutinol p-hydroxybenzoate), teferin (ferutinol vanillate) and jaesekanadiol p-methoxybenzoate. 4,11 Previous reports on the essential oil of F. ovina surprisingly lack these esters although volatile bornyl 4-hydroxybenzoates and vanillates, e.g. tschimganin and tschimgin, were isolated from taxa belonging to this genus. 12 Esters of these acids are known to activate transient receptor potential (TRP) channels that are implicated in pain percep- tion. 13 Targeting TRP channels has been an important strategy a Department of Chemistry, Faculty of Science and Mathematics, University of Ni ˇ s, Vi ˇ segradska 33, RS-18000 Ni ˇ s, Serbia. E-mail: nikoradulovic@yahoo.com; Fax: +381-18533014; Tel: +381-18533015 b Department of Physiology, Faculty of Medicine, University of Ni ˇ s, Bulevar dr Zorana Đind  i´ ca 81, RS-18000 Ni ˇ s, Serbia c Faculty of Medicine, University of Ni ˇ s, Bulevar dr Zorana Đind  i´ ca 81, RS-18000 Ni ˇ s, Serbia d Vinˇ ca Institute of Nuclear Sciences, Laboratory of Theoretical Physics and Condensed Matter Physics, University of Belgrade, P.O. Box 522, RS-11001 Belgrade, Serbia e Department of Basic Sciences, Islamic Azad University, Sabzevar Branch, Sabzevar, Iran † Electronic supplementary information (ESI) available. See DOI: 10.1039/c3fo60319a Cite this: Food Funct., 2013, 4, 1751 Received 7th August 2013 Accepted 9th September 2013 DOI: 10.1039/c3fo60319a www.rsc.org/foodfunction This journal is ª The Royal Society of Chemistry 2013 Food Funct., 2013, 4, 1751–1758 | 1751 Food & Function PAPER Published on 13 September 2013. Downloaded by University of Belgrade on 09/08/2014 08:10:11. 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