Chemical Constituents from Ferula songarica and Ferula foetida: a Dereplication Approach
DOI:
https://doi.org/10.18321/ectj1701Keywords:
Ferula, Flavonoids, Sesquiterpenes, ApiaceaeAbstract
The genus Ferula (Apiaceae) is widely distributed across Central and Southwest Asia and is recognized for its diverse secondary metabolites and traditional medicinal uses. However, the phytochemical composition of Ferula songarica and Ferula foetida from Kazakhstan remains poorly explored. In this study, UHPLC–ESI–MS/MS-based metabolite profiling coupled with in silico annotation was applied to characterize methanolic extracts of F. songarica and F. foetida. A total of 20 metabolites were tentatively identified in F. songarica, dominated by daucane-type sesquiterpenes, along with flavonol glycosides, prenylated benzoic acids, and a fatty acid. In F. foetida, nine metabolites were annotated, primarily caffeoylquinic acid derivatives and fatty acids. Compound identification was achieved with high mass accuracy (<5 ppm) using a curated Apiaceae and Ferula-specific database integrated into SIRIUS. Several metabolites were confirmed at Level 1 confidence based on prior isolation in this laboratory, while the remainder were assigned as Level 3 annotations. Mechanistic MS/MS analysis revealed characteristic fragmentation pathways for each compound class. Notably, this study represents the first comprehensive UHPLC–ESI–MS/MS profiling of F. songarica and F. foetida from Kazakhstan. These findings expand the phytochemical knowledge of Ferula and highlight their potential as sources of bioactive natural products.
References
(1) Royal Botanic Gardens, Kew, Plants of the World Online. Available at: https://powo.science.kew.org/
(2) Y. Bahetjan, M. Muhaxi, K. Pang, et al., Chemistry, Bioactivity, and Prediction of the Quality Marker (Q-Marker) of Ferula Plants in China: A Review, Molecules 28 (2023) 5191. Crossref
(3) L.M.G. Grudzinskaia, N.G. Pavlov, N.V. Nelina, Zh.Zh. Karzhaubekova, Annotated listing of medicinal plants of Kazakhstan: reference edition, (2014).
(4) N.V. Pavlov, Flora of Kazakhstan, Vol. 6. Academy of Sciences of the Kazakh SSR (1963).
(5) M.K. Smagulov, Y.K. Levaya, K.Z. Badekova, et al., Phytochemical Profiling of Ferula varia Extract and Its Antibiofilm Activity Against Streptococcus mutans, Molecules 30 (2025) 4178. Crossref
(6) Z. Boghrati, M. Iranshahi, Ferula species: A rich source of antimicrobial compounds, J. Herb. Med. 16 (2019) 100244. Crossref
(7) M. Akaberi, M. Iranshahy, M. Iranshahi, Review of the traditional uses, phytochemistry, pharmacology and toxicology of giant fennel (Ferula communis L. subsp. communis), Iranian J. Basic Med. Sci. 18 (2015) 1050–1062. PMID: 26949491
(8) Z. Sattar, M. Iranshahi, Phytochemistry and pharmacology of Ferula persica Boiss.: A review, Iranian J. Basic Med. Sci. 20 (2017) 1–8. PMID: 28133517
(9) Z.E. Nazari, M. Iranshahi, Biologically active sesquiterpene coumarins from Ferula species, Phytother. Res. 25 (2011) 315-323. Crossref
(10) M. Mohammadhosseini, A. Venditti, S.D. Sarker, et al., The genus Ferula: Ethnobotany, phytochemistry and bioactivities – A review, Ind. Crops Prod. 129 (2019) 350-394. Crossref
(11) M.T. Khayat, M. Alharbi, K.F. Ghazawi, et al., Ferula sinkiangensis (Chou-AWei, Chinese Ferula): Traditional Uses, Phytoconstituents, Biosynthesis, and Pharmacological Activities. Plants 12 (2023) 902. Crossref
(12) Z.A. Turdiyeva, M.Y. Ishmuratova, G.A. Atazhanova, Component composition and antimicrobial activity of essential oil of Ferula songarica growing in Central Kazakhstan, In: Proceedings of The X International Scientific and Practical Conference of Young Scientists “Current Trends in Health-Saving Technologies”, Moscow, Russia, December 2022, p. 188-192. Crossref
(13) T. Khosnutdinova, H.A. Abd Karim, A.I. Norazhar, et al., Chemical constituents from Ferula songarica Pall. ex Spreng. and its chemotaxonomic significance, Biochem. Syst. Ecol. 126 (2026) 105241. Crossref
(14) M. Iranshahy, M. Iranshahi, Traditional uses, phytochemistry and pharmacology of asafoetida (Ferula assa-foetida oleo-gum-resin) – A review, J. Ethnopharmacol. 134 (2011) 1-10. Crossref
(15) H. Hashemzadeh, M. Iranshahi, M. Iranshahi, H. Raissi, In silico exploration of disulfide derivatives of Ferula foetida oleo-gum (Covexir ®) as promising therapeutics against SARS-CoV-2, Comput. Biol. Med. 146 (2022) 105566. Crossref
(16) A. Oyarhossein, S. Maskoukian, S. Tavakoli, et al., Ferula assa-foetida fruits: antioxidant activity, toxicity potential and phytochemical constituents, Res. J. Pharmacog. 12 (2025) 57–64.
(17) H.A. Abd Karim, N.E. Rasol, N.H. Ismail, et al., Metabolites annotation of dichloromethane extract of Kibatalia maingayi woods using Orbitrap high-resolution mass spectrometry, Malays. J. Chem. 24 (2022) 161–172. Crossref
(18) A.C. Schrimpe-Rutledge, S.G. Codreanu, S.D. Sherrod, J.A. McLean, Untargeted metabolomics strategies–challenges and emerging directions, J. Am. Soc. Mass Spectrom. 27 (2016) 1897–1905. Crossref
(19) C. Kahraman, G. Topcu, E. Bedir, et al., Phytochemical screening and evaluation of the antimicrobial and antioxidant activities of Ferula caspica M. Bieb. extracts, Saudi Pharm. J. 27(2019) 525–531. Crossref
(20) J. Harborne, H. Baxter, Flavonol O-glycosides, in: The Handbook of Natural Flavonoids, 1st ed., Harborne J.B., Baxter H. (Eds.), (1999) 297–548.
(21) S. Doganca, A. Ulubelen, E. Tuzlaci, 1-Acetylhydroquinone 4-galactoside from Ferulago aucheri, Phytochemistry 30 (1991) 2803–2805. Crossref
(22) G.J. Niemann, Acylated flavonol glycosides from Larix needles, Phytochemistry 14 (1975) 1437–1438. Crossref
(23) T. Nagai, H. Kiyohara, K. Munakata, et al., Pinellic acid from the tuber of Pinellia ternata Breitenbach as an effective oral adjuvant for nasal influenza vaccine, Int. Immunopharmacol. 2 (2002) 1183–1193. Crossref
(24) B. Chen, K. Kawazoe, Y. Takaishi, et al., Prenylated benzoic acid derivatives from Ferula kuhistanica, J. Nat. Prod. 63 (2000) 362–365. Crossref
(25) B. Chen, R. Teranishi, K. Kawazoe, et al., Sesquiterpenoids from Ferula kuhistanica, Phytochemistry 54 (2000) 717–722. Crossref
(26) R. Alkhatib, T. Hennebelle, S. Joha, et al., Activity of elaeochytrin A from Ferula elaeochytris on leukemia cell lines, Phytochemistry 69 (2008) 2979–2983. Crossref
(27) A.Y. Kushmuradov, A.S. Kadyrov, A.I. Saidkhodzhaev, V.M. Malikov, Structures of akiferidin and akiferidinin, Chem. Nat. Compd. 14 (1978) 617–619. Crossref
(28) L.A. Golovina, T.K. Khasanov, A.I. Saidkhodzhaev, et al., Coumarins and esters of Ferula microcarpa, Chem. Nat. Compd. 14 (1978) 487–490. Crossref
(29) A.I. Saidkhodzhaev, V.M. Malikov, M.G. Pimenov, S. Melibaev, Esters from the roots of Ferula kyzylkumica and F. karategina, Chem. Nat. Compd. 29 (1993) 253–254. Crossref
(30) K. Tamemoto, Y. Takaishi, B. Chen, et al., Sesquiterpenoids from the fruits of Ferula kuhistanica and antibacterial activity of the constituents of F. kuhistanica, Phytochemistry 58 (2001) 763–767. Crossref
(31) A. Lhuillier, N. Fabre, E. Cheble, et al., Daucane sesquiterpenes from Ferula hermonis, J. Nat. Prod. 68 (2005) 468–471. Crossref
(32) A.S. Kadyrov, A.I. Saidkhodzhaev, G.K. Nikonov, The structure of akichenol and akichenin, Chem. Nat. Compd. 12 (1976) 93–94. Crossref
(33) L. Arnoldi, M. Ballero, N. Fuzzati, et al., HPLC-DAD-MS identification of bioactive secondary metabolites from Ferula communis roots, Fitoterapia 75 (2004) 342–354. Crossref
(34) I. Parejo, F. Viladomat, J. Bastida, G. Schmeda-Hirschmann, J. Burillo, C. Codina, Bioguided isolation and identification of the nonvolatile antioxidant compounds from fennel (Foeniculum vulgare Mill.) waste, J. Agric. Food Chem. 52 (2004) 1890–1897. Crossref
(35) L.-C. Lin, Y.-C. Kuo, C.-J. Chou, Immunomodulatory principles of Dichrocephala bicolor, J. Nat. Prod. 62 (1999) 405–408. Crossref
(36) M. Znati, H. Ben Jannet, S. Cazaux, et al., Antioxidant, 5-lipoxygenase inhibitory and cytotoxic activities of compounds isolated from Ferula lutea flowers, Molecules 19 (2014) 16959–16975. Crossref
(37) J.H. Cardellina, R.E. Moore, Malyngic acid, a new fatty acid from Lyngbya majuscula, Tetrahedron 36 (1980) 993–996. Crossref
(38) A.M. Nandutu, M. Clifford, N. K. Howell, Analysis of phenolic compounds in Ugandan sweet potato varieties (NSP, SPK and TZ), African J. Biochem. Res. 1 (2007) 29–36.
(39) J. Wang, Q. Zheng, H. Wang, et al., Sesquiterpenes and sesquiterpene derivatives from Ferula: their chemical structures, biosynthetic pathways, and biological properties, Antioxidants 13 (2024) 7. Crossref







