Mosquitoes (Diptera: Culicidae) are vectors of various pathogens of public health concern and replacing conventional insecticides remains a challenge. In this regard, natural products represent valuable sources of potential insecticidal compounds, thus increasingly attracting research interest. Commiphora myrrha (T.Nees) Engl. (Burseraceae) is a medicinal plant whose oleo-gum resin is used in food, cosmetics, fragrances, and pharmaceuticals. Herein, the larvicidal potential of its essential oil (EO) was assessed on four mosquito species (Aedes albopictus Skuse, Aedes aegypti L., Anopheles gambiae Giles and Anopheles stephensi Liston), with LC50 values ranging from 4.42 to 16.80 μg/mL. The bio-guided EO fractionation identified furanosesquiterpenes as the main larvicidal compounds. A GC-MS-driven untargeted metabolomic analysis revealed 32 affected metabolic pathways in treated larvae. The EO non-target toxicity on Daphnia magna Straus (LC50 = 4.51 μL/L) and its cytotoxicity on a human kidney cell line (HEK293) (IC50 of 14.38 μg/mL) were also assessed. This study shows the potential of plant products as innovative insecticidal agents and lays the groundwork for the possible exploitation of C. myrrha EO in sustainable approaches for mosquito management.

Chemistry Interdisciplinary Project Research Center School of Pharmacy University of Camerino Via Madonna delle Carceri 62032 Camerino Italy

Crop Research Institute Drnovska 507 161 06 Prague Czech Republic

Department of Agriculture Food and Environment University of Pisa Via del Borghetto 80 56124 Pisa Italy

Department of Plant Biotechnology College of Life Sciences and Biotechnology Korea University Seoul 02841 Republic of Korea

Dipartimento di Scienze Agrarie e Ambientali Produzione Territorio Agroenergia Università Statale di Milano Via Celoria N 2 20133 Milan Italy

Grupo Productos Naturales Marinos Facultad de Ciencias Farmacéuticas y Alimentarias Universidad de Antioquia Calle 70 No 52 21 050010 Medellín Colombia

Instituto de Física Universidad de Antioquia UdeA Calle 70 No 52 21 050010 Medellín Colombia

School of Biosciences and Veterinary Medicine University of Camerino Via Gentile 3 Da Varano 62032 Camerino Italy

School of Pharmacy University of Camerino Camerino Italy

Zobrazit více v PubMed

Chala B, Hamde F. Emerging and re-emerging vector-borne infectious diseases and the challenges for control: a review. Front Public Health. 2021;9:1–10. 10.3389/fpubh.2021.715759. PubMed DOI PMC

Benelli G, Wilke AB, Beier JC. PubMed DOI

Pustijanac E, Buršić M, Millotti G, Paliaga P, Iveša N, Cvek M. Tick-borne bacterial diseases in Europe: threats to public health. Eur J Clin Microbiol Infect Dis. 2024. 10.1007/s10096-024-04836-5. PubMed DOI

Hemingway J, Ranson H. Insecticide resistance in insect vectors of human disease. Annu Rev Entomol. 2000;45:371–91. 10.1146/annurev.ento.45.1.371. PubMed DOI

Haddi K, Nauen R, Benelli G, Guedes RNC. Global perspectives on insecticide resistance in agriculture and public health. Entomol Gen. 2023;43:495–500. 10.1127/entomologia/2023/2186. DOI

Modafferi A, Giunti G, Benelli G, Campolo O. Ecological costs of botanical nano-insecticides. Curr Opin Environ Sci Health. 2024;42: 100579. 10.1016/j.coesh.2024.100579. DOI

Dolara P, Corte B, Ghelardini C, Pugliese AM, Cerbai E, Menichetti S, Nostro AL. Local anaesthetic, antibacterial and antifungal properties of sesquiterpenes from myrrh. Planta Med. 2000;66(04):356–8. 10.1055/s-2000-8532. PubMed DOI

Abdul-Ghani RA, Loutfy N, Hassan A. Myrrh and trematodoses in Egypt: an overview of safety, efficacy and effectiveness profiles. Parasitol Internat. 2009;58(3):210–4. 10.1016/j.parint.2009.04.006. PubMed DOI

Batiha GES, Wasef L, Teibo JO, Shaheen HM, Zakariya AM, Akinfe OA, Teibo TKA, Al-kuraishy HM, Al-Garbee AI, Alexiou A, Papadakis M. PubMed DOI PMC

Leung AY, Foster S. Encyclopedia of common natural ingredients (used in food, drugs, and cosmetics). Hoboken: A John Wiley & Sons Inc.; 2003. p. 366–7.

Lubbe A, Verpoorte R. Cultivation of medicinal and aromatic plants for specialty industrial materials. Ind Crops Prod. 2011;34(1):785–801. 10.1016/j.indcrop.2011.01.019. DOI

Nomicos EY. Myrrh: medical marvel or myth of the magi? Holist Nurs Pract. 2007;21(6):308–23. 10.1097/01.HNP.0000298616.32846.34. PubMed DOI

Wahba TF, Aly HM, Hassan NA. The antifeedant properties of bio-oil from DOI

Zhu Y, Wu T, Hu Q, He W, Zheng Y, Xie Y, Rao Q, Liu X. Plant essential oils: dual action of toxicity and egg-laying inhibition on PubMed DOI PMC

Dekebo A, Dagne E, Sterner O. Furanosesquiterpenes from PubMed DOI

Marongiu B, Piras A, Porcedda S, Scorciapino A. Chemical composition of the essential oil and supercritical CO2 extract of PubMed DOI

Morteza-Semnani K, Saeedi M. Constituents of the essential oil of DOI

Baldovini N, Tomi F, Casanova J. Identification and quantitative determination of furanodiene, a heat‐sensitive compound, in essential oil by PubMed

Van den Dool H, Krat PD. A generalization of the retention index system including linear temperature programmed gas-liquid partition chromatography. J Chromatogr. 1963;2:463–71. PubMed DOI

Adams DRP. Identification of essential oil components by gas chromatography/. 2005.

NIST N. Mass Spectral Library (NIST/EPA/NIH). 2005.

Mondello L. FFNSC 2: flavors and fragrances of natural and synthetic compounds, mass spectral database. Software. 2011.

Maggi F, Barboni L, Papa F, Caprioli G, Ricciutelli M, Sagratini G, Vittori S. A forgotten vegetable ( PubMed DOI

https://jadebloom.com/media/wysiwyg/myrrh-gcms.pdf 2017. Accessed on 16 Aug 2024.

Brieskorn CH, Noble P. Two furanoeudesmanes from the essential oil of myrrh. Phytochem. 1983;22(1):187–9. 10.1016/S0031-9422(00)80085-0. DOI

Pavela R, Pavoni L, Bonacucina G, Cespi M, Kavallieratos NG, Cappellacci L, Petrelli R, Maggi F, Benelli G. Rationale for developing novel mosquito larvicides based on isofuranodiene microemulsions. J Pest Sci. 2019;92:909–21. 10.1007/s10340-018-01076-3. DOI

Weyerstahl P, Marschall-Weyerstahl H, Christiansen C, Oguntimein BO, Adeoye AO. Volatile constituents of PubMed DOI

Alanazi NAH, Alamri AA, Mashlawi AM, Almuzaini N, Mohamed G, Salama SA. Gas chromatography-mass spectrometry chemical profiling of commiphora myrrha resin extracts and evaluation of larvicidal, antioxidant, and cytotoxic activities. Molecules. 2024;29:1778. 10.3390/molecules29081778. PubMed DOI PMC

Baranitharan M, Dhanasekaran S. Mosquito larvicidal properties of

Baranitharan M, Dhanasekaran S, Gokulakrishnan J, Mahesh Babu S, Thushimenan S. Nagapattinam medicinal plants against the dengue fever mosquito,

Mkangara M, Chacha M, Kazyoba PE. Larvicidal potential of

Muturi EJ, Hay WT, Doll KM, Ramirez JL, Selling G. Insecticidal activity of PubMed DOI

Pavela R. Essential oils for the development of eco-friendly mosquito larvicides: a review. Ind Crops Prod. 2015;76:174–87. 10.1016/j.indcrop.2015.06.050. DOI

Costa JG, Pessoa OD, Menezes EA, Santiago GM, Lemos TL. Composition and larvicidal activity of essential oils from heartwood of DOI

Shaalan EAS, Canyon DV, Bowden B, Younes MWF, Abdel-Wahab H, Mansour AH. Efficacy of botanical extracts from PubMed

Triba MN, Le Moyec L, Amathieu R, Goossens C, Bouchemal N, Nahon P, Rutledge DN, Savarin P. PLS/OPLS models in metabolomics: the impact of permutation of dataset rows on the K-fold cross-validation quality parameters. Mol Biosyst. 2015;11(1):13–9. 10.1039/c4mb00414k. PubMed DOI

Hu T, Zhang W, Fan Z, Sun G, Likhodi S, Randell E, Zhai G. Metabolomics differential correlation network analysis of osteoarthritis. In Biocomputing: Proceedings of the Pacific Symposium. World Scientific Publishing Company. Singapore; 2016. pp. 120–131. PubMed

Chong J, Soufan O, Li C, Caraus I, Li S, Bourque G, Wishart DS, Xia J. MetaboAnalyst 4.0: towards more transparent and integrative metabolomics analysis. Nucleic Acids Res. 2018;46(W1):W486–94. 10.1093/nar/gky310. PubMed DOI PMC

Brinzer RA, Henderson L, Marchiondo AA, Woods DJ, Davies SA, Dow JA. Metabolomic profiling of permethrin-treated PubMed DOI

Gao YP, Luo M, Wang XY, He XZ, Lu W, Zheng XL. Pathogenicity of PubMed DOI PMC

Cerstiaens A, Huybrechts J, Kotanen S, Lebeau I, Meylaers K, De Loof A, Schoofs L. Neurotoxic and neurobehavioral effects of kynurenines in adult insects. Biochem Biophys Res Commun. 2003;312(4):1171–7. 10.1016/j.bbrc.2003.11.051. PubMed DOI

Li Y, Li Y, Wang G, Li J, Zhang M, Wu J, Liang C, Zhou H, Tang J, Zhu G. Differential metabolome responses to deltamethrin between resistant and susceptible PubMed DOI

Mansingh A. The effect of malathion on the metabolism of amino acids in the German cockroach PubMed DOI

Rand EED, Smit S, Beukes M, Apostolides Z, Pirk CW, Nicolson SW. Detoxification mechanisms of honeybees ( PubMed DOI PMC

Marco L, Sassera D, Epis S, Mastrantonio V, Ferrari M, Ricci I, Comandatore F, Bandi C, Porretta D, Urbanelli S. The choreography of the chemical defensome response to insecticide stress: insights into the PubMed DOI PMC

Mack L. Time-series analysis of transcriptomic changes due to permethrin exposure reveals that PubMed DOI PMC

Zhang C, Yuan H, Hu Y, Li X, Gao Y, Ma Z, Lei P. Structural diversity design, synthesis, and insecticidal activity analysis of ester-containing isoxazoline derivatives acting on the GABA receptor. J Agric Food Chem. 2023;71(7):3184–91. 10.1021/acs.jafc.2c07910. PubMed DOI

Homberg U, Humberg T, Seyfarth J, Bode K, Pérez M. GABA immunostaining in the central complex of dicondylian insects. J Comp Neurol. 2018;526(14):2301–18. 10.1002/cne.24497. PubMed DOI

Zulfiqar F, Akram N, Ashraf M. Osmoprotection in plants under abiotic stresses: new insights into a classical phenomenon. Planta. 2019. 10.1007/s00425-019-03293-1. PubMed DOI

Darkó É, Végh B, Khalil R, Marček T, Szalai G, Pál M, Janda T. Metabolic responses of wheat seedlings to osmotic stress induced by various osmolytes under iso-osmotic conditions. PLoS ONE. 2019;14(12): e0226151. 10.1371/journal.pone.0226151. PubMed DOI PMC

USEPA, United States Environmental Protection Agency. Methods for Measuring the Acute Toxicity of Effluent to Freshwater and Marine Organisms. 3rd ed. USEPA. United States Environmental Protection Agency. Washington, DC, United States; 1985.

FATMA, Limites Máximos de Toxidade Aguda para efluentes de diferentes origins. In: PORTARIA No. 017/02; 2002.

Ural MS, Saglam N. A study on the acute toxicity of pyrethroid deltamethrin on the fry rainbow trout ( DOI

Başer S, Erkoç F, Selvi M, Koçak O. Investigation of acute toxicity of permethrin on guppies PubMed DOI

Barata C, Baird DJ, Nogueira AJA, Soares AMVM, Riva MC. Toxicity of binary mixtures of metals and pyrethroid insecticides to PubMed DOI

Imgrund H. Environmental Fate of Permethrin. In Environmental Monitoring Branch. Department of Pesticide Regulation. Sacramento, CA, USA; 2003.

Maranho LA, Botelho RG, Mitie Inafuku M, Nogueira L, de Olinda AR, InaciodeSousa BAI, Tornisielo VL. Testing the neem biopesticide (

Ulrich J, Stiltz S, St-Gelais A, El Gaafary M, Simmet T, Syrovets T, Schmiech M. Phytochemical composition of PubMed DOI PMC

Sun X-Y, Zheng Y-P, Lin D-H, Zhang H, Zhao F, Yuan C-S. Potential anti-cancer activities of furanodiene, a sesquiterpene from PubMed DOI

Quassinti L, Bramucci M, Lupidi G, Barboni L, Ricciutelli M, Sagratini G, Papa F, Caprioli G, Petrelli D, Vitali LA, Vittori S, Maggi F. In Vitro biological activity of essential oils and isolated furanosesquiterpenes from the neglected vegetable PubMed DOI

Wang C-C, Chen L-G, Yang L-L. Cytotoxic activity of sesquiterpenoids from PubMed DOI

Wang K-T, Chen L-G, Yang L-L, Ke W-M, Chang H-C, Wan C-C. Analysis of the sesquiterpenoids in processed PubMed DOI

Spinozzi E, Ferrati M, Baldassarri C, Petrelli R, Cappellacci L, De Fazi L, Benelli G, Maggi F. Unlocking the potential of alexanders ( DOI

Wang Y, Li J, Guo J, Wang Q, Zhu S, Gao S, Yang C, Wei M, Pan X, Zhu W, Ding D, Gao R, Zhang W, Wang J, Zang L. Cytotoxic and antitumor effects of curzerene from PubMed DOI

Pavela R, Pavoni L, Bonacucina G, Cespi M, Cappellacci L, Petrelli R, Spinozzi E, Aguzzi C, Zeppa L, Ubaldi M, Desneux N, Canale A, Maggi F, Benelli G. Encapsulation of DOI

Stepanenko AA, Dmitrenko VV. HEK293 in cell biology and cancer research: phenotype, karyotype, tumorigenicity, and stress-induced genome-phenotype evolution. Gene. 2015;569(2):182–90. 10.1016/j.gene.2015.05.065. PubMed DOI

Gugliuzzo A, Francardi V, Simoni S, Roversi PF, Ferrati M, Spinozzi E, Perinelli DR, Bonacucina G, Maggi F, Tortorici S, Tropea Garzia G, Biondi A, Rizzo R. Role of plant essential oil nanoemulsions on host colonization by the invasive ambrosia beetle DOI

Maggi F, Papa F, Giuliani C, Maleci Bino L, Venditti A, Bianco A, Nicoletti M, Iannarelli R, Caprioli G, Sagratini G, Cortese M, Ricciutelli M, Vittori S. Essential oil chemotypification and secretory structures of the neglected vegetable DOI

Williams CM, Mander LN. Chromatography with silver nitrate. Tetrahedron. 2001;57(3):425–47. 10.1016/S0040-4020(00)00927-3. DOI

Mander LN, Williams CM. Chromatography with silver nitrate: part 2. Tetrahedron. 2016;72(9):1133–50. 10.1016/j.tet.2016.01.004. DOI

Damiens D, Benedict M, Wille M, Gilles J. An inexpensive and effective larval diet for PubMed DOI

WHO. Report of the WHO Informal Consultation on the Evaluation and Testing of 854 Insecticides. WHO Geneva. 1996;10:1026–1032.

Page M, Bejaoui N, Cinq-Mars B, Lemieux P. Optimization of the tetrazoliun-based colorimetric assay for the measurement of cell number and cytotoxicity. Int J Immunopharmacol. 1998;10(7):785–93. 10.1016/0192-0561(88)90001-X. PubMed DOI

Misra BB, Das V, Landi M, Abenavoli MR, Araniti F. Short-term effects of the allelochemical umbelliferone on PubMed DOI

Misra B. Steps for building an open source EI-MS mass spectral library for GC-MS -based metabolomics. Metabolomics Protocols & Workflows. 2019; 10.17504/protocols.io.8txhwpn

Sumner LW, Amberg A, Barrett D, Beale MH, Beger R, Daykin CA, Fan W-MT, Fiehn O, Goodacre R, Griffin JL, Hankemeier T, Hardy N, Harnly J, Higashi R, Kopka J, Lane AN, Lindon JC, Marriott P, Nicholls AW, Reily MD, Thaden JJ, Viant MR. Proposed minimum reporting standards for chemical analysis: chemical analysis working group (CAWG) metabolomics standards initiative (MSI). Metabolomics. 2007;3:211–21. 10.1007/s11306-007-0082-2. PubMed DOI PMC

OECD. Guideline for testing of chemicals.

Hlina BL, Birceanu O, Robinson CS, Dhiyebi H, Wilkie MP. The relationship between thermal physiology and lampricide sensitivity in larval sea lamprey ( DOI

R Development Core Team. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing. 2008. http://www.R-project.org. Accessed 26 Jul 2024.

Abbott WS. A method of computing the effectiveness of an insecticide. J Econ Entomol. 1925;18(2):265–7. DOI

Finney DJ. Probit analysis. London: Cambridge University Press; 1971.

Pang Z, Lu Y, Zhou G, Hui F, Xu L, Viau C, Spigelman AF, MacDonald PE, Wishart DS, Li S, Xia J. MetaboAnalyst 6.0: towards a unified platform for metabolomics data processing, analysis and interpretation. Nucleic Acids Res. 2024;52:W398–406. 10.1093/nar/gkae253. PubMed DOI PMC

Basu S, Duren W, Evans CR, Burant CF, Michailidis G, Karnovsky A. Sparse network modeling and metscape-based visualization methods for the analysis of large-scale metabolomics data. Bioinformatics. 2017;33(10):1545–53. 10.1093/bioinformatics/btx012. PubMed DOI PMC

Harnessing carlina oxide scaffold for the management of vector-borne diseases: synthesis and structure-activity relationship