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DOI: 10.1055/a-2640-4274
The Therapeutic Potential of Topically Applied Essential Oils in Preventing or Treating Early Borrelia burgdorferi Infection: A Review
Authors
Abstract
Lyme disease, caused by Borrelia burgdorferi, presents significant diagnostic challenges, often leading to delayed treatment and decreased therapeutic response to conventional antibiotics. This review aims to evaluate the potential of plant essential oils, known for their bacteriostatic, bactericidal, and anti-quorum sensing properties, as prophylactic, adjunct, or complementary treatments during the early stages of B. burgdorferi infection. The authors explore how these essential oils can target adaptive mechanisms and interactions of B. burgdorferi, including complement regulator-acquiring surface proteins (CRASPs), immune modulation, motility, chemotaxis, biofilm formation, efflux-pump mechanisms, and cyst formation. The authors identify current research gaps and propose frameworks to substantiate the clinical efficacy of essential oils for Lyme disease treatment. This review indicates that essential oils have multifaceted therapeutic potential and could provide a viable option for early intervention in Lyme disease. Further research is necessary to confirm their clinical applicability and safety.
Publication History
Received: 13 March 2025
Accepted after revision: 18 June 2025
Accepted Manuscript online:
20 June 2025
Article published online:
04 September 2025
© 2025. Thieme. All rights reserved.
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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References
- 1 Kugeler KJ, Earley A, Mead PS, Hinckley AF. Surveillance for lyme disease after implementation of a revised case definition – United States, 2022. MMWR Morb Mortal Wkly Rep 2024; 73: 118-123
- 2 CDC. Lyme Disease Surveillance and Data. Lyme Dis 2022. Accessed June 24, 2024 at: https://www.cdc.gov/lyme/data-research/facts-stats/index.html
- 3 Steinbrink A, Brugger K, Margos G, Kraiczy P, Klimpel S. The evolving story of Borrelia burgdorferi sensu lato transmission in Europe. Parasitol Res 2022; 121: 781-803
- 4 Pritt BS, Mead PS, Johnson DKH, Neitzel DF, Respicio-Kingry LB, Davis JP, Schiffman E, Sloan LM, Schriefer ME, Replogle AJ, Paskewitz SM, Ray JA, Bjork J, Steward CR, Deedon A, Lee X, Kingry LC, Miller TK, Feist MA, Theel ES, Patel R, Irish CL, Petersen JM. Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: A descriptive study. Lancet Infect Dis 2016; 16: 556-564
- 5 Hatchette T, Davis I, Johnston B. Lyme disease: clinical diagnosis and treatment. Can Commun Dis Rep 2014; 40: 194-208
- 6 Branda JA, Body BA, Boyle J, Branson BM, Dattwyler RJ, Fikrig E, Gerald NJ, Gomes-Solecki M, Kintrup M, Ledizet M, Levin AE, Lewinski M, Liotta LA, Marques A, Mead PS, Mongodin EF, Pillai S, Rao P, Robinson WH, Roth KM, Schriefer ME, Slezak T, Snyder J, Steere AC, Witkowski J, Wong SJ, Schutzer SE. Advances in serodiagnostic testing for lyme disease are at hand. Clin Infect Dis 2018; 66: 1133-1139
- 7 CDC. Diagnosis and testing of Lyme disease. Cent Dis Control Prev 2021. Accessed December 17, 2023 at: www.cdc.gov/lyme/diagnosistesting
- 8 CDC. Lyme Disease Prophylaxis After Tick Bite | Tick-borne Diseases | Ticks? 2022. Accessed January 02, 2024 at: https://www.cdc.gov/lyme/resources/pdfs/lyme-pep-low-ink-p.pdf
- 9 Trevisan G, Bonin S, Ruscio M. A practical approach to the diagnosis of lyme borreliosis: From clinical heterogeneity to laboratory methods. Front Med 2020; 7: 265-279
- 10 Cook MJ. Lyme borreliosis: A review of data on transmission time after tick attachment. Int J Gen Med 2015; 8: 1-8
- 11 Tufts DM, Hart TM, Chen GF, Kolokotronis SO, Diuk-Wasser MA, Lin YP. Outer surface protein polymorphisms linked to host-spirochete association in Lyme Borreliae . Mol Microbiol 2019; 111: 868-882
- 12 Kraiczy P, Stevenson B. Complement regulator-acquiring surface proteins of Borrelia burgdorferi: Structure, function and regulation of gene expression. Ticks Tick Borne Dis 2013; 4: 26-34
- 13 Kelesidis T. The cross-talk between spirochetal lipoproteins and immunity. Front Immunol 2014; 5: 310-321
- 14 Skotarczak B. Adaptation factors of Borrelia for host and vector. Ann Agric Environ Med 2009; 16: 1-8
- 15 Tilly K, Rosa PA, Stewart PE. Biology of infection with Borrelia burgdorferi . Infect Dis Clin North Am 2008; 22: 217-234
- 16 Perronne C. Lyme and associated tick-borne diseases: Global challenges in the context of a public health threat. Front Cell Infect Microbiol 2014; 4: 74-79
- 17 Njoroge J, Sperandio V. Jamming bacterial communication: New approaches for the treatment of infectious diseases. EMBO Mol Med 2009; 1: 201-210
- 18 Berndtson K. Review of evidence for immune evasion and persistent infection in Lyme disease. Int J Gen Med 2013; 291: 291-306
- 19 Alban PS, Johnson PW, Nelson DR. Serum-starvation-induced changes in protein synthesis and morphology of Borrelia burgdorferi . Microbiology 2000; 146: 119-127
- 20 Brorson O, Brorson S. An in vitro study of the susceptibility of mobile and cystic forms of Borrelia burgdorferi to hydroxychloroquine. Int Microbiol 2002; 5: 25-31
- 21 Ionescu D, Cotar A, Badescu D, Dumitriu S. Comparative evaluation of three Western Blot assays for the diagnosis of Lyme borreoliosis in Romania. Biointerface Res Appl Chem 2013; 3: 628-634
- 22 Piesman J, Hojgaard A, Ullmann AJ, Dolan MC. Efficacy of an experimental azithromycin cream for prophylaxis of tick-transmitted lyme disease spirochete infection in a murine model. Antimicrob Agents Chemother 2014; 58: 348-351
- 23 Mayaud L, Carricajo A, Zhiri A, Aubert G. Comparison of bacteriostatic and bactericidal activity of 13 essential oils against strains with varying sensitivity to antibiotics. Lett Appl Microbiol 2008; 47: 167-173
- 24 Prabuseenivasan S, Jayakumar M, Ignacimuthu S. In vitro antibacterial activity of some plant essential oils. BMC Complement Altern Med 2006; 6: 39-46
- 25 Yap PSX, Yiap BC, Ping HC, Lim SHE. Essential oils, a new horizon in combating bacterial antibiotic resistance. Open Microbiol J 2014; 8: 6-14
- 26 Toroglu S. In vitro antimicrobial activity and antagonistic effect of essential oils from plant species. J Environ Biol 2007; 28: 551-559
- 27 Kong J, Wang Y, Yao Z, Lin Y, Zhang Y, Han Y, Zhou T, Ye J, Cao J. Eugenol works synergistically with colistin against colistin-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae isolates by enhancing membrane permeability. Microbiol Spectr 2023; 11: e03666-e03722
- 28 Gan C, Langa E, Valenzuela A, Ballestero D, Pino-Otín MR. Synergistic activity of thymol with commercial antibiotics against critical and high WHO priority pathogenic bacteria. Plants 2023; 12: 1868
- 29 Asadi S, Nayeri-Fasaei B, Zahraei-Salehi T, Yahya-Rayat R, Shams N, Sharifi A. Antibacterial and anti-biofilm properties of carvacrol alone and in combination with cefixime against Escherichia coli . BMC Microbiol 2023; 23: 55
- 30 Langeveld WT, Veldhuizen EJA, Burt SA. Synergy between essential oil components and antibiotics: A review. Crit Rev Microbiol 2013; 40: 76-94
- 31 do Nascimento AS, Tamiasso RSS, Morais SFM, Rizzo Gnatta J, Turrini RNT, Calache ALSC, de Brito Poveda V. Essential oils for healing and/or preventing infection of surgical wounds: A systematic review. Rev Esc Enferm USP 2022; 56: e20210442
- 32 Zhang X, Lin X, Cao J, Xie G, Yang X, Liu B, Xu X, Cheng F, Chen H, Pang Y. Application of Cinnamomum burmannii essential oil in promoting wound healing. Molecules 2024; 29: 2080
- 33 Gorain B, Pandey M, Leng NH, Yan CW, Nie KW, Kaur SJ, Marshall V, Sisinthy SP, Panneerselvam J, Molugulu N, Kesharwani P, Choudhury H. Advanced drug delivery systems containing herbal components for wound healing. Int J Pharm 2022; 617: 121617
- 34 Vasile BS, Birca AC, Musat MC, Holban AM. Wound dressings coated with silver nanoparticles and essential oils for the management of wound infections. Materials (Basel) 2020; 13: 1682
- 35 Balaure PC, Holban AM, Grumezescu AM, Mogoşanu GD, Bălşeanu TA, Stan MS, Dinischiotu A, Volceanov A, Mogoantă L. In vitro and in vivo studies of novel fabricated bioactive dressings based on collagen and zinc oxide 3D scaffolds. Int J Pharm 2019; 557: 199-207
- 36 Goc A, Niedzwiecki A, Rath M. Anti-borreliae efficacy of selected organic oils and fatty acids. BMC Complement Altern Med 2019; 19: 40
- 37 Hutschenreuther A, Birkemeyer C, Grötzinger K, Straubinger RK, Rauwald HW. Growth inhibiting activity of volatile oil from Cistus creticus L. against Borrelia burgdorferi s.s. in vitro. Pharmazie 2010; 65: 290-295
- 38 Chary-Valckenaere I, Jaulhac B, Champigneulle J, Piemont Y, Mainard D, Pourel J. Ultrastructural demonstration of intracellular localization of Borrelia burgdorferi in Lyme arthritis. Br J Rheumatol 1998; 37: 468-470
- 39 Rauwald HW, Liebold T, Grötzinger K, Lehmann J, Kuchta K. Labdanum and Labdanes of Cistus creticus and C. ladanifer: Anti-Borrelia activity and its phytochemical profiling. Phytomedicine 2019; 60: 152977
- 40 Feng J, Zhang S, Shi W, Zubcevik N, Miklossy J, Zhang Y. Selective Essential oils from spice or culinary herbs have high activity against stationary phase and biofilm Borrelia burgdorferi . Front Med 2017; 4: 169
- 41 Feng J, Shi W, Miklossy J, Tauxe GM, McMeniman CJ, Zhang Y. Identification of essential oils with strong activity against stationary phase Borrelia burgdorferi . Antibiotics (Basel) 2018; 7: 89
- 42 Chaieb K, Hajlaoui H, Zmantar T, Kahla-Nakbi AB, Rouabhia M, Mahdouani K, Bakhrouf A. The chemical composition and biological activity of clove essential oil, Eugenia caryophyllata (Syzigium aromaticum L. Myrtaceae): A short review. Phytother Res 2007; 21: 501-506
- 43 Evans WC, Evans D, Trease GE. Trease and Evans Pharmacognosy. 16th ed. Edinburgh, New York: Saunders/Elsevier; 2009
- 44 Shapiro S, Meier A, Guggenheim B. The antimicrobial activity of essential oils and essential oil components towards oral bacteria. Oral Microbiol Immunol 1994; 9: 202-208
- 45 Moon SE, Kim HY, Cha JD. Synergistic effect between clove oil and its major compounds and antibiotics against oral bacteria. Arch Oral Biol 2011; 56: 907-916
- 46 Serafino A, Vallebona PS, Andreola F, Zonfrillo M, Mercuri L, Federici M, Rasi G, Garaci E, Pierimarchi P. Stimulatory effect of eucalyptus essential oil on innate cell-mediated immune response. BMC Immunol 2008; 9: 17
- 47 Carrasco FR, Schmidt G, Romero AL, Sartoretto JL, Caparroz-Assef SM, Bersani-Amado CA, Cuman RKN. Immunomodulatory activity of Zingiber officinale Roscoe, Salvia officinalis L. and Syzygium aromaticum L. essential oils: Evidence for humor- and cell-mediated responses. J Pharm Pharmacol 2009; 61: 961-967
- 48 Sandner G, Heckmann M, Weghuber J. Immunomodulatory activities of selected essential oils. Biomolecules 2020; 10: 1139
- 49 Masyita A, Sari RM, Astuti AD, Yasir B, Rumata NR, Emran TB, Nainu F, Simal-Gandara J. Terpenes and terpenoids as main bioactive compounds of essential oils, their roles in human health and potential application as natural food preservatives. Food Chem X 2022; 13: 100217
- 50 Kuriyama H, Watanabe S, Nakaya T, Shigemori I, Kita M, Yoshida N, Masaki D, Tadai T, Ozasa K, Fukui K, Imanishi J. Immunological and psychological benefits of aromatherapy massage. Evid-Based Complement Altern Med 2005; 2: 179-184
- 51 Chen PJ, Chou CC, Yang L, Tsai YL, Chang YC, Liaw JJ. Effects of aromatherapy massage on pregnant womenʼs stress and immune function: A longitudinal, prospective, randomized controlled trial. J Altern Complement Med 2017; 23: 778-786
- 52 Hart PH, Brand C, Carson CF, Riley TV, Prager RH, Finlay-Jones JJ. Terpinen-4-ol, the main component of the essential oil of Melaleuca alternifolia (tea tree oil), suppresses inflammatory mediator production by activated human monocytes. Inflamm Res 2000; 49: 619-626
- 53 Nogueira MNM, Aquino SG, Rossa Junior C, Spolidorio DMP. Terpinen-4-ol and alpha-terpineol (tea tree oil components) inhibit the production of IL-1β, IL-6 and IL-10 on human macrophages. Inflamm Res 2014; 63: 769-778
- 54 Taniguchi K, Karin M. NF-κB, inflammation, immunity and cancer: Coming of age. Nat Rev Immunol 2018; 18: 309-324
- 55 Lee SY, Chen PY, Lin JC, Kirkby NS, Ou CH, Chang TC. Melaleuca alternifolia induces heme oxygenase-1 expression in murine RAW264.7 cells through activation of the Nrf2-ARE pathway. Am J Chin Med 2017; 45: 1631-1648
- 56 Yadav N, Chandra H. Suppression of inflammatory and infection responses in lung macrophages by eucalyptus oil and its constituent 1, 8-cineole: Role of pattern recognition receptors TREM-1 and NLRP3, the MAP kinase regulator MKP-1, and NFκB. PLoS One 2017; 12: e0188232
- 57 Juergens UR, Engelen T, Racké K, Stöber M, Gillissen A, Vetter H. Inhibitory activity of 1, 8-cineol (eucalyptol) on cytokine production in cultured human lymphocytes and monocytes. Pulm Pharmacol Ther 2004; 17: 281-287
- 58 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 Invest 2016; 45: 11-28
- 59 Fuqua C, Winans SC, Greenberg EP. Census and consensus in bacterial ecosystems: The LuxR-LuxI family of quorum-sensing transcriptional regulators. Annu Rev Microbiol 1996; 50: 727-751
- 60 Miller MB, Bassler BL. Quorum sensing in bacteria. Annu Rev Microbiol 2001; 55: 165-199
- 61 Winans SC, Bassler BL. Mob psychology. J Bacteriol 2002; 184: 873-883
- 62 Khan MSA, Zahin M, Hasan S, Husain FM, Ahmad I. Inhibition of quorum sensing regulated bacterial functions by plant essential oils with special reference to clove oil. Lett Appl Microbiol 2009; 49: 354-360
- 63 Chugani S, Greenberg EP. An evolving perspective on the Pseudomonas aeruginosa orphan quorum sensing regulator QscR. Front Cell Infect Microbiol 2014; 4: 152
- 64 Durán N, Justo GZ, Durán M, Brocchi M, Cordi L, Tasic L, Castro GR, Nakazato G. Advances in Chromobacterium violaceum and properties of violacein-Its main secondary metabolite: A review. Biotechnol Adv 2016; 34: 1030-1045
- 65 Pena RT, Blasco L, Ambroa A, González-Pedrajo B, Fernández-García L, López M, Bleriot I, Bou G, García-Contreras R, Wood TK, Tomás M. Relationship between quorum sensing and secretion systems. Front Microbiol 2019; 10: 1100
- 66 Rajamanikandan S, Jeyakanthan J, Srinivasan P. Molecular docking, molecular dynamics simulations, computational screening to design quorum sensing inhibitors targeting LuxP of Vibrio harveyi and its biological evaluation. Appl Biochem Biotechnol 2017; 181: 192-218
- 67 Saeki EK, Kobayashi RKT, Nakazato G. Quorum sensing system: Target to control the spread of bacterial infections. Microb Pathog 2020; 142: 104068
- 68 Vadakkan K, Choudhury AA, Gunasekaran R, Hemapriya J, Vijayanand S. Quorum sensing intervened bacterial signaling: Pursuit of its cognizance and repression. J Genet Eng Biotechnol 2018; 16: 239-252
- 69 Camele I, Elshafie HS, Caputo L, De Feo V. Anti-quorum sensing and antimicrobial effect of mediterranean plant essential oils against phytopathogenic bacteria. Front Microbiol 2019; 10: 2619
- 70 Szabó MÁ, Varga GZ, Hohmann J, Schelz Z, Szegedi E, Amaral L, Molnár J. Inhibition of quorum-sensing signals by essential oils. Phytother Res 2009; 24: 782-786
- 71 Ahmad A, Viljoen AM, Chenia HY. The impact of plant volatiles on bacterial quorum sensing. Lett Appl Microbiol 2014; 60: 8-19
- 72 Bouyahya A, Dakka N, Et-Touys A, Abrini J, Bakri Y. Medicinal plant products targeting quorum sensing for combating bacterial infections. Asian Pac J Trop Med 2017; 10: 729-743
- 73 Lu L, Hu W, Tian Z, Yuan D, Yi G, Zhou Y, Cheng Q, Zhu J, Li M. Developing natural products as potential anti-biofilm agents. Chin Med 2019; 14: 11
- 74 Sapi E, Balasubramanian K, Poruri A, Maghsoudlou JS, Socarras KM, Timmaraju AV, Filush KR, Gupta K, Shaikh S, Theophilus PAS, Luecke DF, MacDonald A, Zelger B. Evidence of in vivo existence of Borrelia biofilm in borrelial lymphocytomas. Eur J Microbiol Immunol 2016; 6: 9-24
- 75 Elken EM, Tan Z, Wang Q, Jiang X, Wang Y, Wang Y, Ma H. Impact of Sub-MIC eugenol on Klebsiella pneumoniae biofilm formation via upregulation of rcsB. Front Vet Sci 2022; 9: 945491
- 76 Wang W, Li D, Huang X, Yang H, Qiu Z, Zou L, Liang Q, Shi Y, Wu Y, Wu S, Yang C, Li Y. Study on antibacterial and quorum-sensing inhibition activities of Cinnamomum camphora leaf essential oil. Molecules 2019; 24: 3792
- 77 Aizawa SI. Chapter 6: Borrelia burgdorferi – Periplasmic Flagella in a Flat Wave Body. In: Aizawa SI, Hrsg. The Flagellar World Academic Press;; 2014: 28-29
- 78 Charon NW, Cockburn A, Li C, Liu J, Miller KA, Miller MR, Motaleb MA, Wolgemuth CW. The unique paradigm of spirochete motility and chemotaxis. Annu Rev Microbiol 2012; 66: 349-370
- 79 Bakker RG, Li C, Miller MR, Cunningham C, Charon NW. Identification of specific chemoattractants and genetic complementation of a Borrelia burgdorferi chemotaxis mutant: Flow cytometry-based capillary tube chemotaxis assay. Appl Environ Microbiol 2007; 73: 1180-1188
- 80 Considine RV, Cooksey RC, Williams LB, Fawcett RL, Zhang P, Ambrosius WT, Whitfield RM, Jones R, Inman M, Huse J, McClain DA. Hexosamines regulate leptin production in human subcutaneous adipocytes. J Clin Endocrinol Metab 2000; 85: 3551-3556
- 81 Tsuiki S, Miyagi T. Carcinofetal alterations in glucosamine-6-phosphate synthetase. Ann N Y Acad Sci 1975; 259: 298-306
- 82 Kovács JK, Felső P, Makszin L, Pápai Z, Horváth G, Ábrahám H, Palkovics T, Böszörményi A, Emődy L, Schneider G. Antimicrobial and virulence-modulating effects of clove essential oil on the foodborne pathogen Campylobacter jejuni . Appl Environ Microbiol 2016; 82: 6158-6166
- 83 Nazzaro F, Fratianni F, De Martino L, Coppola R, De Feo V. Effect of essential oils on pathogenic bacteria. Pharmaceuticals 2013; 6: 1451-1474
- 84 Burt SA, van der Zee R, Koets AP, de Graaff AM, van Knapen F, Gaastra W, Haagsman HP, Veldhuizen EJA. Carvacrol induces heat shock protein 60 and inhibits synthesis of flagellin in Escherichia coli O157:H7. Appl Environ Microbiol 2007; 73: 4484-4490
- 85 Gabel CV, Berg HC. The speed of the flagellar rotary motor of Escherichia coli varies linearly with protonmotive force. Proc Natl Acad Sci U S A 2003; 100: 8748-8751
- 86 Marini E, Magi G, Ferretti G, Bacchetti T, Giuliani A, Pugnaloni A, Rippo MR, Facinelli B. Attenuation of Listeria monocytogenes Virulence by Cannabis sativa L. essential oil. Front Cell Infect Microbiol 2018; 8: 293-303
- 87 Sarengaowa, Hu W, Feng K, Xiu Z, Jiang A, Lao Y. Tandem mass tag-based quantitative proteomic analysis reveal the inhibition mechanism of thyme essential oil against flagellum of Listeria monocytogenes. Food Res Int 2019; 125: 108508
- 88 Kohlert C, Rensen I, Maerz R, Schindler G, Graefe EU, Veit M. Bioavailability and pharmacokinetics of natural volatile terpenes in animals and humans. Planta Med 2000; 66: 495-505
- 89 Schäfer R, Schäfer W. [Percutaneous absorption of various terpenes – menthol, camphene, limonene, isoborneol-acetate, alpha-pinene – from foam baths (authorʼs transl)]. Arzneimittelforschung 1982; 32: 56-58
- 90 Römmelt H, Zuber A, Dirnagl K, Drexel H. [The absorption of terpenes from bath additives (authorʼs transl)]. MMW Munch Med Wochenschr 1974; 116: 537-540
- 91 Schuster O, Hagg F, Priester H. Transdermale Absorption von Terpenen aus den etherischen Ölen der Pinimenthol-S-Salbe. Med Welt 1986; 37: 100-102
- 92 Kleinschmidt J, Römmelt H, Zuber A. The pharmacokinetics of the bronchosecretolytic ozothin after intravenous injection. Int J Clin Pharmacol 1985; 23: 200-203
- 93 Choi J, Lee KT, Ka H, Jung WT, Jung HJ, Park HJ. Constituents of the essential oil of Cinnamomum cassia stem bark and the biological properties. Arch Pharm Res 2001; 24: 418-423
- 94 Lassila T, Mattila S, Turpeinen M, Pelkonen O, Tolonen A. Tandem mass spectrometric analysis of S- and N-linked glutathione conjugates of pulegone and menthofuran and identification of P450 enzymes mediating their formation. Rapid Commun Mass Spectrom 2016; 30: 917-926
- 95 Thompson D, Constantin-Teodosiu D, Egestad B, Mickos H, Moldéus P. Formation of glutathione conjugates during oxidation of eugenol by microsomal fractions of rat liver and lung. Biochem Pharmacol 1990; 39: 1587-1595
- 96 Hayes JD, Flanagan JU, Jowsey IR. GLUTATHIONE TRANSFERASES. Annu Rev Pharmacol Toxicol 2005; 45: 51-88
- 97 Kovar KA, Gropper B, Friess D, Ammon HP. Blood levels of 1, 8-cineole and locomotor activity of mice after inhalation and oral administration of rosemary oil. Planta Med 1987; 53: 315-318
- 98 Falk AA, Hagberg MT, Löf AE, Wigaeus-Hjelm EM, Wang ZP. Uptake, distribution and elimination of alpha-pinene in man after exposure by inhalation. Scand J Work Environ Health 1990; 16: 372-378
- 99 Jäger W, Nasel B, Nasel C, Binder R, Stimpfl T, Vycudilik W, Buchbauer G. Pharmacokinetic studies of the fragrance compound 1, 8-cineol in humans during inhalation. Chem Senses 1996; 21: 477-480
- 100 Jäger W, Buchbauer G, Jirovetz L, Fritzer M. Percutaneous absorption of lavender oil from a massaDe oil. J Soc Cosmet Chem 1992; 43: 49-54
- 101 Sadgrove NJ, Padilla-González GF, Leuner O, Melnikovova I, Fernandez-Cusimamani E. Pharmacology of natural volatiles and essential oils in food, therapy, and disease prophylaxis. Front Pharmacol 2021; 12: 740302
- 102 Nöldner M, Germer S, Koch E. Pharmacokinetics of linalool and linalyl acetate, the two main constituents of silexan, an essential oil from Lavandula angustifolia flowers, in rats. Planta Med 2011; 77: PM44
- 103 Friedl SM, Heuberger E, Oedendorfer K, Kitzer S, Jaganjac L, Stappen I, Reznicek G. Quantification of 1, 8-Cineole in human blood and plasma and the impact of liner choice in head-space chromatography. Curr Bioact Compd 2015; 11: 49-55
- 104 Sarkic A, Stappen I. Essential oils and their single compounds in cosmetics–A critical review. Cosmetics 2018; 5: 11
- 105 Serrano E, Cornu A, Kondjoyan N, Figueredo G, Agabriel J, Micol D. Terpene accumulation in muscle and fatty tissues of calves supplemented with essential oils. J Anim Feed Sci 2007; 16: 168-179
- 106 Gerber PA, Buhren BA, Schrumpf H, Homey B, Zlotnik A, Hevezi P. The top skin-associated genes: A comparative analysis of human and mouse skin transcriptomes. Biol Chem 2014; 395: 577-591
- 107 Wang LH, Tso M. Determination of 5-methoxypsoralen in human serum. J Pharm Biomed Anal 2002; 30: 593-600
- 108 Samer CF, Gloor Y, Rollason V, Guessous I, Doffey-Lazeyras F, Saurat JH, Sorg O, Desmeules J, Daali Y. Cytochrome P450 1A2 activity and incidence of thyroid disease and cancer after chronic or acute exposure to dioxins. Basic Clin Pharmacol Toxicol 2020; 126: 296-303
- 109 Zehetner P, Höferl M, Buchbauer G. Essential oil components and cytochrome P450 enzymes: A review. Flavour Fragr J 2019; 34: 223-240
- 110 Jiang Q, Wu Y, Zhang H, Liu P, Yao J, Yao P, Chen J, Duan J. Development of essential oils as skin permeation enhancers: Penetration enhancement effect and mechanism of action. Pharm Biol 2017; 55: 1592-1600
- 111 Furuishi T, Kato Y, Fukami T, Suzuki T, Endo T, Nagase H, Ueda H, Tomono K. Effect of terpenes on the skin permeation of lomerizine dihydrochloride. J Pharm Pharm Sci 2013; 16: 551-563
- 112 Moghadam SH, Saliaj E, Wettig SD, Dong C, Ivanova MV, Huzil JT, Foldvari M. Effect of chemical permeation enhancers on stratum corneum barrier lipid organizational structure and interferon alpha permeability. Mol Pharm 2013; 10: 2248-2260
- 113 Monti D, Chetoni P, Burgalassi S, Najarro M, Saettone MF, Boldrini E. Effect of different terpene-containing essential oils on permeation of estradiol through hairless mouse skin. Int J Pharm 2002; 237: 209-214
- 114 Prasad R, Koul V, Anand S, Khar RK. Effect of DC/mDC iontophoresis and terpenes on transdermal permeation of methotrexate: In vitro study. Int J Pharm 2007; 333: 70-78
- 115 Lan Y, Li H, Chen Y, Zhang Y, Liu N, Zhang Q, Wu Q. Essential oil from Zanthoxylum bungeanum Maxim. and its main components used as transdermal penetration enhancers: A comparative study. J Zhejiang Univ Sci B 2014; 15: 940-952
- 116 Chen J, Jiang QD, Chai YP, Zhang H, Peng P, Yang XX. Natural terpenes as penetration enhancers for transdermal drug delivery. Molecules 2016; 21: 1709
- 117 Schmitt S, Schaefer U, Sporer F, Reichling J. Comparative study on the in vitro human skin permeation of monoterpenes and phenylpropanoids applied in rose oil and in form of neat single compounds. Pharm 2010; 65: 102-105
- 118 Schmitt S, Schaefer UF, Doebler L, Reichling J. Cooperative interaction of monoterpenes and phenylpropanoids on the in vitro human skin permeation of complex composed essential oils. Planta Med 2009; 75: 1381-1385
- 119 Herman A, Herman AP. Essential oils and their constituents as skin penetration enhancer for transdermal drug delivery: A review. J Pharm Pharmacol 2014; 67: 473-485
- 120 Sieniawska E, Świątek Ł, Wota M, Rajtar B, Polz-Dacewicz M. Microemulsions of essentials oils – Increase of solubility and antioxidant activity or cytotoxicity?. Food Chem Toxicol 2019; 129: 115-124
- 121 Ghosh J, Hasan Z, Chakrabortty A. Development of antimicrobial and wound healing properties on cotton medical bandage by using the extract of eco-friendly herbs. J Inst Eng India Ser E 2021; 102: 75-86
- 122 Jantrawut P, Boonsermsukcharoen K, Thipnan K, Chaiwarit T, Hwang KM, Park ES. Enhancement of antibacterial activity of orange oil in pectin thin film by microemulsion. Nanomaterials 2018; 8: 545
- 123 Shaaban HA, Sadek Z, Edris AE, Saad-Hussein A. Analysis and antibacterial activity of Nigella sativa essential oil formulated in microemulsion system. J Oleo Sci 2015; 64: 223-232
- 124 Zhang QH, Schneidmiller RG, Hoover DR, Zhou G, Margaryan A, Bryant P. Essential oils as spatial repellents for the brown marmorated stink bug, alyomorpha halys (Stål) (Hemiptera: Pentatomidae). J Appl Entomol 2014; 138: 490-499
- 125 Aparicio RM, José García-Celma M, Pilar Vinardell M, Mitjans M. In vitro studies of the hemolytic activity of microemulsions in human erythrocytes. J Pharm Biomed Anal 2005; 39: 1063-1067
- 126 Jiao J. Polyoxyethylated nonionic surfactants and their applications in topical ocular drug delivery. Adv Drug Deliv Rev 2008; 60: 1663-1673
- 127 Andrade-Ochoa S, Nevárez-Moorillón GV, Sánchez-Torres LE, Villanueva-García M, Sánchez-Ramírez BE, Rodríguez-Valdez LM, Rivera-Chavira BE. Quantitative structure-activity relationship of molecules constituent of different essential oils with antimycobacterial activity against Mycobacterium tuberculosis and Mycobacterium bovis . BMC Complement Altern Med 2015; 15: 332
- 128 Hasanzadeh Baboli N, Hosseini SF, Gharsallaoui A. Antibacterial and anti-biofilm properties of cinnamaldehyde-loaded nanoliposomes against Listeria monocytogenes and Salmonella enteritidis adhered to stainless steel. Int J Food Sci Technol 2023; 58: 5275-5282
- 129 Leimann FV, Gonçalves OH, Machado RAF, Bolzan A. Antimicrobial activity of microencapsulated lemongrass essential oil and the effect of experimental parameters on microcapsules size and morphology. Mater Sci Eng C 2009; 29: 430-436
- 130 Arechabala B, Coiffard C, Rivalland P, Coiffard LJ, de Roeck-Holtzhauer Y. Comparison of cytotoxicity of various surfactants tested on normal human fibroblast cultures using the neutral red test, MTT assay and LDH release. J Appl Toxicol 1999; 19: 163-165
- 131 McClements DJ. Crystals and crystallization in oil-in-water emulsions: Implications for emulsion-based delivery systems. Adv Colloid Interface Sci 2012; 174: 1-30
- 132 de Groot A, Schmidt E. Essential Oils: Contact Allergy and Chemical Composition. New York: Routledge; 2021
- 133 Akermi S, Smaoui S, Fourati M, Elhadef K, Chaari M, Chakchouk Mtibaa A, Mellouli L. In-depth study of Thymus vulgaris essential oil: Towards understanding the antibacterial target mechanism and toxicological and pharmacological aspects. Biomed Res Int 2022; 2022: 3368883
- 134 Cuba R. Toxicity myths essential oils and their carcinogenic potential. Int J Aromather 2001; 11: 76-83
- 135 Kejlová K, Jírová D, Bendová H, Gajdoš P, Kolářová H. Phototoxicity of essential oils intended for cosmetic use. Toxicol In Vitro 2010; 24: 2084-2089
- 136 Van Houten B, Woshner V, Santos JH. Role of mitochondrial DNA in toxic responses to oxidative stress. DNA Repair (Amst) 2006; 5: 145-152
- 137 Bunse M, Daniels R, Gründemann C, Heilmann J, Kammerer DR, Keusgen M, Lindequist U, Melzig MF, Morlock GE, Schulz H, Schweiggert R, Simon M, Stintzing FC, Wink M. Essential oils as multicomponent mixtures and their potential for human health and well-being. Front Pharmacol 2022; 13: 956541
- 138 US Food and Drug Administration. Aromatherapy. FDA; 2024. Accessed May 29, 2025 at: https://www.fda.gov/cosmetics/cosmetic-products/aromatherapy
- 139 European Chemicals Agency. Essential Oils. Available online May 29, 2025 at: https://echa.europa.eu/support/substance-identification/sector-specific-support-for-substance-identification/essential-oils
- 140 International Fragrance Association. The fragrance industry key recommendations for the REACH revision: Enhancing economic resilience while safeguarding high safety standards. Available online May 29, 2025 at: https://d3t14p1xronwr0.cloudfront.net/docs/Position-papers/ifra-position-paper-reach-revision-1-april-2025.pdf
- 141 Dryden MS, Saeed K, Ogborn S, Swales P. Lyme borreliosis in southern United Kingdom and a case for a new syndrome, chronic arthropod-borne neuropathy. Epidemiol Infect 2015; 143: 561-572
- 142 Fida M, Challener D, Hamdi A, Oʼhoro J, Abu Saleh O. Babesiosis: A retrospective review of 38 cases in the upper Midwest. Open Forum Infect Dis 2019; 6: ofz311
- 143 Berghoff W. Chronic lyme disease and co-infections: Differential diagnosis. Open Neurol J 2012; 6: 158-178
- 144 Boyer PH, Lenormand C, Jaulhac B, Talagrand-Reboul E. Human co-infections between Borrelia burgdorferi s.l. and other Ixodes-borne microorganisms: A systematic review. Pathogens 2022; 11: 282
- 145 Wormser GP, McKenna D, Scavarda C, Cooper D, El Khoury MY, Nowakowski J, Sudhindra P, Ladenheim A, Wang G, Karmen CL, Demarest V, Dupuis AP, Wong SJ. Co-infections in persons with early lyme disease, New York, USA. Emerg Infect Dis 2019; 25: 748-752
- 146 Anguita J, Ramamoorthi N, Hovius JWR, Das S, Thomas V, Persinski R, Conze D, Askenase PW, Rincón M, Kantor FS, Fikrig E. Salp15, an Ixodes scapularis salivary protein, inhibits CD4(+) T cell activation. Immunity 2002; 16: 849-859
- 147 Ramamoorthi N, Narasimhan S, Pal U, Bao F, Yang XF, Fish D, Anguita J, Norgard MV, Kantor FS, Anderson JF, Koski RA, Fikrig E. The Lyme disease agent exploits a tick protein to infect the mammalian host. Nature 2005; 436: 573-577
- 148 Grazul M, Kwiatkowski P, Hartman K, Kilanowicz A, Sienkiewicz M. How to naturally support the immune system in inflammation-essential oils as immune boosters. Biomedicines 2023; 11: 2381
- 149 Zhou L, Zheng H, Tang Y, Yu W, Gong Q. Eugenol inhibits quorum sensing at sub-inhibitory concentrations. Biotechnol Lett 2013; 35: 631-637
- 150 Lazutka J, Mierauskiene J, Slapsyte G, Dedonyte V. Genotoxicity of dill (Anethum graveolens L.), peppermint (Mentha × piperita L.) and pine (Pinus sylvestris L.) essential oils in human lymphocytes and Drosophila melanogaster . Food Chem Toxicol 2001; 39: 485-492
- 151 Matura M, Sköld M, Börje A, Andersen KE, Bruze M, Frosch P, Goossens A, Johansen JD, Svedman C, White IR, Karlberg AT. Selected oxidized fragrance terpenes are common contact allergens. Contact Dermatitis 2005; 52: 320-328
- 152 Hart PH, Brand C, Carson CF, Riley TV, Prager RH, Finlay-Jones JJ. Terpinen-4-ol, the main component of the essential oil of Melaleuca alternifolia (tea tree oil), suppresses inflammatory mediator production by activated human monocytes. Inflamm Res 2000; 49: 619-626
