Authors : Angsuman Das Chaudhuri; Anirban Majumder; Sounik Manna

Volume/Issue : Volume 9 - 2024, Issue 9 - September

Google Scholar : https://tinyurl.com/mptxpxv4

Scribd : https://tinyurl.com/mr2cr69n

DOI : https://doi.org/10.38124/ijisrt/IJISRT24SEP1121

Note : A published paper may take 4-5 working days from the publication date to appear in PlumX Metrics, Semantic Scholar, and ResearchGate.

Abstract : Geraniol, a naturally occurring monoterpenoid found in essential oils of several aromatic plants, exhibits numerous therapeutic properties, including anti-inflammatory, antimicrobial, and anticancer activities. However, its therapeutic potential is hindered by poor water solubility, limited bioavailability, and rapid metabolism. Nanotechnology- based delivery systems offer a promising solution to these challenges, by enhancing the solubility, stability, and bioavailability of geraniol through advanced delivery systems in cancer treatment. This review critically examines recent advances in nanotechnology- based delivery systems for geraniol, exploring various nanocarriers such as liposomes, polymeric nanoparticles, dendrimers, and solid lipid nanoparticles. The review also highlights the mechanisms by which these nanocarriers improve geraniol's pharmacokinetic profile, its targeted delivery to cancer cells, and its impact on overcoming multidrug resistance. Future perspectives and potential clinical applications are discussed, emphasizing the need for further research to fully harness the potential of geraniol in cancer therapy.

Keywords : Geraniol, Anticancer, Drug-Delivary, Nanotechnology.

References :

1. Bhanot A, Sharma R, Noolvi MN. Natural sources as potential anti-cancer agents: A review. International journal of phytomedicine. 2011 Jan 1;3(1):9-26.
2. Baker BP, Grant JA. Geraniol Profile.2018.
3. Elterlein F, Bugdahn N, Kraft P. Sniffing out the sustainable future: The renewability revolution in fragrance chemistry. Chemistry–A European Journal. 2024 Apr 2;30(19):e202400006.
4. Khoshnazar SM, Zeinali N, Mohagheghi M, Shafieipour S. Safety and Efficacy of Geraniol in Gastrointestinal System. Revista Brasileira de Farmacognosia. 2024 Aug 7:1-5.
5. Ben Ammar R. Potential effects of geraniol on cancer and inflammation-related diseases: A review of the recent research findings. Molecules. 2023 Apr 23;28(9):3669.
6. Zhang L, Lin J, Zhang C, Hu S, Dong Y, Fan G, He F.Recent Advances in the Nanotechnology-Based Applications of Essential Oils.Current Nanoscience. 2024 Sep 1;20(5):630-43.
7. Lei Y, Fu P, Jun X, Cheng P. Pharmacological properties of geraniol–a review.Planta medica. 2019 Jan;85(01):48-55.
8. Wu Y, Wang Z, Fu X, Lin Z, Yu K. Geraniol-mediated osteoarthritis improvement by down-regulating PI3K/Akt/NF-κB and MAPK signals: In vivo and in vitro studies. International immunopharmacology. 2020 Sep 1;86:106713.
9. Mohamed Abdoul-Latif F, Ainane A, Houmed Aboubaker I, Mohamed J, Ainane T. Exploring the potent anticancer activity of essential oils and their bioactive compounds: Mechanisms and prospects for future cancer therapy. Pharmaceuticals. 2023 Jul 31;16(8):1086.
10. Lira MH, Andrade Júnior FP, Moraes GF, Macena GD, Pereira FD, Lima IO. Antimicrobial activity of geraniol: An integrative review. Journal of Essential Oil Research. 2020 May 3;32(3):187-97.
11. Butnariu M. Plants as source of essential oils and perfumery applications.Bioprospecting of plant biodiversity for industrial molecules.2021 Jul 19:261-92.
12. Saifullah M, Shishir MR, Ferdowsi R, Rahman MR, Van Vuong Q. Micro and nano encapsulation, retention and controlled release of flavor and aroma compounds: A critical review. Trends in Food Science & Technology. 2019 Apr 1;86:230-51.
13. Chen W, Viljoen AM. Geraniol—A review of a commercially important fragrance material.South African Journal of Botany. 2010 Oct 1;76(4):643-51.
14. Jugreet BS, Suroowan S, Rengasamy RK, Mahomoodally MF. Chemistry, bioactivities, mode of action and industrial applications of essential oils.Trends in Food Science & Technology. 2020 Jul 1;101:89-105.
15. Srivastava G, Mukherjee E, Mittal R, Ganjewala D. Geraniol and citral: recent developments in their anticancer credentials opening new vistas in complementary cancer therapy. Zeitschrift für Naturforschung C. 2024 Apr 19(0).
16. Perri F, Coricello A, Adams JD. Monoterpenoids: the next frontier in the treatment of chronic pain?. J. 2020 May 28;3(2):195-214.
17. Vennekens R, Vriens J, Nilius B. Herbal compounds and toxins modulating TRP channels. Current neuropharmacology. 2008 Mar 1;6(1):79-96.
18. Stobiecka A. Comparative study on the free radical scavenging mechanism exerted by geraniol and geranylacetone using the combined experimental and theoretical approach.Flavour and Fragrance Journal. 2015 Sep;30(5):399-409.
19. Al-Harrasi A, Bhatia S, Sharma PB, Ahmed MM, Anwer K. Anti-Inflammatory, Antioxidant, and Immunomodulatory Effects of EOs. InRole of Essential Oils in the Management of COVID-19 2022 Mar 30 (pp. 239-255). CRC Press.
20. Li J, Zhang X, Luan F, Duan J, Zou J, Sun J, Shi Y, Guo D, Wang C, Wang X. Therapeutic Potential of Essential Oils Against Ulcerative Colitis: A Review. Journal of Inflammation Research. 2024;17:3527.
21. Kim T, Song B, Cho KS, Lee IS.Therapeutic potential of volatile terpenes and terpenoids from forests for inflammatory diseases.International journal of molecular sciences. 2020 Mar 22;21(6):2187.
22. Wittig C, Scheuer C, Parakenings J, Menger MD, Laschke MW. Geraniol suppresses angiogenesis by down-regulating vascular endothelial growth factor (VEGF)/VEGFR-2 signaling. PLoS One. 2015;10:e0131946..
23. Sharma SH, Thulasingam S, Nagarajan S. Terpenoids as anti-colon cancer agents–A comprehensive review on its mechanistic perspectives.European journal of pharmacology. 2017 Jan 15;795:169-78.
24. Barik MR, Kaur H, Amin T, Tiwari H, Kour G, Goswami A, Ahmed Z, Nargotra A. Network pharmacology and in vitro validation to elucidate the molecular mechanism of Boswellia serrata phytoconstituents on inflammation. Journal of Proteins and Proteomics.2024 Jul 30:1-7.
25. Bagheri S, Salehi I, Ramezani-Aliakbari F, Kourosh-Arami M, Komaki A. Neuroprotective effect of geraniol on neurological disorders: a review article. Molecular Biology Reports. 2022 Nov;49(11):10865-74.
26. Wu Y, Wang L, Hu K, Yu C, Zhu Y, Zhang S, Shao A. Mechanisms and therapeutic targets of depression after intracerebral hemorrhage. Frontiers in Psychiatry. 2018 Dec 17;9:682.
27. Siddique YH, Naz F, Jyoti S, Ali F, Fatima A, Khanam S. Protective effect of Geraniol on the transgenic Drosophila model of Parkinson’s disease. Environmental Toxicology and Pharmacology. 2016 Apr 1;43:225-31.
28. Matera R, Lucchi E, Valgimigli L. Plant essential oils as healthy functional ingredients of nutraceuticals and diet supplements: A review. Molecules. 2023 Jan 16;28(2):901.
29. Setlur AS, Karunakaran C, Panhalkar V, Sharma S, Sarkar M, Niranjan V. Multifaceted computational profiling of thymol and geraniol against the human proteome for bio-repellent alternatives: Toxicity predictions, degradation analysis, and quantum mechanical approaches. Acta Tropica. 2024 Oct 1;258:107359.
30. Siddiqui T, Sharma V, Khan MU, Gupta K. Terpenoids in Essential Oils: chemistry, classification, and potential impact on human health and industry. Phytomedicine plus. 2024 Mar 24:100549.
31. Bordoloi M, Saikia S, Kolita B, Sarmah R, Roy S, Narzary B. Volatile inhibitors of phosphatidylinositol-3-kinase (PI3K) pathway: anticancer potential of aroma compounds of plant essential oils. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). 2018 Jan 1;18(1):87-109.
32. Almalki SG, Alsaweed M, Muteb Albadrani H, Alqurashi YE, Bazuhair MA, Ahmed HH, Ahmad P, Alfahed A, Al Othaim A, Iqbal D. A molecular informatics and in-vitro approach to evaluate the HMG-CoA reductase inhibitory efficacy of monoterpenes, carvacrol and geraniol. Journal of Taibah University for Science. 2024 Dec 31;18(1):2297456.
33. Vyhlídalová B, Ondrová K, Zůvalová I. Dietary monoterpenoids and human health: Unlocking the potential for therapeutic use. Biochimie.2024 Sep 10.
34. Jäger T, Bäcker S, Brodbeck T, Leibold E, Bader M. Quantitative determination of urinary metabolites of geraniol by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Analytical Methods. 2020;12(47):5718-28.
35. Huang J, Huang T, Li J. Regulation Mechanism and Potential Value of Active Substances in Spices in Alcohol–Liver–Intestine Axis Health.International Journal of Molecular Sciences. 2024 Mar 27;25(7):3728.
36. Pavan B, Dalpiaz A, Marani L, Beggiato S, Ferraro L, Canistro D, Paolini M, Vivarelli F, Valerii MC, Comparone A, De Fazio L. Geraniol pharmacokinetics, bioavailability and its multiple effects on the liver antioxidant and xenobiotic-metabolizing enzymes. Frontiers in pharmacology. 2018 Jan 25;9:18.
37. Zehetner P, Höferl M, Buchbauer G. Essential oil components and cytochrome P450 enzymes: a review. Flavour and Fragrance Journal. 2019 Jul;34(4):223-40.
38. Sharma K, Lanzilotto A, Yakubu J, Therkelsen S, Vöegel CD, Du Toit T, Jørgensen FS, Pandey AV. Effect of Essential Oil Components on the Activity of Steroidogenic Cytochrome P450. Biomolecules. 2024 Feb 8;14(2):203.
39. 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. Frontiers in Pharmacology. 2021 Oct 21;12:740302.
40. Crespo R, Galle ME, Bravo MG, Polo MP. Geraniol inhibits tumor cell proliferation in vitro and in vivo by posttranscriptional regulation of HMGCR. 2012.
41. Alamgir AN, Alamgir AN. Secondary metabolites: Secondary metabolic products consisting of C and H; C, H, and O; N, S, and P elements; and O/N heterocycles. Therapeutic use of medicinal plants and their extracts: volume 2: phytochemistry and bioactive compounds. 2018:165-309.
42. Bunse M, Daniels R, Gründemann C, Heilmann J, Kammerer DR, Keusgen M, Lindequist U, Melzig MF, Morlock GE, Schulz H, Schweiggert R. Essential oils as multicomponent mixtures and their potential for human health and well-being. Frontiers in Pharmacology. 2022 Aug 24;13:956541.
43. Alves-Silva JM, Zuzarte M, Girão H, Salgueiro L. The role of essential oils and their main compounds in the management of cardiovascular disease risk factors. Molecules. 2021 Jun 9;26(12):3506.
44. Silva H, Bárbara R. Exploring the anti-hypertensive potential of lemongrass—a comprehensive review. Biology. 2022 Sep 22;11(10):1382.
45. Medeiros KA, Dos Santos JR, Melo TC, de Souza MF, Santos LD, de Gois AM, Cintra RR, Lins LC, Ribeiro AM, Marchioro M. Depressant effect of geraniol on the central nervous system of rats: Behavior and ECoG power spectra. biomedical journal. 2018 Oct 1;41(5):298-305.
46. Pezzani R, Salehi B, Vitalini S, Iriti M, Zuñiga FA, Sharifi-Rad J, Martorell M, Martins N. Synergistic effects of plant derivatives and conventional chemotherapeutic agents: an update on the cancer perspective. Medicina. 2019 Apr 17;55(4):110.
47. Martins MS, Ferreira MS, Almeida IF, Sousa E. Occurrence of allergens in cosmetics for sensitive skin.Cosmetics. 2022 Mar 17;9(2):32.
48. Burke YD, Stark MJ, Roach SL, Sen SE, Crowell PL. Inhibition of pancreatic cancer growth by the dietary isoprenoids farnesol and geraniol. Lipids. 1997 Feb;32(2):151-156.
49. Carnesecchi S, Schneider Y, Ceraline J, Duranton B, Gosse F, Seiler N, Raul F. Geraniol, a component of plant essential oils, inhibits growth and polyamine biosynthesis in human colon cancer cells. Journal of Pharmacology and Experimental Therapeutics. 2001 Jul 1;298(1):197-200.
50. Carnesecchi S, Langley K, Exinger F, Gosse F, Raul F. Geraniol, a component of plant essential oils, sensitizes human colonic cancer cells to 5-fluorouracil treatment. Journal of Pharmacology and Experimental Therapeutics. 2002 May 1;301(2):625-30.
51. Kim SH, Bae HC, Park EJ, Lee CR, Kim BJ, Lee S, Park HH, Kim SJ, So I, Kim TW, et al. Geraniol inhibits prostate cancer growth by targeting cell cycle and apoptosis pathways. Biochem Biophys Res Commun. 2011;407(1):129–134.
52. Ahmad ST, Arjumand W, Seth A, Nafees S, Rashid S, Ali N, Sultana S. Preclinical renal cancer chemopreventive efficacy of geraniol by modulation of multiple molecular pathways. Toxicology. 2011 Nov 28;290(1):69-81.
53. Vinothkumar V, Manoharan S; Chemopreventive efficacy of geraniol against 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis; Redox Rep. 2011;16(3):91-100
54. Vinothkumar V, Manoharan S, Sindhu G, Nirmal MR, Vetrichelvi V. Geraniol modulates cell proliferation, apoptosis, inflammation, and angiogenesis during 7, 12-dimethylbenz [a]anthracene-induced hamster buccal pouch carcinogenesis. Mol Cell Biochem 2012;369(1-2):17-25.
55. Polo MP, Crespo R, de Bravo MG. Geraniol and simvastatin show a synergistic effect on a human hepatocarcinoma cell line. Cell Biochem Funct 2011;29(6):452-8.
56. Chaudhary SC, Siddiqui MS, Athar M, Alam MS. Geraniol inhibits murine skin tumorigenesis by modulating COX‐2 expression, Ras‐ERK1/2 signaling pathway and apoptosis. Journal of Applied Toxicology. 2013 Aug;33(8):828-37.
57. Jin X, Sun J, Miao X, Liu G, Zhong D. Inhibitory effect of geraniol in combination with gemcitabine on proliferation of BXPC-3 human pancreatic cancer cells. J Int Med Res 2013;41(4):993-1001.
58. Madankumar A, Jayakumar S, Gokuladhas K, Rajan B, Raghunandhakumar S, Asokkumar S, Devaki T. Geraniol modulates tongue and hepatic phase I and phase II conjugation activities and may contribute directly to the chemopreventive activity against experimental oral carcinogenesis. Eur J Pharmacol. 2013;705:148–155.
59. Crespo R, Montero Villegas S, Abba MC, de Bravo MG, Polo MP. Transcriptional and posttranscriptional inhibition of HMGCR and PC biosynthesis by geraniol in 2 Hep-G2 cell proliferation linked pathways. Biochem Cell Biol. 2013;91:131–139.
60. Galle M, Crespo R, Kladniew BR, Villegas SM, Polo M, de Bravo MG. Suppression by geraniol of the growth of A549 human lung adenocarcinoma cells and inhibition of the mevalonate pathway in culture and in vivo: Potential use in cancer chemotherapy. Nutr Cancer. 2014;66:888–895.
61. Soubh AA, Abdallah DM, El-Abhar HS. Geraniol ameliorates TNBS-induced colitis: Involvement of Wnt/β-catenin, p38MAPK, NF-κB, and PPARγ signaling pathways. Life Sci. 2015;136:142–150.
62. Hasan SK, Sultana S. Geraniol attenuates 2-acetylamino-fluorene induced oxidative stress, inflammation and apoptosis in the liver of wistar rats. Toxicol Mech Methods. 2015;25:559–573.
63. Liu W, Zhang R, Tian N, Xu X, Cao Y, Xian M, Liu H; Utilization of alkaline phosphatase PhoA in the bioproduction of geraniol by metabolically engineered Escherichia coli; Bioengineered. 2015;6(5):288-93.
64. Sawada S, Okano J, Imamoto R, Yasunaka Y, Abe R, Koda M, Murawaki Y, Isomoto H; Preventive Effect of Geraniol on Diethylnitrosamine-Induced Hepatocarcinogenesis in Rats; Yonago Acta Med. 2016 Mar;59(1):37-43.
65. Cho M, So I, Chun JN, Jeon JH. The antitumor effects of geraniol: Modulation of cancer hallmark pathways. International journal of oncology. 2016 May 1;48(5):1772-82.
66. Lee S, Park YR, Kim SH, Park EJ, Kang MJ, So I, Chun JN, Jeon JH. Geraniol suppresses prostate cancer growth through down-regulation of E2F8.Cancer Med. 2016 Oct;5(10):2899-2908.
67. Wang J, Su B, Zhu H, Chen C, Zhao G; Protective effect of geraniol inhibits inflammatory response, oxidative stress and apoptosis in traumatic injury of the spinal cord through modulation of NF-κB and p38 MAPK; Exp Ther Med. 2016 Dec;12(6):3607-3613.
68. Queiroz TB, Santos GF, Ventura SC, Hiruma-Lima CA, Gaivão IOM, Maistro EL. Cytotoxic and genotoxic potential of geraniol in peripheral blood mononuclear cells and human hepatoma cell line (HepG2).Genet Mol Res. 2017 Sep 27;16(3).
69. Qi F, Yan Q, Zheng Z, Liu J, Chen Y, Zhang G. Geraniol and geranyl acetate induce potent anticancer effects in colon cancer Colo-205 cells by inducing apoptosis, DNA damage and cell cycle arrest. J BUON. 2018 Mar-Apr;23(2):346-352.
70. Silva Pontes C, Garcia de Carvalho G, Rosa Perin Leite A, Chorilli M, Palomari Spolidorio DM. Improving Drug Delivery on Candida Albicans Using Geraniol Nanoemulsion. Pharmaceutics. 2023 Oct 17;15(10):2475.
71. Radwan IT, Ghazawy NA, Alkhaibari AM, Gattan HS, Alruhaili MH, Selim A, Salem ME, AbdelFattah EA, Hamama HM. Nanostructure Lipid Carrier of Curcumin Co-Delivered with Linalool and Geraniol Monoterpenes as Acetylcholinesterase Inhibitor of Culex pipiens. Molecules. 2024 Jan 4;29(1):271
72. Cimino C, Maurel OM, Musumeci T, Bonaccorso A, Drago F, Souto EM, Pignatello R, Carbone C. Essential oils: Pharmaceutical applications and encapsulation strategies into lipid-based delivery systems. Pharmaceutics. 2021 Mar 3;13(3):327.
73. Rodenak-Kladniew B, Gambaro R, Cisneros JS, Huck-Iriart C, Padula G, Castro GR, Chain CY, Islan GA. Enhanced anticancer activity of encapsulated geraniol into biocompatible lipid nanoparticles against A549 human lung cancer cells. Journal of Drug Delivery Science and Technology. 2023 Feb 1;80:104159.
74. Ekonomou SI, Akshay Thanekar P, Lamprou DA, Weaver E, Doran O, Stratakos AC. Development of Geraniol-Loaded Liposomal Nanoformulations against Salmonella Colonization in the Pig Gut. Journal of Agricultural and Food Chemistry. 2022 Jun 2;70(23):7004-14.
75. Kaur IP, Sharma G, Singh M, Ramzan M, Singh J, Sandhu SK, Gulati JS. Solid lipid nanoparticles in dermaceuticals.InNanomaterials for clinical applications 2020 Jan 1 (pp. 1-27).Elsevier.
76. Menossi M, Ollier RP, Casalongué CA, Alvarez VA.Essential oil‐loaded bio‐nanomaterials for sustainable agricultural applications.Journal of chemical technology & biotechnology. 2021 Aug;96(8):2109-22.
77. García-Pinel B, Porras-Alcalá C, Ortega-Rodríguez A, Sarabia F, Prados J, Melguizo C, López-Romero JM. Lipid-based nanoparticles: application and recent advances in cancer treatment. Nanomaterials. 2019 Apr 19;9(4):638.
78. Nair A, Mallya R, Suvarna V, Khan TA, Momin M, Omri A. Nanoparticles—Attractive carriers of antimicrobial essential oils. Antibiotics. 2022 Jan 14;11(1):108.
79. Ramachandraiah K, Hong GP. Polymeric nanomaterials for the development of sustainable plant food value chains. Food Bioscience. 2021 Jun 1;41:100978..
80. Hassan SF, Asghar S, Ullah Khan I, Munir R, Khalid SH. Curcumin Encapsulation in Geranium Oil Microemulsion Elevates Its Antibacterial, Antioxidant, Anti-Inflammatory, and Anticancer Activities. ACS omega. 2024 Jan 23;9(5):5624-36.
81. Christoforides E, Fourtaka K, Andreou A, Bethanis K. X-ray crystallography and molecular dynamics studies of the inclusion complexes of geraniol in β-cyclodextrin, heptakis (2, 6-di-O-methyl)-β-cyclodextrin and heptakis (2, 3, 6-tri-O-methyl)-β-cyclodextrin. Journal of Molecular Structure. 2020 Feb 15;1202:127350.
82. Farooq S, Ngaini Z. Lemongrass and Lemon Monometallic and Bimetallic Nanoparticles Synthesis and Their Applications.Chemistry Africa. 2024 Mar;7(2):565-81.
83. Sousa F, Ferreira D, Reis S, Costa P. Current insights on antifungal therapy: Novel nanotechnology approaches for drug delivery systems and new drugs from natural sources. Pharmaceuticals. 2020 Sep 15;13(9):248.
84. K Narang J, S Narang R, Ali J, Baboota S, Nagpal N, Kaur S, Kaur H. Nanoemulsions for improved efficacy of phytotherapeutics-A patent perspective. Recent Patents on Nanotechnology. 2017 Dec 1;11(3):194-213.
85. Tiwari M, Kakkar P. Plant derived antioxidants–geraniol and camphene protect rat alveolar macrophages against t-BHP induced oxidative stress. Toxicology in vitro. 2009 Mar 1;23(2):295-301.
86. Fajdek-Bieda A, Pawlińska J, Wróblewska A, Łuś A. Evaluation of the Antimicrobial Activity of Geraniol and Selected Geraniol Transformation Products against Gram-Positive Bacteria. Molecules. 2024 Feb 21;29(5):950.
87. La Rocca V, da Fonsêca DV, Silva‐Alves KS, Ferreira‐da‐Silva FW, de Sousa DP, Santos PL, Quintans‐Júnior LJ, Leal‐Cardoso JH, de Almeida RN. Geraniol induces antinociceptive effect in mice evaluated in behavioural and electrophysiological models. Basic & Clinical Pharmacology & Toxicology. 2017 Jan;120(1):22-9.
88. Qneibi M, Bdir S, Maayeh C, Bdair M, Sandouka D, Basit D, Hallak M. A Comprehensive Review of Essential Oils and Their Pharmacological Activities in Neurological Disorders: Exploring Neuroprotective Potential. Neurochemical Research. 2024 Feb;49(2):258-89.
89. Sun H, Wang Z, Sebastian Yakisich J. Natural products targeting autophagy via the PI3K/Akt/mTOR pathway as anticancer agents.Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). 2013 Sep 1;13(7):1048-56.
90. Shiau JP, Chuang YT, Tang JY, Yang KH, Chang FR, Hou MF, Yen CY, Chang HW.The impact of oxidative stress and AKT pathway on cancer cell functions and its application to natural products.Antioxidants. 2022 Sep 19;11(9):1845.
91. Koyama S, Heinbockel T. The effects of essential oils and terpenes in relation to their routes of intake and application.International journal of molecular sciences. 2020 Feb 25;21(5):1558.
92. Horn TL, Long L, Cwik MJ, Morrissey RL, Kapetanovic IM, McCormick DL. Modulation of hepatic and renal drug metabolizing enzyme activities in rats by subchronic administration of farnesol.Chemico-biological interactions. 2005 Apr 15;152(2-3):79-99.
93. Crespo R, Rodenak-Kladniew BE, Castro MA, Soberón MV, Lavarias SM. Induction of oxidative stress as a possible mechanism by which geraniol affects the proliferation of human A549 and HepG2 tumor cells. Chemico-Biological Interactions. 2020 Apr 1;320:109029.
94. Duncan RE, Lau D, El-Sohemy A, Archer MC. Geraniol and β-ionone inhibit proliferation, cell cycle progression, and cyclin-dependent kinase 2 activity in MCF-7 breast cancer cells independent of effects on HMG-CoA reductase activity. Biochemical pharmacology. 2004 Nov 1;68(9):1739-47.
95. Jiang K, Zhang T, Yin N, Ma X, Zhao G, Wu H, Qiu C, Deng G. Geraniol alleviates LPS-induced acute lung injury in mice via inhibiting inflammation and apoptosis. Oncotarget. 2017 Sep 9;8(41):71038.