Linalool: Therapeutic Indication And Their Multifaceted Biomedical Applications

Abstract

This comprehensive review endeavors to illuminate the nuanced facets of linalool, a prominent monoterpene found abundantly in essential oils, constituting a massive portion of their composition. The biomedical relevance of linalool is a key focus, highlighting its therapeutic attributes observed through anti-nociceptive effects, anxiolytic properties, and behavioral modulation in individuals affected by dementia. These findings underscore the compound's potential application in biomedical applications. This review further explores contemporary formulations, delineating the adaptability of linalool in nano-emulsions, microemulsions, bio-capsules, and various topical formulations, including topical gels and lotions. This review covers published and granted patents between 2018–2024 and sheds light on the evolving landscape of linalool applications, revealing advancements in dermatological, anti-inflammatory, and antimicrobial domains.

Keywords

linalool - monoterpenes - linalool sources - linalool formulations - anti-inflammatory.

Publication History

Received: 23 March 2024

Accepted: 29 April 2024

Article published online:
05 July 2024

• References

• 1 Pereira I, Severino P, Santos AC. et al. Linalool bioactive properties and potential applicability in drug delivery systems. Colloids Surfaces B Biointerfaces 2018; 171: 566-578
• 2 Migheli R, Lostia G, Galleri G. et al. Neuroprotective effect of (R)-(-)-linalool on oxidative stress in PC12 cells. Phytomedicine Plus 2021; 1: 100073
• 3 An Q, Ren JN, Li X. et al. Recent updates on bioactive properties of linalool. Food Funct 2021; 12: 10370-10389
• 4 de Lucena JD, Gadelha-Filho CVJ, da Costa RO. et al. L-linalool exerts a neuroprotective action on hemiparkinsonian rats. Naunyn Schmiedebergs Arch Pharmacol 2020; 393: 1077-1088
• 5 Soulimani R, Joshi RK. Toxicological aspects and pharmaco-therapeutic properties of linalool, a natural terpene derivative of essential oils: Literature studies. Am J Essent Oils Nat Prod 2020; 8: 24-34
• 6 Zhang L, Su Q, Wang L. et al. Linalool: A ubiquitous floral volatile mediating the communication between plants and insects. J Syst Evol 2023; 61: 538-549
• 7 Rodríguez-López MI, Mercader-Ros MT, Lucas-Abellán C. et al. Comprehensive characterization of linalool-HP-β-cyclodextrin inclusion complexes. Molecules. 2020; 25: 5069
• 8 Yamada Y. Neurological activities of linalool and other fragrant compounds.
• 9 Dos Santos ÉRQ, Maia JGS, Fontes-Júnior EA. et al. Linalool as a therapeutic and medicinal tool in depression treatment: a review. Curr Neuropharmacol 2022; 20: 1073
• 10 Francois EL, Yaszemski MJ. Preclinical bone repair models in regenerative medicine. In: Principles of regenerative medicine. Elsevier; 2019. p 761-767
• 11 Miao Z, Dong M, Wang Z. et al. Linalool inhibits the progression of osteoarthritis via the Nrf2/HO-1 signal pathway both in vitro and in vivo. Int Immunopharmacol 2022; 113: 109338
• 12 Sabogal-Guáqueta AM, Hobbie F, Keerthi A. et al. Linalool attenuates oxidative stress and mitochondrial dysfunction mediated by glutamate and NMDA toxicity. Biomed Pharmacother 2019; 118: 109295
• 13 Varia RD, Patel JH, Modi FD. et al. In vitro and In vivo Antibacterial and Anti-inflammatory Properties of Linalool. Int J Curr Microbiol Appl Sci 2020; 9: 1481-1489
• 14 Conforti F, Perri MR, Guerrini A. et al Lavandula austroapennina and Lavandula angustifolia essential oils and bioactive components: in vitro anti-denaturation effect of lavender from the Pollino massif (Southern Italy). Plant Biosyst - An Int J Deal with all Asp Plant Biol [Internet] 2023; Mar 4 157: 339-345
• 15 Becker V, Hui X, Nalbach L. et al. Linalool inhibits the angiogenic activity of endothelial cells by downregulating intracellular ATP levels and activating TRPM8. Angiogenesis. 2021; 24: 613-630
• 16 Kim MG, Kim SM, Min JH. et al. Anti-inflammatory effects of linalool on ovalbumin-induced pulmonary inflammation. Int Immunopharmacol 2019; 74: 105706
• 17 Sun XB, Wang SM, Li T. et al. Anticancer activity of linalool terpenoid: apoptosis induction and cell cycle arrest in prostate cancer cells. Trop J Pharm Res 2015; 14: 619-625
• 18 Pushpalatha R, Sindhu G, Sharmila R. et al. Linalool Induces Reactive Oxygen Species Mediated Apoptosis in Human Oral Squamous Carcinoma Cells. Indian J Pharm Sci. 2021 83. 906-917
• 19 Ke J, Zhu C, Zhang Y. et al Anti-Arrhythmic Effects of Linalool via Cx43 Expression in a Rat Model of Myocardial Infarction. Front Pharmacol 2020; 11 (June) 1-8
• 20 Cheng BH, Sheen LY, Chang ST. Hypolipidemic effects of S-(+)-linalool and essential oil from Cinnamomum osmophloeum ct. linalool leaves in mice. J Tradit Complement Med [Internet] 2018; 8: 46-52
• 21 Hong SJ, Kim DS, Lee J. et al Inhalation of low-dose basil (Ocimum basilicum) essential oil improved cardiovascular health and plasma lipid markers in high fat diet-induced obese rats. J Food Sci [Internet] 2022; Jun 1 87: 2450-62.
• 22 Oner Z, Altınoz E, Elbe H. et al. The protective and therapeutic effects of linalool against doxorubicin-induced cardiotoxicity in Wistar albino rats. Hum Exp Toxicol 2019; 38: 803-813
• 23 Mohamed ME, Abduldaium MS, Younis NS. Cardioprotective effect of linalool against isoproterenol-induced myocardial infarction. Life. 2021; 11: 1-17
• 24 Camargo SF, Medeiros CF, Santos VV. et al Pharmacokinetics and Antihypertensive effect of linalool is improved after incorporation in β-cyclodextrin as a drug delivery system. FASEB J [Internet] 2020; Apr 1 34 S1 1
• 25 Raffalli C, Clouet E, Kuresepi S. et al. Fragrance allergens linalool and limonene allylic hydroperoxides in skin allergy: Mechanisms of action focusing on transcription factor Nrf2. Toxicol Sci 2018; 161: 139-148
• 26 Duan J, Li J, Wang Y. et al. Therapeutic effects and mechanism of action of lavender essential oil on atopic dermatitis by modulating the STAT3/RORγt pathway. Arab J Chem [Internet] 2024; 17: 105525
• 27 Rai VK, Sinha P, Yadav KS. et al. Anti-psoriatic effect of Lavandula angustifolia essential oil and its major components linalool and linalyl acetate. J Ethnopharmacol [Internet] 2020; 261: 113127
• 28 Ayurvedic T, Tm H. Pain and Inflammation Management: Part-I Pre-clinical Study of a 2023; 6: 259-270
• 29 Nawaz S, Muhammad Irfan H, Alamgeer, et al. Linalool: Monoterpene alcohol effectiveness in chronic synovitis through lowering Interleukin-17, spleen and thymus indices. Int Immunopharmacol [Internet]. 2023 121. 110517
• 30 Labone Azzahra V, Mahdi C, Aulanni’am A. The Potency of Monoterpenes Contained in Essential Oils of Canary Sap (Canarium indicum L.) as Anti-inflammatory Agent on Asthmatic Rats (Rattus norvegicus). J Pure Appl Chem Res 2018; 7: 292-300
• 31 Almohawes ZN, Alruhaimi HS. Effect of lavandula dentata extract on ovalbumin-induced asthma in male Guinea pigs. Brazilian. J Biol 2020; 80: 87-96
• 32 Katsuyama S, Otowa A, KAmio S. et al. Effect of plantar subcutaneous administration of bergamot essential oil and linalool on formalin-induced nociceptive behavior in mice. Biomed Res 2015; 36: 47-54
• 33 Phuong TNT, Jang SH, Rijal S. et al. GABA-and glycine-mimetic responses of linalool on the substantia gelatinosa of the trigeminal subnucleus caudalis in juvenile mice: pain management through linalool-mediated inhibitory neurotransmission. Am J Chin Med 2021; 49: 1437-1448
• 34 Tekeli İO, Ateşşahin A, Sakin F. et al. Protective effects of conventional and colon-targeted lycopene and linalool on ulcerative colitis induced by acetic acid in rats. Inflammopharmacology. 2019; 27: 313-322
• 35 Straface M, Makwana R, Palmer A. et al. Inhibition of neuromuscular contractions of human and rat colon by bergamot essential oil and linalool: Evidence to support a therapeutic action. Nutrients. 2020; 12: 1381
• 36 Chang C, Chang S, Liao VH. Potential anti-Parkinsonian’s effect of S-(+)-linalool from Cinnamomum osmophloeum ct. linalool leaves are associated with mitochondrial regulation via gas-1, nuo-1, and mev-1 in Caenorhabditis elegans. Phyther Res 2022; 36: 3325-3334
• 37 Vieira G, Cavalli J, Gonçalves ECD. et al. Antidepressant-like effect of terpineol in an inflammatory model of depression: Involvement of the cannabinoid system and D2 dopamine receptor. Biomolecules. 2020; 10: 1-23
• 38 Yuan C, Shin M, Park Y. et al. Linalool Alleviates A β 42-Induced Neurodegeneration via Suppressing ROS Production and Inflammation in Fly and Rat Models of Alzheimer’s Disease. Oxid Med Cell Longev. 2021: 8887716
• 39 Koriem KMM, El-Qady SWB. Linalool attenuates hypothalamus proteome disturbance facilitated by methamphetamine induced neurotoxicity in rats. Neurotoxicology [Internet] 2023; 99: 70-81
• 40 Liu X, Cai J, Chen H. et al. Antibacterial activity and mechanism of linalool against Pseudomonas aeruginosa. Microb Pathog 2020; 141: 103980
• 41 Guo F, Chen Q, Liang Q. et al. Antimicrobial activity and proposed action mechanism of linalool against Pseudomonas fluorescens. Front Microbiol 2021; 12: 562094
• 42 He R, Chen W, Chen H. et al. Antibacterial mechanism of linalool against L. monocytogenes, a metabolomic study. Food Control [Internet] 2022; 132: 108533
• 43 Kanekar S, Rao SS, Yuvarajan S. et al. Linalool-encapsulated alginate microspheres as anti-virulence target against wound infections using In vitro and In vivo models. J Drug Deliv Sci Technol 2022; 77: 103848
• 44 Singulani JL, Pedroso RS, Ribeiro AB. et al Geraniol and linalool anticandidal activity, genotoxic potential and embryotoxic effect on zebrafish. Future Microbiol [Internet] 2018; Nov 1 13: 1637-1646
• 45 Hamdi A, Aouf I, Viaene J. et al. Cytotoxicity and Antiviral Activities of Haplophyllum tuberculatum Essential Oils, Pure Compounds, and Their Combinations against Coxsackievirus B3 and B4. Planta Med [Internet] 2021; 87: 827-835
• 46 Choi HJ. Chemical constituents of essential oils possessing anti-influenza A/WS/33 virus activity. Osong Public Heal Res Perspect 2018; 9: 348-353
• 47 Jana S, Patra K, Sarkar S. et al. Antitumorigenic potential of linalool is accompanied by modulation of oxidative stress: an in vivo study in sarcoma-180 solid tumor model. Nutr Cancer 2014; 66: 835-848
• 48 Zhao Y, Meng X, Zeng Y. et al. Linalool inhibits MCF-7 tumor growth in a xenograft model by apoptosis induction and immune modulation. Nat Prod Commun 2021; 16 1934578X211015125
• 49 Tsai MJ, Chang WY, Chiu IH. et al. Improvement in Skin Penetration Capacity of Linalool by Using Microemulsion as a Delivery Carrier: Formulation Optimization and In Vitro Evaluation. Pharmaceutics. 2023 15. 5. 1446
• 50 Uzkuç NMÇ, Uzkuç H, Berber MM. et al. Stabilisation of lavender essential oil extracted by microwave-assisted hydrodistillation: Characteristics of starch and soy protein-based microemulsions. Ind Crops Prod 2021; 172: 114034
• 51 Prakash A, Vadivel V, Rubini D. et al. Antibacterial and antibiofilm activities of linalool nanoemulsions against Salmonella Typhimurium. Food Biosci 2019; 28: 57-65
• 52 Zhong W, Tang P, Liu T. et al. Linalool nanoemulsion preparation, characterization and antimicrobial activity against Aeromonas hydrophila. Int J Mol Sci 2021; 22: 11003
• 53 Dallay C, Malhiac C, Duchemin B. et al. Effect of linalool on lamellar-structured emulsions: From molecular organization to organoleptic properties. Food Hydrocoll 2024; 149: 109575
• 54 SOUTO EB. Optimization of Linalool-loaded Solid Lipid Nanoparticles using Experimental Factorial Design and Long-term Stability Studies with a New Centrifugal Sedimentation Method. 2018
• 55 Campos EVR, Proença PLF, Oliveira JL. et al. Carvacrol and linalool co-loaded in β-cyclodextrin-grafted chitosan nanoparticles as sustainable biopesticide aiming pest control. Sci Rep 2018; 8: 1-14
• 56 Spirescu VA, Șuhan R, Niculescu AG. et al. Biofilm-resistant nanocoatings based on ZnO nanoparticles and linalool. Nanomaterials. 2021; 11: 2564
• 57 Jabir MS, Taha AA, Sahib UI. et al. Novel of nano delivery system for Linalool loaded on gold nanoparticles conjugated with CALNN peptide for application in drug uptake and induction of cell death on breast cancer cell line. Mater Sci Eng C 2019; 94: 949-964
• 58 Shi F, Zhao Y, Firempong CK. et al. Preparation, characterization and pharmacokinetic studies of linalool-loaded nanostructured lipid carriers. Pharm Biol 2016; 54: 2320-2328
• 59 Wi TI, Won JE, Lee CM. et al. Efficacy of combination therapy with linalool and doxorubicin encapsulated by liposomes as a two-in-one hybrid carrier system for epithelial ovarian carcinoma. Int J Nanomedicine 2020; 8427-8436
• 60 Gupta I, Adin SN, Rashid MA. et al. Linalool-Incorporated Synergistically Engineered Modified Liposomal Nanocarriers for Enhanced Transungual Delivery of Terbinafine against Onychomycosis. Materials (Basel). 2023 16. 12. 4424
• 61 Kothandaraman GP, Kumar KS, Rithika J. et al. Synthesis and Anti-Proliferative Effect of Linalool propionate Loaded Carbon Nanoparticles. Beilstein Arch 2019; 2019: 56
• 62 Parasuraman V, Sharmin AM, Anand MAV. et al. Fabrication and bacterial inhibitory activity of essential oil linalool loaded biocapsules against Escherichia coli. J Drug Deliv Sci Technol 2022; 74: 103495
• 63 Hu J, Liu S, Deng W. Dual responsive linalool capsules with high loading ratio for excellent antioxidant and antibacterial efficiency. Colloids Surfaces B Biointerfaces 2020; 190: 110978
• 64 Akram MA, Khan BA, Khan MK. et al. Fabrication and characterization of polymeric pharmaceutical emulgel co-loaded with eugenol and linalool for the treatment of trichophyton rubrum infections. Polymers (Basel) 2021; 13: 3904
• 65 Sosnowska k, tomczykowa m, winnicka k. et al. In vivo evaluation of the antipsoriatic effect of hydrogel with lavandin essential oil and its main components after topical application. acta pol pharm 2022; 79: 757-770
• 66 Chatterjee R, Gadgil VR. Topical composition for enhancement of barrier function. Google Patents. 2020
• 67 Freeze CD, Freeze A. Cannabinoid and Terpene-Infused Topical Cream. Google Patents. 2020
• 68 Dias PM, Gadgil VR, Jagadish N. Topical composition for antiaging benefits. Google Patents. 2020
• 69 Li QX. Bioinsecticidal compositions containing monoterpenes and methods of use thereof. Google Patents. 2020
• 70 Elzinga S, Raber JC. Terpene-based compositions, processes, methodologies for creation and products thereby. Google Patents. 2020
• 71 Hoshino Y, Moriya M, Matsudaira A. et al. Stereospecific linalool production utilizing two-phase cultivation system in Pantoea ananatis. J Biotechnol 2020; 324: 21-27
• 72 Camacho S, Gonzalez SM, Le Coutre J. et al. Treatment or prevention of autism disorders using menthol, linalool and/or icilin. Google Patents. 2022
• 73 Nakajima T, Kikuchi K, Yonezawa D. et al. Solid composition having floral scent. Google Patents. 2022
• 74 Wicker NK, Poole LB, Stedronsky E. Personalized, precise, consistent botanical formulations on demand. Google Patents. 2023
• 75 Yonezawa D, Otsuka M, Mukai T. et al. Tea aromatizing composition having floral aroma. Google Patents. 2023