Compendio degli studi più significativi con riferimento a proprietà, assunzione, effetti.

Brito RG, Guimarães AG, Quintans JS, Santos MR, De Sousa DP, Badaue-Passos D Jr, de Lucca W Jr, Brito FA, Barreto EO, Oliveira AP, Quintans LJ Jr. Citronellol, a monoterpene alcohol, reduces nociceptive and inflammatory activities in rodents. J Nat Med. 2012 Oct;66(4):637-44. doi: 10.1007/s11418-012-0632-4. 

Abstract. We describe the antinociceptive and anti-inflammatory properties of citronellol (CT) in rodents. CT, a monoterpene alcohol, is a naturally occurring monoterpene compound prevalent in essential oils of various aromatic plant species, such as Cymbopogon citratus. In mice, when evaluated against acetic-acid-induced abdominal writhing, CT (25, 50 and 100 mg/kg, i.p.) reduced (P < 0.001) the amount of writhing compared to the control group. In the formalin test, CT also significantly inhibited both the early (neurogenic pain) and the late (inflammatory pain) phases of formalin-induced licking (P < 0.001). When assessed in a thermal model of pain, CT (100 mg/kg, i.p.) caused a significant increase (P < 0.05) in the latency response on the hot-plate test. Such results were unlikely to be caused by motor abnormality. The anti-inflammatory activity of CT was investigated through carrageenan-induced pleurisy in mice. Pretreatment with CT was able to inhibit both neutrophil infiltration and the increase in TNF-α level in the exudates from carrageenan-induced pleurisy. In in vitro experiments, CT (1 and 100 μg/ml) also decreased nitric oxide production by LPS-stimulated macrophage. Together, these results indicate that CT is effective as an analgesic compound in various pain models, with its action probably mediated by the inhibition of peripheral mediators as well as central inhibitory mechanisms that could be related to its strong antioxidant effect observed in vitro.

Lapczynski A, Letizia CS, Api AM. Fragrance material review on (+)-(R)-citronellol. Food Chem Toxicol. 2008 Nov;46 Suppl 11:S114-6. doi: 10.1016/j.fct.2008.06.018. 

Abstract. A toxicologic and dermatologic review of (+)-(R)-citronellol when used as a fragrance ingredient is presented.

Staudt A, Duarte PF, Amaral BPD, Peixoto Andrade BCO, Simas NK, Correa Ramos Leal I, Sangenito LS, Santos ALSD, de Oliveira D, Junges A, Cansian RL, Paroul N. Biological properties of functional flavoring produced by enzymatic esterification of citronellol and geraniol present in Cymbopogon winterianus essential oil. Nat Prod Res. 2021 Dec;35(24):5981-5987. doi: 10.1080/14786419.2020.1810032.

Abstract. The chemical composition and biological properties of citronella essential oil were modified by enzymatic esterification reaction of the major monoterpenic alcohols with cinnamic acid. The almost complete conversion of geraniol and citronellol present in the citronella (Cymbopogon winterianus) essential oil, into geranyl (99%) and citronellyl (98%) cinnamates was obtained after 48 hours of reaction using a molar ratio of 3:1 (cinnamic acid/alcohol), lipase concentration (Novozym 435) of 15% (w/w) and 70 °C. The esterified oil showed higher antimicrobial activity against Staphylococcus aureus bacteria resistant to oxacillin and penicillin and also greater larvicidal activity against Aedes aegypti larvae compared to unesterified oil. The results concerning the evaluation of toxicity against Artemia salina and cytotoxicity against monkey kidney epithelial cells also showed the superiority of the esterified oil.

Pino-Otín MR, Langa E, Val J, Mainar AM, Ballestero D. Impact of citronellol on river and soil environments using non-target model organisms and natural populations. J Environ Manage. 2021 Jun 1;287:112303. doi: 10.1016/j.jenvman.2021.112303.

Abstract. ...Our results show that citronellol has a negative impact on the environment. Although acute effects cannot be expected, it is necessary to quantify the environmental levels as well as the long-term and persistent effects of this monoterpene. Copyright © 2021 The Author(s). 

Rajendran J, Pachaiappan P, Thangarasu R. Citronellol, an Acyclic Monoterpene Induces Mitochondrial-Mediated Apoptosis through Activation of Proapoptotic Factors in MCF-7 and MDA-MB-231 Human Mammary Tumor Cells. Nutr Cancer. 2021;73(8):1448-1458. doi: 10.1080/01635581.2020.1800766. 

Abstract. The present study investigated the anticancer activity of citronellol (CT) by analyzing the mitochondrial-mediated activation of apoptosis in MCF-7 and MDA-MB-231 human mammary tumor cell lines. Cytotoxicity, cell growth, and apoptosis were determined by measuring reactive oxygen species (ROS), the level of mitochondrial membrane potential (ΔΨm), DNA damage, and changes in morphology and expression of proteins involved in apoptosis in MCF-7 and MDA-MB-231 cells. Our results indicate that CT induces apoptosis as evidenced by the loss of cell viability, increase ROS generation, altered ΔΨm, and enhanced DNA damage. Further, CT inhibits Bcl-2 expression with the up-regulation of Bax, caspase-9, and -7 in both cancer cells. CT induces apoptosis in MCF-7 human mammary tumor cells by inducing oxidative damage and modulating the expression of various pro and anti-apoptotic proteins. Hence, CT might be a potential therapeutic agent for the treatment of breast cancer.

Kayishaer A, Fadlallah S, Mouterde LMM, Peru AAM, Werghi Y, Brunois F, Carboué Q, Lopez M, Allais F. Unprecedented Biodegradable Cellulose-Derived Polyesters with Pendant Citronellol Moieties: From Monomer Synthesis to Enzymatic Degradation. Molecules. 2021 Dec 18;26(24):7672. doi: 10.3390/molecules26247672.

Abstract. Levoglucosenone (LGO) is a cellulose-derived molecule that is present commercially on a multi-ton/year scale. Taking advantage of the α,β-conjugated ketone of LGO, a new citronellol-containing 5-membered lactone (HBO-citro) was synthesized through a one-pot two-step pathway involving oxa-Michael addition and Baeyer-Villiger oxidation. The solvent-free treatment of HBO-citro with NaBH4 at room temperature led to the full reduction of the lactone moiety which gave a novel fully renewable triol monomer having a citronellol side chain (Triol-citro). Noticeably, by simply changing the reducing agent, temperature and reaction duration, the partial reduction of HBO-citro can be achieved to yield a mixture of 5- and 6-membered Lactol-citro molecules. Triol-citro was chosen to prepare functional renewable polyesters having citronellol pendant chains via polycondensation reactions with diacyl chlorides having different chain lengths. Good thermal stability (Td5% up to 170 °C) and low glass transition temperatures (as low as -42 °C) were registered for the polyesters obtained. The polymers were then hydrolyzed using a commercial lipase from Thermomyces lanuginosus (Lipopan® 50 BG) to assess their biodegradability. A higher degradation profile was found for the polyesters prepared using co-monomers (acyl chlorides) having longer chain lengths. This is likely due to the decreased steric hindrance around the ester bonds which allowed enhanced accessibility of the enzyme.

Katsukawa M, Nakata R, Koeji S, Hori K, Takahashi S, Inoue H. Citronellol and geraniol, components of rose oil, activate peroxisome proliferator-activated receptor α and γ and suppress cyclooxygenase-2 expression. Biosci Biotechnol Biochem. 2011;75(5):1010-2. doi: 10.1271/bbb.110039. 

Abstract. We evaluated the effects of rose oil on the peroxisome proliferator-activated receptor (PPAR) and cyclooxygenase-2 (COX-2). Citronellol and geraniol, the major components of rose oil, activated PPARα and γ, and suppressed LPS-induced COX-2 expression in cell culture assays, although the PPARγ-dependent suppression of COX-2 promoter activity was evident only with citronellol, indicating that citronellol and geraniol were the active components of rose oil.

Citronellol is an oxygenated acyclic monoterpenoid alcohol produced by the secondary metabolism of plants and is present in flowers (Cymbopogon winterianu, Cymbopogon citratus.  Xylopia aromatica, Eupatorium cannabinum) citrus fruits, where it exerts various activities including anti-parasitic and growth-inhibiting.

Name breakdown and function of the components

• Citronellol - Derived from the term "citronella", the plant from which it was originally identified. It's a natural terpene and is part of the monoterpenic alcohols.

Description and function of the raw materials used in production

• Geranium or rose oil - These are the primary natural sources of citronellol. The oil is distilled from plants and flowers to obtain the compound.

Summary of the extraction process step by step

• Distillation - Essential oils containing citronellol, such as geranium or rose oil, undergo distillation to separate citronellol from other components.
• Refinement - Post-distillation, citronellol is further purified to remove impurities and achieve a high-quality product.
• Isolation - Finally, citronellol is separated and isolated as a pure compound.

Synthesised it appears as a colourless or slightly yellowish oily liquid with a pinkish odour and bitterish taste. Insoluble in water and glycerol, soluble in propylene glycol, ethanol and most non-volatile oils. Incompatible with oxidising agents.

What it is used for and where

Citronellol is an organic compound primarily used as a constituent in essential oils like rose and geranium. It has a characteristic scent similar to that of roses, which is why it's widely used in the cosmetic and fragrance industry. Additionally, it serves as an intermediate in the production of other chemical compounds.

Medical

Diabetes mellitus is a disease characterised by chronic hyperglycaemia with metabolic disturbances. This study showed that administration of citronellol attenuated hyperglycaemia in diabetic rats, improved key metabolic carbohydrate enzymes and could be developed as a functional and nutraceutical ingredient in the fight against diabetes mellitus (1). Citronellol may also exert an effective treatment, due to its anti-inflammatory and antioxidant effects, for allergic diseases (2) and may be considered as a potential drug against chronic dermatophytosis, due to its antimicrobial properties (3), properties that contribute to the preservation of food hygiene often compromised by the formation of biofilms against which citronellol prevented the formation of native microcolonies (4).

Cosmetics

It is a restricted ingredient as  III/86 a Relevant Item in the Annexes of the European Cosmetics Regulation 1223/2009. Substance or ingredient reported: Citronellol /+- 3,7-dimethyloct-6-en-1-ol

Perfuming. Unlike fragrance, which can also contain slightly less pleasant or characteristic odours, the term perfume indicates only very pleasant fragrances. Used for perfumes and aromatic raw materials.

Citronellol has shown good tolerability on the skin due to its low permeability and low skin penetration potential. It is added as a fragrance to liquid soaps, shampoos and other personal care products as a rose-scented cosmetic essence. As far as safety is concerned, the risk of sensitisation to this ingredient is possible, but very low (5).

Food

A food flavouring found in many confectionery products such as candies, baked goods and others. The function of citronellol in food is also as a preservative as it has been shown to destroy both the cell membrane and cell wall of the pathogenic fungus Aspergillus flavus, the main culprit of food mould, and against other fungi such as  Cladosporium spp., Cladosporium carrioni, C. cladosporioides, and C. oxysporum.  (6).

Other uses

Used in insecticides, insect repellents and for room scenting.

Perfumery: Given its pleasant fragrance, citronellol is often used in perfume-making.

Cosmetic and skincare products: Used as a fragrance component in a broad range of products such as lotions, creams, and bath gels.

Cleansing products: Citronellol can be found in soaps, cleansers, and other cleaning products due to its aromatic properties.

Insect repellents: Although different from citronella, citronellol may have some repelling properties.

Properties

Fragrance: It has a light floral scent that can vary slightly depending on its source.

Monoterpene alcohol: This chemical structure is what gives it its aromatic properties.

It's crucial to note that while citronellol is generally safe in the concentrations found in cosmetics and personal care products, some individuals may be sensitive or allergic to it. Always check product labels and conduct a patch test if you're unsure about sensitivities.

For more information:

Citronellol studies

Typical commercial product characteristics Citronellol

Appearance	Colourless or Yellowish oily liquid
Boiling Point	224.5±0.0°C at 760 mmHg
Melting Point	77-83°C
Flash Point	98.3±0.0°C
Density	0.8±0.1 g/cm3
Vapor Density	5.4
Vapor Pressure	0.0±0.9 mmHg at 25°C
Refraction Index	1,451
LogP	3.38
PSA	20.23000
Optical rotation	-0.3~+0.3°(D/20°C)
Shelf Life	24 months
Chemical Safety

• Molecular Formula    C₁₀H₂₀O
• Molecular Weight   156.26 g/mol
• Exact Mass    156.151413
• CAS  106-22-9  
• EC Number: 203-375-0  
• DSSTox Substance ID    DTXSID3026726   DTXSID20101583
• IUPAC  3,7-dimethyloct-6-en-1-ol
• InChl=1S/C10H20O/c1-9(2)5-4-6-10(3)7-8-11/h5,10-11H,4,6-8H2,1-3H3
• InChl Key      QMVPMAAFGQKVCJ-UHFFFAOYSA-N
• SMILES   CC(CCC=C(C)C)CCO
• MDL number  
• PubChem Substance ID    
• ChEBI  50462
• RTECS    RH3400000
• NCI    C65508
• FEMA     2309
• JECFA    1219
• NSC    8779

Synonyms:

• 2,6-DIMETHYL-2-OCTEN-8-OL
• 6-OCTEN-1-OL, 3,7-DIMETHYL
• 3,7-dimethyloct-6-en-1-ol
• Cephrol
• Elenol
• Rodinol

References_________________________________________________________________

(1) Srinivasan S, Muruganathan U. Antidiabetic efficacy of citronellol, a citrus monoterpene by ameliorating the hepatic key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats. Chem Biol Interact. 2016 Apr 25;250:38-46. doi: 10.1016/j.cbi.2016.02.020. 

(2) Kobayashi Y, Sato H, Yorita M, Nakayama H, Miyazato H, Sugimoto K, Jippo T. Inhibitory effects of geranium essential oil and its major component, citronellol, on degranulation and cytokine production by mast cells. Biosci Biotechnol Biochem. 2016 Jun;80(6):1172-8. doi: 10.1080/09168451.2016.1148573. 

(3) Pereira Fde O, Mendes JM, Lima IO, Mota KS, Oliveira WA, Lima Ede O. Antifungal activity of geraniol and citronellol, two monoterpenes alcohols, against Trichophyton rubrum involves inhibition of ergosterol biosynthesis. Pharm Biol. 2015 Feb;53(2):228-34. doi: 10.3109/13880209.2014.913299.

(4) Olszewska MA, Gędas A, Simões M. The Effects of Eugenol, Trans-Cinnamaldehyde, Citronellol, and Terpineol on Escherichia coli Biofilm Control as Assessed by Culture-Dependent and -Independent Methods. Molecules. 2020 Jun 6;25(11):2641. doi: 10.3390/molecules25112641.

(5) Lapczynski, A., Bhatia, S. P., Letizia, C. S., & Api, A. M. (2008). Fragrance material review on dl-citronellol. Food and chemical toxicology, 46(11), S103-S109.

(6) dos Santos, A. S., Silva, G. S., Silva, K. V. S., de Oliveira Lima, M. I., Arrua, J. M. M., de Oliveira Lima, E., & de Oliveira Pereira, F. (2017). Antifungal activity of geraniol and citronellol against food-relevant dematiaceous fungi Cladosporium spp. Revista Do Instituto Adolfo Lutz, 76, 1-8.