Citronellol modulates the expression of several genes and proteins involved in inflammation, oxidative stress, and apoptosis. It increases the expression of anti-inflammatory cytokines (IL-10) and decreases pro-inflammatory cytokines (NF-κB) [1]. It modulates the ROS-NO, MAPK/ERK, and PI3K/Akt signaling pathways [2]. It enhances Nrf2 expression and reduces COX-2 and iNOS expression [4]. It also modulates the Bcl-2/Bax pathway and mTOR expression [4].

In SH-SY5Y cells, Citronellol treatment (up to 200 μg/mL) did not affect cell viability, indicating non-toxic nature. At 400 μg/mL, cell viability was maintained at 72.65%, with an IC50 of 512.45 μg/mL [2].
Citronellol (50 μg/mL) significantly prevented 6-OHDA-induced cell death, maintaining cell viability at 96.25% compared to 46.56% in 6-OHDA-only treated cells [2].
Citronellol treatment significantly suppressed the expression levels of inflammatory cytokines IL-1β, IL-6, and TNF-α in 6-OHDA-treated SH-SY5Y cells [2].
Citronellol (50 μg/mL) reduced 6-OHDA-induced intracellular ROS and MDA levels and reversed the decrease in SOD activity in SH-SY5Y cells [2].
Citronellol (50 μg/mL) reduced 6-OHDA-induced intracellular NO and 3-NT (an ONOO- signature) levels in SH-SY5Y cells [2].
JC-1 staining showed that Citronellol (50 μg/mL) significantly increased the red/green fluorescence ratio, indicating protection against 6-OHDA-induced mitochondrial membrane potential (MMP, Ψm) rupture in SH-SY5Y cells [2].
AO/EtBr and Hoechst 33258 staining demonstrated that Citronellol (50 μg/mL) hindered 6-OHDA-induced apoptosis and restored morphometric destruction in SH-SY5Y cells [2].
Western blot analysis showed that Citronellol suppressed 6-OHDA-induced expression of pro-apoptotic Bax and increased anti-apoptotic Bcl-2, reducing the Bax/Bcl-2 ratio in SH-SY5Y cells [2].
Citronellol reduced 6-OHDA-induced phosphorylation of nNOS and iNOS [2].
Citronellol treatment reverted the 6-OHDA-induced reduction in ERK1/2 and Akt phosphorylation in SH-SY5Y cells [2].
In silico ADMET prediction suggested Citronellol has the ability to cross the blood-brain barrier (BBB) with 94.8% probability [2].

In a doxorubicin (DOX)-induced cardiotoxicity rat model, Citronellol (25, 50, and 100 mg/kg, oral) dose-dependently reduced elevated serum cardiac markers (CK-MB, LDH, CPK, SGOT) and lipid profile markers (TC, TG, LDL-C) while increasing HDL-C levels compared to the disease control group [1].
Citronellol (25, 50, and 100 mg/kg) prevented DOX-induced decrease in cardiac antioxidant enzymes (CAT, SOD, GSH) and dose-dependently reduced MDA levels. The effect on GSH was not significant at 25 and 50 mg/kg, but was moderately effective at 100 mg/kg [1].
qPCR analysis showed that Citronellol dose-dependently increased the expression of eNOS, IL-10, and VEGF (at 50 and 100 mg/kg), and decreased NFkB1 expression in DOX-treated rats. It also increased PPAR-γ expression [1].
In a rotenone-induced Parkinson's disease rat model, oral administration of Citronellol (25 mg/kg) for four weeks prevented rotenone-induced decrease in Nrf2 expression and increased antioxidant enzymes (catalase, GSH, SOD) while decreasing lipid peroxidation (MDA) in the brain [4].
Citronellol (25 mg/kg) reduced rotenone-induced secretion of pro-inflammatory factors IL-6, IL-1β, TNF-α, and MMP-9, and decreased the expression of COX-2 and iNOS in the midbrain [4].
Immunofluorescence staining showed that Citronellol (25 mg/kg) significantly reduced rotenone-induced activation of microglia (Iba-1) and astrocytes (GFAP) in the striatum [4].
Immunohistochemistry analysis demonstrated that Citronellol (25 mg/kg) prevented rotenone-induced loss of tyrosine hydroxylase (TH)-positive dopaminergic neurons in the substantia nigra pars compacta (SNpc) and preserved TH expression in striatal fibers [4].
Western blot analysis showed that Citronellol (25 mg/kg) reduced rotenone-induced over-expression of α-synuclein, decreased pro-apoptotic Bax, increased anti-apoptotic Bcl-2, and restored mTOR expression in the midbrain [4].
Citronellol (25 mg/kg) decreased rotenone-induced accumulation of autophagic markers LC3 and p62 in the midbrain [4].

Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. SH-SY5Y cells were plated into 96-well plates at a density of 10^3 cells/well and incubated with 10 μL of CCK-8 solution for 2 hours. Absorbance was measured at 450 nm with a microplate reader. This was used to assess the toxicity of Citronellol alone and its protective effect against 6-OHDA-induced toxicity [2].
The amounts of inflammatory markers (IL-1β, IL-6, TNF-α) in SH-SY5Y cells were detected using ELISA kits, following the manufacturer's instructions [2].
Oxidative stress was measured using commercial kits. MDA levels were determined using an MDA kit. Intracellular ROS levels were measured using a ROS/superoxide detection kit. SOD levels were determined using an SOD kit. Corresponding absorbance was measured using a multi-label reader [2].
Intracellular NO level in SH-SY5Y cells was quantified using DAF-FM DA staining. Cells were incubated with 5 μM DAF-FM DA for 20 minutes at 37°C. After washing, fluorescence intensity was measured using a multilabel reader with Ex495nm and Em515nm [2].
Protein-bound 3-nitrotyrosine (3-NT) was identified using an ELISA assay. Cell samples were pipetted into 96-well plates and treated with mouse anti-NT primary antibody (1:8000). After washing and secondary antibody incubation, LumiGLO chemiluminescent substrate was added, and luminescence was measured with a microplate reader [2].
Mitochondrial membrane potential (Δψm) was assessed using JC-1 staining. SH-SY5Y cells were stained with JC-1 solution (2.5 μg/mL) for 10 minutes at 37°C in the dark. Cells were imaged using a fluorescence microscope at 40x magnification with Ex490nm for Em530nm (green, monomers) and Em590nm (red, aggregates). The red/green fluorescence intensity ratio was measured using ImageJ software [2].
Apoptosis was detected using AO/EtBr and Hoechst 33258 staining. For AO/EtBr, cells were stained with AO/EtBr solution (100 μg/mL). For Hoechst 33258, cells were fixed in 4% paraformaldehyde and stained with Hoechst 33258 (10 μg/mL for 10 minutes). Stained cells were photographed using a fluorescence microscope at 40x magnification, and the percentage of apoptotic cells was measured using ImageJ software [2].
Western blot assay: Total proteins from SH-SY5Y cells were collected, separated using SDS gel electrophoresis, and transferred to PVDF membranes. Membranes were blocked and treated with primary antibodies (anti-Bax, anti-Bcl-2, anti-nNOS, anti-iNOS, anti-ERK1/2, anti-Akt, anti-β-actin) overnight at 4°C, then with secondary antibodies. A chemiluminescence probe was used to generate protein bands, and signal intensities were analyzed using ImageJ software [2].

For the doxorubicin (DOX)-induced cardiotoxicity model: Wistar rats (150-200g) were divided into 6 groups (n=6). Myocardial ischemia was induced by DOX (2.5 mg/kg, i.p.) given via six injections on alternate days for a total cumulative dose of 15 mg/kg. Citronellol (25, 50, and 100 mg/kg) was dissolved in Tween 80 (0.2%) and administered orally via gavage for 14 days concurrently with DOX. Group I (control) received Tween 80 (0.2%). Group II received vehicle and DOX. Group III received standard drug dexrazoxane (10:1, i.v.) and DOX. After treatment, rats were euthanized, and blood and tissue samples were collected [1].
For the rotenone-induced Parkinson's disease model: Adult male Wistar rats (280-300g) were divided into 4 groups (n=15/group). Rotenone (2.5 mg/kg, i.p.) was administered once a day for four weeks. Citronellol (25 mg/kg, oral) was prepared just before treatment and given once daily for four weeks, 30 minutes before rotenone. Group I (control) received miglyol (i.p.) and olive oil (oral). Group II received rotenone only. Group III received rotenone + Citronellol. Group IV received Citronellol alone. After four weeks, animals were anesthetized with pentobarbital (40 mg/kg) and perfused with PBS. Tissue samples (midbrain and striatum) were collected for biochemical and immunohistochemistry studies [4].

Metabolism / Metabolites
In rabbits, this alcohol is metabolized into 7-carboxy- and 7-hydroxymethyl-3-methyloctanoic acid, which are excreted in urine.

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In silico prediction suggested that Citronellol has the ability to cross the blood-brain barrier (BBB) with 94.8% probability [2].

Toxicity Summary
Identification and Uses: Citronellol is naturally occurring and has been reported in approximately 70 essential oils. It is registered for use as an insecticide in the United States, but its approved insecticide uses may change periodically; therefore, it is essential to consult federal, state, and local authorities for information on currently approved uses. It is also used in perfumery. Human Exposure and Toxicity: Back patch tests were performed on adult male volunteers with no known allergic reactions for 48 hours using a 32% citronellol patch. After 48 hours, the patch was removed and the test substance was cleaned from the skin. Moderate irritation was observed. Patch tests using a 1% citronellol acetone solution resulted in positive reactions in subjects allergic to citronella oil. Animal Studies: Applying undiluted citronellol to intact or abraded rabbit skin under closed conditions for 24 hours resulted in moderate irritation. Severe irritation was observed in rabbits and guinea pigs after exposure to 100% of the compound (unclosed) for 24, 48, or 72 hours. Mutagenicity tests of citronellol against Salmonella Typhimurium strains TA98 and TA100, with or without metabolic activation, showed that citronellol was not mutagenic. Ecotoxicity studies: Carp (Leuciscus idus) were exposed to the chemical under static conditions for 96 hours. No deaths were observed in the control group and the 4.64 mg/L group. At a concentration of 10 mg/L, lethargy was observed in carp within 24 hours, but no deaths were observed at 96 hours. At concentrations of 21.5, 46.4, and 100 mg/L, the mortality rate was 100% after 1 hour of exposure.

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Non-human toxicity values
Mouse intramuscular LD50: 4 g/kg
Rabbit dermal LD50: 2.65 g/kg
Rat oral LD50: 3.45 g/kg

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In SH-SY5Y cells, Citronellol treatment up to a concentration of 200 μg/mL did not affect cell viability, indicating non-toxic nature. At 400 μg/mL, cell viability was maintained at 72.65%, and the IC50 was found to be 512.45 μg/mL [2].
A limitation noted in one study is the inability to demonstrate the cumulative toxicity profile of Citronellol, and its pharmacokinetic characteristics are unknown [1].

[1]. The Protective Effect of Citronellol against Doxorubicin-Induced Cardiotoxicity in Rats. Biomedicines. 2023 Oct 18;11(10):2820.

[2]. Citronellol Prevents 6-OHDA-Induced Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis in Parkinson Disease Model of SH-SY5Y Cells via Modulating ROS-NO, MAPK/ERK, and PI3K/Akt Signaling Pathways. Neurotox Res. 2022 Dec;40(6):2221-2237.

[3]. Autoxidized citronellol: Free radicals as potential sparkles to ignite the fragrance induced skin sensitizing pathway. Food Chem Toxicol. 2022 Aug;166:113201.

[4]. Effect of citronellol on oxidative stress, neuroinflammation and autophagy pathways in an in vivo model of Parkinson's disease. Heliyon. 2022 Nov 3;8(11):e11434.

[5]. Protective effect of citronellol in rhabdomyolysis-induced acute kidney injury in mice. J Med Life. 2023 Jul;16(7):1057-1061.

[6]. Citronellol Induces Necroptosis of Human Lung Cancer Cells via TNF-α Pathway and Reactive Oxygen Species Accumulation. In Vivo. 2019 Jul-Aug;33(4):1193-1201.

Citronellol is a monoterpenoid compound in which the octyl-6-ene molecule is substituted with a hydroxyl group at the 1-position and with methyl groups at the 3- and 7-positions. It is a plant metabolite. Citronellol has been reported in Ambrosiozyma monospora, Artemisia princeps, and other organisms with relevant data. 3,7-Dimethyl-6-octen-1-ol is a metabolite found or produced in Saccharomyces cerevisiae. See also: Java lemongrass oil (partial); lemongrass oil, geranium oil, soapberry oil. (Notes moved to)

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Mechanism of Action
We evaluated the effects of rose oil on peroxisome proliferation-activated receptor (PPAR) and cyclooxygenase-2 (COX-2). The major components of rose oil, citronellol and geraniol, activated PPAR α and γ and inhibited LPS-induced COX-2 expression in cell culture experiments. Although only citronellol exhibited PPARγ-dependent COX-2 promoter activity inhibition, this suggests that citronellol and geraniol are active components of rose oil.

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Citronellol is a natural compound with a pleasant floral aroma, classified as a monoterpene alcohol with the molecular formula C10H20O [1].
The volatile oil extracted from Cymbopogon winterianus, a primary source of Citronellol, has reported antihypertensive, vasorelaxant, antioxidant, and anti-inflammatory effects [1].
This was the first study to evaluate the cardioprotective activity of Citronellol against doxorubicin-induced myocardial ischemia [1].
This was the first study to report the neuroprotective property of Citronellol against 6-OHDA-induced neurotoxicity in SH-SY5Y cells for Parkinson's disease [2].
This was the first study to evaluate and understand the neuroprotective mechanisms of Citronellol in a rotenone-induced PD rat model, including its effect on α-synuclein expression and autophagy modulation [4].

C10H20O

156.2652

156.151

106-22-9

(R)-Citronellol;1117-61-9

8842

Colorless to light yellow liquid

0.8±0.1 g/cm3

224.5±0.0 °C at 760 mmHg

77-83 °C(lit.)

98.3±0.0 °C

0.0±0.9 mmHg at 25°C

1.451

3.38

1

1

5

11

112

0

O([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])/C(/[H])=C(\C([H])([H])[H])/C([H])([H])[H]

QMVPMAAFGQKVCJ-UHFFFAOYSA-N

InChI=1S/C10H20O/c1-9(2)5-4-6-10(3)7-8-11/h5,10-11H,4,6-8H2,1-3H3

3,7-dimethyloct-6-en-1-ol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 100 mg/mL (~639.92 mM)
H2O : ~1 mg/mL (~6.40 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (16.00 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (16.00 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (16.00 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 33.33 mg/mL (213.28 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)