Metabolism / Metabolites
A bacterium capable of utilizing Citronellal or citral as its sole carbon and energy source was isolated from soil using enrichment culture techniques. This bacterium metabolizes Citronellal into Citronellalic acid (65%), Citronellal (0.6%), dihydroCitronellal (0.6%), menthol (0.75%), and 3,7-dimethyl-1,7-octanediol (1.7%). Citral metabolites include geranilic acid (62%), 6-methyl-5-heptanoic acid (0.5%), 3-methyl-2-butenoic acid (1%), and 1-hydroxy-3,7-dimethyl-6-octen-2-one (0.75%). Cytochrome P450 has been shown to catalyze a series of exogenous aldehydes to produce olefinic products. Citronellal, a β-branched aldehyde, was found to undergo oxidative deformylation only under P450 2B4 catalysis to produce 2,6-dimethyl-1,5-heptadiene.
Rabbits were fed 50 g of citronellal, and 13 g of cyclohexanol glucuronide was subsequently isolated, identified as p-menthane-3,8-diol-D-glucuronide. Citronellal appears to have undergone non-enzymatic cyclization, and the resulting glucuronide is identical to that obtained using p-menthane-3,8-diol (menthol) as a substrate.
Citronellal can be converted to menthane-3,8-diol by suspension culture of Solanum aviculare. The content of cis-menthane-3,8-diol is much higher than that of the trans isomer (39% and 15%, respectively). The absolute configuration of menthane-3,8-diol was determined by key analysis of the ¹H and ¹⁹F NMR spectra of the prepared 2-methoxy-2-phenyl-3,3,3-trifluoropropionate. Citronellal and isoprene are other products of this conversion process (23% and 17%, respectively). The reaction process for the two Citronellal enantiomers is the same. For more complete data on the metabolism/metabolites of Citronellal (6 in total), please visit the HSDB record page.

Toxicity Summary
Identification and Uses: Citronellal is a colorless to slightly yellow liquid with a strong lemon scent. It is used as a flavoring agent and insect repellent. It has also been tested for pharmaceutical use. Human Exposure and Toxicity: Maximum dose tests were conducted on 25 volunteers. The substance was tested at a 4% concentration in petrolatum without sensitizing reactions. Three cases of eczematous contact hypersensitivity to Citronellal oil have been recorded. In two cases, detailed patch studies were conducted using components of Citronellal oil and related substances. Citronellal has been reported as the primary allergen in Citronellal oil. Animal Studies: Applying undiluted Citronellal to intact or abraded rabbit skin and maintaining it under closed conditions for 24 hours showed moderate irritation. Injection of Citronellal into white leghorn embryos resulted in dose-dependent teratogenicity. Morphological deformities primarily occurred in the craniofacial region. Citronellal has analgesic effects in mice and is a potent skin sensitizer in guinea pigs. The mutagenicity of Citronellal was assessed using a Salmonella/microsomal assay (TA97a, TA98, TA100, and TA102 test strains), performed with and without metabolic activation. This assay showed that Citronellal is not mutagenic. Ecotoxicity studies: Citronellal inhibited embryonic development of Aedes aegypti eggs laid on the water surface. Citronellal is highly phytotoxic to weeds.

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Interactions
Citronellal is a monoterpene found in the essential oils of many plants, including citronella (Cymbopogon winterianus Jowitt, Poaceae). This study investigated the effects of Citronellal on inflammatory nociception induced by different stimuli and examined the role of the NO-cGMP-ATP-sensitive potassium channel pathway. This study used male Swiss mice (n=6 per group) that received 20 μL carrageenan (CG; 30 μg/paw), tumor necrosis factor-α (TNF-α; 100 pg/paw), prostaglandin E2 (PGE2; 100 ng/paw), or dopamine (DA; 30 μg/paw) via paw injection for 0.5 hours, followed by intraperitoneal injection of citronellal (25, 50, or 100 mg/kg). Mechanoreception was assessed using a von Frey digital analgesia system at 0.5, 1, 2, and 3 hours post-injection. The effects of citronellal were also evaluated in the presence of L-NAME (30 mg/kg) or glibenclamide (5 mg/kg). At all time points, all doses of citronellal inhibited the development of mechanoreception induced by CG (p<0.001 and p<0.01) and TNF-α (p<0.001, p<0.01, and p<0.05). Citronellal increased the pain threshold in the DA test (p<0.001, p<0.01, and p<0.05) and the PGE2 test (p<0.001 and p<0.05). In the PGE2 test, L-NAME and glibenclamide reversed the analgesic effect of high-dose Citronellal. These data suggest that Citronellal can alleviate mechanoreception, partly mediated by the NO-cGMP-ATP-sensitive K+ channel pathway. Complementary and alternative medicines can be used concurrently with conventional medicines; however, pharmacological information on these interactions is limited. Previously, we reported the inhibitory effects of citrus herbal extracts and monoterpenes (e.g., (R)-(+)-Citronellal) on P-glycoprotein (P-gp) using P-gp-overexpressing LLC-PK1 cells. This study aimed to investigate the effects of (R)-(+)-Citronellal on P-gp-mediated transport during intestinal absorption in vitro and in vivo. We measured the transcatheter transport of [(3)H]digoxin across the Caco-2 cell monolayer with and without (R)-(+)-Citronellal. (R)-(+)-Citronellal significantly reduced the basolateral to apical transport and efflux ratio of [(3)H]digoxin. This study analyzed serum concentration-time curves and pharmacokinetic parameters of digoxin in rats pre-orally administered (R)-(+)-Citronellal via intravenous and oral administration. Results showed that the bioavailability of oral digoxin was significantly reduced to 75.8% of that after intravenous administration of the same dose. (R)-(+)-Citronellal increased the bioavailability of oral digoxin to 99.9% without affecting systemic clearance, volume of distribution, or elimination rate. These results suggest that (R)-(+)-Citronellal can improve the bioavailability of oral digoxin by blocking P-gp-mediated transport of digoxin from intestinal epithelial cells to the intestinal lumen.

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Non-human toxicity values
Rabbit dermal LD50 >2.5 g/kg
Rat oral LD50 >5 g/kg

[1]. Melo MS, et al. Antinociceptive effect of citronellal in mice. Pharm Biol. 2010 Apr;48(4):411-6.

[2]. de\nSantana MT, et al. Citronellal, a monoterpene present in Java\ncitronella oil, attenuates mechanical nociception response in mice.\nPharm Biol. 2013 Sep;51(9):1144-9.

[3]. Chemical composition and antibacterial activity of essential oils from Citrus aurantifolia leaves and fruit peel against oral pathogenic bacteria. An Acad Bras Cienc. 2018 Apr-Jun;90(2):1285-1292.

Citronellal is a monoterpenoid compound and the main component of citronella oil, giving it its distinctive lemon aroma. It is both a metabolite and an antifungal agent. It is a monoterpenoid compound and also an aldehyde compound. Citronellal has been reported in Micromeria biflora, Curcuma kwangsiensis, and other organisms with relevant data. See also: Java lemongrass oil (partial); lemongrass oil (note moved to).

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Therapeutic Uses
Exploratory Treatment: This study evaluated the anti-inflammatory and redox protective effects of Citronellal (CT) using in vivo and in vitro assays. Intraperitoneal injection (ip) of CT (50, 100, and 200 mg/kg) inhibited (p < 0.05) carrageenan-induced leukocyte migration to the peritoneum. Furthermore, intraperitoneal injection of the compound at 100 and 200 mg/kg significantly inhibited carrageenan and arachidonic acid-induced hind paw edema in rats (p < 0.05). In assessing redox activity, CT (200 mg/kg) significantly reduced hepatic lipid peroxidation (p < 0.001), as well as plasma (p < 0.05) and liver (p < 0.01) protein oxidation. These results support the hypothesis that CT possesses anti-inflammatory and redox protective activities. It suggests that its mechanism of action may involve inhibition of enzymes in the arachidonic acid pathway, thereby preventing cell migration by inhibiting leukotriene production, edema formation, and increased reactive oxygen species in tissues. Therefore, CT may have potential benefits in treating inflammatory diseases and oxidative-related damage.
Therapeutic Exploration: This study evaluated the anti-Candida activity of six terpenoid compounds against different fluconazole-sensitive Candida strains (including Candida albicans (n=39) and non-Candida albicans (n=9)). All six tested terpenoids exhibited excellent activity and were effective against all Candida strains tested in this study. Linalool and citral showed the strongest activity, inhibiting all strains at concentrations ≤0.064% (v/v). Five of the six tested terpenoids possessed bactericidal activity. Time-dependent bactericidal curve assays showed that the minimum fungicide concentrations (MFCs) of linalool and eugenol were highly toxic to Candida albicans, killing 99.9% of colony-forming units within 7 minutes of exposure, while Citronellal, linalyl acetate, and citral required 15 minutes, 1 hour, and 2 hours, respectively, to achieve the same bactericidal effect. The FIC index values (0.140 for linalool, 0.156 for benzyl benzoate, 0.265 for eugenol, 0.281 for citral, and 0.312 for linalyl acetate and Citronellal) determined by the checkerboard method and the isomorphic curves showed that all six tested terpenoids, when used in combination with fluconazole, exhibited excellent synergistic antibacterial activity against fluconazole-resistant Candida albicans strains. The tested terpenoids caused Candida albicans cells to arrest at different stages of the cell cycle; for example, linalool and lactate (LA) arrested cells in the G1 phase, citral and Citronellal arrested cells in the S phase, and benzyl benzoate arrested cells in the G2-M phase, and induced apoptosis. Linalool, citral, Citronellal, and benzyl benzoate inhibited more than 50% of germ tube formation at a concentration of 0.008%, while eugenol and lactic acid (LA) required concentrations of 0.032% and 0.016% (v/v), respectively, to achieve the same effect. All terpenoids exhibited no toxicity to HeLa cells at their minimum inhibitory concentrations (MICs) against Candida albicans growth. At concentrations non-toxic to HeLa cells, the tested terpenoids showed excellent inhibitory activity against both yeast-type and hyphal-type Candida albicans growth. The terpenoids tested in this study can be used in antifungal chemotherapy, not only as antifungal drugs but also as synergists with traditional drugs such as fluconazole.

C10H18O

154.25

154.135

106-23-0

7794

Colorless to light yellow liquid

0.8±0.1 g/cm3

208.4±9.0 °C at 760 mmHg

147 °C

75.6±0.0 °C

0.2±0.4 mmHg at 25°C

1.437

3.48

0

1

5

11

132

0

CC(=CCCC(C)CC=O)C

NEHNMFOYXAPHSD-UHFFFAOYSA-N

InChI=1S/C10H18O/c1-9(2)5-4-6-10(3)7-8-11/h5,8,10H,4,6-7H2,1-3H3

6-Octenal, 3,7-dimethyl-

NSC 46106 NSC-46106 NSC46106

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

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 (~648.30 mM)
Ethanol : ~100 mg/mL (~648.30 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (16.21 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 (16.21 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 (16.21 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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 (Please use freshly prepared in vivo formulations for optimal results.)