Nerolol causes the saprophytic fungus Aspergillus flavus to undergo apoptosis in response to the generation of ROS and Ca2+ overload [1]. Through an apoptosis-like mechanism, nerolidol (NEL)'s antifungal action against the pathogenic fungus Candida albicans, with a minimum inhibitory concentration (MIC) of 4.4 μM, can induce substantial Candida activity [2]. By raising Ca2+ and ROS levels in Candida albicans, nerolidol causes mitochondrial malfunction and destruction [2].

Absorption, Distribution and Excretion
As part of a corresponding study on the effects of the test substance on the locomotor ability of mice (four female Swiss inbred mice aged 4–6 weeks and 6 months in each group), the concentration of the test substance in blood samples was determined after inhalation exposure. Air was introduced into the cages through glass tubes containing 1.5 mL of the test substance, with a total volume of 20–50 mg. Blood samples were collected from the animals at 0, 30, 60, and 90 minutes after inhalation exposure. One hour after inhalation, the concentration of nerol in the blood samples was 5.7 ng/mL. Metabolism/Metabolites The biotransformation of nerol in common cutworm (Spodoptera litura) larvae was investigated. The major metabolites are (2Z,6E)-1-hydroxy-3,7-dimethyl-2,6-octadien-8-acid and 8-hydroxynerol, while the minor metabolites are 9-hydroxynerol and (2Z,6E)-1-hydroxy-3,7-dimethyl-2,6-octadien-8-aldehyde. (2Z,6E)-1-hydroxy-3,7-dimethyl-2,6-octadien-8-acid is a novel compound. The results indicate that the biotransformation of nerol by Spodoptera litura larvae involves two pathways: the primary pathway is the oxidation of the C-8 geminimethyl methyl group, followed by carboxylation; the secondary pathway is the oxidation of the C-9 geminimethyl methyl group. The biotransformation of geraniol, nerol, and citral by Aspergillus niger was investigated. This study compared immersion liquid culture, sporulated surface culture, and spore suspension culture. Furthermore, biotransformation was also performed using surface culture of Penicillium sp. The main products of the biotransformation of geraniol and nerol in Aspergillus niger liquid culture were linalool and α-terpineol. The main products of the biotransformation of nerol and citral in sporulated surface cultures were linalool, α-terpineol, and limonene, while geraniol was mainly converted to linalool in higher yield. The biotransformation of nerol in Penicillium chrysogenum mainly produced α-terpineol and some unidentified compounds. The main product of the biotransformation of nerol and citral in Penicillium rugulosum was linalool. This study also investigated the biotransformation of nerol into α-terpineol and linalool in Aspergillus niger spore suspension. Finally, solid-phase microextraction (SPME) was used to monitor the biotransformation process in sporulated surface cultures. The results showed that SPME is a rapid and efficient screening technique for biotransformation experiments. Allyl alcohols, such as geraniol 1, are readily oxidized through a variety of mechanisms, including the formation of 2,3-epoxides and/or aldehydes. These epoxides, aldehydes, and epoxyaldehydes can interconvert, and their reactivity must be considered when assessing the sensitizing potential of the parent allyl alcohol. This paper describes an in-depth study of the possible metabolites and autoxidation products of allyl alcohols, covering their formation, interconversion, reactivity, and sensitizing potential, combining in vivo, in vitro, chemical, and computer simulation methods. This multimodal study integrates multiple techniques to explore the sensitizing potential of molecules, thereby identifying the true sensitizers of allyl alcohol-related allergic reactions. Overall, the study found that the sensitizing potential of the epoxy alcohols and unsaturated alcohols studied primarily stems from metabolic oxidation to more potent aldehydes. If this probability is low, the compound is less sensitizing or non-sensitizing. Metabolic activation of the double bond to form non-conjugated, non-terminal epoxy groups is insufficient to convert non-sensitizing alcohols into sensitizers, as such epoxy groups have low reactivity and sensitizing potency. Furthermore, even allyl 2,3-epoxy groups are not necessarily potent sensitizers; for example, in compound 2, the formation of the epoxy group actually weakens its sensitizing potential. /geraniol/

Toxicity Summary
Identification and Uses: Nerol is a colorless, oily liquid. It has been reported to be found in Nerol oil (containing geraniol) and various essential oils. It is used as a base for perfumes and fragrances. Human Exposure and Toxicity: A single sensitization test was conducted on 25 volunteers. The substance was tested at a 4% concentration in petrolatum, and no sensitization reaction was observed. In another study, a closed patch test was performed on the back or forearm of 314 subjects for 24–48 hours. Mild erythema was observed in 10 subjects (3.19%). In an in vitro assay of chromosome aberration in cultured human lymphocytes, nerol did not induce chromosome breakage, regardless of metabolic activation. Animal Studies: Eye irritation was observed in rabbits. Mild skin irritation was observed in guinea pigs and rabbits. Respiratory irritation was assessed by recording respiratory rate in mice after exposure to nerol. Mice were nebulized with the test substance for 1 minute in a 2600 mL nebulization chamber. A mild to moderate decrease in respiratory rate was observed, and the calculated ED25 (the dose at which respiratory rate decreases by 25%) was 591 μg/L. Rats (10 males per dose group) were administered the test substance at doses ranging from 2560 to 9800 mg/kg and observed for 14 days. The number of deaths in each dose group was as follows: 1 rat in the 2560 mg/kg group, 4 rats in the 4000 mg/kg group, 7 rats in the 6250 mg/kg group, and 10 rats in the 9800 mg/kg group. All deaths occurred within two days of administration. Clinical symptoms in rats included exophthalmos, excessive flexion, restlessness, lethargy, and loss of righting reflex. Nerolmol was not mutagenic against Salmonella Typhimurium (TA 1535, TA 1537, TA 98, TA 100, and TA 102), regardless of activation. In in vitro mammalian cell gene mutation assays, nerol showed no mutagenicity at the hprt site in L5178Y mouse lymphoma cells, regardless of metabolic activation.

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Interactions
Oral cancer development is a multi-step process with complex etiologies, resulting from the accumulation of heterogeneous genetic alterations in genes involved in fundamental cellular functions, including cell division, differentiation, and cell death. These genetic alterations in affected cells gradually increase cell proliferation, angiogenesis, and inhibit apoptosis. This study investigated the regulatory effects of geraniol on the expression patterns of cell proliferation (PCNA, cyclin D1, c-fos), inflammation (NF-κB, COX-2), apoptosis (p53, Bax, Bcl-2, caspase-3 and -9), and angiogenesis (VEGF) markers in a 7,12-dimethylbenzo[a]anthracene (DMBA)-induced hamster buccal pouch carcinoma model. Topical application of 0.5% DMBA liquid paraffin solution to the cheek pouches of canaries three times a week for 14 weeks induced well-differentiated squamous cell carcinoma (SCC). Tumors developed in the cheek pouches in all hamsters treated with DMBA alone (100%) after 14 weeks. Overexpression of mutant p53, PCNA, Bcl-2, and VEGF, and decreased Bax expression were observed in DMBA-only treated hamsters. Furthermore, increased expression of c-fos, COX-2, NF-κB, and cyclin D1, and decreased caspase-3 and caspase-9 activities were also observed in DMBA-only treated hamsters. Oral administration of geraniol at 250 mg/kg body weight not only completely prevented the formation of oral tumors in DMBA-treated hamsters but also prevented the dysregulation of the above molecular markers. Therefore, the results of this study indicate that geraniol has significant anti-inflammatory, anti-angiogenic, anti-proliferative, and apoptosis-inducing effects in DMBA-induced cheek pouch carcinogenesis in hamsters. Geraniol (GO) possesses potent antitumor and chemopreventive effects, attributed to its antioxidant and anti-inflammatory properties. This study elucidates the potential efficacy of GO (250 mg/kg) in improving fructose-induced metabolic syndrome (MetS) in drinking water. Furthermore, this study investigated the role of pioglitazone (5 and 10 mg/kg; PIO) in a MetS model and the potential interaction between GO and PIO5 combination therapy. After 4 weeks of treatment, both GO and/or PIO reduced fasting blood glucose and glycemic variability in the intraperitoneal glucose tolerance test. Both GO and PIO5/10 inhibited visceral fat accumulation and partially suppressed weight gain. Peroxisome proliferation-activating receptor (PPAR)-γ transcriptional activity was reduced in visceral adipose tissue of MetS rats, while monotherapy regimens increased this activity. Although GO had no effect on MetS-induced hyperinsulinemia, PIO5/10 reduced it. Furthermore, both GO and PIO5/10 inhibit the expression of glycated hemoglobin and receptor for advanced glycation end products (RAGE). These monotherapy regimens also improved MetS-induced hyperuricemia, dyslipidemia, and elevated systolic blood pressure. Monotherapy regimens reduced serum transaminase, interleukin-1β, and tumor necrosis factor-α levels, as well as hepatic lipid peroxide and nitric oxide (NO) levels to varying degrees. In addition, monotherapy regimens increased hepatic non-protein thiol levels, as well as serum NO and adiponectin levels. GO combined with PIO5 achieved similar effects; however, the reduction in fasting serum insulin levels showed an enhanced interaction, while the synergistic effect was reflected in increased insulin sensitivity and reduced RAGE and triglyceride levels. Therefore, GO alleviates inflammation and free radical damage caused by metabolic syndrome (MetS) through transcriptional activation of PPAR-γ. These effects provide new mechanistic insights into GO's regulation of key MetS-related risk factors. Furthermore, the combination of GO and PIO5 enhanced the efficacy of antidiabetic drugs against MetS. Geraniol/
In recent years, researchers have been exploring the potential neuromodulatory effects of various plant components in neurological diseases. Repeated exposure to acrylamide (ACR) can lead to varying degrees of neuronal damage in experimental animals and humans. Therefore, this study investigated the efficacy of geraniol (GE, a natural monoterpene) in alleviating oxidative stress, mitochondrial dysfunction, and neurotoxicity in an acrylamide (ACR)-induced rat model, and compared its efficacy with that of curcumin (CU, a spice active ingredient with multiple biological activities). Intraperitoneal injection of ACR (50 mg/kg body weight, three times a week) for four consecutive weeks induced typical neuropathy symptoms in growing rats. Rats with ACR who received daily oral supplementation of plant components (GE: 100 mg/kg body weight/day; CU: 50 mg/kg body weight/day for four weeks) showed significant improvements in behavioral tests. Both plant components significantly attenuated ACR-induced oxidative stress, manifested as a decrease in reactive oxygen species, malondialdehyde, and nitric oxide levels, and restored reduced glutathione levels in the sciatic nerve (SN) and brain regions (cortex-Ct, cerebellum-Cb). Furthermore, both plant components effectively reduced ACR-induced increases in cytoplasmic calcium ion levels in the SN and Cb. Moreover, the decrease in mitochondrial oxidative marker levels was associated with an increase in antioxidant enzyme activity. Although both active components reduced ACR-mediated increases in acetylcholinesterase activity, only CU was able to restore the decrease in dopamine levels in brain regions. In summary, our results demonstrate for the first time that GE's neuromodulatory effects are comparable to CU, and it can serve as an adjunct therapy for various human neuropathies. This study used an in vitro LLNA-BrdU ELISA method to compare the sensitizing potency differences of fragrance mixtures and their components (oaksmoky absolute, isoeugenol, eugenol, cinnamaldehyde, hydroxycitronellol, geraniol, cinnamyl alcohol, and α-pentylcinnamaldehyde). SI and EC3 values were calculated, and the potency of the mixture and each component was classified. Furthermore, the release of TH1 cytokines (IL-2, IFN-γ) and TH2 cytokines (IL-4, IL-5) in lymph node cell cultures was detected as endpoints for contact sensitization. EC3 values were calculated, and the contact sensitization potency of the fragrance mixture, oakmoss absolute, isoeugenol, eugenol, cinnamaldehyde, hydroxycitronellol, geraniol, cinnamyl alcohol, and α-pentylcinnamaldehyde were classified as follows: 4.4% (moderate), 3.4% (moderate), 0.88% (strong), 16.6% (weak), 1.91% (moderate), 9.77% (moderate), 13.1% (weak), 17.93% (weak), and 7.74% (moderate), respectively. Based on our results, we can conclude that contact with the fragrance mixture does not pose a significantly increased risk compared to contact with any of the eight fragrance components individually. Cytokine analysis results showed that both TH1 and TH2 cytokines are involved in the regulation of contact senescence in mice and can serve as useful endpoint indicators. Geraniol
For more complete data on interactions of nerol (a total of 6), please visit the HSDB record page.
Non-human toxicity values

Oral LD50 in rats: 4.5 g/kg
Dermal LD50 in rabbits: > 5000 mg/kg
Intramuscular LD50 in mice: 3000 mg/kg

[1]. Nerol-induced apoptosis associated with the generation of ROS and Ca2+ overload in saprotrophic fungus Aspergillus flavus. Appl Microbiol Biotechnol. 2018 Aug;102(15):6659-6672.

[2]. Nerol triggers mitochondrial dysfunction and disruption via elevation of Ca2+ and ROS in Candida albicans. Int J Biochem Cell Biol. 2017 Apr;85:114-122.

Nerol is the (2Z)-stereoisomer of 3,7-dimethyloctyl-2,6-dien-1-ol. It has been isolated from the essential oils of plants such as lemongrass. It is a volatile oil component, plant metabolite, and fragrance. Nerol has been reported in tea tree (Camellia sinensis), lemongrass (Cymbopogon martinii), and several other organisms with relevant data. Nerol is a metabolite found in or produced by the yeast Saccharomyces cerevisiae.
Therapeutic Uses
Veterinary: Antitumor and antiviral properties have been detected in chick lymphoma and chick leukemia. It has been found to be used as a sedative and antispasmodic at doses of 0.01-1 gram. Veterinary: It has vasodilatory effects in dogs, rabbits, and mice. Pharmacology of Nerol: The search for therapeutic agents that can provide a foundation for improving the quality of life in humans continues. Nerol (cis-2,6-dimethyl-2,6-octadien-8-ol) is a monoterpene found in various medicinal plants, such as Lippia spp. and Melissa officinalis L. This study aimed to analyze the acute effects of nerol on the central nervous system (CNS) using behavioral tests in mice (open field test, elevated cruciate maze test, light-dark box test, and rotarod test). We used 2-month-old male Swiss albino mice (Mus musculus). Mice were randomly divided into five groups (n=8 per group) and administered intraperitoneal injections of 0.05% Tween 80 (dissolved in 0.9% saline), nerol (30, 60, or 90 mg/kg), or diazepam (2 mg/kg), respectively. In the open field test, compared with the control group, all nerol-treated groups showed significantly reduced motor activity (number of crossings, number of standing, and number of groomings). In the elevated cruciform maze test, the nerol-treated group showed a significant increase in the number of times they entered the open arms and the duration of their stay compared to the control group. In the light-dark chamber test, the nerol-treated group showed a significant increase in the time spent in the chamber compared to the control group. In the rotundus test, the nerol-treated group showed no change in the duration of their stay on the rotundus or the number of falls compared to the control group. These results suggest that nerol may have an anxiolytic effect in mice.
For more complete data on the therapeutic uses of nerol (out of 8), please visit the HSDB record page.

C10H18O

154.253

154.135

106-25-2

643820

Colorless to light yellow liquid

0.9±0.1 g/cm3

229.5±0.0 °C at 760 mmHg

< -10ºC

76.7±0.0 °C

0.0±1.0 mmHg at 25°C

1.471

3.28

1

1

4

11

150

0

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

GLZPCOQZEFWAFX-YFHOEESVSA-N

InChI=1S/C10H18O/c1-9(2)5-4-6-10(3)7-8-11/h5,7,11H,4,6,8H2,1-3H3/b10-7-

(2Z)-3,7-dimethylocta-2,6-dien-1-ol

cis-Geraniol; (Z)-Geraniol; Nerol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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)

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.)