Absorption, Distribution and Excretion
Following oral administration of the emulsified formulation, the geraniol concentration curve in rat blood was characterized by a peak concentration of approximately 270 μg/mL at 30 minutes. The area under the concentration-time curve (AUC) was similar to that obtained with the same dose of geraniol administered intravenously, indicating an absolute bioavailability of 92%. After oral administration, geraniol appeared to penetrate directly from the bloodstream into the central nervous system, reaching detectable concentrations in the cerebrospinal fluid (CSF); the peak CSF concentration was approximately 2.5 μg/mL, observed 30 minutes after oral administration. Metabolisms/Metabolites Following oral administration of geraniol (I), the following metabolites were isolated from rat urine: geraniol (II), 3-hydroxycitronellolic acid (III), 8-hydroxygeraniol (IV), 8-carboxygeraniol (V), and Hildebrand acid (VI). Following oral administration of linalool (VII), the following metabolites were isolated from rat urine: 8-hydroxylinalool (VIII) and 8-carboxylinalool (IX). Feeding rats with geraniol or linalool for three days increased hepatic microsomal cytochrome P-450 activity. During the six-day treatment period, neither NADH nor NADPH cytochrome c reductase activity showed significant changes. Oral administration of these two terpenoids had no effect on any of the measured lung microsomal parameters. Geraniol, a fragrance compound, is readily autoxidized upon exposure to air and can be metabolized through the skin. In both processes, isoform aldehydes geranialdehyde and neraldehyde are generated. … Male IISc rats were administered (1-(3)H)geraniol by gavage daily for 20 consecutive days. Five urinary metabolites were identified via two main pathways. In one pathway, the alcohol is oxidized to geranilic acid (3,7-dimethyl-2,6-octadienoic acid), which is then hydrated to 3,7-dimethyl-3-hydroxy-6-octenenoic acid (3-hydroxycitronellolic acid). In the second metabolic pathway, the alcohol undergoes selective ω-oxidation of the C8-methyl group to produce 8-hydroxygeraniol and 8-carboxygeraniol, the latter of which is further oxidized to the major urinary metabolite 2,6-dimethyl-2,6-octadienoic acid (Hildebrand acid)... Studies have shown that oral administration of 600 mg/kg body weight of geraniol to rats for 1, 3, or 6 consecutive days can induce the expression of cytochrome P450 in rat liver microsomes and the hydroxylation of geraniol, but it does not induce the activity of cytochrome b5, NADPH-cytochrome c reductase, and NADH-cytochrome c reductase in rat liver microsomes, nor does it induce the activity of these enzymes in rat lung microsomes... Rabbits can also undergo ω-oxidation of geraniol, as Hildebrand acid and its dihydroform (2,6-dimethyl-2-octenedioic acid; reduced or dihydroHildebrand acid) have been isolated from treated animal urine… In both rabbits and rats, ω-hydroxylation is mediated by the cytochrome P450 system and requires NADPH and oxygen… It has been confirmed that not only rat liver microsomes can ω-hydroxylate geraniol, but also rat lung and kidney microsomes can perform this reaction. Known metabolites of geraniol include [(2E)-3,7-dimethyloctyl-2,6-dienyl]hydrosulfate. Biological half-life: In vitro measurements show that geraniol is highly stable in whole blood of humans and rats, while the half-life of geraniol cleared from the blood after intravenous injection is relatively short (approximately 12 minutes), with an initial concentration of approximately 300 μg/mL.

Toxicity Summary
Identification and Uses: Geraniol is a colorless to pale yellow liquid oil with a sweet rose aroma. Geraniol is one of the most commonly used terpenoid fragrance ingredients and can be used in all floral rose fragrances without discoloring soap. In fragrance formulations, small amounts of geraniol are used to enhance citrus notes. It is also used in alcoholic and non-alcoholic beverages, baked goods, chewing gum, frozen dairy products, gelatin (pudding), gravy, hard candy, meat products, and soft candy. It is an important intermediate in the production of geraniol esters, citronellol, and citral. Human Exposure and Toxicity: A report showed that a 32-year-old female patient working at a baking ingredient company developed allergic contact dermatitis on her fingers due to prolonged exposure to lemon peel and lemon oil. Geraniol, found in lemon peel and lemon oil, was identified as the causative agent and was confirmed as the sole allergen. In human patch tests, 32% geraniol was severely irritating, while geraniol acetate was mildly irritating. Occupational exposure to geraniol can occur in workplaces where it is produced or used, through inhalation and skin contact. Surveillance data indicate that the general population may be exposed to geraniol through inhalation (e.g., use of consumer products), ingestion of food, and skin contact with geraniol and other consumer products containing geraniol. The effect of a single component (SC) in a flavor blend (FM) on FM patch test responses varies. This study analyzed data collected between 1996 and 2002 by a multicenter project of the Dermatology Information Network. Single component testing was performed annually on a selected cohort of patients (n=1083 to n=1924). In fibromyalgia (FM)-positive patients, the response rate to synthetic cannabinoids (SCs) ranged from 29% (oakmoss ale) to 5.9% (geraniol). Although the relative proportions of isoeugenol, cinnamaldehyde, and geraniol increased in 1999, there was no time trend in responses to synthetic cannabinoids. Animal studies: Geraniol was described as non-irritating in an acute skin irritation corrosion test in rabbits. Geraniol did not exhibit sensitization in the maximum sensitization test in guinea pigs. Five male and five female weaned rats were divided into groups and fed a diet containing geraniol for 16 weeks. No treatment-related growth, hematological parameters, organ weight, or macroscopic or microscopic tissue changes were observed. An in vitro chromosomal aberration assay was performed in unactivated Chinese hamster fibroblasts. Three doses of geraniol were tested, with inconclusive results. A polyploidization effect was observed. The 48-hour chromosomal aberration rate was negative. Ecotoxicity studies: The neurophysiological effects of the essential oil components in American cockroaches (Periplaneta americana) and discoid cockroaches (Blaberus discoidalis) were tested. Geraniol showed similar inhibitory effects, but increased spontaneous firing at lower doses. Similar effects were observed in dorsal unpaired midline (DUM) neurons in isolated terminal ventral ganglia of American cockroaches via intracellular recordings.

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Interactions
Geraniol, an aromatic terpene compound, forms sensitizing compounds through auto-oxidation and skin metabolism. Geranialdehyde and neraldehyde are two isomers of citral and are also the main haptens formed in these two activation pathways. The aim of this study was to investigate whether testing with oxidized geraniol could detect more cases of contact sensitization than testing with pure geraniol. This study aimed to explore the importance of auto-oxidation or skin metabolism in geraniol contact sensitization, therefore the response patterns of pure geraniol, oxidized geraniol, and their metabolites/auto-oxidation products were investigated. Patch tests were performed on pure geraniol and oxidized geraniol using 2.0% petrolatum solution in 2227 and 2179 consecutive patients, respectively. Simultaneously, patch tests were performed on geranialdehyde, neraldehyde, and citral in 2152, 1626, and 1055 consecutive patients, respectively. The positive rates for patch tests with pure geraniol and oxidized geraniol were 0.13% and 0.55%, respectively. Of the 11 patients with positive geraniol patch tests, 8 also showed positive reactions to citral or its components. In 11 of the 14 patients, positive patch tests were associated with dermatitis. Testing with geraniol could identify more cases of geraniol contact sensitization. The response patterns presented in the 14 cases suggest that both auto-oxidation and metabolism may play important roles in geraniol sensitization. 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-added metabolic syndrome (MetS) in rats. Furthermore, this study investigated the role of pioglitazone (5 and 10 mg/kg; PIO) in the MetS model and the potential interaction between GO and PIO in 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. GO and PIO5/10 inhibited visceral fat accumulation and partially suppressed weight gain. In metabolic syndrome (MetS) rats, the transcriptional activity of peroxisome proliferation-activating receptor (PPAR)-γ in visceral adipose tissue was decreased, while monotherapy regimens increased this activity. Although GO had no effect on MetS-induced hyperinsulinemia, PIO5/10 reduced its levels. Furthermore, GO and PIO5/10 inhibited 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 increased hepatic non-protein thiols, serum NO, and adiponectin levels. Similar effects were achieved with the combination of GO and PIO5; however, there was an enhancing effect on fasting serum insulin levels, while the synergistic effect manifested as increased insulin sensitivity and decreased RAGE and triglyceride levels. Therefore, GO alleviates inflammation and free radical damage caused by metabolic syndrome by transcriptionally activating PPAR-γ. These effects provide new mechanistic insights into the treatment of key risk factors associated with metabolic syndrome by GO. Furthermore, the combination of GO and PIO5 enhances the anti-metabolic syndrome efficacy of antidiabetic drugs. This study aimed to determine whether blocking the differentiation of human colon cancer Caco-2 cells could enhance the sensitivity of cells to 5-fluorouracil (5-FU) treatment. We found that, in the confluence state, geraniol (400 μM) inhibited brush border membrane formation and suppressed the expression of intestinal hydrolases (sucrase, lactase, alkaline phosphatase). The antiproliferative effect of geraniol (400 μM) combined with 5-fluorouracil (5 μM) was twice that of 5-fluorouracil alone. Geraniol enhanced 5-fluorouracil-induced cytotoxicity, as evidenced by a 50% increase in lactate dehydrogenase release in the culture medium. These effects were associated with enhanced intracellular accumulation of 5-FU in the presence of geraniol, manifested as a two-fold increase in intracellular 5-[6-(3)H]FU concentration (1.5 uCi/mL). The antitumor efficacy of geraniol and 5-fluorouracil was also evaluated in a TC-118 human tumor model transplanted into Swiss nude mice. In nude mice, co-administration of 5-fluorouracil (20 mg/kg, for 5 consecutive days) with geraniol (150 mg/kg, for 5 consecutive days) resulted in a 53% reduction in tumor volume, while geraniol alone resulted in a 26% reduction, and 5-fluorouracil alone had no such effect. For more complete data on interactions of geraniol (6 in total), please visit the HSDB record page.

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Non-human toxicity values
Mouse intramuscular LD50: 4000 mg/kg
Mouse subcutaneous LD50: 1090 mg/kg
Rat oral LD50: 3600 mg/kg

[1]. Geraniol interferes with membrane functions in strains of Candida and Saccharomyces. Lipids. 1988 Jun;23(6):534-8.

[2]. Geraniol inhibits prostate cancer growth by targeting cell cycle and apoptosis pathways. Biochem Biophys Res Commun. 2011 Apr 1;407(1):129-34.

[3]. Geraniol, a natural monoterpene, ameliorates hyperglycemia by attenuating the key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats. Pharm Biol. 2017 Dec;55(1):1442-1449.

[4]. Geraniol attenuates oxidative stress, bioaccumulation, serological and histopathological changes during aluminum chloride-hepatopancreatic toxicity in male Wistar rats. Environ Sci Pollut Res Int. 2020 Jun;27(16):20076-20089.

[5]. 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.

Therapeutic Uses
Oral cancer development is a complex, multi-step, and multifactorial process 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 gradually increase cell proliferation, angiogenesis, and inhibit apoptosis in affected cells. 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 7,12-dimethylbenzo[a]anthracene (DMBA)-induced buccal pouch carcinoma in hamsters. Topical application of 0.5% DMBA liquid paraffin to the buccal pouches of canary hamsters three times a week for 14 weeks induced well-differentiated squamous cell carcinoma (SCC). All hamsters treated with DMBA alone (100%) developed oral tumors in their cheek pouches after 14 weeks. Overexpression of mutant p53, PCNA, Bcl-2, and VEGF, and decreased Bax expression were observed in DMBA-only 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 hamsters. Oral administration of geraniol (250 mg/kg body weight) not only completely prevented oral tumor formation but also prevented the dysregulation of the above molecular markers in DMBA-treated oral submucosal tumors. Therefore, these results indicate that geraniol has significant anti-inflammatory, anti-angiogenic, anti-proliferative, and apoptosis-inducing effects in the development of DMBA-induced oral submucosal tumors in hamsters.
/Experimental Treatment/ /The purpose of this study/ was to investigate the inhibitory effect of geraniol alone or in combination with gemcitabine on the proliferation of BXPC-3 pancreatic cancer cells. BXPC-3 cells were treated under different conditions: with geraniol at concentrations of 10, 20, 40, 80, and 160 μmol/L for 24, 48, or 72 hours; with geraniol for 24 hours or 0 hours before treatment with 20 μmol/L gemcitabine for 24 hours; after treatment with 20 μmol/L gemcitabine for 24 hours, BXPC-3 cells were treated with geraniol for 24, 48, and 72 hours; or with 20 μmol/L gemcitabine alone as a control. Cell proliferation and morphological changes were assessed using optical and fluorescence microscopy. Apoptosis was detected by flow cytometry. Geraniol inhibited BXPC-3 cell proliferation in a time- and dose-dependent manner. Geraniol, alone or in combination with gemcitabine, induced apoptosis in BXPC-3 cells. The inhibition rates of BXPC-3 cells after combination treatment were 55.24%, 50.69%, 49.83%, 41.85%, and 45.27% after treatment with 20 μmol/L geraniol for 24 hours, 0 hours before treatment with 20 μmol/L gemcitabine, and 24, 48, and 72 hours after treatment with 20 μmol/L gemcitabine, respectively. Geraniol inhibited the proliferation of BXPC-3 cells. Geraniol significantly enhanced the anti-proliferative and pro-apoptotic effects of gemcitabine on BXPC-3 cells. Treatment with geraniol 24 hours before gemcitabine treatment maximally inhibited BXPC-3 cell proliferation. Geraniol is a commonly used acyclic monoterpene alcohol used as a flavoring agent. This study aimed to investigate the anti-ulcer effects of geraniol and its possible mechanisms. In an ethanol-induced ulcer model, oral administration of geraniol significantly inhibited gastric ulcers in rats, with inhibition rates ranging from 70% (7.50 mg/kg) to 99% (200 mg/kg). Analysis of gastric tissue from rats treated with geraniol (7.50 mg/kg) revealed increased total glutathione (GSH) content and decreased myeloperoxidase (MPO) levels in the gastric mucosa. Oral administration of geraniol significantly reduced the number of ischemia/reperfusion injury-induced ulcerative lesions by up to 71% and reduced the number of cysteine-induced duodenal ulcers by up to 68%. Geraniol's mechanism of action involves activating mucosal protective defense factors, such as the nitric oxide (NO) pathway, endogenous prostaglandins, increased mucus secretion, increased thiol compounds, and antioxidant effects, as well as stimulating the release of calcitonin gene-related peptide (CGRP) through activation of transient receptor potential vanillic acid receptors (TRPV). Geraniol's multifaceted gastric protective mechanism offers a promising option for treating gastric and duodenal mucosal injuries. Parkinson's disease (PD) is a common disabling motor disorder caused by progressive dopamine depletion in the nigrostriatal region, and the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can accelerate its progression. MPTP-treated mice are a representative animal model for finding PD treatments without adverse reactions. This study investigated the effects of geraniol (GE) on chronic MPTP/probenecid (MPTP/p)-induced apoptosis in the nigrostriatal region. We observed that chronic exposure to MPTP/p led to increased expression of apoptosis markers in the substantia nigra and striatum of mice, resulting in neurodegeneration and motor dysfunction. Pretreatment of MPTP/p with geraniol (GE) significantly improved motor function and striatal antioxidant balance. Furthermore, GE attenuated the expression of apoptosis markers, manifested as normalization of the Bcl-2/Bax ratio and decreased expression of cytochrome C and caspase-9 in the substantia nigra and striatum of a MPTP/p-induced Parkinson's disease mouse model. These results suggest that geraniol, as a novel potential therapeutic approach, may play a beneficial role in delaying or halting the progression of Parkinson's disease and other neurodegenerative diseases. For more complete data on the therapeutic uses of geraniol (12 in total), please visit the HSDB record page.

C10H18O

154.25

154.135

106-24-1

637566

Colorless to light yellow liquid

0.9±0.1 g/cm3

229.5±0.0 °C at 760 mmHg

-15 °C

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-JXMROGBWSA-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+

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

NSC-9279; NSC 9279; Geraniol

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 (~648.30 mM)
H2O : ~1 mg/mL (~6.48 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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Solubility in Formulation 4: 100 mg/mL (648.30 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.)