Isoborneol, or (±)-Isoborneol, inhibits the rise in caspase-3 activity caused by 6-OHDA and the movement of cytochrome C from mitochondria to the cytoplasm. Bax/Bcl-2 ratio reduction by 6-OHDA is inhibited by isoborneol [1].

Absorption, Distribution and Excretion
To establish a GC-FID method for determining borneol concentration in mouse tissues and to investigate the tissue distribution of borneol after intravenous and intranasal administration, brain, heart, liver, spleen, lung, and kidney tissues were collected from mice at 1, 3, 5, 10, 20, 30, 60, 90, and 120 minutes after intravenous and intranasal administration. Ethyl acetate was used to extract the drug from the tissues, and octadecane was used as an internal standard. The concentration of borneol was detected by GC. The calibration curves showed good linearity. The extraction recovery, inter-day and intra-day precision, and stability all met the analytical requirements for biological samples. Borneol was mainly distributed in most tissues, with higher concentrations in the heart, brain, and kidneys, and lower concentrations in the liver, spleen, and lungs. The established GC-FID method is suitable for determining borneol content in tissues. After intravenous and intranasal administration in mice, borneol was mainly distributed in tissues with rich blood supply. After intranasal administration, brain tissue showed the highest targeting coefficient and targeting effect. To understand the pharmacokinetics of borneol in blood and brain tissue after intravenous, intranasal, or oral administration, and to explore the advantages and feasibility of intranasal administration, this study established a simple GC-FID method for the quantitative analysis of borneol. Blood and brain tissue samples were collected from mice at 1, 3, 5, 10, 20, 30, 60, 90, and 120 minutes after intravenous, intranasal, or oral administration of 30.0 mg/kg borneol. Liquid-liquid extraction was performed using octadecane internal standard solution to prepare samples. Pharmacokinetic parameters were calculated using computer software. Calibration curves for borneol in plasma and brain tissue showed linearity in the ranges of 0.11–84.24 μg/mL and 0.16–63.18 μg/g, respectively. The method recovery and extraction recovery were both in the range of 85%–115%. The intra-day and inter-day coefficients of variation for plasma and brain tissue samples were ≤5.00% relative standard deviation (RSD). The absolute bioavailability (F) of intranasal and oral administration was 90.68% and 42.99%, respectively. The relative brain targeting coefficients (Re) of intranasal and oral administration were 68.37% and 38.40%, respectively. The established GC-FID method can be used for determination and pharmacokinetic studies. Borneol administered by injection is rapidly distributed and metabolized, with no absorption process. Orally administered borneol is distributed more slowly and has the lowest absolute bioavailability. Nasal administration of borneol is rapidly absorbed by the blood and brain tissue, is convenient to use, and has a higher safety profile than other routes of administration, thus warranting further development as a route of administration for the treatment of encephalopathy. This study aimed to investigate the in situ and in vivo absorption of borneol in the nasal cavity. We used a novel single-dose nasal perfusion technique to detect the absorption rate and extent of borneol in the rat nasal cavity. The effects of perfusion rate, pH, and drug concentration were investigated. In situ experiments showed that nasal absorption of borneol was independent of drug concentration and conformed to first-order kinetics. The absorption rate constant Ka increased with increasing perfusion rate. Borneol was well absorbed intranasally within the physiological pH range. We also conducted an in vivo borneol absorption study in rats, comparing pharmacokinetic parameters between intranasal (in) and intravenous (iv) administration. The bioavailability of borneol was 90.82% (oral), with a time to peak concentration (Tmax) of 10 minutes. The mean residence time (MRT) for oral and intravenous administration was 262.55 ± 67.35 minutes and 204.22 ± 14.50 minutes, respectively. These results indicate that borneol can be rapidly and adequately absorbed in mice via the oral route. Previous studies have shown that borneol has dual side effects on the central nervous system (CNS), but the mechanism remains unclear. This study aimed to elucidate the relationship between the ratio of excitatory amino acids (AAs) to inhibitory amino acids and the content of natural borneol after a single oral administration. Mice were orally administered 1.2 g/kg of natural borneol (containing 98% D-borneol). Brain tissue samples were collected before administration and at 0.083, 0.167, 0.25, 0.333, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, and 5 hours after administration. The concentrations of natural borneol and the levels of amino acid neurotransmitters in mouse brain tissue were determined using gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography-fluorescence detector (HPLC-FLU), respectively. After oral administration, natural borneol was rapidly absorbed by brain tissue and was detectable within 5 minutes. The maximum concentration in brain tissue (86.52 μg/g) was reached 1 hour after administration. Natural borneol affected the levels of amino acid neurotransmitters in the mouse brain: L-aspartate levels significantly increased from 0.083 to 1 hour after administration; L-glutamate levels significantly increased at 0.333 hours, then decreased from 1.5 to 5 hours; γ-aminobutyric acid (GABA) levels significantly increased from 0.167 to 5 hours; while glycine levels were unaffected. The excitatory ratio, or excitatory amino acid to inhibitory amino acid ratio, reflects the body's excitatory or inhibitory state. Within 0.5 hours after administration, the excitatory ratio briefly increases and then decreases; significant differences are observed between 1.5 and 5 hours after administration and before administration. This study indicates that natural borneol can affect the content of AA neurotransmitters, and changes in the excitatory ratio lead to dual side effects of borneol on the central nervous system. This study used radiolabeled components to determine the dermal absorption of camphene, isoborneol-acetate, limonene, menthol, and α-pinene in a prickly ash bath. Pharmacokinetic measurements showed that all tested components reached peak plasma concentrations within 10 minutes of the onset of dermal absorption. No preferential absorption was observed for any component. Ten minutes after dermal absorption, the plasma concentrations of all components were positively correlated with the skin absorption area.

Toxicity Summary
Identification and Uses: Borneol is a solid. It is used as a flavoring agent and in medicines, including traditional Chinese medicine. Human Exposure and Toxicity: Borneol does not cause skin sensitization. Its toxicity is essentially the same as camphor. Human peripheral blood lymphocytes were exposed to L-bornol at concentrations up to 600 μg/mL in DMSO for 4 hours (with/without metabolic activation) and 24 hours (without metabolic activation). Under the study conditions, L-bornol was not considered to be chromosome-breaking induced. Animal Studies: Similar to camphor, laboratory animals appear to be far less sensitive to borneol toxicity than humans. Oral administration of borneol for 7 consecutive days increased CYP2D activity in rats. Borneol has been evaluated for analgesic and anti-inflammatory activity in mice. Borneol significantly reduced noxious behavior in the early and late stages of paw-licking behavior in mice and reduced writhing reflexes. High doses of borneol inhibited noxious behavior in the hot plate test. Furthermore, borneol treatment reduced carrageenan-induced leukocyte migration to the peritoneum in mice. The mutagenicity of borneol was assessed using the Ames test, in which Salmonella Typhimurium strains TA1535, TA1537, TA1538, TA98, and TA100 were treated with borneol at concentrations up to 5000 μg/plate, with and without metabolic activation. Other studies have also confirmed that borneol is not mutagenic to Salmonella Typhimurium strains TA98 and TA100. Under the conditions of this study, borneol was considered non-mutagenic to bacteria. Identification and Uses: Isoborneol is a white solid used as a flavoring agent in food and beverages, and also in perfume manufacturing and the preparation of chemical esters. Human Studies: In maximum-dose human studies, no sensitization was observed with a 10% isoborneol petrolatum solution. Isoborneol did not show significant cytotoxicity to human cell lines within the concentration range of 0.016% to 0.08%. Animal studies: Isoborneol did not show significant cytotoxicity in monkey cell lines within the concentration range of 0.016% to 0.08%. Genotoxicity, repeated-dose toxicity, developmental toxicity, and reproductive toxicity were evaluated for the homologous compounds levonorgestrel and isoborneol acetate. In a 13-week subchronic toxicity study in rats, the no-observed-adverse-effect level (NOEL) of isoborneol acetate was determined to be 15 mg/kg/day based on increased urinary cellular excretion. The no-observed-adverse-effect level (NOAEL) of isoborneol acetate for parental reproductive toxicity was 300 mg/kg/day. Levoborneol did not show mutagenicity in the Ames assay. Genotoxicity of isoborneol was assessed in the Bluescreen assay, and the results showed no genotoxicity or cytotoxicity regardless of metabolic activation.

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Interactions
To investigate the enhancing effect of borneol on the corneal penetration of compounds with different hydrophilicities and molecular weights, we selected six compounds as model drugs: rhodamine B, sodium fluorescein, fluorescein isothiocyanate (FITC), and dextran with molecular weights of 4, 10, 20, and 40 kDa. Permeability studies were conducted using an isolated rabbit cornea with a Franz diffusion apparatus. The safety of borneol was assessed based on corneal hydration and the Draize eye test. After applying 0.2% borneol to the cornea, the apparent permeability coefficients of rhodamine B, sodium fluorescein, and 4 kDa and 10 kDa FITC-dextran increased by 1.82-fold (p<0.05), 2.49-fold (p<0.05), 4.18-fold (p<0.05), and 1.11-fold (not statistically significant), respectively. Compared with the control group, borneol had no significant effect on the permeability of 10 kDa, 20 kDa, and 40 kDa FITC-glucan. The permeability enhancement coefficient of 0.2% borneol was linearly correlated with the molecular weight of the model drug (R²=0.9976). After using 0.05%, 0.1%, and 0.2% borneol, the corneal hydration value was below 83%, and the Draize score was below 4. Borneol may improve the corneal permeability of both hydrophilic and lipophilic compounds without causing toxic reactions, especially hydrophilic compounds. In addition, 0.2% borneol can enhance the permeability of hydrophilic compounds with a molecular weight ≤4 kDa. Therefore, borneol can be considered a safe and effective permeability enhancer for ocular drug delivery. This study aimed to investigate the synergistic effect of natural borneol/curcumin (NB/Cur) on the growth and apoptosis of the A375 human melanoma cell line using the MTT assay, flow cytometry, and Western blotting. Our results indicate that NB and Cur can synergistically enhance their anti-proliferative activity against A375 human melanoma cells by inducing apoptosis, manifested as an increased proportion of cells in the sub-G1 phase, DNA fragmentation, PARP cleavage, and caspase activation. Further mechanistic studies using Western blotting showed that NB/Cur treatment upregulated phosphorylated JNK expression while downregulating phosphorylated ERK and Akt expression, which collectively promoted apoptosis in A375 cells. Furthermore, NB enhanced Cur's ability to induce excessive intracellular ROS production and DNA damage, as evidenced by upregulation of phosphorylated ATM, phosphorylated Brca1, and phosphorylated p53 expression. These results suggest that the combined use of NB and Cur has potential application value in cancer treatment.
Dopamine (DA)-induced oxidative stress may play an important role in the pathogenesis of Parkinson's disease (PD). Isobellol (+/-) is a monoterpene alcohol found in various medicinal plant essential oils and has known antioxidant activity. This study investigated the neuroprotective effect of isoborneol against 6-hydroxydopamine (6-OHDA)-induced death in human neuroblastoma SH-SY5Y cells. Pretreatment of SH-SY5Y cells with isoborneol significantly reduced 6-OHDA-induced reactive oxygen species (ROS) production and increased intracellular calcium ion concentration. Furthermore, isoborneol treatment reversed 6-OHDA-induced apoptosis. Isoborneol inhibited 6-OHDA-induced increases in caspase-3 activity and cytochrome C translocation from mitochondria to the cytosol. Isoborneol also prevented 6-OHDA from reducing the Bax/Bcl-2 ratio. We also observed that isoborneol reduced the activity of c-Jun N-terminal kinase and induced the activity of protein kinase C (PKC), which is inhibited by 6-OHDA. Our results suggest that the protective effect of isoborneol depends on its antioxidant capacity and strongly indicate that isoborneol may be an effective treatment for neurodegenerative diseases associated with oxidative stress.

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Non-human toxicity values
Oral LD50 in mice: 1059 mg/kg
Oral LD50 in mice: 3720 mg/kg (L-type)
Oral LD50 in mice: 4960 mg/kg (D-type)
Oral LD50 in mice: 3830 mg/kg (DL-type)
Oral LD50 in rats: 5200 mg/kg
Intravenous LD50 in mice: 56 mg/kg

[1]. Protective effect of (+/-) isoborneol against 6-OHDA-induced apoptosis in SH-SY5Y cells. Cell Physiol Biochem. 2007;20(6):1019‐1032.

[2]. Armaka M, Papanikolaou E, Sivropoulou A, Arsenakis M. Antiviral properties of isoborneol, a potent inhibitor of herpes simplex virus type 1. Antiviral Res. 1999;43(2):79‐92.

Borneol is a white, lumpy solid with a strong camphor-like odor and is flammable. It has a density slightly greater than water and is insoluble in water. It is used in the manufacture of perfumes. Borneol is a borneol monoterpene, a compound of 1,7,7-trimethylbicyclo[2.2.1]heptane with a hydroxyl group substituted at the 2-position. It is a volatile oil component and metabolite. Isoborneol has been reported to be found in turmeric, valerian, and other organisms with relevant data. See also: Borneol (note moved to); Isoborneol (note moved to).

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Therapeutic Uses
Helps relieve local itching and discomfort caused by hemorrhoids. Temporarily shrinks hemorrhoid tissue, relieving burning sensation. Temporarily forms a protective film, relieving anal and rectal discomfort. Temporarily protects the inflamed, irritated anal and rectal surface, helping to reduce pain during defecation. Temporarily relieves mild muscle and joint pain caused by: arthritis, strains, bruises, sprains, mild back pain.
Antibacterial
Borneol is widely used in China and Southeast Asian countries, especially in compound preparations for the prevention of cardiovascular disease, but research on its effects on thrombosis is scarce. This study investigated the antithrombotic and antiplatelet activities of borneol in in vivo thrombosis and in vitro platelet aggregation. Furthermore, its effects on coagulation parameters and fibrinolytic activity were evaluated. Results showed that borneol had a concentration-dependent inhibitory effect on arteriovenous shunts and venous thrombosis, but had no effect on ADP- and AA-induced platelet aggregation. Simultaneously, borneol prolonged coagulation parameters such as prothrombin time (PT) and thrombin time (TT), but showed no fibrinolytic activity. This suggests that the antithrombotic activity of borneol and its role in compound preparations for the prevention of cardiovascular disease may be related to its anticoagulant activity rather than its antiplatelet activity. /Traditional Medicine/
For more complete data on the therapeutic uses of borneol (6 types), please visit the HSDB record page.
/Exploratory Treatment/ Isoborneol is a monoterpene compound and a component of many plant essential oils. It exhibits dual antiviral activity against herpes simplex virus type 1 (HSV-1). First, it reduced the inactivation rate of HSV-1 by nearly 4 log10 values within 30 minutes of exposure; second, a concentration of 0.06% isoborneol completely inhibited viral replication without affecting viral adsorption. Isoborneol did not show significant cytotoxicity in human and monkey cell lines within the concentration range of 0.016% to 0.08%. Based on the following data, isoborneol specifically inhibits viral peptide glycosylation: (1) No fully mature glycosylated forms of the two viral glycoproteins gB and gD were detected during viral replication in the presence of isoborneol; (2) No significant changes in the glycosylation patterns of cellular peptides were observed between untreated Vero cells and Vero cells treated with isoborneol; (3) Isoborneol does not affect the glycosylation of gB generated by copies of the gB gene in the cellular genome; (4) Other monoterpenoids, such as 1,8-cineole and the stereoisomer of isoborneol, borneol, do not inhibit HSV-1 glycosylation.

C10H18O

154.25

154.135

124-76-5

64685

White to off-white solid powder

1.0±0.1 g/cm3

212.0±0.0 °C at 760 mmHg

208-214ºC

65.6±0.0 °C

0.0±0.9 mmHg at 25°C

1.502

2.71

1

1

0

11

185

0

DTGKSKDOIYIVQL-UHFFFAOYSA-N

InChI=1S/C10H18O/c1-9(2)7-4-5-10(9,3)8(11)6-7/h7-8,11H,4-6H2,1-3H3

1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol

Isoborneol NSC-26350 NSC 26350

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.)