(+)-Borneol primarily targets GABAA receptors. It acts as a positive modulator at these receptors, enhancing GABA-induced chloride influx and neuronal inhibition. The compound has a highly efficacious positive modulating action, enhancing low concentrations of GABA by more than 1000% with an EC50 of 248 μM. (+)-Borneol also exhibits antiapoptotic, antioxidative, and neuroprotective effects. It alleviates mechanical hyperalgesia in models of chronic inflammatory and neuropathic pain.

In vitro, (+)-Borneol (100 μM) inhibits increases in reactive oxygen species (ROS) levels and cytotoxicity in SH-SY5Y neuroblastoma cells incubated with amyloid-β (1-42). The compound enhances GABA receptor activity with an EC50 of 248 μM. It exhibits antiapoptotic, antioxidative, and neuroprotective effects in human neuroblastoma cells. (+)-Borneol has been shown to protect against amyloid-β-induced neurotoxicity. Its positive modulation of GABAA receptors has been confirmed in cell-based functional assays.

In vivo, (+)-Borneol has remarkable anti-hyperalgesic effects on neuropathic and inflammatory pain in animal models. Both oral administration (125, 250, or 500 mg/kg) and intrathecal injection (15, 30, and 60 μg) of (+)-Borneol reduce mechanical hypersensitivity dose-dependently in SNL and CFA models. The compound alleviates mechanical hyperalgesia in models of chronic inflammatory and neuropathic pain in mice. It is used for analgesia and anesthesia in traditional medicine. Further in vivo studies have evaluated its neuroprotective and anti-inflammatory effects.

In vitro enzyme/receptor binding assays for (+)-Borneol involve GABAA receptor binding and functional modulation studies. Receptor binding is assessed using radioligand binding displacement assays with membranes from cells expressing recombinant α1β2γ2L GABAA receptors. Functional modulation is measured by electrophysiology or fluorescence-based assays monitoring chloride influx. The compound’s EC50 of 248 μM for GABA enhancement is determined through these assays. For antioxidant activity, ROS scavenging assays such as DCFH-DA are used. Assays are performed in appropriate buffer systems with positive controls (e.g., diazepam for GABAA positive modulation).

In vitro cell-based assays for (+)-Borneol are conducted in SH-SY5Y neuroblastoma cells. Cells are cultured in appropriate media at 37°C with 5% CO2 and treated with (+)-Borneol at varying concentrations (e.g., 100 μM). For neuroprotection studies, cells are exposed to amyloid-β (1-42) and cell viability is assessed by MTT assay. ROS levels are measured using fluorescent probes such as DCFH-DA. Apoptosis is evaluated by Annexin V/PI staining and caspase activity assays. GABAA receptor modulation is assessed in cells expressing recombinant receptors. Experiments are performed in triplicate with appropriate controls.

In vivo animal studies for (+)-Borneol are conducted in rodent models of pain. For neuropathic pain, the spinal nerve ligation (SNL) model in mice is used. For inflammatory pain, the complete Freund’s adjuvant (CFA) model is employed. (+)-Borneol is administered orally (125, 250, or 500 mg/kg) or intrathecally (15, 30, and 60 μg). Mechanical hypersensitivity is measured using von Frey filaments. For neuroprotection studies, animal models of neurodegeneration may be used. Animals are monitored for clinical signs. Studies are conducted in accordance with institutional animal care guidelines.

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.
(+)-Borneol (MW 154.25 g/mol, C10H18O) is a lipophilic monoterpene alcohol with favorable oral bioavailability. The compound is found in essential oils of medicinal plants. It is well-absorbed following oral administration and can cross the blood-brain barrier, as evidenced by its CNS effects. (+)-Borneol is metabolized by hepatic enzymes. Pharmacokinetic parameters including Cmax, Tmax, and half-life have been characterized in preclinical studies. The compound shows stability under recommended storage conditions. It is typically formulated in appropriate vehicles for oral or parenteral administration.

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

(+)-Borneol is generally recognized as safe based on its long history of use in traditional Chinese and Japanese medicine. The compound has been used for analgesia and anesthesia with a favorable safety profile. In preclinical studies, it has shown acceptable tolerability at therapeutic doses. No significant adverse effects have been reported at research-use concentrations. The compound is intended for research use only. Standard safety precautions should be followed when handling. Comprehensive toxicological evaluation is available from traditional medicine use and preclinical studies.

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 type of borneol, an enantiomer of (-)-borneol. (+)-Borneol has been reported to be found in sage, cyperus, and other organisms with relevant data. See also: black pepper (partial); hemp (partial); angelica root; borneol; peppermint (ingredient)...see more...

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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 bowel movements. 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.
(+)-Borneol is a bicyclic monoterpene alcohol found in essential oils of medicinal plants such as valerian, lavender, and chamomile. It is used for analgesia and anesthesia in traditional Chinese and Japanese medicine. (+)-Borneol has a highly efficacious positive modulating action at GABAA receptors, enhancing GABA action by more than 1000% (EC50=248 μM). The compound exhibits antiapoptotic, antioxidative, and neuroprotective effects. It has remarkable anti-hyperalgesic effects on neuropathic and inflammatory pain in animal models. All applications are limited to non-human research use.

C10H18O

154.2493

154.135

464-43-7

6552009

White to off-white crystals
White translucent lumps
White solid
Tablets from petroleum ether

1.0±0.1 g/cm3

212.0±0.0 °C at 760 mmHg

206-209ºC(lit.)

80.7±10.9 °C

0.0±0.9 mmHg at 25°C

1.502

2.71

1

1

0

11

185

3

O([H])[C@@]1([H])C([H])([H])[C@@]2([H])C([H])([H])C([H])([H])[C@]1(C([H])([H])[H])C2(C([H])([H])[H])C([H])([H])[H]

DTGKSKDOIYIVQL-WEDXCCLWSA-N

InChI=1S/C10H18O/c1-9(2)7-4-5-10(9,3)8(11)6-7/h7-8,11H,4-6H2,1-3H3/t7-,8+,10+/m1/s1

(1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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