(+)-Borneol   中文名称: (+)-冰片

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

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.

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

20.23

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

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。