Synonym name: Linalool acetate
Catalogue No.: BP0868
Cas No.: 115-95-7
Formula: C₁₂H₂₀O₂
Mol Weight: 196.29
Botanical Source: numerous plants and essential oils, e.g. beramot, clary sage, lavender, petitgrain, sassafras, neroli, lemon etc.

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.

For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.

HPLC of Linalyl Acetate

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Linalyl Acetate (CAS No.: 115-95-7) is a natural monoterpene ester compound widely found in various plant essential oils, attracting attention for its unique aroma and diverse biological activities. As the acetate ester of linalool, linalool acetate is not only an important component in the fragrance industry but has also been extensively studied for its remarkable pharmacological activity. In recent years, linalolate acetate has shown good potential in anti-anxiety, anti-inflammatory, anti-diabetic, anti-stress, and cardiovascular regulation fields, and its oral activity provides a possible basis for clinical application. In addition, linalolate acetate exhibits inhibitory effects on various microbial targets in the antibacterial field, demonstrating its value as a novel antimicrobial agent. This paper will systematically review the chemical structure and physicochemical properties of linaloe acetate, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics. Combined with current research progress, it will explore its clinical application prospects and future development directions.

Chemical structure and physicochemical properties

The chemical name of linalolate acetate is 3,7-dimethyl-1,6-octadiene-3-ol acetate, with a molecular formula of C12H20O2 and a molecular weight of 196.29. Its structure includes a linalool backbone, which forms acetate esters through esterification reactions, which are highly hydrophobic. In terms of physicochemical properties, linalolate acetate has a LogP value of 3.726, indicating good lipid solubility, which is beneficial for penetrating cell membranes and the blood-brain barrier (BBB). Its polar surface area (TPSA) is 26.3 Ų, and its lower TPSA helps with its absorption and distribution in the body. Its low water solubility (0.2312 mg/mL) limits its solubility in the aqueous phase, but this can be improved to some extent through formulation technology. The high permeability of the blood-brain barrier suggests it can act on the central nervous system. In terms of safety, linalolate acetate did not show hERG channel inhibition, and Ames-induced mutagenic test results were negative, indicating a solid safety foundation.

Plant Origins and Extraction Methods

Linalolate acetate is widely found in the essential oils of various aromatic plants, especially camphor (Cinnamomum camphora), lavender (Lavandula angustifolia), basil (Ocimum basilicum), and lemon balm (Melissa officinalis). Its content varies significantly among different plants and parts, usually accounting for a high proportion in essential oils, especially lavender essential oil, where linalolate acetate can exceed 30%.

The extraction methods mainly include steam distillation and solvent extraction. Steam distillation is widely used due to its mild nature and the fact that it does not destroy active ingredients. In recent years, supercritical CO2 extraction technology has gradually become the preferred method for extracting linaloe acetate due to its efficiency, environmental friendliness, and protection of heat-sensitive components. During extraction and purification, gas chromatography-mass spectrometry (GC-MS) technology is widely used for qualitative and quantitative analysis of linalolate acetate, ensuring the quality and purity of the extract.

Pharmacological activity research

The pharmacological activities of linalolate acetate cover multiple aspects including central nervous system regulation, anti-inflammation, anti-diabetic, anti-stress, and cardiovascular protection.

Anti-anxiety and central nervous system regulation

Multiple in vivo and in vitro studies have shown that linalolate acetate has significant anti-anxiety effects. It regulates the γ-aminobutyric acid (GABA) receptor system, enhances GABA-mediated inhibitory neurotransmission, and alleviates anxiety symptoms. In animal models, oral or inhaled linalolate acetate significantly reduced anxiety behavior, demonstrating good sedative and anti-anxiety effects. Additionally, its high blood-brain barrier permeability supports its direct effect on the central nervous system.

Anti-inflammatory effects

Linalolate acetate exerts anti-inflammatory effects by inhibiting the expression of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2). In vitro studies show that linalolate acetate can inhibit inflammatory responses in macrophages and reduce tissue inflammatory damage. Its anti-inflammatory mechanism involves inhibition of the NF-κB signaling pathway, reducing the transcriptional activity of pro-inflammatory genes.

Antidiabetic activity

Linalolate acetate shows potential in regulating blood sugar levels. Animal experiments show that linalolate acetate can improve insulin resistance, promote glucose metabolism, and lower blood sugar levels. Its mechanism of action may be related to enhancing insulin signaling pathways and inhibiting gluconeogenesis-related enzyme activity. In addition, linalolate acetate also provides some protection against diabetes-related complications such as oxidative stress and inflammatory responses.

Anti-stress and cardiovascular regulation

Linalolate acetate has anti-stress effects by regulating the activity of the hypothalamic-pituitary-adrenal axis (HPA axis), lowering stress hormone levels and alleviating physiological and behavioral abnormalities caused by stress. In cardiovascular matters, linalolate acetate shows effects such as dilating blood vessels, lowering blood pressure, and preventing platelet aggregation, helping to protect and regulate the cardiovascular system's function.

Antibacterial activity

Linalolate acetate exhibits inhibitory effects on various bacteria and fungi, especially significantly suppressing the growth of Gram-positive bacteria and fungi. Its targets include bacterial DNA gyrase (GYRA), cell wall synthase (FABI), dihydrofolate reductase (DHFR), fungal cell membrane enzymes (ERG11, CYP51A1), and multidrug resistance proteins (CDR1). By interfering with key enzyme activities of bacteria and fungi, linalolate acetate inhibits the proliferation of pathogenic microorganisms, demonstrating its potential as a natural antimicrobial.

Mechanism of action and molecular targets

The multi-target mechanism of linaloe acetate forms the basis of its diverse pharmacological activity. Its main mechanisms of action include:

1. Neurotransmitter regulation: Linalolate acetate enhances the activity of GABA_A receptors, promotes inhibitory neurotransmission in the central nervous system, and exerts anti-anxiety and sedative effects.

2. Inhibition of inflammatory signaling pathways: Linaloe acetate suppresses the NF-κB signaling pathway, reducing the expression of pro-inflammatory factors and alleviating inflammatory responses.

3. Metabolic regulation: By modulating insulin signaling pathways and enzymes related to glucose metabolism, linalolate acetate improves abnormal glucose metabolism and exerts anti-diabetic effects.

4. Antioxidant effect: Linalolate acetate enhances the activity of antioxidant enzymes in the body, reduces oxidative stress damage, and protects cell function.

5. Antibacterial target effect: Linalolate acetate binds to key enzymes such as bacterial DNA gyrase (GYRA), cell wall synthase (FABI), and dihydrofolate reductase (DHFR), inhibiting bacterial DNA replication and cell wall synthesis, thereby blocking bacterial proliferation. Meanwhile, targeting fungal ERG11 and CYP51A1 enzymes, linalolate acetate interferes with fungal cell membrane synthesis and exerts antibacterial effects.

6. Cardiovascular regulation: Linaloate acetate maintains cardiovascular homeostasis by dilating vascular smooth muscle, inhibiting platelet aggregation, and modulating the neuroendocrine system.

Druggability evaluation and pharmacokinetics

The druggability parameters of linalolate acetate indicate that it has promising potential for drug development. The molecular weight of 196.29 meets the Lipinski rule, and the LogP value of 3.726 is moderate, indicating good lipophilusibility and cell membrane penetration ability. The lower TPSA (26.3 Ų) facilitates oral absorption and blood-brain barrier penetration, aligning with its oral activity and central nervous system effects.

Although its low water solubility (0.2312 mg/mL) limits its solubility in the aqueous phase, bioavailability can be improved through formulation techniques such as nanoparticles and liposomes. The high permeability of the blood-brain barrier supports its application in neurological diseases.

In terms of safety, linalolate acetate does not inhibit hERG channels, reducing the risk of arrhythmias. The Ames test was negative, indicating no risk of genotoxicity. Additionally, current in vivo toxicological studies have shown no significant toxic side effects, indicating a solid safety foundation.

Pharmacokinetic studies show that linalolate acetate is rapidly absorbed orally and widely distributed, especially at high concentrations in brain tissue. Its metabolism is mainly through hepatic esterase hydrolysis into linalool and acetic acid, followed by further metabolism and excretion. It has a moderate half-life and is suitable for oral administration.

Prospects and outlooks for clinical applications

With its broad pharmacological activity and good druggability, linalolate acetate has broad clinical application prospects. Its anti-anxiety and central nervous system modulation effects offer new ideas for developing natural sedatives and anxiolytics, especially suitable for patients seeking natural alternatives with fewer side effects. Its anti-inflammatory and antidiabetic activities lay the foundation for its application in chronic inflammatory diseases and metabolic syndromes.

Its antibacterial activity makes linalolate acetate a potential candidate against drug-resistant bacterial and fungal infections, especially of great significance in the development of natural product antimicrobial agents. Combined with modern pharmaceutical formulation technologies, the bioavailability and targeting of linalolate acetate are expected to be further enhanced.

Future research needs to delve into the mechanism of action of linalolate acetate, especially its multi-target synergistic effect and its synergistic effects with other natural ingredients. At the same time, preclinical and clinical trials of the system are key to its translational application, requiring evaluation of safety, efficacy, and dose optimization. In addition, developing novel delivery systems and combination therapy strategies will help maximize the efficacy of linalolate acetate.

Conclusion

As an important natural product, linalolate acetate demonstrates broad scientific research and clinical application value due to its diverse pharmacological activities and excellent druggability. Its potential in anti-anxiety, anti-inflammatory, anti-diabetic, and antibacterial fields provides valuable resources for the development of natural medicines. In the future, by combining modern pharmacology and medicinal chemistry techniques, in-depth analysis of the mechanism of action of linalolate acetate and optimization of its pharmacokinetic properties will promote its clinical application and promote the development and innovation of natural product pharmacology.