Product name: trans-Nerolidol
Synonym name:
Catalogue No.: BP4220
Cas No.: 40716-66-3
Formula: C₁₅H₂₆O
Mol Weight: 222.372
Botanical Source: Acorus tatarinowii Schott
Type of Compound: Aliphatics

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle

Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

The product could be supplied from milligrams to grams
Inquire for bulk scale.

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

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

Introduction/Overview

Trans-nerolidol (CAS No.: 40716-66-3) is a naturally occurring sesquiterpenol compound widely distributed in various aromatic plants, especially neroli, lemongrass, and other spice plants. As an important natural product, trans-neroli tertiethol has attracted widespread attention in pharmacological research in recent years due to its unique chemical structure and diverse biological activities. It shows significant potential in anti-tumor, anti-anxiety, and neuroprotective effects, especially in enhancing the anticancer effects of chemotherapy drugs such as doxorubicin (DOX) and regulating central nervous system function, showing promising application prospects.

This paper aims to systematically review the chemical structure and physicochemical properties, plant origin and extraction methods, pharmacological activity and mechanism of action of trans-neroli tertiary alcohol, druggability evaluation and pharmacokinetic characteristics, and, combined with the latest research advances, explore its clinical application potential and future directions, providing theoretical basis and reference for related research and drug development.

Chemical structure and physicochemical properties

Trans-neroli tertiary alcohol belongs to the sesquiterpene alcohol class of compounds, with a molecular formula of C15H26O and a molecular weight of 222.3720. Its structural feature is a linear sesquiterpene skeleton containing three pairs of double bonds, with a tertiary alcohol hydroxyl group at the end, chemically named 3,7,11-trimethyl-1,6,10-dodecen-3-ol. Its trans configuration gives the molecule high spatial stability and specific stereochemical properties.

In terms of physicochemical properties, trans-neroli tertiary alcohol exhibits high lipid solubility, with a LogP value of about 4.9054, indicating good lipid affinity and facilitating penetration of cell membranes and the blood-brain barrier (BBB). Its polar surface area (TPSA) is 20.2300, and its lower polarity helps with its distribution and penetration within the body. Poor water solubility (0.0074 mg/mL) suggests limited solubility in aqueous media, which may affect oral bioavailability. Toxicological evaluation showed that trans-neroli tertiary alcohol had no significant hERG channel suppression, and Ames' mutagenicity test was negative, indicating high safety.

Plant Origins and Extraction Methods

Trans-neroli tert-alcohol is widely found in the essential oils of various aromatic plants, especially lemongrass (Cymbopogon citratus), orange blossom (Citrus aurantium), lemongrass (Cymbopogon nardus), and certain pine plants. Its content varies depending on the plant species, growing environment, and extraction process.

Traditional extraction methods mainly use distillation (such as steam distillation) to separate essential oils from fresh leaves or flowers, followed by gas chromatography-mass spectrometry (GC-MS) to identify and quantify the content of trans-neroli tertiary alcohol. In recent years, supercritical CO2 extraction technology, due to its low solvent residue and high extraction efficiency, has gradually become an advanced method for extracting trans-neroli tertiary alcohol. In addition, solvent extraction and molecular distillation technologies are also applied in the purification process of trans-neroli tertiary alcohol to improve its purity and yield.

Pharmacological activity research

Antitumor activity

Numerous in vitro and in vivo studies have shown that trans-nerolitert-tertiethyl has significant antitumor activity. Especially in colorectal and breast cancer cell lines, trans-nerolitertary alcohol can enhance the antiproliferative effect of the chemotherapy drug doxorubicin (DOX). Mechanistically, trans-neroli tertiary alcohol promotes the accumulation of DOX within cancer cells, overcoming the drug efflux mechanism in tumor cells, thereby enhancing the cytotoxicity of the drug. Additionally, in vivo experiments showed that trans-neroli tertiary alcohol can activate tumor cell apoptosis pathways, induce programmed cell death, and reduce tumor burden.

Anti-anxiety and neuroprotective effects

Trans-nerolitanol exhibits good anti-anxiety activity in the central nervous system. Its targets cover various neurotransmitter systems, including monoamine oxidase A (MAOA), serotonin transporter (SLC6A4), serotonin receptor (HTR2A, HTR1A), dopamine receptor D2 (DRD2), and γ-aminobutyric acid receptor subunits (GABRA1, GABRB2, GABRG2). Additionally, trans-neroli tertiol can regulate the expression of CREB1 and brain-derived neurotrophic factor (BDNF), promoting neuroplasticity and neuronal survival, further supporting its anti-anxiety and neuroprotective effects.

Other biological activities

In addition to anti-tumor and anti-anxiety effects, trans-nerolitan tertiary alcohol also exhibits multiple pharmacological effects, including anti-inflammatory, antioxidant, and antibacterial effects. Its anti-inflammatory effects are mainly achieved by inhibiting the release of pro-inflammatory factors and activating the NF-κB signaling pathway, while antioxidant activity manifests as scavenging free radicals and enhancing cellular antioxidant enzyme system function.

Mechanism of action and molecular targets

The pharmacological effects of trans-neroli tertiary alcohol involve multiple signaling pathways and molecular targets. The mechanisms by which DOX enhances its antitumor effects include:

1. Enhanced drug accumulation: Trans-neroliter can inhibit drug efflux pumps (such as P-glycoprotein) on tumor cell membranes, increasing intracellular DOX concentration.
2. Apoptosis induction: Activates mitochondrial pathways, regulates Bcl-2 family protein expression, promotes cytochrome C release, activates the caspase cascade, and induces apoptosis.
3. Cell cycle blockade: By regulating cell cycle-related proteins, it blocks tumor cell progression during the G0/G1 or G2/M phases, inhibiting cell proliferation.

In the nervous system, trans-nerolithertiol exerts anti-anxiety effects through multi-target synergy:

1. Monoamine system regulation: Inhibits MAOA activity and increases the levels of neurotransmitters such as serotonin and dopamine.
2. Receptor agonism/antagonism: regulates the functions of 5-HT1A, 5-HT2A, and dopamine D2 receptors, balancing neurotransmitter signal transduction.
3. GABA energy system enhancement: Enhances the expression of GABAA receptor subunits, improving GABA-mediated inhibitory nerve conduction.
4. Regulation of neurotrophic factors: Upregulate CREB1 and BDNF expression, promote neuron survival and synaptic plasticity, and improve mood and cognitive function.

Additionally, trans-nerolitan tertiary alcohol regulates inflammation-related signaling pathways (such as NF-κB) and oxidative stress responses, providing a molecular basis for its multiple pharmacological effects.

Druggability evaluation and pharmacokinetics

Trans-neroli tertiethyl alcohol has good druggability characteristics. Its molecular weight is 222.3720, meeting the requirements of the Lipinski rule. A high LogP value (4.9054) indicates strong lipid solubility, facilitating cell membrane penetration and blood-brain barrier penetration, and supporting central nervous system activity. A low TPSA value (20.2300) further benefits its oral absorption and brain distribution.

Low water solubility (0.0074 mg/mL) may limit its oral bioavailability, and solubility and stability need to be improved through formulation optimization (such as nanocarriers, liposomes, etc.). Toxicological evaluation showed that trans-nerolitertary alcohol did not inhibit hERG channels, reducing the risk of cardiotoxicity. The Ames mutagenicity test was negative, indicating a low genotoxicity risk.

Currently, pharmacokinetic research on trans-nerolitonol is still insufficient. Preliminary data indicate that metabolism in the body mainly occurs through hepatic enzyme systems, and the metabolites still require further identification. Its in vivo parameters such as half-life, volume of distribution, and clearance rate require further study to guide clinical dose design and safety evaluation.

Prospects and outlooks for clinical applications

Trans-nerolitonol, as a natural product, demonstrates broad clinical application potential due to its multi-target and multi-pathway pharmacological effects. Its application in adjuvant anti-tumor therapy is particularly prominent, as it can enhance the efficacy of traditional chemotherapy drugs, reduce drug resistance, alleviate side effects, and has good clinical translational value.

In the field of neuropsychiatric disorders, the anti-anxiety and neuroprotective effects of trans-nerolitert-tertitol offer new ideas for the development of novel central nervous system drugs. It can regulate various neurotransmitter systems and neurotrophic factors, and may have potential therapeutic effects for anxiety, depression, and neurodegenerative diseases.

Future research should focus on the following aspects:

1. Systematic review of pharmacokinetics and toxicology: Improving in vivo metabolism, distribution, and long-term safety data of trans-nerolitanol.
2. In-depth mechanism analysis: Combining multi-omics techniques, revealing the molecular network of its multi-target synergistic effects.
3. Dosage form development and dosage optimization: Overcoming limitations of poor water solubility, enhancing bioavailability and targeting.
4. Clinical trial design: Conduct early-stage clinical studies to verify safety and efficacy, and promote clinical application.

Conclusion

Trans-nerolitonol, as a natural sesquiterpene alcohol with a unique structure and multiple biological activities, demonstrates significant scientific value and application prospects due to its anti-tumor, anti-anxiety, and neuroprotective pharmacological effects. Its excellent druggability parameters and safety foundation lay a solid foundation for subsequent drug development. With continuous advances in modern pharmacology and medicinal chemistry technologies, trans-neroli tertiary alcohol is expected to become an important candidate molecule in the development of natural product drugs, providing new therapeutic strategies and drug options for the clinical management of tumor treatment and neuropsychiatric diseases. Future systematic research and clinical validation will further drive its clinical translation, benefiting a wide range of patients.