Synonym name: Bergaptol geranyl ether; 5-Geranyloxypsoralen; Bergaptin
Catalogue No.: BP0255
Cas No.: 7380-40-7
Formula: C₂₁H₂₂O₄
Mol Weight: 338.403
Botanical Source: bergamot oil. Also from lemon oil and oils of other Citrus spp. and Daucus carota and the fruit of Tetradium danielli

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  Bergamottin

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

Introduction/Overview

Bergamottin (CAS number: 7380-40-7) is a furanocoumarin-type compound naturally found in bergamot (Citrus bergamia) and other citrus fruits. As an important natural product, bergamot extract has attracted widespread attention for its unique bioactivity and potential pharmacological applications. In recent years, with the deepening of pharmacological research on natural products, bergamotin has shown significant competitive inhibitory effects in regulating cytochrome P450 enzyme activity (especially CYP1A1), with a Ki value as low as 10.703 nM, indicating high enzyme inhibitory efficacy. Moreover, bergamotin interacts with various disease-related targets, especially showing potential value in the treatment of complex conditions such as obstructive sleep apnea (OSA).

This article aims to systematically review the chemical structure and physicochemical properties of bergamot extraction, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation and pharmacokinetic characteristics, and to explore its prospects and challenges in clinical application. By integrating existing literature, it is hoped that scientific basis and theoretical support will be provided for further drug development and clinical translation of bergamotin.

Chemical structure and physicochemical properties

Bergamotin is a furanocoumarin-class compound with the molecular formula C21H22O4 and a molecular weight of 326.40. Its structural features include the fusion of a coumarin backbone with a furan ring, exhibiting the typical aromatic and conjugated system of furanocoumarin-type compounds. The LogP value of bergamotin is 4.20, indicating strong hydrophobicity, which facilitates penetration of cell membranes but may affect its water solubility and bioavailability. Its topological pole surface area (TPSA) is 55.76 Ų, indicating that the molecule has certain polarity, which helps bind the molecule to biological targets.

In terms of molecular structure, bergamot extract contains four hydrogen bond receptor sites that may participate in hydrogen bonding with protein targets, enhancing binding affinity. Its low blood-brain barrier permeability suggests limited distribution in the central nervous system, which may affect its application in neuro-related diseases. Existing data have not yet clarified the hepatotoxicity and cardiotoxicity of bergamotin. The hERG channel inhibition test results were negative, suggesting good cardiac safety, but further systematic toxicological evaluation is still needed.

Plant Origins and Extraction Methods

Bergamot extract is mainly found in the peel and essential oil of bergamot (Citrus bergamia), and is also present in other citrus plants such as citrus (Citrus paradisi) and lemon (Citrus limon). The natural accumulation of bergamotin is influenced by plant variety, growing environment, harvest time, and processing methods, resulting in significant differences in its content.

Bergamot extract commonly uses solvent extraction combined with chromatographic separation. Traditional extraction mostly uses organic solvents such as ethanol, methanol, or ethyl acetate, improving extraction efficiency through extraction extraction, ultrasound-assisted extraction, or microwave-assisted extraction. After rotary evaporation and concentration, the extract is purified using silica gel column chromatography, high-performance liquid chromatography (HPLC), or preparative liquid chromatography, ultimately yielding high-purity bergamot extract. In recent years, green extraction technologies such as supercritical CO2 extraction and deep eutectic solvent-assisted extraction have gradually been applied to bergamotin extraction, offering advantages of environmental friendliness and high energy efficiency.

Pharmacological activity research

Research on the pharmacological activity of bergamotin covers multiple aspects including enzyme inhibition, anti-inflammation, anti-tumor, neuroprotection, and metabolic regulation. Its most notable biological function is competitive inhibition of CYP1A1 in the cytochrome P450 enzyme lineage, with a Ki value of 10.703 nM, demonstrating extremely strong enzyme inhibitory efficacy. This mechanism of action makes bergamotin of significant importance in drug metabolism regulation and drug interaction research.

Additionally, bergamotin has regulatory potential for multiple targets related to obstructive sleep apnea (OSA), including APP (amyloid precursor protein), MAOA (monoamine oxidase A), ESR1/ESR2 (estrogen receptor α/β), ABCG2 (ATP-binding box transporter G2), PTGS1 (cyclooxygenase 1), carbonic anhydrase family members CA4, CA9, CA12, and HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase), among others. These targets involve multiple pathophysiological pathways, including neuroprotection, inflammatory response, lipid metabolism, and respiratory regulation, suggesting that bergamotin may alleviate OSA and related complications through multi-target synergistic effects.

In terms of anti-inflammatory effects, bergamotin can inhibit PTGS1 activity, reduce prostaglandin synthesis, and exert anti-inflammatory and analgesic effects. Its regulatory effect on MAOA may influence neurotransmitter metabolism, thereby improving sleep quality and cognitive function. Some in vitro and animal experiments have also shown bergamotin has antioxidant and antitumor potential, but the mechanisms require further elucidation.

Mechanism of action and molecular targets

The main mechanism of action of bergamotin is its competitive inhibition of CYP1A1. CYP1A1 is a member of the cytochrome P450 family and participates in the metabolism of various exogenous and endogenous substances, including the activation of carcinogens. By inhibiting CYP1A1, bergamotin can reduce the production of harmful metabolites, lowering the risk of cytotoxicity and gene damage.

In the pathological mechanism of obstructive sleep apnea, bergamot extract works by modulating multiple targets:

• APP (amyloid precursor protein): regulates neuronal function and amyloid metabolism, and may affect neurodegenerative changes related to OSA.
• MAOA (Monoamine Oxidase A): Regulates the metabolism of neurotransmitters such as serotonin and dopamine, affecting sleep regulation and emotional state.
• ESR1/ESR2 (estrogen receptors α/β): Involved in inflammatory responses and neuroprotection, regulating respiratory center function.
• ABCG2 (ATP-binding cassette transporter G2): affects the transmembrane transport of drugs and metabolites, regulating intracellular environmental stability.
• PTGS1 (cyclooxygenase 1): mediates the production of inflammatory mediators; bergamotin reduces inflammatory responses by inhibiting its activity.
• Carbonic anhydrase family (CA4, CA9, CA12): Regulates the acid-base balance inside and outside cells, affecting respiratory gas exchange and tissue metabolism.
• HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase): a key cholesterol biosynthesizer that regulates lipid metabolism and may affect OSA-related metabolic syndromes.

Through comprehensive regulation of these multiple targets, bergamotin demonstrates multidimensional therapeutic potential, especially with unique advantages in the multifactorial pathological mechanisms of complex diseases such as OSA.

Druggability evaluation and pharmacokinetics

The druggability parameters of bergamotin showed a moderate molecular weight (326.40 Da), meeting the basic requirements of the Lipinski rule. The LogP was 4.20, indicating good lipid solubility that facilitates cell membrane penetration, but may limit its water solubility and oral bioavailability. TPSA was 55.76 Ų, indicating moderate polarity, which is conducive to binding to target proteins.

Bergamotin has low blood-brain barrier permeability, suggesting limited distribution in the central nervous system. This may affect its therapeutic effectiveness in neurological diseases, but it also reduces the risk of CNS toxicity. Data on hepatotoxicity and cardiotoxicity are still unclear. The hERG channel inhibition test results were negative, suggesting good cardiac safety. Ames trial data are lacking, and further evaluation of its genotoxicity is needed.

Pharmacokinetic studies show that bergamotin has a certain degree of metabolic stability in the body, but as a CYP1A1 inhibitor, it may affect the metabolism of other drugs, posing potential risks of drug interactions. Its oral absorption, distribution, metabolism, and excretion (ADME) characteristics still require systematic study, especially in-depth analysis of its bioavailability, half-life, and metabolic pathways, which will help optimize dosing regimens and formulation design.

Prospects and outlooks for clinical applications

As a natural product, bergamot extract shows broad application prospects in the treatment of obstructive sleep apnea and related metabolic and neurological diseases, thanks to its remarkable CYP1A1 inhibitory activity and multi-target regulatory capabilities. By regulating multiple pathological pathways such as inflammatory response, oxidative stress, neurotransmitter metabolism, and lipid metabolism, it may improve sleep quality and reduce related complications in OSA patients.

In addition, bergamotin has potential value in the fields of anti-tumor, anti-inflammatory, and cardiovascular diseases. Future research should focus on the molecular details of its mechanism of action, pharmacokinetic optimization, and safety evaluation, promoting its transition from laboratory research to clinical application.

However, the drug-making limitations of bergamotin, such as poor water solubility, low oral bioavailability, and potential drug interaction risks, must be overcome through strategies such as structural modification, nanocarrier delivery, and dosage form innovation. At the same time, systematic toxicology and preclinical studies are key steps in its clinical development.

Conclusion

As a natural furanocoumarin-type compound with significant CYP1A1 competitive inhibitory activity, bergamot extract demonstrates significant value in the treatment of obstructive sleep apnea and related diseases due to its multi-target regulatory ability and good pharmacological activity. Its unique chemical structure and physicochemical properties provide a solid foundation for drug design, but druggability and safety still require further exploration.

In the future, through multidisciplinary collaboration and combining modern medicinal chemistry, molecular biology, and pharmacokinetic technologies, bergamot extract is expected to become an important candidate molecule for the development of novel natural drugs, providing new ideas and strategies for the treatment of complex diseases.