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Synonym name: 4-Hydroxypsoralen
Catalogue No.: BP0257
Cas No.: 486-60-2
Formula: C11H6O4
Mol Weight: 202.165
Botanical Source: bergamot oil (Citrus bergamia). Also from various other Citrus spp., Ficus religiosa and Ficus infectoria
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 Bergaptol
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
69.0900
1.7400
1.7400
Low
Unknown
Unknown
No
Unknown
Yes
Unknown
Bergamotol (Bergamotol, CAS number: 486-60-2) is a naturally occurring furanocoumarin-type compound, widely distributed in various citrus species, especially Bergamot (Citrus medica var. sarcodactylis). As an important natural product, bergamot phenol has attracted widespread attention in pharmacology and natural medicine research in recent years due to its unique chemical structure and diverse biological activities. Recent studies show that bergamotol not only inhibits the debenzyl action of cytochrome P450 enzyme CYP3A4 (IC50 about 24.92 μM), but also exhibits significant antiproliferative and anticancer activities. Moreover, its potential role in antioxidant damage also provides a theoretical basis for its clinical application.
This paper aims to systematically review the chemical structure and physicochemical properties of bergamotol, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation and pharmacokinetic characteristics, and to explore its prospects and challenges for future clinical application, aiming to provide reference and inspiration for related research.
The chemical name of bergamotol is 7-hydroxyfuranocoumarin, with a molecular formula of C10H6O4 and a molecular weight of 206.16. Its structural feature is the fusion of a furan ring with the coumarin-based backbone, and the presence of a 7-position hydroxyl group gives it strong polarity and biological activity. The molecular structure contains four hydrogen bond receptors, which greatly affect its ability to bind to biological macromolecules.
In terms of physicochemical properties, bergamotol has a LogP value of 1.74, indicating moderate lipid solubility, which facilitates penetration of cell membranes without excessive hydrophobicity, making it suitable for oral absorption. The topological pole surface area (TPSA) is 69.09 Ų, meeting the polarity requirements for most drug molecules and benefiting their bioavailability. According to existing data, bergamotol has a low blood-brain barrier penetration ability, suggesting its role in the central nervous system may be limited. Hepatotoxicity and cardiotoxicity remain unclear. The hERG channel inhibition test results are negative, preliminarily indicating good cardiac safety, but further systematic evaluation is still needed.
Bergamotol is mainly found in citrus plants, especially abundant in the fruits and peels of bergamot, oranges, and pomelos. Bergamot is widely used in traditional Chinese medicinal materials, with its medicinal value partly attributed to bergamotol and its related derivatives.
There are various methods for extracting bergamot, commonly including solvent extraction, ultrasound-assisted extraction, and supercritical fluid extraction. Ethanol or methanol is generally used as the extraction solvent, improving extraction efficiency by optimizing extraction time, temperature, and solvent concentration. The extract undergoes liquid-liquid separation, column chromatography, and other purification steps, ultimately yielding high-purity bergamotol. In recent years, green extraction technologies such as ultrasonic-assisted extraction and microwave-assisted extraction have been applied to bergamotol extraction, significantly improving yield and purity, while better meeting environmental friendliness and sustainable development requirements.
As a hydroxyl-containing furanocoumarin, bergamotol exhibits good antioxidant activity. It can eliminate free radicals and reduce cellular damage caused by oxidative stress. Relevant in vitro experiments show that bergamotol can activate intracellular antioxidant enzyme systems, such as superoxide dismutase (SOD1, SOD2), catalase (CAT), and glutathione peroxidase (GPX1), thereby reducing reactive oxygen species (ROS) levels and protecting cells from oxidative damage.
In recent years, the anti-cancer potential of bergamotol has gradually been revealed. Multiple in vitro cell experiments have shown that bergamotol can inhibit the proliferation of various cancer cell lines, including liver cancer, breast cancer, and colorectal cancer cells. Its mechanism of action may involve inducing cell cycle arrest, promoting apoptosis, and inhibiting tumor cell migration and invasion. Additionally, bergamotol exerts synergistic anti-cancer effects by regulating the activity of cytochrome P450 enzyme CYP3A4, affecting drug metabolism and changes in the tumor microenvironment.
Bergamotol also exhibits multiple pharmacological effects, including anti-inflammatory, antibacterial, and neuroprotective effects. Its anti-inflammatory effects are mainly achieved by inhibiting the expression of inflammatory factors and activating signaling pathways. Neuroprotective effects may be related to its antioxidant and regulatory effects of apoptosis, suggesting its potential application value in neurodegenerative diseases.
The pharmacological effects of bergamotol are closely related to its regulation of various molecular targets. Its antioxidant effects are mainly achieved by activating the NFE2L2 (NRF2) signaling pathway. NRF2, as a key intracellular transcription factor, regulates the expression of various antioxidant and detoxifying enzymes, such as SOD1, SOD2, CAT, GPX1, and HMOX1 (heme oxygenase 1), enhancing the cell's ability to resist oxidative stress.
In terms of anticancer mechanisms, bergamotol inhibits the debenzyl action of the CYP3A4 enzyme, affecting the activity of drug-metabolizing enzymes and potentially altering tumor cells' sensitivity to drugs. Additionally, bergamotol can regulate cell cycle-related proteins and apoptosis signaling pathways, such as p53, Bcl-2 family proteins, and caspase enzyme systems, inducing cancer cell apoptosis and blocking its proliferation.
Its anti-inflammatory and neuroprotective mechanisms involve inhibition of the NF-κB signaling pathway and reduction of ROS generation, alleviating inflammatory responses and cellular damage. Overall, bergamotol achieves its diverse biological effects through multi-target and multi-pathway synergistic effects.
The druggability parameters of bergamotol indicate that it has good therapeutic potential. Molecular weight 206.16, LogP 1.74, TPSA 69.09 all meet the Lipinski rule, indicating good oral bioavailability. It has 4 hydrogen bond receptors, which helps the molecule bind to its target.
The blood-brain barrier has low permeability, limiting its direct application in central nervous system diseases but reducing the risk of central side effects. There are no definitive data on hepatotoxicity and cardiotoxicity. Negative hERG suppression suggests good cardiac safety, but further in vivo toxicology studies are still needed for validation.
In terms of pharmacokinetics, current research is relatively limited. It is speculated that bergamotol is well absorbed orally, but its metabolic pathway and in vivo half-life have not been systematically reported. Given its inhibitory effect on CYP3A4, there may be a risk of drug interactions, which should be closely monitored in future studies.
As a natural product, bergamotol shows broad clinical application prospects thanks to its diverse pharmacological activities and good druggability. Its antioxidant and anticancer effects make it an ideal candidate for developing novel antitumor drugs. Especially in adjuvant therapy for malignant tumors such as liver cancer and breast cancer, bergamotol is expected to improve treatment efficacy and reduce side effects by regulating oxidative stress and drug-metabolizing enzyme activity.
Moreover, bergamotol's potential in anti-inflammatory and neuroprotective fields is worth further exploration, and it is expected to be used in the treatment of chronic inflammatory diseases and neurodegenerative diseases in the future. With advances in green extraction technologies and pharmaceutical formulation processes, the industrialization and clinical translation of bergamotol will become more feasible.
However, clinical research on bergamotol is still in its early stages, with systematic pharmacokinetics, toxicology, and clinical safety evaluations lacking. In the future, research on its in vivo metabolic mechanisms, drug interactions, and long-term safety should be strengthened, while exploring strategies for its combined application with other drugs to promote its clinical application.
As a natural product with a unique structure and multiple biological activities, bergamot demonstrates broad application potential in fields such as antioxidant, anti-cancer, and anti-inflammatory properties. By regulating the NRF2 signaling pathway and CYP3A4 enzyme activity, it achieves multi-target and multi-mechanism pharmacological effects. The druggability parameters are good, laying the foundation for further drug development.
Future research should focus on its pharmacokinetic characteristics, toxicological safety evaluation, and clinical efficacy verification, promoting bergamot phenol from the laboratory to clinical application. With deeper understanding of the pharmacological mechanisms of natural products, bergamotol is expected to become an important research subject and a new clinical treatment option in the field of natural product pharmacology.
Shenshuai
Wenjing
Hedandan
