Synonym name:
Catalogue No.: BP0109
Cas No.: 1603-47-0
Formula: C₁₂H₈O₅
Mol Weight: 232.191
Botanical Source:

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.

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

Introduction/Overview

8-Hydroxybergapten (CAS No. 1603-47-0) is a naturally occurring furanocoumarin, widely distributed in Rutaceae plants, especially those of the Bergamot and Ruta genera. As an important member of the furanocoumarins family, 8-hydroxyberga's olide has attracted widespread attention in the field of natural product pharmacology in recent years due to its unique chemical structure and diverse biological activities. This compound not only transforms into isopimpinellin in plants through O-methyltransferase-mediated reactions but also exhibits significant bioactivity, showing promising application prospects in anti-wrinkle beauty treatments and potential treatments related to obstructive sleep apnea (OSA).

This paper aims to systematically review the chemical structure and physicochemical properties, plant origin and extraction methods, pharmacological activity and mechanism of action of 8-hydroxyberga's lactone, druggability evaluation, and pharmacokinetic characteristics, as well as its potential for clinical application and future development directions, providing a theoretical basis and reference for in-depth research and drug development of this natural product.

Chemical structure and physicochemical properties

8-Hydroxybergamot lactone belongs to the furanocoumarin-class compounds, with a molecular formula of C12H8O5 and a molecular weight of 232.19. Its structural features include a coumarin-based core structure combined with a furan ring and a hydroxyl substituent at position 8. This hydroxyl group imparts strong polarity and biological activity, while also providing a site for subsequent enzymatic modification.

In terms of physicochemical properties, the LogP value of 8-hydroxybergamot lactone is 1.78, indicating moderate lipid solubility, which facilitates cell membrane penetration and distribution in vivo. The polar surface area (TPSA) is 77.58 Ų, indicating a certain degree of hydrophilicity and hydrogen bonding ability. The molecule contains five hydrogen bond receptors that may participate in interactions with various hydrogen bonds targeting biological sites. The blood-brain barrier has low permeability, indicating limited penetration ability in the central nervous system. Toxicological evaluation showed no hepatotoxicity, cardiotoxicity, or hERG channel inhibitory effects, indicating high safety, but Ames-related mutagenicity test results remain unclear.

Plant Origins and Extraction Methods

8-Hydroxybergamot lactone is mainly found in Rutaceae plants, especially Ruta species such as Ruta graveolens and Bergamot (Citrus medica var. sarcodactylis), etc. Ruta plants have been widely studied due to their abundance of furanocoumarin-class compounds, with 8-hydroxybergamot lactone as a representative component and possessing significant chemical and pharmacological value.

The extraction method typically uses organic solvent extraction combined with chromatography separation technology. Common extraction solvents include ethanol, methanol, and ethyl acetate, which can effectively dissolve furanocoumarin-type compounds. The extraction process generally includes the following steps:

1. Plant materials are dried and crushed to increase surface area.
2. Ultrasound-assisted extraction or reflux extraction is used to improve extraction efficiency.
3. After concentration of the crude extract, purification is performed by silica gel column chromatography and reversed-phase high-performance liquid chromatography (RP-HPLC).
4. The purified product structure is identified using techniques such as mass spectrometry (MS) and nuclear magnetic resonance (NMR).

Additionally, biosynthetic pathway studies have shown that 8-hydroxybergamot lactone can be catalyzed by O-methyltransferase conversion into isopenicillin in cell-free extracts of Ruta cells, suggesting its metabolic dynamics and biosynthetic regulatory mechanisms in plants.

Pharmacological activity research

Pharmacological research on 8-hydroxybergamot lactone covers multiple aspects including anti-wrinkle beauty, antioxidant, anti-inflammatory, and neuroprotective effects, with significant effects especially in the skin anti-aging field.

Anti-wrinkle and skin-protective effects

Multiple in vitro and in vivo studies have shown that 8-hydroxybergamot lactone can effectively inhibit collagenase (MMPs) activity, reduce collagen degradation, and promote the synthesis of skin elastin, thereby achieving anti-wrinkle and improved skin texture. Additionally, this compound reduces UV-induced skin damage by modulating oxidative stress-related signaling pathways, demonstrating excellent photoprotective effects.

Anti-inflammatory and antioxidant activities

8-Hydroxybergago lactone can inhibit the activity of inflammatory mediators such as prostaglandins (PTGS1) and monoamine oxidase A (MAOA), reducing inflammatory responses. Its antioxidant capacity mainly works by scavenging free radicals and regulating intracellular antioxidant enzyme systems, helping to alleviate the pathological progression of oxidative stress-related diseases.

Neuroprotective and obstructive sleep apnea (OSA)

Research shows that 8-hydroxyberga's bergamot lactone may participate in the pathological mechanisms of obstructive sleep apnea by modulating various molecular targets (such as APP, ESR1/2, HMGCR, etc.). Its potential effects on neuronal protection, inflammation suppression, and metabolic regulation offer new ideas for the treatment of OSA and related neurological diseases.

Mechanism of action and molecular targets

The bioactivity of 8-hydroxybergamot lactone is attributed to its interactions with several key molecular targets, involving signal transduction, enzyme activity regulation, and gene expression regulation.

Key molecular targets

• APP (amyloid precursor protein): involved in neurodegenerative diseases and sleep regulation. 8-Hydroxyberga's polychrome lactone may affect neuroprotection and cognitive function by modulating APP metabolism.
• MAOA (Monoamine Oxidase A): Regulates neurotransmitter metabolism and inhibits its activity, helping to reduce neuroinflammation and oxidative damage.
• ESR1/ESR2 (estrogen receptors α and β): Regulates skin elasticity and metabolism. 8-Hydroxybergamot lactone promotes collagen synthesis and anti-wrinkle effects by activating estrogen receptors.
• PTGS1 (cyclooxygenase-1): mediates inflammatory responses, inhibits its activity, aids in anti-inflammatory and skin damage.
• CA4/CA9/CA12 (carbonic anhydrase subtypes): regulate intracellular pH and metabolism, involved in tumor and inflammatory processes.
• ABCG2 (ATP-binding box transporter G2): affects drug efflux and cell protection.
• HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase): a key cholesterol synthase, regulating lipid metabolism.

Mechanism of action

8-Hydroxybergamot lactone regulates cellular signaling pathways by binding to the above targets, exerting multiple pharmacological effects. For example, its inhibitory effects on MAOA and PTGS1 reduce neuroinflammation and oxidative stress, promoting neuroprotection; Activation of ESR1/2 enhances collagen synthesis in the skin and improves skin structure; Regulation of HMGCR helps balance lipid metabolism and indirectly affects the metabolic basis of sleep apnea.

Additionally, 8-hydroxybergago lactone is converted into isopenicillin in Rota cells by O-methyltransferase catalyzion, suggesting that it may exert broader biological activity in vivo via metabolites.

Druggability evaluation and pharmacokinetics

Druggability is an important consideration in developing natural products into medicines. 8-Hydroxybergago lactone performs excellently in multiple pharmacokinetic and safety indicators.

Pharmacokinetic parameters

• Molecular weight: 232.19, suitable for small molecule drug development.
• Lipophilic (LogP=1.78): moderate, facilitating oral absorption and membrane penetration.
• Polar surface area (TPSA=77.58 Ų): suitable for good bioavailability.
• Number of hydrogen bond receptors (5): Facilitates stable binding to the target.

Safety evaluation

• Hepatotoxicity: No significant risk of hepatotoxicity.
• Cardiotoxicity: No hERG channel inhibition, good cardiac safety.
• Blood-brain barrier penetration: Lower, indicating a lower risk of side effects on the central nervous system.
• Mutagenicity: Ames test data are still lacking and require further evaluation.

Overall, 8-hydroxybergamot lactone has good pharmacokinetic characteristics and a safety foundation, making it suitable as a candidate drug for further preclinical research.

Prospects and outlooks for clinical applications

8-Hydroxybergamot lactone, as a versatile natural product, has broad clinical application potential.

Anti-wrinkle beauty field

Its anti-collagenase activity and ability to promote collagen synthesis make it an ideal ingredient for anti-aging skincare products. In the future, nanocarriers or composite formulations can enhance skin permeability and stability, expanding their market applications.

Obstructive Sleep Apnea (OSA)

OSA, as a common sleep disorder, is associated with various metabolic and inflammatory pathways. 8-Hydroxybergago lactone has potential therapeutic value by modulating multiple targets such as APP, MAOA, and ESR. Future research should focus on validating its efficacy in OSA animal models and clinical trials.

Other potential applications

Its anti-inflammatory, antioxidant, and neuroprotective effects suggest potential for development in neurodegenerative diseases, metabolic syndrome, and inflammation-related diseases. By combining modern drug design with targeted delivery technologies, its clinical value can be further explored.

Research challenges and future directions

Currently, the pharmacokinetics, metabolic pathways, and long-term safety of 8-hydroxy-bergamot lactone in vivo still require systematic research. In-depth analysis of its biosynthesis mechanisms and enzymatic transformation processes will help achieve efficient production through biosynthetic engineering. In addition, network pharmacology research based on multi-target mechanisms will promote its precision medicine applications.

Conclusion

8-Hydroxybergamot lactone, as a natural furanocoumarin-type compound with a unique structure and multiple biological activities, shows broad application prospects in anti-wrinkle beauty and obstructive sleep apnea treatment. Its excellent druggability and safety lay a solid foundation for subsequent drug development. In the future, by integrating modern molecular biology, pharmacology, and medicinal chemistry techniques, in-depth exploration of its mechanisms of action and clinical efficacy will promote the clinical translation of this natural product and benefit human health.