Product name: Oleuropein Aglycone
Synonym name: 3,4-DHPEA-EA; Oleoeuropein Aglycone; Oleoeuropeine Aglycone; Oleuropein Aglycon; Oleuropeine Aglycone
Catalogue No.: BP2079
Cas No.: 31773-95-2
Formula: C₁₉H₂₂O₈
Mol Weight: 378.377
Botanical Source: Olive
Type of Compound: Iridoids

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.

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

Introduction/Overview

Oleuropein Aglycone (3,4-DHPEA-EA, CAS No.: 31773-95-2), as one of the important polyphenolic natural products in olive trees (Olea europaea L.), has attracted significant attention in recent years due to its broad biological activity and potential medicinal value. Oleuropein is the aglycogenic form of oleuropein (HY-N0292), usually obtained from oleuropein through enzymatic hydrolysis, acidic hydrolysis, or acetyl hydrolysis. As one of the main active forms of polyphenols in olive oil, oleuropein demon demonstrates significant pharmacological effects in antioxidant, anti-inflammatory, neuroprotective, and metabolic regulation fields, especially showing good application potential in the prevention and treatment of neurodegenerative diseases, metabolic syndromes, and inflammatory diseases.

This paper aims to systematically review the chemical structure and physicochemical properties of oleuropein matroglycoside, plant origin and extraction methods, pharmacological activity, and its mechanism of action. Combined with druggability evaluation and pharmacokinetic data, it explores its clinical application prospects and future research directions, aiming to provide theoretical support and reference for scientific research and drug development in the field of natural product pharmacology and related fields.

Chemical structure and physicochemical properties

The chemical name of oleuropein is 3,4-dihydroxyphenylethanol-acetate (3,4-DHPEA-EA), with a molecular formula C20H22O9 and a molecular weight of 378.37. Its structure consists of a phenolic hydroxyl-rich aromatic ring system connected to acetate groups, exhibiting typical polyphenolic compound characteristics. Its LogP value is about 1.45, indicating moderate lipid solubility, which is beneficial for cell membrane penetration and bioavailability. The polar surface area (TPSA) is 146.54 Ų, and the number of hydrogen bond acceptors is 8, suggesting strong hydrophilicity and potential for binding to biomacromolecules.

The structural characteristics of oleuropein determine its excellent antioxidant capacity and multi-target regulatory capacity. Its phenolic hydroxyl group can effectively scavenge free radicals and reduce oxidative stress damage; At the same time, the spatial configuration of aromatic rings and ester groups facilitates binding with various enzymes and receptors, exerting multi-layered biological effects.

Plant Origins and Extraction Methods

Oleuropein is mainly found in olive leaves, olive fruit, and olive oil, with higher levels in olive leaves and immature fruits. Its precursor compound oleuropein is the main component of olive polyphenols, while oleuropein is obtained through enzymatic or chemical hydrolysis of oleuropein.

Common extraction methods include:

1. Enzymatic hydrolysis: enzymes such as β-glucosidase are used to catalyze oleuropein hydrolysis, obtaining oleuropein under mild conditions and maintaining its biological activity.

2. Acid hydrolysis: Uses dilute acid to hydrolyze oleuropein under heating conditions; reaction time and temperature must be strictly controlled to avoid product degradation.

3. Acetyl hydrolysis: Treats oleuropein with acetylation reagents, breaks glycosidic bonds, and releases oleuropein glycosides.

After extraction, purity identification and structural confirmation are typically performed using techniques such as high-performance liquid chromatography (HPLC), mass spectrometry (MS), and nuclear magnetic resonance (NMR). In recent years, green technologies such as ultrasound-assisted extraction and microwave-assisted extraction have also been applied to the preparation of olivia picr, improving extraction efficiency and product quality.

Pharmacological activity research

The pharmacological activities of oleuropein include neuroprotection, metabolic regulation, anti-inflammation, and antioxidant properties. Most related studies are based on cell and animal models, showing significant biological effects.

1. Neuroprotective effects

Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by β-amyloid protein deposition, neuronal loss, and cognitive impairment. Research shows that dietary intake of oleuropein (50 mg/kg diet) can significantly increase the number of autophagocytic vesicles in neurons in the brains of TgCRND8 transgenic mice with Alzheimer's disease, promote the clearance of abnormal proteins, and reverse cognitive deficits. Additionally, oleuropein can lower histone deacetylase 2 (HDAC2) levels in the cortex and hippocampus, regulate epigenetic mechanisms, and promote neuroplasticity and memory recovery.

2. Metabolic regulation

In a model of obese rats induced by a high-fat diet, oleuropein demonstrated potential to regulate energy metabolism and adipose tissue function. It can increase the excretion of norepinephrine in urine, enhance adrenaline levels and the expression of uncoupling protein 1 (UCP1) in brown adipose tissue between the scapula, and promote calorie consumption and fat breakdown in adipose tissue. At the same time, oleuropein lowers plasma leptin levels and total abdominal adipose tissue weight, demonstrating its value in anti-obesity and improving metabolic syndrome.

3. Anti-inflammatory and antioxidant effects

In a mouse model of carrageenan-induced pleurisy, oleuropein significantly inhibited pulmonary neutrophil infiltration and reduced inflammatory responses. It can also reduce lipid peroxidation levels in lung tissue and the expression of pro-inflammatory cytokine IL-1β, demonstrating good anti-inflammatory and antioxidant activity. In addition, oleuropein has regulatory effects on various inflammatory mediators and oxidative stress-related signaling pathways, offering potential value for broad-spectrum anti-inflammatory drug development.

Mechanism of action and molecular targets

The multi-target mechanism of oleuropein is the basis of its pharmacological activity, mainly involving the following aspects:

1. Regulating autophagy pathways: By promoting the formation and function of neuronal autophagocytic vesicles, oleuropein facilitates the degradation of abnormal proteins, reduces neurotoxicity, and improves cognitive function.

2. Epigenetic regulation: Lowers histone deacetylase 2 (HDAC2) levels, modulates gene expression, and promotes neuroplasticity and cell survival.

3. Activates the sympathetic nervous system: Increases norepinephrine and adrenaline levels, activates UCP1 in brown adipose tissue, and promotes energy expenditure and fat metabolism.

4. Antioxidant and anti-inflammatory signaling pathways: Inhibits inflammation-related signaling pathways such as NF-κB and MAPK, reduces the release of pro-inflammatory cytokines, and decreases oxidative stress damage.

5. Regulates lipid metabolism: By affecting leptin levels and adipose tissue function, it improves lipid metabolic disorders and prevents obesity and related metabolic diseases.

Although the specific molecular targets of oleuropein are not yet fully understood, its multi-target and multi-pathway mode of action provides a theoretical basis for its broad biological effects.

Druggability evaluation and pharmacokinetics

The molecular weight of oliposide is 378.37, with a LogP value of 1.45, indicating moderate lipid solubility, which is beneficial for transmembrane absorption and bioavailability. Its high TPSA (146.54 Ų) and abundant number of hydrogen bond receptors (8) suggest that it may have some hydrophilicity and ability to bind to targets in vivo.

Currently, there is no clear data on the blood-brain barrier penetration ability of oleuropein. Safety indicators such as hepatotoxicity, cardiotoxicity, hERG channel inhibition, and genotoxicity (Ames assay) have not been systematically evaluated, urgently requiring further toxicological and pharmacokinetic studies.

Preliminary animal experiments indicate that oral oligosinin can exert biological activity in the body, but its absorption, distribution, metabolism, and excretion (ADME) characteristics remain unclear. In the future, it is necessary to systematically evaluate pharmacokinetic parameters and safety by combining in vivo and in vitro experiments with computational simulations, providing a basis for clinical translation.

Prospects and outlooks for clinical applications

As a natural polyphenolic compound, oleuropein demonstrates broad application prospects in the prevention and treatment of neurodegenerative diseases, metabolic syndromes, and inflammatory diseases due to its multi-target and multifunctional pharmacological properties. Especially in adjunctive therapy for Alzheimer's disease, regulation of obesity and metabolic diseases, and intervention in chronic inflammatory states, oleuropein has unique advantages.

Future research should focus on the following directions:

1. In-depth mechanism analysis: Using modern molecular biology and omics techniques, key molecular targets and signaling pathways of oleuropein are identified, revealing its multi-level regulatory mechanisms.

2. Pharmacokinetics and safety assessment: Systematic ADME studies and toxicological evaluations of oleuropein to ensure the safety and efficacy of clinical application.

3. Dosage form development and administration route optimization: Combining its physicochemical properties, develop suitable dosage forms and delivery methods to improve bioavailability and targeting.

4. Clinical trial validation: Conduct evidence-based clinical trials to verify efficacy and safety in related diseases, driving the transition from the laboratory to clinical practice.

5. Combination drug research: Exploring the synergistic effects of oleuropein with existing drugs or other natural products, expanding its clinical applications.

Conclusion

As an important aglycogen form of olive polyphenols, oleuropein has become a research hotspot in the field of natural product pharmacology due to its excellent antioxidant, anti-inflammatory, neuroprotective, and metabolic regulatory activities. Although the understanding of its mechanism of action and druggability is still incomplete, existing studies have laid a solid foundation for its application in neurodegenerative diseases, metabolic syndromes, and inflammatory diseases. In the future, through systematic mechanistic research, pharmacokinetic and safety evaluations, and clinical validation, oleuropein is expected to become an important candidate for natural drug development, contributing new natural drug resources to human health.