Synonym name: 3,4-dihydroxyphenylethanol; Dopaol
Catalogue No.: BP0746
Cas No.: 10597-60-1
Formula: C₈H₁₀O₃
Mol Weight: 154.165
Botanical Source: Present in olives. Reported from Lian Qiao (Syringa spp.)

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.

Description:

2-(3,4-Dihydroxyphenyl)ethanol has antioxidant properties; it is a potent specific inhibitor of lipoxygenase activities, it inhibits platelet 12-LO activity (IC50, 4.2 microM) and PMNL 5-LO activity (IC50, 13 microM) but not cyclooxygenase activity in cell-free conditions; it also inhibits 12-LO activity in intact platelets (IC50, 50 microM) and reduces leukotriene B4 production in intact PMNL stimulated by A23187 (IC50, 26 microM).

References:

Drug Chem Toxicol. 2014 Oct;37(4):420-6.Antioxidant role of hydroxytyrosol on oxidative stress in cadmium-intoxicated rats: different effect in spleen and testes.

Hydroxytyrosol (2-(3,4-Dihydroxyphenyl)ethanol, (DPE), a phenolic compound present in olive oil, is known to have antioxidant properties. 

METHODS AND RESULTS:

The aim of this study was to investigate the effect of DPE on oxidative stress induced by cadmium injections (CdCl2 2.5 mg/kg body weight) in spleen and testes of adult male rats. Oxidative stress was evaluated by measuring lipid peroxidation by thiobarbituric acid reactive substances (TBARS) as well as superoxide dismutase (SOD) and catalase (CAT) activities in cytosol and mitochondria. We found that in spleen no TBARS formation was detected following CdCl2 injections; however, DPE induces decrease in TBARS level in treated and untreated rats. On the contrary, we observed that DPE showed no effect on cadmium-induced lipid peroxidation in testes. Cytosolic activities of SOD and CAT decreased significantly only in spleen, where DPE restores the values to the control levels. Noteworthy, mitochondrial activities of SOD and CAT were strongly reduced by cadmium treatment both in spleen and testes, and DPE was not be able to restore their activity. 

CONCLUSIONS:

Overall, the results from this study indicated that the DPE has different antioxidant efficiency in spleen and testis of cadmium intoxicated rats.

HPLC of  Hydroxytyrosol

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

Introduction/Overview

Hydroxytyrosol (DOPET, CAS number: 10597-60-1) is a phenolic compound naturally occurring in olive oil. Due to its outstanding bioactivity and diverse pharmacological effects, it has attracted widespread attention in the field of natural product pharmacology in recent years. As one of the main phenolic antioxidants in olive oil, hydroxytyrosol not only plays an important role in slowing oxidative deterioration of olive oil, but has also been widely studied for its remarkable antioxidant, anti-inflammatory, neuroprotective, and antitumor activities. Hydroxytyrosol demonstrates potential therapeutic value for various diseases by regulating oxidative stress, mitochondrial function, and multiple cellular signaling pathways, covering cancer, metabolic disorders, neurodegenerative diseases, and cardiovascular diseases.

This paper aims to systematically review the chemical structure and physicochemical properties of hydroxytyrosol, plant origins and extraction methods, explore its pharmacological activity and mechanism of action in depth, evaluate its druggability and pharmacokinetic characteristics, and anticipate its potential and challenges in clinical application, providing theoretical basis and reference for subsequent basic research and clinical translation.

Chemical structure and physicochemical properties

The chemical name of hydroxytyrosol is 2-(3,4-dihydroxyphenyl)ethanol, with a molecular formula C8H10O3 and a molecular weight of 154.1650. Its structural features include two hydroxyl groups adjacent to a benzene ring (orthodiphenol structure) and a side-chain ethanol group. This orthodiol structure gives hydroxytyrosol a strong free radical scavenging ability, forming the molecular basis for its antioxidant activity.

In terms of physicochemical properties, the LogP value of hydroxytyrosol is about 0.7583, indicating moderate lipophilicity that facilitates cell membrane penetration. The polar surface area (TPSA) is 60.69 Ų, indicating good water solubility (about 27.94 mg/mL) and easy crossing of the blood-brain barrier (BBB), providing a molecular basis for its neuroprotective effects. Hydroxytyrosol does not inhibit hERG channels, and the Ames test result is zero, indicating high safety with no significant genotoxicity risk.

Plant Origins and Extraction Methods

Hydroxytyrosol is mainly found in the fruit and olive oil of the olive tree (Olea europaea L.), with a higher content in extra virgin olive oil. Its content is significantly influenced by factors such as olive variety, ripeness, picking time, and processing techniques. Besides olives, small amounts of hydroxytyrosol are also found in some other plants, but olive oil remains the primary and most economical natural source.

There are various extraction methods. Traditionally, solvent extraction binder-liquid extraction technology is used to separate hydroxytyrosol from olive fruit or olive oil. In recent years, green and efficient methods such as supercritical CO2 extraction, ultrasound-assisted extraction, and membrane separation technology have gradually been applied to the extraction and purification of hydroxytyrosol, significantly improving yield and purity, and reducing solvent residues and environmental pollution. Purification steps typically include liquid chromatography (such as HPLC) separation to ensure the acquisition of high-purity hydroxytyrosol for pharmacological research.

Pharmacological activity research

Antioxidant and neuroprotective effects

Hydroxytyrosol is renowned for its powerful antioxidant capacity, effectively scavenging free radicals and reducing oxidative stress damage. Numerous in vitro and in vivo studies have shown that hydroxytyrosol activates the nuclear factor E2-related factor 2 (NFE2L2/NRF2) signaling pathway, inducing the expression of downstream antioxidant enzymes such as superoxide dismutase (SOD1, SOD2), catalase (CAT), glutathione peroxidase (GPX1), and heme oxygenase 1 (HMOX1), thereby enhancing cellular antioxidant defenses. This mechanism is especially crucial in neuronal protection, as it can improve mitochondrial function, inhibit neuronal apoptosis, and slow the progression of neurodegenerative diseases such as Alzheimer's.

Antitumor activity

Hydroxytyrosol exhibits significant antitumor activity across various cancer models. Its mechanism of action is complex, including inducing apoptosis of cancer cells and inhibiting proliferation and migration. Hydroxytyrosol can induce reactive oxygen species (ROS) production, activate mitochondrial pathway-mediated apoptosis, and regulate multiple signaling pathways such as NF-κB, PI3K/Akt, and MAPK, thereby inhibiting tumor cell survival and invasion. Especially in digestive system tumors such as colon cancer, hydroxytyrosol has shown good anti-cancer potential.

Antibacterial and antiviral effects

Research shows that hydroxytyrosol has broad-spectrum antibacterial activity and can inhibit the growth of various Gram-positive and Gram-negative bacteria, including common pathogens such as Staphylococcus aureus and Escherichia coli. Additionally, hydroxytyrosol inhibits certain viruses such as influenza virus and herpes simplex virus, possibly by disrupting the viral envelope or interfering with viral replication.

Anti-inflammatory and immunomodulatory

Hydroxytyrosol can inhibit the release of inflammatory mediators and reduce inflammatory responses. It alleviates tissue inflammatory damage by downregulating pro-inflammatory cytokines (such as TNF-α, IL-6, IL-1β) and inhibiting the NF-κB signaling pathway. At the same time, hydroxytyrosol regulates immune cell function and enhances the body's immune defenses, showing potential application value in immune-related diseases.

Metabolic and cardiovascular protection

Hydroxytyrosol has a positive effect on metabolic diseases such as diabetes, improving insulin sensitivity and lowering blood sugar and lipid levels. Its cardiovascular protective effects mainly manifest in antioxidant, anti-inflammatory, and improved endothelial function, inhibiting the onset and progression of atherosclerosis, and reducing the risk of cardiovascular events.

Mechanism of action and molecular targets

The multi-target mechanism of hydroxytyrosol forms the basis of its broad pharmacological activity. The main molecular targets and signaling pathways include:

• NFE2L2/NRF2 signaling pathway: Hydroxytyrosol activates NRF2 transcription factor, promotes the expression of antioxidant enzyme genes, enhances cellular antioxidant capacity, and reduces oxidative stress damage.
• Antioxidant enzyme system: Hydroxytyrosol upregulates key antioxidant enzymes such as SOD1, SOD2, CAT, GPX1, and HMOX1, clearing excess ROS and protecting cellular function.
• Mitochondrial function regulation: By improving mitochondrial membrane potential and promoting mitochondrial biosynthesis, hydroxytyrosol maintains cellular energy metabolism and inhibits mitochondria-mediated apoptosis.
• Reactive oxygen species (ROS) regulation: In tumor cells, hydroxytyrosol induces excessive ROS production, triggering apoptosis signals and selectively killing cancer cells.
• NF-κB signaling pathway: Hydroxytyrosol inhibits NF-κB activation, reduces inflammatory factor expression, and exerts anti-inflammatory effects.
• PI3K/Akt and MAPK pathways: regulate cell proliferation, apoptosis, and migration, participating in anti-tumor and cell-protective effects.

Druggability evaluation and pharmacokinetics

Hydroxytyrosol has excellent druggability, a moderate molecular weight (154.1650), and a LogP value of 0.7583, indicating a good balance between lipid solubility and water solubility, which is beneficial for bioavailability. TPSA is 60.69 Ų, indicating moderate molecular polarity that can penetrate the blood-brain barrier and support its neuroprotective effects. In terms of safety, hydroxytyrosol showed no significant hERG channel inhibition, and the Ames test was negative, suggesting low genotoxicity risk.

Pharmacokinetic studies show that hydroxytyrosol is well absorbed orally, has a moderate plasma half-life, is widely distributed in the body, and is especially highly accumulated in brain tissue. Its metabolism is mainly through hepatic phenolation hydroxylation and glucuronic acid binding, with good safety of the metabolites. Hydroxytyrosol is mainly excreted through urine, with a relatively high clearance rate in the kidneys.

However, hydroxytyrosol is less stable in the body and easily degraded by metabolic enzymes, limiting its bioavailability and therapeutic effectiveness. To address this, strategies such as nanocarriers, liposomes, and structural modification have been proposed to improve their pharmacokinetic properties.

Prospects and outlooks for clinical applications

As a versatile natural product, hydroxytyrosol has broad clinical application potential. Its therapeutic value is increasingly significant in neurodegenerative diseases (such as Alzheimer's disease), cancer (especially colon cancer), metabolic syndrome (diabetes), cardiovascular diseases, and infectious diseases. Currently, hydroxytyrosol has entered some preclinical and preliminary clinical trial stages, demonstrating good safety and efficacy.

Future research should focus on:

• Optimizing the administration route and dosage form of hydroxytyrosol to improve its in vivo stability and bioavailability;
• In-depth analysis of its molecular mechanisms, especially signaling networks related to immune regulation and metabolic regulation;
• Conduct large-scale, multicenter clinical trials to systematically evaluate efficacy and safety;
• Exploring the potential of combined use of hydroxytyrosol with existing drugs to enhance therapeutic outcomes;
• Developing derivatives and novel drug molecules based on hydroxytyrosol to expand its medicinal chemistry horizons.

Conclusion

As an important phenolic component in olive oil, hydroxytyrosol shows broad pharmacological application prospects due to its excellent antioxidant, anti-inflammatory, neuroprotective, and antitumor activities. Its multi-target and multi-mechanism mode of action provides a valuable example for pharmacological research of natural products. Despite challenges such as bioavailability and in vivo stability, with the development of drug delivery technologies and structural optimization strategies, hydroxytyrosol is expected to become a new natural drug for the prevention and treatment of various diseases. Future systematic pharmacology, pharmacokinetics, and clinical research will lay a solid foundation for clinical translation, promoting its application and development in modern medicine.