Synonym name:
Catalogue No.: BP0577
Cas No.: 514-47-6
Formula: C₃₀H₅₀O
Mol Weight: 426.729
Botanical Source: Euphorbia 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.

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

Introduction/Overview

Euphol (CAS No.: 514-47-6) is a tetracyclic triterpene alcohol natural product derived from the Euphorbia tirucalli plant in the Euphorbiaceae family. As one of the main active components in the plant's sap, Euphorbia dienol has attracted attention for its remarkable anti-inflammatory, immunomodulatory, and antitumor properties. In recent years, with in-depth research into the endocannabinoid system (ECS) and its role in inflammation and pain regulation, the potential of Euphorbia Glycerol as a monoacylglycerol lipase (MGL) inhibitor has gradually been revealed. MGL, as a key enzyme in ECS, regulates the degradation of 2-arachidonylglycerol (2-AG). Its inhibition enhances endocannabinoid signaling, thereby exerting anti-inflammatory and analgesic effects. In addition, the regulatory effects of Euphorbia Dienol on various tumor-related targets demonstrate its broad prospects as a candidate anti-tumor drug. This paper will systematically review the chemical structure and physicochemical properties of Euphorbia dienol, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and clinical application potential, aiming to provide a theoretical foundation and reference for in-depth research and drug development of this natural product.

Chemical structure and physicochemical properties

Eugeniol is a tetracyclic triterpene alcohol compound, with the molecular formula C30H50O and a molecular weight of 426.7290. Its structure is based on a tetracyclic framework, containing a hydroxyl (-OH) functional group that imparts a certain polarity. The LogP value reaches as high as 8.7805, demonstrating extremely strong lipid solubility, which matches its hydrophobic framework structure. The extremely low topological polar surface area (TPSA) is 20.2300 Ų, indicating fewer polar groups, which facilitates lipid membrane penetration. Its extremely low water solubility (0.0001 mg/mL) suggests poor solubility in the aqueous phase, but its high lipid solubility makes it easy to cross cell membranes and the blood-brain barrier (BBB), which is especially important in pharmacokinetics. The hERG channel inhibition test was negative, indicating that Eus Turbidienol is less likely to trigger arrhythmia-related toxicity risks. Ames test results were 0.0, showing no mutagenicity and relatively high safety. Overall, the physicochemical properties of Euphorbia dienol align with typical characteristics of hydrophobic natural products, indicating its wide distribution in the body, especially in the central nervous system.

Plant Origins and Extraction Methods

Euphorbia dienol is mainly isolated from the milk of Euphorbia tirucalli. E. tirucalli is a succulent shrub in the Euphorbiaceae family, widely distributed in tropical and subtropical regions, commonly used in traditional medicine to treat inflammation, infections, tumors, and other diseases. Its milk contains abundant triterpene compounds, with a high content of Euspurge dienol.

The extraction process usually involves collecting milk and then extracting it using organic solvents such as ethanol, methanol, or ethyl acetate. After the extract is concentrated by rotary evaporation, it is separated and purified by column chromatography (silica gel column, C18 reversed phase column, etc.). High-performance liquid chromatography (HPLC) and mass spectrometry (MS) technologies are used for component identification and purity analysis. In recent years, green extraction technologies such as supercritical CO2 extraction and microwave-assisted extraction have also been attempted to improve the extraction efficiency and purity of Euphorbia dienol.

Pharmacological activity research

Anti-inflammatory and immunomodulatory effects

Euspurge dienol exhibits significant anti-inflammatory activity, mainly by inhibiting the production of inflammatory mediators and regulating immune cell function. In vitro studies have shown that Euphorbia dienol can inhibit the expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 in macrophages, thereby reducing inflammatory responses. Its oral activity also enables it to demonstrate good anti-inflammatory effects in in vivo models.

Importantly, Euphorbia dienol reversibly inhibits monoacylglycerol (MGL) activity (IC50=315 nM), blocks the degradation of 2-AG, enhances endocannabinoid signaling, and regulates immune responses and inflammatory processes. After MGL inhibition, 2-AG levels increase, activating CB1 and CB2 receptors, exerting analgesic and anti-inflammatory effects, especially showing significant relief of inflammatory pain in peripheral tissues.

Antitumor activity

Euphorbia dienol exhibits the ability to inhibit proliferation and induce apoptosis across various tumor cell lines. Its targets cover various tumor-associated proteins, including anti-apoptotic proteins MCL1 and BCL2, signal transduction factor STAT3, matrix metalloproteinase MMP2, DNA topoisomerase TOP1 and TOP2A, transcription factor HIF1A, mitogen-activated protein kinase MAPK1, estrogen receptor ESR1, and aromatase CYP19A1.

Mechanistic studies have shown that Eugenedienol regulates these targets to inhibit tumor cell proliferation, migration, and invasion, promotes cell cycle arrest and apoptosis, and suppresses tumor-related angiogenesis and metabolic adaptation. Especially in models of breast, lung, and colorectal cancers, Euphorbia dienol demonstrates strong antitumor potential.

Mechanism of action and molecular targets

MGL inhibition and endogenous cannabinoid system regulation

Euphorbia dienol inhibits MGL activity through reversible binding, blocking the hydrolysis of 2-AG and leading to elevated levels of 2-AG both extracellular and intracellular. 2-AG acts as an endogenous cannabinoid that activates CB1 and CB2 receptors, regulating neuroinflammation and immune responses. CB2 receptors are mainly distributed in immune cells; upon activation, they inhibit the release of pro-inflammatory cytokines and reduce inflammatory responses. CB1 receptors are mainly distributed in the central nervous system, participating in pain regulation and neuroprotection. Euphorbia dienol regulates the ECS and blocks the development of inflammatory pain, demonstrating potential dual analgesic and anti-inflammatory effects.

Regulation of anti-tumor-related molecular targets

• MCL1 and BCL2: Euphorbia dienol downregulates the expression of anti-apoptotic proteins MCL1 and BCL2, promoting tumor cell apoptosis.
• STAT3: Inhibits the STAT3 signaling pathway, blocking tumor cell proliferation and immune evasion.
• MMP2: Reduces MMP2 activity and inhibits the ability of tumor cells to degrade and metastasize in the stromal.
• TOP1 and TOP2A: Affect DNA topoisomerase activity, interfering with DNA replication and transcription in tumor cells.
• HIF1A: Inhibits tumor hypoxia-inducing factors, interfering with the tumor's ability to adapt to hypoxic environments.
• MAPK1: Regulates the MAPK signaling pathway, affecting cell proliferation and apoptosis.
• ESR1 and CYP19A1: regulate estrogen receptors and aromatase, affecting the growth of hormone-dependent tumors.

The multiple regulation of these targets gives Eupheridian Alcohol multi-target antitumor effects, making it suitable for therapeutic strategies in complex tumor microenvironments.

Druggability evaluation and pharmacokinetics

Although the molecular weight of Eupolidon dienol is 426.7, slightly below the 500 recommended by Lipinski's rules, it remains within the acceptable range. Its extremely high LogP value (8.78) shows strong lipid solubility, potentially leading to widespread distribution in the body, especially crossing the blood-brain barrier, suggesting its potential application advantages in central nervous system diseases. However, high lipid solubility may also lead to reduced bioavailability and the risk of accumulation in vivo, which needs to be addressed through formulation optimization.

A low TPSA value (20.23) favors membrane permeability and supports the feasibility of oral administration. Its extremely low water solubility (0.0001 mg/mL) is a major challenge in clinical development, potentially limiting absorption and distribution in the body. Pharmacological methods such as nanocarriers, liposomes, or solid dispersions can improve their solubility and bioavailability.

In terms of safety, Euphorbia dienol does not inhibit hERG channels, reducing the risk of cardiotoxicity; Ames test was negative, indicating no significant mutagenicity and good safety. Currently, there is limited in vivo pharmacokinetic research. Future studies need to systematically evaluate its absorption, distribution, metabolism, and excretion (ADME) characteristics to clarify in vivo exposure and half-life, providing a basis for clinical development.

Prospects and outlooks for clinical applications

Euphorbia dienol, as a natural product with a unique mechanism of action, demonstrates broad clinical application potential. It regulates the endocannabinoid system by inhibiting MGL, possessing anti-inflammatory, analgesic, and immunomodulatory effects, and is suitable for treating inflammatory diseases, chronic pain, and autoimmune diseases. Moreover, its multi-target antitumor activity offers new ideas for cancer treatment, especially in the context of multidrug resistance and complex tumor microenvironments, where it holds potential synergistic therapeutic value.

Future research should focus on:

1. Pharmacokinetics and safety assessment: Systematic in vivo pharmacokinetic studies are conducted to clarify dose-exposure relationships and long-term safety.
2. Dosage Form Optimization: Develop efficient delivery systems to improve water solubility and bioavailability, ensuring clinical feasibility.
3. In-depth analysis of the mechanism of action: By combining multi-omics techniques such as genomics and proteomics, the action nodes of Euphorbia dienol in the cellular signaling network were revealed.
4. Preclinical and clinical trials: Conduct multicenter, multi-phase preclinical animal models and human clinical trials to verify efficacy and safety.
5. Combination therapy strategy: Explore synergies with existing anti-inflammatory drugs, immunomodulators, and antitumor drugs to enhance treatment outcomes.

In summary, Euphorbidiaeneol, as a natural compound with multiple pharmacological activities, has the potential to become a novel anti-inflammatory, immunomodulatory, and antitumor drug and is worth further development.

Conclusion

Euphrid dienol, as an important tetracyclotriterpene alcohol in Euphorbia tirucalli, holds a significant position in the field of natural product pharmacology due to its unique chemical structure and remarkable biological activity. By inhibiting MGL, it regulates the endocannabinoid system, exerts anti-inflammatory and immunomodulatory effects, and simultaneously modulates tumor-associated proteins with multiple targets, demonstrating broad anti-tumor potential. Although its high lipid solubility and low water solubility pose certain druggability challenges, its good safety and oral activity provide a solid foundation for its clinical development. In the future, through pharmacokinetic optimization, mechanistic research, and clinical validation, Euphorbidiaenol is expected to become a new natural drug for treating inflammatory diseases and tumors, advancing natural product pharmacology and drug development.