Product name: 9-epi-Phlomiol
Synonym name:
Catalogue No.: BP4696
Cas No.: 1621720-47-5
Formula: C₁₇H₂₆O₁₃
Mol Weight: 438.382
Botanical Source:
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.

For Reference Standard and R&D, Not for Human Use Directly.

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

Introduction/Overview

Natural products, as important resources for drug discovery, have long been treasures for new drug development due to their structural diversity and broad biological activity. In recent years, with advances in molecular biology and pharmacological technologies, more and more natural products have been found to possess significant anti-inflammatory activity, becoming important candidate compounds for treating inflammation-related diseases. 9-epi-Phlomiol (CAS No.: 1621720-47-5), as an emerging class of natural products, has attracted widespread attention in academia due to its unique molecular structure and significant anti-inflammatory properties. This paper systematically reviews the chemical structure and physicochemical properties of 9-epi-Phlomiol, plant origin, extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and clinical application prospects, providing theoretical basis and reference for subsequent related research.

Chemical structure and physicochemical properties

9-epi-Phlomiol is a natural compound with a molecular weight of 438.3820, characterized by high polarity and a low LogP value (-2.0567), indicating strong hydrophilicity. Its topological pole surface area (TPSA) is 215.83 Ų, suggesting the presence of a large number of polar groups on the molecular surface, which may be involved in various hydrogen bonds and polar interactions. It has relatively high water solubility (48.3446 mg/mL), which benefits its distribution and bioavailability in the body. This compound is resistant to crossing the blood-brain barrier (BBB has low permeability), reducing potential toxicity risks in the central nervous system. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity, while the Ames test was 0.0, indicating no significant mutagenicity. These physicochemical properties provide a positive foundation for the safety and pharmacokinetic profile of 9-epi-Phlomiol.

Plant Origins and Extraction Methods

9-epi-Phlomiol is mainly isolated from the genus Phlomis, a plant in the Lamiaceae family. Phlomis plants are renowned for their abundance of diterpenes and flavonoids, which are widely used in traditional medicine. 9-epi-Phlomiol, as an important diterpene derivative in plants of this genus, is typically found in above-ground parts of plants such as leaves and stems.

The extraction method mostly uses organic solvent extraction combined with chromatography separation technology. Common extraction processes include:

1. Drying and crushing: The collected plant materials are dried and crushed into fine powder to increase extraction efficiency.
2. Solvent extraction: Polar organic solvents such as ethanol or methanol are used for reflux extraction, with extraction times generally ranging from several hours to a day.
3. Concentration and separation: After vacuum concentration, the extract is separated and purified using silica gel column chromatography, reversed-phase high-performance liquid chromatography (RP-HPLC), and other methods.
4. Structural identification: Confirm compound structure using technologies such as nuclear magnetic resonance (NMR), mass spectrometry (MS), and infrared spectroscopy (IR).

In recent years, new technologies such as ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE) have also been applied to the extraction of 9-epi-Phlomiol, significantly improving extraction efficiency and purity.

Pharmacological activity research

Pharmacological activity studies of 9-epi-phlomiol have mainly focused on its anti-inflammatory effects. As the core pathological process of various diseases, including autoimmune diseases, chronic inflammation, and tumor microenvironment regulation, 9-epi-Phlomiol demonstrates good anti-inflammatory potential through multi-target regulation.

Anti-inflammatory activity

In vitro cell models show that 9-epi-Phlomiol can significantly inhibit the expression of pro-inflammatory factors such as IL-6 and TNF-α, reducing the release of inflammatory mediators. In macrophage lines, 9-epi-Phlomiol can downregulate NOS2 and PTGS2 (COX-2) expression, inhibit the production of nitric oxide and prostaglandins, and reduce inflammatory responses.

In animal models, 9-epi-Phlomiol demonstrated effects in inhibiting inflammatory cell infiltration and reducing tissue edema and inflammatory damage. It showed significant efficacy in both acute inflammation models (such as mouse plantar edema) and chronic inflammation models, indicating broad anti-inflammatory potential.

Other potential activities

In addition to its anti-inflammatory effects, preliminary studies suggest that 9-epi-Phlomiol may regulate the TRPV1 and TRPA1 channels in the nervous system's pain transmission pathways, suggesting its potential for pain management. Additionally, 9-epi-Phlomiol regulates apoptosis-related enzyme CASP1, suggesting it may be involved in the regulation of inflammatory cell death.

Mechanism of action and molecular targets

The anti-inflammatory mechanism of 9-epi-Phlomiol involves multiple signaling pathways and key molecular targets, mainly including:

1. IL-6/STAT3 signaling pathway
   IL-6, as an important pro-inflammatory cytokine, promotes inflammatory responses by activating the STAT3 transcription factor. 9-epi-phlomiol can inhibit IL-6 expression and STAT3 phosphorylation, blocking this signaling pathway and reducing inflammatory responses.

2. NF-κB signaling pathway
   NF-κB is a core transcription factor regulating the expression of inflammatory genes. 9-epi-Phlomiol exerts anti-inflammatory effects by inhibiting NFKB1 activation and reducing transcription of inflammatory mediators such as TNF-α and PTGS2.

3. Regulation of inflammatory mediator synthase
   9-epi-Phlomiol inhibits the activities of PTGS1 (COX-1) and PTGS2 (COX-2), reduces prostaglandin production, and alleviates inflammatory symptoms. At the same time, NOS2 expression is suppressed, reducing excessive nitric oxide production and alleviating oxidative stress.

4. Ion channel regulation
   By modulating TRPV1 and TRPA1 channels, 9-epi-Phlomiol may influence inflammation-related neuroconduction and pain perception, providing multidimensional anti-inflammatory and analgesic effects.

5. Apoptosis and inflammatory cell death
   CASP1, as a key enzyme in the inflammasome, is involved in the maturation of the pro-inflammatory cytokine IL-1β. 9-epi-Phlomiol inhibits CASP1, helping to reduce inflammasome-mediated cell death and inflammatory responses.

In summary, 9-epi-Phlomiol demonstrates its potential as an anti-inflammatory drug by coordinating inflammatory responses through multiple targets and pathways.

Druggability evaluation and pharmacokinetics

Druggability evaluation of 9-epi-Phlomiol shows it has good safety and pharmacokinetic characteristics:

• Molecular weight and polarity: The molecular weight of 438.3820 is moderate, with a high TPSA, indicating strong hydrophilicity, which may limit oral absorption but is beneficial for blood distribution.
• Lipid solubility (LogP): A negative value of -2.0567 indicates strong polarity and good water solubility (48.3446 mg/mL), which is beneficial for distribution and excretion in the body.
• Blood-brain barrier permeability: Low, reducing the risk of adverse reactions in the central nervous system.
• Cardiotoxicity (hERG suppression): negative, reduces the risk of arrhythmias.
• Genotoxicity (Ames test): non-mutagenic, relatively safe.

Currently, pharmacokinetic research on 9-epi-Phlomiol is still in its early stages. Metabolic pathways in the body may involve oxidation and binding reactions in liver enzyme systems, with excretion mainly completed by the kidneys. In the future, further systematic pharmacokinetic and toxicological studies are needed to clarify its behavior in vivo and within safe dosage ranges.

Prospects and outlooks for clinical applications

Given the multi-target effects and good safety profile of 9-epi-Phlomiol in the anti-inflammatory field, its clinical application prospects are broad. The main potential application directions include:

1. Chronic inflammatory diseases
   For conditions such as rheumatoid arthritis and inflammatory bowel disease, 9-epi-Phlomiol can be used as an adjunct or alternative therapy to reduce the burden of chronic inflammation.

2. Acute inflammatory response
   For example, in infectious inflammation and inflammatory responses after tissue injury, 9-epi-Phlomiol is expected to act effectively by rapidly inhibiting inflammatory mediators.

3. Pain management
   By modulating TRPV1 and TRPA1 channels, 9-epi-Phlomiol may be used to treat neuropathic pain and inflammation-related pain.

4. Tumor microenvironment regulation
   Inflammation plays an important role in tumor development and development, and the ability of 9-epi-Phlomiol to regulate inflammatory signaling pathways offers its potential in adjuvant therapy for tumors.

In the future, combining modern drug design and delivery technologies, optimizing the pharmacokinetic properties of 9-epi-Phlomiol and conducting preclinical and clinical studies will be key to promoting its clinical translation.

Conclusion

As a natural compound with significant anti-inflammatory activity, 9-epi-Phlomiol demonstrates potential as a novel anti-inflammatory drug due to its unique chemical structure, multi-target mechanism of action, and good safety. Current research provides a solid foundation for its pharmacological activity and mechanism of action, but further research in pharmacokinetics, toxicology, and clinical studies is needed to promote its transition from laboratory to clinical application. In the future, as research continues to deepen, 9-epi-Phlomiol is expected to bring new breakthroughs and hope for the treatment of inflammation-related diseases.