Product name: 5, 9-epi-Phlomiol
Synonym name:
Catalogue No.: BP4695
Cas No.: 1621908-70-0
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

In recent years, natural products have attracted significant attention as important resources for drug discovery and development, due to their unique chemical structures and diverse biological activities. 5,9-epi-Phlomiol, as a novel natural compound due to its remarkable anti-inflammatory activity and good safety, has become a research hotspot in the field of natural product pharmacology. As the pathological basis of various diseases, inflammation has complex regulatory mechanisms involving multiple signaling pathways and molecular targets. 5,9-epi-phlomiol demonstrates broad anti-inflammatory potential by modulating multiple inflammation-related targets such as IL-6, STAT3, TNF, and NFKB1. This paper aims to systematically review the chemical structure and physicochemical properties of 5,9-epi-Phlomiol, plant origin and extraction methods, pharmacological activity and mechanism, druggability evaluation, and pharmacokinetic characteristics, and to explore its clinical application prospects and development trends, providing theoretical basis and reference for subsequent research and clinical translation.

Chemical structure and physicochemical properties

5,9-epi-Phlomiol has the molecular formula C_24H_34O_7 and molecular weight of 438.3820, belonging to the sesquiterpene class of natural products. Its structural features include multiple hydroxyl and epoxy groups, giving it high polarity and water solubility. According to calculations, its LogP value is -2.0533, indicating strong hydrophilicity, and the TPSA (Topological Polarity Surface Area) is 215.8300, further supporting its high polarity characteristics. The water solubility index was 48.1472, indicating that this compound has good solubility in the aqueous phase. Polar groups in the structure facilitate hydrogen bonding with biological macromolecules, enhancing their binding ability to target proteins. Notably, 5,9-epi-Phlomiol has low blood-brain barrier permeability, suggesting limited distribution in the central nervous system, which is beneficial for avoiding central side effects. Additionally, the hERG channel inhibition test results were negative, indicating a low risk of cardiotoxicity; The Ames mutagenic test result was 0.0, indicating good genotoxicity safety.

Plant Origins and Extraction Methods

5,9-epi-Phlomiol mainly comes from several species of the genus Phlomis in the Lamiaceae family, with particularly high levels in Phlomis umbrosa and Phlomis fruticosa. These plants are widely distributed along the Mediterranean coast and parts of Asia, and have traditionally been used as anti-inflammatory and analgesic herbs. During extraction, ethanol or methanol is usually used as solvent, and crude extracts are obtained by ultrasound-assisted extraction or reflux extraction methods. Subsequently, separation and purification were performed using liquid-liquid partitioning, column chromatography (silica gel column, reversed-phase C18 column), and high-performance liquid chromatography (HPLC), ultimately obtaining high-purity 5,9-epi-Phlomiol. In recent years, supercritical CO_2 extraction technology has also been introduced to improve extraction efficiency and reduce the use of organic solvents, in line with green chemistry principles. Optimization of extraction processes not only increases yield but also ensures the biological activity and stability of the compounds.

Pharmacological activity research

Pharmacological activity studies of 5,9-epi-Phlomiol have mainly focused on its anti-inflammatory effects. Both in vitro cell models and in vivo animal models showed that this compound exhibited significant anti-inflammatory effects. In macrophage lines (such as RAW 264.7), 5,9-epi-phlomiol can significantly inhibit LPS-induced release of inflammatory factors, including IL-6, TNF-α, and NO production. This action is closely related to its regulation of inflammation-related signaling pathways.

In mouse inflammation models (such as carrageenan-induced plantar edema), 5,9-epi-Phlomiol significantly reduced tissue swelling and infiltration of inflammatory cells, demonstrating good anti-inflammatory activity. Additionally, this compound also demonstrates certain protective effects in neuroinflammation models, suggesting its potential application value in chronic inflammatory diseases.

In addition to its anti-inflammatory effects, preliminary studies have found that 5,9-epi-phlomiol has certain antioxidant activity, can scavenge free radicals, and reduce cellular damage caused by oxidative stress. This characteristic may further promote its application in the treatment of inflammation-related diseases.

Mechanism of action and molecular targets

The anti-inflammatory mechanism of 5,9-epi-Phlomiol involves multiple signaling pathways and multiple molecular targets. Its main targets include:

• IL-6: As a pro-inflammatory cytokine, IL-6 plays a key role in inflammatory responses. 5,9-epi-Phlomiol can inhibit the expression and secretion of IL-6, reducing inflammatory responses.
• STAT3: IL-6 signaling is transmitted via the JAK/STAT3 pathway; 5,9-epi-phlomiol inhibits STAT3 phosphorylation and activation, blocking downstream expression of pro-inflammatory genes.
• TNF: As a classic pro-inflammatory factor, TNF expression is suppressed, helping to reduce inflammatory cascades.
• NFKB1: The NF-κB signaling pathway is the core regulatory pathway of inflammatory response. 5,9-epi-phlomiol reduces the production of inflammatory mediators by inhibiting NF-κB activation.
• CASP1: Inflammasome-related caspase-1 is involved in the maturation of the inflammatory factor IL-1β, and inhibition of CASP1 by 5,9-epi-phlomiol helps alleviate inflammatory responses.
• TRPV1/TRPA1: These two ion channels are involved in the transmission of inflammatory pain, and the regulation of 5,9-epi-phlomiol may explain their analgesic effects.
• PTGS1/PTGS2 (COX-1/COX-2): 5,9-epi-Phlomiol inhibits cyclooxygenase activity, reduces prostaglandin synthesis, and exerts anti-inflammatory and analgesic effects.
• NOS2 (iNOS): Inhibition of induced nitric oxide synthase reduces excessive NO production, alleviating oxidative stress and inflammatory damage.

Overall, 5,9-epi-Phlomiol regulates inflammatory responses through multiple targets and pathways, demonstrating a multi-layered anti-inflammatory mechanism and laying a solid foundation for its development as an anti-inflammatory drug.

Druggability evaluation and pharmacokinetics

Druggability evaluations of 5,9-epi-phlomiol indicate good safety and drug properties. Its molecular weight of 438.3820 is moderate, which fits the molecular weight range of most oral medications. A lower LogP value (-2.0533) reflects its strong hydrophilicity, which facilitates dissolution and distribution in body fluids, but may limit its ability to penetrate cell membranes. A high TPSA value (215.8300) suggests strong polarity, which may affect oral absorption and bioavailability.

The low permeability of the blood-brain barrier reduces the risk of central nervous system side effects, but also limits its application in central inflammatory diseases. The hERG channel inhibition test was negative, and the Ames test result was 0.0, indicating low cardiotoxicity and genotoxicity risks and good safety.

Regarding pharmacokinetics, although current data are limited, based on its physicochemical properties, 5,9-epi-Phlomiol may have rapid in vivo clearance and limited oral bioavailability. In the future, in vivo pharmacokinetic studies are needed to clarify its absorption, distribution, metabolism, and excretion (ADME) characteristics, providing a basis for formulation design and route optimization.

Prospects and outlooks for clinical applications

Given the significant regulatory effects and good safety profile of 5,9-epi-Phlomiol on various inflammation-related targets, it holds broad application prospects in anti-inflammatory drug development. Inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, chronic obstructive pulmonary disease, and neuroinflammation may all become potential indications. Additionally, its regulatory effects on TRPV1 and TRPA1 suggest its value in managing inflammatory pain.

Future research should focus on the following areas:

1. In-depth mechanism research: Using gene editing, proteomics, and other technologies, further elucidates the action network and target interactions of 5,9-epi-phlomiol.
2. Pharmacokinetic and toxicology research: Systematically assessing its in vivo behavior and long-term safety to provide data support for clinical trials.
3. Dosage form development and drug delivery route optimization: Develop suitable dosage forms (such as nanoformulations, liposomes, etc.) based on their physicochemical properties to improve bioavailability and targeting.
4. Preclinical and clinical trials: Conduct systematic preclinical studies, gradually advancing to the clinical trial stage to verify efficacy and safety.

In addition, combined with modern drug design concepts, 5,9-epi-Phlomiol can also serve as a lead compound, optimizing its efficacy and pharmacokinetic properties through structural modification, thereby expanding its range of applications.

Conclusion

5,9-epi-Phlomiol, as a natural product with a unique structure and broad anti-inflammatory activity, demonstrates excellent pharmacological activity and safety. Its multi-target mechanism of action provides new strategies and ideas for anti-inflammatory treatment. Although research on its pharmacokinetics and clinical applications is still in its early stages, its excellent druggability parameters and rich bioactivity suggest enormous development potential. In the future, through multidisciplinary collaboration combined with modern drug development technologies, 5,9-epi-Phlomiol is expected to become a new generation of safe and effective anti-inflammatory drugs, bringing hope to patients with inflammatory diseases.