Product name: Linocinnamarin
Synonym name:
Catalogue No.: BP5125
Cas No.: 554-87-0
Formula: C₁₆H₂₀O₈
Mol Weight: 340.328
Botanical Source:
Type of Compound:

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, attract much attention for their structural diversity and biological activity. In recent years, plant-derived natural compounds have shown significant potential in the field of anti-inflammatory treatment. Linocinnamarin (CAS No.: 554-87-0) is a natural compound isolated from strawberries (Fragaria ananassa Duch), and its unique anti-inflammatory activity has attracted widespread interest in the pharmacological community. Linocinnamarin demonstrates good anti-inflammatory effects by regulating intracellular free Ca²⁺ concentration and reactive oxygen species (ROS) levels, inhibiting inflammatory signaling pathways. This paper will systematically review the chemical structure and physicochemical properties of Linocinnamarin, plant origin and extraction methods, pharmacological activity studies, mechanisms of action and molecular targets, druggability evaluation and pharmacokinetics, as well as its clinical application prospects and development trends, aiming to provide theoretical basis and reference for in-depth research and drug development of this natural product.

Chemical structure and physicochemical properties

Linocinnamarin has a molecular weight of 340.3280. Its molecular formula and specific structure have not been fully disclosed, but its structural features are characteristic of natural phenolic compounds containing polyhydroxyl groups and benzene rings. Its LogP value was -0.0766, indicating low lipid solubility, suggesting good hydrophilicity. The topological pole surface area (TPSA) is 125.68 Ų, indicating that Linocinnamarin has strong polarity and a high number of hydrogen bond donors/acceptors, which have an important impact on its binding to biomacromolecules. Water solubility is 10.6199 mg/mL, indicating good solubility in water and beneficial for absorption and distribution in the body. The low permeability of the blood-brain barrier suggests it mainly acts on peripheral tissues, reducing the risk of central nervous system side effects. The hERG channel inhibition test results were negative, indicating a low risk of cardiac toxicity in linocinnamarin. The Ames-induced mutagenic test scored 0.3, indicating a low genotoxicity risk and a certain safety foundation.

Plant Origins and Extraction Methods

Linocinnamarin is mainly isolated from strawberries (Fragaria ananassa Duch). As a widely cultivated fruit, strawberries are rich in various bioactive components, including polyphenols, flavonoids, and organic acids. Linocinnamarin is usually extracted by solvent, with ethanol or methanol as the main solvent, and extraction efficiency improved by ultrasound-assisted extraction or reflux extraction. The extract undergoes concentration, liquid-liquid partitioning, and column chromatography separation, and is finally purified by high-performance liquid chromatography (HPLC) to obtain high-purity Linocinnamarin. In recent years, the application of supercritical CO₂ extraction and membrane separation technologies has also provided a new green and efficient method for extracting linocinnamarin. Optimizing the extraction process not only helps improve yield and purity but also preserves the compound's biological activity, laying the foundation for subsequent pharmacological research and industrial production.

Pharmacological activity research

The main pharmacological activity of linocinnamarin is focused on its anti-inflammatory effects. In vitro experiments have shown that linocinnamarin can significantly inhibit the increase in intracellular free Ca²⁺ concentration caused by antigen stimulation, blocking activation of calcium signaling pathways and thereby suppressing the release of downstream inflammatory mediators. At the same time, linocinnamarin effectively lowers reactive oxygen species (ROS) levels and lessens cellular damage caused by oxidative stress. Multiple cell model studies have shown that Linocinnamarin can inhibit the secretion of inflammatory factors by macrophages and mast cells, such as tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), thereby reducing inflammatory responses.

In animal models, Linocinnamarin demonstrated significant anti-inflammatory effects. In the mouse acute inflammation model, Linocinnamarin can reduce edema at the site of inflammation and infiltration of inflammatory cells, lowering the expression levels of inflammatory factors. Additionally, Linocinnamarin has shown potential in chronic inflammation models to inhibit arthritis and enteritis, suggesting therapeutic value for various inflammatory diseases. Its anti-inflammatory activity carries a lower risk of gastrointestinal side effects compared to traditional nonsteroidal anti-inflammatory drugs (NSAIDs), demonstrating a strong safety advantage.

Mechanism of action and molecular targets

The anti-inflammatory mechanism of linocinnamarin mainly involves regulating intracellular signaling pathways and the expression of key inflammatory molecules. Its targets include:

• IL-6 and TNF: Linocinnamarin inhibits the expression of pro-inflammatory cytokines IL-6 and TNF, alleviating the cascading amplification effects of inflammatory responses.
• STAT3: As a key transcription factor in the IL-6 signaling pathway, its activity is inhibited by linocinnamarin, blocking the transcription of inflammatory genes.
• CASP1: Linocinnamarin inhibits inflammasome-related caspase-1 (CASP1) activity, reducing the maturation and release of pro-inflammatory cytokines.
• TRPV1 and TRPA1: These two ion channels play important roles in inflammation and pain conduction. Linocinnamarin regulates its activity to relieve inflammation-related pain symptoms.
• PTGS1 and PTGS2: Linocinnamarin inhibits the expression of cyclooxygenases 1 and 2 (COX-1 and COX-2), reducing prostaglandin synthesis and thus exerting anti-inflammatory effects.
• NOS2: By inhibiting induced nitric oxide synthase (iNOS), linocinnamarin lowers nitric oxide (NO) levels, alleviating oxidative stress and inflammatory damage.
• NFKB1: As a core transcription factor for inflammatory signals, NF-κB activity is significantly inhibited by linocinnamarin, blocking the expression of inflammatory genes and the persistence of inflammatory responses.

Linocinnamarin regulates inflammatory responses through multi-target and multi-pathway synergistic regulation, demonstrating a complex and effective anti-inflammatory mechanism. This multi-target mode of action not only enhances therapeutic efficacy but also reduces the risk of drug resistance.

Druggability evaluation and pharmacokinetics

The druggability parameters of Linocinnamarin indicate that it has promising potential for drug development. Molecular weight is moderate (340.3280), meeting the basic requirements of the Lipinski rule. A LogP value close to zero indicates a moderate water and lipid balance, which is beneficial for absorption and distribution in the body. A higher TPSA value suggests strong polarity, which may limit its ability to penetrate cell membranes, but it also facilitates binding to polar targets. Good water solubility, facilitating formulation development.

The blood-brain barrier has low permeability, reducing the risk of central nervous system side effects, making it suitable for treating peripheral inflammatory diseases. hERG channel inhibition was negative, indicating higher cardiac safety. Ames trial results show a low genotoxicity risk, supporting the safety of long-term medication.

Currently, pharmacokinetic data for linocinnamarin are not yet complete, but based on its physicochemical properties, its oral bioavailability is inferred to be moderate, mainly metabolized by the liver, with excretion likely via the kidneys and bile. In the future, systematic pharmacokinetic studies, including absorption, distribution, metabolism, and excretion (ADME) characteristics, are needed to guide clinical dosage design and administration protocol optimization.

Prospects and outlooks for clinical applications

Linocinnamarin, as a natural anti-inflammatory active compound, has broad clinical application potential. Its multi-target mechanism of inhibiting inflammatory signaling pathways gives it advantages in treating various inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, allergic inflammation, and chronic pain. Compared to traditional NSAIDs, Linocinnamarin has fewer side effects and is especially safer for the gastrointestinal and cardiovascular systems, making it promising to become a new generation of safe and effective anti-inflammatory drugs.

Additionally, the antioxidant properties of linocinnamarin offer potential applications in chronic inflammation-related diseases such as neurodegenerative diseases and metabolic syndromes. Its low blood-brain barrier permeability limits direct effects on the central nervous system but also reduces neurological side effects, making it suitable for treating peripheral inflammation.

Future research should focus on preclinical safety evaluation, pharmacokinetic optimization, and formulation development of Linocinnamarin. At the same time, by integrating modern drug design technologies such as structural optimization and nanocarrier delivery, their bioavailability and targeting are enhanced. Conducting multicenter clinical trials will be a key step in verifying their clinical efficacy and safety.

Conclusion

Linocinnamarin, a natural product derived from Fragaria ananassa Duch, shows broad prospects for drug development due to its remarkable anti-inflammatory activity and good druggability. It regulates inflammatory responses through multiple targets and pathways, featuring a unique mechanism of action and a lower risk of toxic side effects. With the advancement of extraction techniques and pharmacological research, Linocinnamarin is expected to become a new safe and effective anti-inflammatory drug, offering new strategies and options for the treatment of inflammatory diseases. Future research should focus on its pharmacokinetic characteristics, clinical safety, and efficacy verification, promoting its transition from the laboratory to clinical application to benefit a broad range of patients.