Product name: 1-O-Acetylbritannilactone
Synonym name: Inulicin; Britannilactone 1-O-acetate; 1-O-Acetylbritannilatone; New CAS No.: 33627-41-7

Catalogue No.: BP1585
Cas No.: 681457-46-5
Formula: C₁₇H₂₄O₅
Mol Weight: 308.374
Botanical Source: Constit. of Inula britannica and Inula japonica
Physical Description:
Type of Compound: Terpenoids

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
The product could be supplied from milligrams to grams. Inquire for bulk scale.
We provide solution to improve the water-solubility of compounds, thereby facilitating the variety of activity tests and clinic uses.

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

1-O-acetylbritannilactone (1-O-acetylbritannilactone, abbreviated as 1-O-ABL) is an active natural product derived from the traditional Chinese medicine Inula britannica L. As a representative flavonoid lactone compound, 1-O-ABL has attracted widespread attention in the field of natural product pharmacology in recent years due to its remarkable anti-inflammatory, anti-tumor, and immune response regulation multiple biological activities. This compound demonstrates potential anti-angiogenic effects by inhibiting the activation of vascular endothelial growth factor (VEGF)-mediated signaling pathways, especially Src and FAK. Additionally, 1-O-ABL can inhibit lipopolysaccharide (LPS)-induced prostaglandin E2 (PGE2) production and cyclooxygenase-2 (COX-2) expression, thereby suppressing activation and nuclear translocation of nuclear factor κB (NF-κB), demonstrating good anti-inflammatory effects. Given its mechanism of action is closely related to various inflammatory and immune-related diseases, especially its potential application value in respiratory diseases such as asthma, this paper will systematically review the chemical properties, pharmacological activity, mechanism of action, druggability, and clinical application prospects of 1-O-ABL, aiming to provide theoretical basis and research directions for its subsequent drug development and clinical translation.

Chemical structure and physicochemical properties

The molecular formula of 1-oxy-acetyl inmulendolide is C_17H_20O_6, with a molecular weight of 308.37. Its structural core is the involva lactone framework, which has a typical lactone ring structure and is acetylated at the hydroxyl group position 1 to form a 1-oxy-acetyl substituent. This modification not only affects its molecular polarity but may also enhance its cell membrane permeability and biological activity.

In terms of physicochemical properties, the LogP value of 1-O-ABL is 2.1, indicating moderate lipid solubility, which is beneficial for its distribution in vivo and cell membrane penetration. The topological pole surface area (TPSA) is 78.96 Ų, indicating that it has certain polar groups capable of forming hydrogen bonds. The number of hydrogen bond acceptors is 5, suggesting that it may form multi-point interactions when binding to protein targets. The blood-brain barrier has lower permeability, reducing the risk of central nervous system toxicity. Hepatotoxicity, cardiotoxicity, and hERG channel inhibition tests all showed no significant toxicity, indicating a relatively high safety profile. Ames-induced mutagenic test results are still unclear and require further research.

Plant Origins and Extraction Methods

1-Oxy-Acetyl Inula lactone is mainly found in the above-ground parts of Inula britannica L., a plant of the Asteraceae family, widely distributed in northern China and East Asia. It has long been used as a traditional Chinese medicinal material to treat cough, asthma, and digestive system diseases. Traditional extraction methods typically use ethanol or methanol to crush dried Inula and perform reflux extraction, followed by liquid-liquid separation and silica gel column chromatography for separation and purification, ultimately obtaining high-purity 1-O-ABL.

Modern extraction technologies combine ultrasound-assisted extraction and microwave-assisted extraction methods to improve extraction efficiency and purity. During purification, reversed-phase high-performance liquid chromatography (RP-HPLC) is widely used for qualitative and quantitative analysis of 1-O-ABL, ensuring stability and repeatability in quality control. Moreover, research on biosynthetic pathways provides a theoretical foundation for synthesizing 1-O-ABL, promoting its large-scale production and drug development.

Pharmacological activity research

Anti-angiogenic and anti-tumor activity

1-O-ABL exerts significant anti-angiogenic effects by inhibiting VEGF-mediated signaling pathways, especially activation of Src and FAK. Src family kinases and caustic kinases FAK are key regulatory factors for cell migration, proliferation, and angiogenesis. 1-O-ABL blocks this pathway by inhibiting endothelial cell migration and lumen formation, thereby suppressing neoangiogenesis in the tumor microenvironment and demonstrating potential antitumor activity. Both in vitro and in vivo experiments confirmed that 1-O-ABL inhibits the proliferation and migration of various tumor cell lines, suggesting its potential as an adjuvant anti-tumor therapy.

Anti-inflammatory effects

1-O-ABL demonstrated good anti-inflammatory effects in inflammation models. By inhibiting LPS-induced PGE2 production and COX-2 expression, it reduces the release of inflammatory mediators and alleviates inflammatory responses. PGE2, as an important mediator of inflammation, participates in vasodilation and pain perception at the site of inflammation, while COX-2 is a key enzyme in its synthesis. 1-O-ABL can also inhibit activation and nuclear translocation of the NF-κB signaling pathway, block the transcriptional expression of inflammation-related genes, and reduce the release of pro-inflammatory cytokines such as TNF-α and IL-1β, demonstrating a multi-target, multi-pathway anti-inflammatory mechanism.

Immunomodulatory effects and asthma-related research

Asthma is a complex immune disease characterized by chronic airway inflammation and hyperreactivity. 1-O-ABL demonstrates therapeutic potential by modulating multiple asthma-related targets, including cholinergic receptor M3 (CHRM3), β2-adrenergic receptor (ADRB2), histamine H1 receptor (HRH1), and several key cytokines such as IL-4, IL-5, IL-13, IL-17A, and IL-25. Studies have shown that 1-O-ABL can regulate Th2-mediated immune responses, inhibit IgE-mediated mast cell degranulation, reduce airway inflammation and mucus secretion, improve airway hyperresponsiveness, and exhibit good anti-asthma activity.

Mechanism of action and molecular targets

The pharmacological mechanism of 1-O-ABL mainly involves regulation of multiple signaling pathways and molecular targets:

1. Suppression of VEGF/SRC/FAK signaling pathways
   1-O-ABL inhibits VEGF-induced activation of Src and FAK kinases, inhibits endothelial cell migration and angiogenesis, and reduces angiogenesis in tumors and inflammatory environments.

2. NF-κB signaling pathway inhibition
   This compound blocks the phosphorylation and degradation of IκBα, inhibits NF-κB translocation from the cytoplasm to the nucleus, reduces the expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and COX-2, and exerts anti-inflammatory effects.

3. LPS-induced inhibition of inflammatory mediators
   By inhibiting LPS-induced PGE2 production and COX-2 expression, 1-O-ABL reduces the release of inflammatory mediators and alleviates inflammatory responses.

4. Regulation of asthma-related immune targets
   1-O-ABL affects the expression of various asthma-related receptors and cytokines, including CHRM3, ADRB2, HRH1 and IL-4, IL-5, IL-13, IL-17A, IL-25, etc., regulating immune cell activity and inflammatory responses, and improving airway function.

These multi-target, multi-pathway regulatory mechanisms give 1-O-ABL broad pharmacological activity and therapeutic potential.

Druggability evaluation and pharmacokinetics

The druggability parameters of 1-O-ABL indicate its promising potential for drug development. The molecular weight of 308.37 meets the Lipinski rule, and the LogP 2.1 is moderate, indicating good oral bioavailability and cell membrane penetration capability. The TPSA was 78.96, indicating moderate polarity, favorable for target binding, and less likely to be rapidly cleared.

Toxicological evaluation showed that 1-O-ABL did not show significant hepatotoxicity, cardiotoxicity, or hERG channel inhibition, and its safety was relatively high. However, Ames-induced mutagenic assay data are missing and require further supplementation to rule out potential genotoxicity risks.

The blood-brain barrier has low permeability, reducing the likelihood of central nervous system side effects, making it suitable for treating non-central nervous system diseases.

In terms of pharmacokinetics, current research is relatively limited. Preliminary in vivo experiments showed that 1-O-ABL was well absorbed orally, with moderate plasma peak concentration timing and a half-life suitable for routine administration. The metabolic pathway mainly involves hepatic enzyme systems, with no significant metabolite toxicity observed. In the future, systematic pharmacokinetic and toxicological studies are needed to improve drug development data.

Prospects and outlooks for clinical applications

1-O-Oxy-Acetyl Inula lactone, as a versatile natural product, has broad clinical application potential. Its significant activity in anti-inflammation, anti-angiogenesis, and immune regulation, especially in chronic inflammatory diseases such as asthma, has attracted significant attention.

As a globally prevalent chronic respiratory disease, asthma currently mainly relies on glucocorticoids and β2 receptor agonists, but long-term use carries risks of resistance and side effects. 1-O-ABL provides a new therapeutic strategy by modulating immune responses and suppressing inflammatory signaling pathways through multiple targets, and is expected to become an adjunct or alternative therapy for asthma.

Moreover, its anti-tumor and anti-angiogenesis effects offer new ideas for cancer treatment, especially in tumor microenvironment regulation and anti-angiogenesis drug development.

Future research should focus on:

• Systematic pharmacokinetic and toxicological assessments to ensure safety and efficacy;
• Structural optimization and derivative design to enhance activity and selectivity;
• Preclinical animal models and clinical trials to verify treatment efficacy and indications;
• Combination therapy strategies, exploring synergies with existing drugs.

Through multidisciplinary collaboration, we promote the development of 1-O-ABL drugs and achieve clinical translation.

Conclusion

1-Oxy-Acetylinulolide, as an important active component in Inula flora, shows broad application prospects in anti-inflammation, anti-angiogenesis, and immune regulation due to its unique chemical structure and multi-target pharmacological activity. Its inhibition of the VEGF-mediated Src/FAK signaling pathway and the NF-κB pathway provides a new molecular basis for the treatment of inflammatory diseases such as asthma. It has good druggability parameters and high safety, offering promising drug development potential.

In the future, in-depth research into its mechanism of action should be strengthened, pharmacokinetics and toxicology data improved, preclinical and clinical studies conducted, and the translation of 1-O-ABL to clinical applications should be promoted. As an important research object in the pharmacology of natural products, 1-O-ABL not only enriches the pharmacological connotations of Inula but also provides valuable resources and ideas for innovative development of natural medicines.