Synonym name:
Catalogue No.: BP0989
Cas No.: 41060-15-5
Formula: C₂₀H₁₈O₄
Mol Weight: 322.36
Botanical Source: Erythrina sigmoidea and Psoralea corylifolia

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.

Description:

Neobavaisoflavone, exhibits inhibitory activity against DNA polymerase and platelet aggregation, it also has striking anti-inflammatory and anti-cancer effects, Neobavaisoflavone can significantly inhibit the production of reactive oxygen species (ROS), reactive nitrogen species (RNS) and cytokines: IL-1β, IL-6, IL-12p40, IL-12p70, TNF-α in LPS+IFN-γ- or PMA- stimulated RAW264.7 macrophages.

References:

Phytomedicine. 2014 Apr 15;21(5):682-8.    

Activity of three cytotoxic isoflavonoids from Erythrina excelsa and Erythrina senegalensis (neobavaisoflavone, sigmoidin H and isoneorautenol) toward multi-factorial drug resistant cancer cells.   

Resistance of cancer cells to chemotherapy has become a worldwide concern. Naturally occuring isoflavonoids possess a variety of biological activities including anti-cancer effects. The present study was aimed at investigating the cytotoxicity and the modes of action of three naturally occuring isoflavonoids, Neobavaisoflavone (1), sigmoidin H (2) and a pterocarpan that is a special type of isoflavonoid, isoneorautenol (3) against a panel of nine cancer cell lines, including various sensitive and drug-resistant phenotypes. 

METHODS AND RESULTS:

The cytotoxicity of the compounds was determined using a resazurin reduction assay, whereas the caspase-Glo assay was used to detect the activation of caspases 3/7, caspase 8 and caspase 9 in cells treated with compounds 3. Flow cytometry was used for cell cycle analysis and detection of apoptotic cells, analysis of mitochondrial membrane potential (MMP) as well as measurement of reactive oxygen species (ROS). Compounds 3 showed significant cytotoxicity toward sensitive and drug-resistant cancer cell lines. Compounds 1 and 2 were selectively active, and IC50 values below 115 μM were obtained on 6/9 and 4/9 cell lines respectively with values ranging from 42.93 μM (toward CCRF-CEM cells) to 114.64 μM [against HCT116 (p53(+/+)) cells] for 1 and 25.59 μM (toward U87MG) to 110.51 μM [against HCT116 (p53(+/+)) cells] for 2. IC50 values ranging from 2.67 μM (against MDA-MB 237BCRP cells) to 21.84 (toward U87MG) were measured for compound 3 and between 0.20 μM (toward CCRF-CEM cells) and 195.12 μM (toward CEM/ADR5000 cells) for doxorubicin as control drug. BCRP-transfected MDA-MB-231 cells, HCT116 (p53(+/+)) and U87MG.ΔEGFR cells were hypersensitive (collateral sensitive) to compound 3 as compared to their counterpart cell lines. Compound 3 induced apoptosis in CCRF-CEM cells via activation of caspases 3/7, 8 and 9 as well as the loss of MMP and increased ROS production. 

CONCLUSIONS:

The cytotoxicity of the studied isoflavonoids and especially the pterocarpan 3 deserve more detailed exploration in the future to develop novel anticancer drugs against sensitive and otherwise drug-resistant phenotypes.    

Life Sci. 2014 Jan 30;95(2):101-7.    

Neobavaisoflavone sensitizes apoptosis via the inhibition of metastasis in TRAIL-resistant human glioma U373MG cells.   

Neobavaisoflavone (NBIF), an isoflavone isolated from Psoralea corylifolia (Leguminosae), has striking anti-inflammatory and anti-cancer effects. Neobavaisoflavone inhibits the proliferation of prostate cancer in vitro and in vivo. 

METHODS AND RESULTS:

In this study, we found that Neobavaisoflavone sensitizes human U373MG glioma cells to TRAIL-mediated apoptosis. Co-treatment of TRAIL and Neobavaisoflavone effectively induced Bid cleavage and activated caspases 3, 8, and 9. Importantly, DR5 expression was upregulated by Neobavaisoflavone. We also observed that the combination Neobavaisoflavone and TRAIL increased expression of BAX. We further demonstrate that Neobavaisoflavone induced TRAIL-mediated apoptosis in human glioma cells by suppressing migration and invasion, and by inhibiting anoikis resistance. 

CONCLUSIONS:

Taken together, our results suggest that Neobavaisoflavone reduces the resistance of cancer cells to TRAIL and that the combination of Neobavaisoflavone and TRAIL may be a new therapeutic strategy for treating TRAIL-resistant glioma cells.    

Molecules. 2011 May 3;16(5):3701-12.    

Inhibition of inflammatory mediators by neobavaisoflavone in activated RAW264.7 macrophages.   

Flavonoids and coumarins are the major bioactive constituents identified in Psoralea corylifolia. The active fraction isolated from fruits, seeds and roots possesses antibacterial, antioxidative and immunomodulatory properties. Neobavaisoflavone is one of the flavonoids found in Psoralea corylifolia. In the present study we investigated in vitro the anti-inflammatory activity of Neobavaisoflavone. 

METHODS AND RESULTS:

Macrophages play an important role in inflammation through the release of inflammatory mediators involved in the immune response. Inappropriate and prolonged macrophage activation is largely responsible for the pathology of acute and chronic inflammatory conditions. Neobavaisoflavone significantly inhibited the production of reactive oxygen species (ROS), reactive nitrogen species (RNS) and cytokines: IL-1β, IL-6, IL-12p40, IL-12p70, TNF-α in LPS+IFN-γ- or PMA- stimulated RAW264.7 macrophages.    

HPLC of Neobavaisoflavone

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

Introduction/Overview

Neobavaisoflavone (CAS No.: 41060-15-5) is a natural isoflavone product isolated from the seeds of the traditional Chinese medicinal herb Psoralea corylifolia. As an important member of the flavonoid family, Psoralea isoflavone has attracted widespread attention due to its diverse biological activities, especially demonstrating significant pharmacological potential in anti-inflammatory, antioxidant, and antitumor fields. In recent years, with advances in natural product pharmacology and molecular biology technologies, the mechanism of action of Xinbu Psoralea isoflavone and its interactions with various molecular targets have gradually been revealed, laying a solid foundation for its development as a potential drug candidate molecule. This paper systematically reviews the chemical structure and physicochemical properties, plant origin and extraction methods, pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects of Psoralea isoflavone, aiming to provide theoretical basis and reference for related research and drug development.

Chemical structure and physicochemical properties

New Psoralea Isoflavone belongs to the isoflavone class of compounds, with a molecular formula of C20H18O5 and a molecular weight of 322.36. Its structural feature is a typical isoflavone backbone, containing a 3-phenyl isoflavone core, with multiple hydroxyl and methoxy substituents in the molecule, which imparts certain polarity and biological activity. According to calculations, its lipid solubility index LogP is 3.6639, indicating good lipid solubility and facilitating cell membrane penetration. The topological pole surface area (TPSA) is 70.67 Ų, indicating moderate solubility of the molecule in polar environments. It has relatively low water solubility (0.0240 mg/mL), which somewhat limits its oral bioavailability, but also provides direction for improving drug formulations.

The new psoralen isoflavone has good chemical stability and no significant hERG channel inhibition. The Ames mutagenic test result is 0.6, indicating a low genotoxicity risk. Additionally, its low blood-brain barrier permeability suggests that the compound is distributed within the central nervous system, potentially reducing CNS-related side effects.

Plant Origins and Extraction Methods

The new psoralen isoflavones mainly come from mature seeds of the leguminous plant Psoralea corylifolia L. Psoralea, as a traditional Chinese medicine, is widely used in the field of Chinese medicine and is known for its effects of tonifying the kidneys and enhancing yang, dispelling wind and dampness. Its seeds are rich in isoflavone compounds, among which psoralen isoflavone is one of the important active components.

Common methods for extracting new psoralen isoflavones include solvent extraction, ultrasound-assisted extraction, and high-performance liquid chromatography (HPLC) separation and purification. Ethanol or methanol is generally used as extraction solvents, optimizing extraction efficiency by adjusting solvent polarity and extraction time. Ultrasound-assisted extraction can significantly increase extraction yield while shortening extraction time. After concentration, separatization, and chromatography separation of the extract, purification is performed using HPLC or preparative liquid chromatography techniques, ultimately yielding high-purity new psoralen isoflavones.

In recent years, with the development of green extraction technologies, supercritical CO2 extraction and microwave-assisted extraction have also been attempted to be applied to the extraction of new psoralen isoflavones, aiming to improve extraction efficiency and environmental friendliness.

Pharmacological activity research

Anti-inflammatory effects

Psoralea isoflavones exhibited significant anti-inflammatory activity. Both in vitro and in vivo studies have shown that this compound can inhibit the release of various inflammatory mediators, such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO). Its anti-inflammatory mechanism mainly regulates the nuclear factor κB (NF-κB) signaling pathway, suppressing the expression of inflammation-related genes and thereby alleviating inflammatory responses. Additionally, psoralen isoflavones can inhibit the activation and migration of inflammatory cells, reducing tissue damage.

Antioxidant effects

As a natural flavonoid, psoralen isoflavone has excellent free radical scavenging ability. The phenolic hydroxyl groups in its structure can effectively capture reactive oxygen species (ROS), preventing cell damage caused by oxidative stress. Multiple in vitro antioxidant experiments have shown that new psoralen isoflavones can significantly increase the activity of intracellular antioxidant enzymes (such as superoxide dismutase SOD and glutathione peroxidase GSH-Px), reduce the production of lipid peroxidation products, and protect cells from oxidative damage.

Antitumor effects

Psoralea isoflavones exhibit good inhibitory effects across various tumor cell lines. Research shows that its antitumor activity involves multiple mechanisms including cell cycle blockade, induction of apoptosis, and inhibition of tumor cell migration and invasion. Especially at medium to high concentrations, psoralen isoflavones can inhibit DNA polymerase activity, block DNA replication, and impede tumor cell proliferation.

Additionally, psoralen isoflavones have shown inhibition of platelet aggregation, which has potential implications for preventing tumor-related thrombosis. Platelets play an important role in tumor cell metastasis; inhibiting platelet aggregation helps block the bloodstream transmission of tumor cells.

Mechanism of action and molecular targets

The multi-target mechanism of the new psoralen isoflavone forms the basis for its pharmacological diversity. Current research reveals that its main targets include:

• MCL1 and BCL2: These two anti-apoptotic proteins play key roles in tumor cell survival. Psoralea isoflavones promote tumor cell apoptosis by downregulating MCL1 and BCL2 expression.
• STAT3: Signal transduction and transcription activator factor 3 (STAT3) is a core regulatory factor in various tumor and inflammatory signaling pathways. Psoralea isoflavone inhibits STAT3 phosphorylation and nuclear translocation, blocking its transcriptional activity and suppressing tumor cell proliferation and inflammatory responses.
• MMP2: Matrix metalloproteinase 2 (MMP2) participates in the degradation and invasion of the tumor cell stromal. Psoralea isoflavone inhibits MMP2 expression, reducing tumor cell migration and invasion capacity.
• TOP1 and TOP2A: Topoisomerases I and IIα are key enzymes in DNA replication and transcription. Psoralea isoflavones inhibit these two enzymes, block changes in DNA topology, and interfere with tumor cell proliferation.
• HIF1A: Hypoxia-inducing factor 1α regulates tumor cell adaptation in hypoxic environments. Psoralea inhibits HIF1A expression, interfering with tumor cell metabolic reprogramming and angiogenesis.
• MAPK1: Mitogen-activated protein kinase 1 is involved in cell proliferation and stress responses. Psoralea isoflavones regulate the MAPK1 signaling pathway, affecting cell growth and apoptosis.
• ESR1 and CYP19A1: estrogen receptor α and aromatases play important roles in hormone-dependent tumors. The regulation of these two targets by the new psoralen isoflavones suggests its potential application value in hormone-related tumors such as breast cancer.

Through the above multi-target synergistic effect, psoralen isoflavone can effectively regulate the tumor microenvironment and inhibit tumor growth and metastasis.

Druggability evaluation and pharmacokinetics

The druggability evaluation of Xinbu Psoralea Isoflavone indicates that it has certain potential for drug development. Its molecular weight is moderate (322.36), meeting the basic requirements of the Lipinski rule. A LogP value of 3.66 indicates good lipid solubility, which is beneficial for absorption by cell membranes, but its lower water solubility (0.0240 mg/mL) may limit oral absorption and bioavailability, requiring improvement through pharmacological methods.

The low permeability of the blood-brain barrier suggests that this compound 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 cardiotoxicity. The Ames test result was 0.6, indicating a low risk of genotoxicity.

In terms of pharmacokinetics, current research is relatively limited. Preliminary in vivo experiments show that psoralen isoflavones are absorbed orally more slowly, their bioavailability is limited, and they are mainly metabolized by the liver. The activity and safety of these metabolites require further study. In the future, systematic pharmacokinetic and toxicological evaluations are needed to guide preclinical development.

Prospects and outlooks for clinical applications

With its multiple pharmacological activities, especially its potential in antitumor and anti-inflammatory fields, the new psoralen isoflavone has promising clinical development prospects. Its regulatory ability to target multiple tumors, making it a strong candidate for the development of novel anticancer drugs. Moreover, its antioxidant and anti-inflammatory effects offer new ideas for the treatment of chronic inflammatory diseases, immune regulation, and aging-related diseases.

However, clinical research on new psoralen isoflavones is still in its early stages and lacks systematic clinical trial data. Future research should focus on the following aspects:

1. Pharmacokinetics and toxicology studies: Clarify its absorption, distribution, metabolism, and excretion characteristics in vivo, and evaluate safety and dosage ranges.
2. Dosage form optimization: To address poor water solubility, develop nano-formulations, liposomes, or other novel formulations to improve bioavailability and targeting.
3. In-depth mechanistic research: Using multi-omics techniques to reveal its network of action, clarify key targets and signaling pathways.
4. Clinical trial design: Conduct early clinical trials to verify safety and efficacy and explore indications.

In summary, as a multi-target, multifunctional natural product, Xinbu Psoralea isoflavone has strong drug development potential and is expected to become an important candidate drug in the fields of anti-tumor and anti-inflammatory treatment in the future.

Conclusion

As an important isoflavone active ingredient in Psoralea seeds, the new psoralen isoflavone has become a hot topic in natural product pharmacology research due to its remarkable anti-inflammatory, antioxidant, and antitumor activities. Its multi-target mechanism of action provides a theoretical basis for the development of novel multifunctional drugs. Although there are still certain challenges in pharmacokinetics and clinical applications, with the support of modern medicinal chemistry and formulation technologies, the new psoralen isoflavone is expected to overcome existing limitations and realize greater clinical value. Future systematic research will further promote clinical translation and support the innovative development of natural product drugs.