Synonym name: DL-Isomucronulatol; 7,2'-Dihydroxy-3',4'-dimethoxyisoflavan
Catalogue No.: BP0791
Cas No.: 52250-35-8
Formula: C₁₇H₁₈O₅
Mol Weight: 302.326
Botanical Source:

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.

HPLC of Isomucronulatol

HNMR of Isomucronulatol

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

Introduction/Overview

Astragalus (Astragalus membranaceus), a traditional Chinese medicinal herb, is widely used in clinical and basic research for its outstanding immunomodulatory and anti-inflammatory effects. Isomucronulatol (CAS No.: 52250-35-8) is a flavonoid natural product derived from the roots of astragalus. In recent years, it has attracted attention in pharmacology and natural product chemistry due to its unique biological activity. Research shows that astragalus isoflavanols can significantly inhibit the expression of lipopolysaccharide (LPS)-induced IL-12 p40 subunits in vitro, demonstrating potential anti-inflammatory activity. Additionally, it has regulatory effects on antioxidant damage-related targets such as NFE2L2 (NRF2), SOD1, CAT, GPX1, HMOX1, and SOD2, suggesting its potential for application in oxidative stress-related diseases. This paper will systematically review the chemical structure, plant origin, extraction methods, pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects of Astragalus isflavanol, providing a theoretical basis and research direction for in-depth research and development of this compound.

Chemical structure and physicochemical properties

Astragalus isoflavanol belongs to the flavonoid class of compounds with a molecular formula of C_18H_18O_5 and a molecular weight of 302.3260. Its structural features include a typical isoflavanol backbone with multiple hydroxyl groups and benzene rings, giving it a solid bioactive foundation. In terms of physicochemical properties, the LogP value of Astragalus isoflavanol is 2.9183, indicating moderate lipid solubility, which facilitates cell membrane penetration and distribution in vivo. Its polar surface area (TPSA) is 68.15 Ų, indicating moderate polarity that facilitates binding with biomacromolecules. Its low water solubility (0.1264 mg/mL) suggests limited solubility in the aqueous phase, but it is suitable for improving bioavailability through techniques such as liposomals or nanocarriers. The high permeability of the blood-brain barrier suggests its potential to function in the central nervous system. Importantly, astragalus isoflavanols did not show hERG channel inhibition, and Ames-induced mutagenic tests were negative, indicating good safety and low toxicity risk.

Plant Origins and Extraction Methods

Astragalus isoflavanol mainly comes from the root of Astragalus membranaceus. As a legume, astragalus has roots rich in various flavonoids, saponins, and polysaccharides. The extraction of astragalus isoflavanols usually uses organic solvent extraction combined with column chromatography separation technology. Specific methods include:

1. Raw material preparation: Collect dried astragalus roots and crush them to suitable particle sizes to facilitate solvent penetration.
2. Solvent extraction: 70%-95% ethanol or methanol is commonly used for reflux extraction, with extraction time generally 2-4 hours, and extraction temperature controlled at 60-80°C.
3. Crude extract concentration: Extract is obtained by removing solvent through vacuum concentration.
4. Separation and purification: Isolated isoflavanols are separated and purified using silica gel column chromatography or reversed-phase high-performance liquid chromatography (RP-HPLC), combined with thin-layer chromatography (TLC) and mass spectrometry (MS) to confirm purity and structure.
5. Crystallization or freeze-drying: After further purification, high-purity astragalus isoflavanol powder is obtained through crystallization or freeze-drying techniques.

In recent years, green extraction technologies such as ultrasound-assisted extraction (UAE) and supercritical fluid extraction (SFE) have also been tried for the extraction of astragalus isoflavanols, significantly improving extraction efficiency and reducing the use of organic solvents, aligning with the environmental trend of modern natural product extraction.

Pharmacological activity research

Pharmacological studies on the pharmacological activity of Astragalus isoflavanol mainly focus on its anti-inflammatory and antioxidant effects. In vitro experiments show that astragalus isoflavanol can effectively inhibit the expression of the IL-12 p40 subunit in LPS-induced macrophages. IL-12, as a pro-inflammatory cytokine, plays a key role in various inflammatory and immune diseases, and its inhibition helps alleviate inflammatory responses. In addition, astragalus isoflavanols regulate the expression and activity of various oxidative stress-related enzymes, including superoxide dismutase (SOD1, SOD2), catalase (CAT), glutathione peroxidase (GPX1), and heme oxygenase-1 (HMOX1). These enzymes work together to maintain intracellular redox balance and prevent oxidative damage.

Animal model studies have shown that astragalus isoflavanols can alleviate tissue damage caused by oxidative stress, such as oxidative damage to the liver, heart, and nervous system, demonstrating significant protective effects. Additionally, its activation of the NFE2L2 (NRF2) signaling pathway is considered the core of its antioxidant mechanism. NRF2, as the main intracellular antioxidant transcription factor, regulates the expression of various antioxidant enzymes, thereby enhancing the cell's resistance to oxidative stress.

Mechanism of action and molecular targets

The mechanism of action of astragalus isoflavanol mainly involves two aspects: anti-inflammatory and antioxidant effects:

1. Anti-inflammatory mechanism
   Astragalus isoflavanol weakens macrophage pro-inflammatory responses by inhibiting the expression of the LPS-induced inflammatory factor IL-12 p40. IL-12, as a key factor in Th1 cell differentiation, helps regulate immune balance and reduce chronic inflammation. Additionally, astragalus isoflavanols may further exert anti-inflammatory effects by modulating the NF-κB signaling pathway and inhibiting the production of inflammatory mediators.

2. Antioxidant mechanism
   Astragalus isoflavanol can activate the NFE2L2 (NRF2) signaling pathway, promoting the translocation of NRF2 from the cytoplasm to the nucleus, binding to antioxidant reaction elements (ARE), inducing the expression of downstream antioxidant enzymes such as SOD1, SOD2, CAT, GPX1, and HMOX1, enhancing cellular antioxidant defenses, reducing the accumulation of reactive oxygen species (ROS) and free radicals, and protecting cells from oxidative damage.

3. Other potential targets
   Due to the structural characteristics of Astragalus isoflavanols, they may bind to various enzymes and receptor proteins, regulating cellular signaling networks. Existing studies suggest that it may affect signaling pathways such as MAPK and PI3K/Akt, and is involved in cell survival, apoptosis, and metabolic regulation, but specific targets and mechanisms require further elucidation.

Druggability evaluation and pharmacokinetics

The druggability evaluation of Astragalus isoflavanol shows it has good potential for drug development:

• Molecular weight and lipid solubility: The molecular weight of 302.3260 and the lipid solubility of LogP 2.9183 comply with the Lipinski rule, facilitating oral absorption.
• Polarity and solubility: TPSA was 68.15 Ų, indicating moderate molecular polarity and low water solubility (0.1264 mg/mL), suggesting possible solubility limits in vivo and requiring formulation optimization to improve bioavailability.
• Blood-brain barrier permeability: Predicted to be high, indicating that astragalus isoflavanol may have central nervous system effects and is suitable for developing drugs for neurological diseases.
• Safety: No hERG channel inhibition, reducing the risk of cardiotoxicity; Ames test was negative, indicating no significant mutagenicity and relatively high safety.

Pharmacokinetics, although current data on in vivo absorption, distribution, metabolism, and excretion (ADME) of astragalus isoflavanol are limited, its good lipid solubility and blood-brain barrier permeability suggest that it can be effectively absorbed and distributed to target tissues after oral administration. In the future, in vivo pharmacokinetic studies are needed to clarify its half-life, bioavailability, and metabolic pathways to provide a basis for clinical development.

Prospects and outlooks for clinical applications

Astragalus isoflavanol, as a natural flavonoid compound, shows broad application prospects in the prevention and treatment of various diseases due to its remarkable anti-inflammatory and antioxidant activities. Its potential indications include:

• Chronic inflammatory diseases: such as rheumatoid arthritis and inflammatory bowel disease. Astragalus isflavanol may reduce inflammatory responses and improve conditions by inhibiting IL-12 and related inflammatory pathways.
• Oxidative stress-related diseases: including cardiovascular diseases, neurodegenerative diseases (such as Alzheimer's and Parkinson's), diabetes and its complications. Astragalus isoflavanol activates the NRF2 pathway, enhances antioxidant defenses, and protects tissue function.
• Central nervous system diseases: Its good blood-brain barrier permeability makes it possible to develop neuroprotective agents, and future applications may be explored in cerebral ischemia, neuroinflammation, and cognitive impairment.

Future research should focus on:

1. Systematic pharmacokinetic and toxicological evaluations to ensure safety and efficacy.
2. In-depth research into mechanisms of action clarifies molecular targets and signaling pathways, promoting structural optimization and derivative development.
3. Preclinical animal models validated to evaluate efficacy and dose-response relationships in disease models.
4. Developing novel formulations to improve water solubility and bioavailability, enhancing clinical application value.

In summary, astragalus isoflavanol is a natural product with multi-target effects and holds potential as a novel anti-inflammatory and antioxidant drug, warranting further research and development.

Conclusion

Astragalus isoflavanol, as an important flavonoid active ingredient in astragalus, demonstrates remarkable anti-inflammatory and antioxidant activities due to its unique chemical structure and excellent physicochemical properties. By regulating IL-12 p40 expression and activating the NRF2 signaling pathway, it participates in regulating inflammatory responses and oxidative stress, offering broad pharmacological significance and clinical application potential. Druggability evaluations have shown good safety and blood-brain barrier penetration ability, offering possibilities for treating neurological diseases. In the future, by integrating modern drug development technologies, deeply elucidating its mechanisms of action and optimizing formulation and pharmacokinetic properties will lay a solid foundation for the clinical translation of astragalus isoflavanol and promote it as a new highlight in natural product drug development.