Synonym name: Apigenin 4'-methyl ether; Linarigenin; Buddleoflavonol
Catalogue No.: BP0114
Cas No.: 480-44-4
Formula: C₁₆H₁₂O₅
Mol Weight: 284.267
Botanical Source: Robinia pseudacacia (common acacia) and Ammi visnaga. Also many other plants incl. Asteraceae, Cistaceae, Clusiaceae, Fabaceae, Liliaceae etc.

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 Acacetin

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

Introduction/Overview

Acacetin (CAS No.: 480-44-4) is a natural monomethoxyflavonoid chemically derived from apigenin (4'-methyl ether). As a functional plant metabolite, acacia extract has demonstrated broad biological activity in both traditional Chinese medicine and modern pharmacological research, covering areas such as anticonvulsant, anticancer, anti-inflammatory, antioxidant, and cardiovascular protection. In recent years, with the deepening development of natural product pharmacology, acacia extract has become one of the hot molecules in research on atrial fibrillation, cancer, and inflammation-related diseases due to its unique molecular mechanism and excellent druggability.

This review aims to systematically summarize the chemical structure and physicochemical properties of acacia extract, plant origin, and extraction process, with a focus on evaluating its pharmacological activity and mechanism of action, exploring its druggability and pharmacokinetic characteristics, and looking ahead to its clinical application potential, providing theoretical basis and reference for subsequent basic and translational research.

Chemical structure and physicochemical properties

The chemical name of acacia acid is the conjugated acid of 5-hydroxy-2-(4-methoxyphenyl)-4-oxo-4H-1 benzopyran-7-phenolic acid, with a molecular formula C16H12O5 and a molecular weight of 284.26. Its structural core is a typical flavonoid backbone, featuring a single 4'-methoxy substituent, distinct from the hydroxyl group of apigenin, which gives it unique physicochemical properties and bioactivity.

In terms of physicochemical properties, acacia extract has a LogP value of about 2.2, showing moderate lipid solubility, which is beneficial for cell membrane penetration and bioavailability. The topological pole surface area (TPSA) is 86.99 Ų, indicating certain polarity that facilitates hydrogen bonding with biological targets. There are 5 hydrogen bond receptors, supporting multi-point binding to protein targets. The blood-brain barrier penetration ability is moderate, suggesting its potential application value in central nervous system diseases. Low risk of hepatotoxicity, negative cardiotoxicity and hERG channel inhibition, indicating good safety.

Plant Origins and Extraction Methods

Acacia extract is mainly found in plants of the Asteraceae family, especially abundant in chrysanthemum (Dendranthema morifolium). This plant is widely used in traditional Chinese medicine for clearing heat and detoxifying, calming the liver and improving eyesight. As one of its important active ingredients, acacia extract carries various pharmacological functions.

In terms of extraction methods, commonly used solvents include ethanol, water, and their mixtures. The conventional extraction steps are: after drying the plant material, it is crushed by reflux extraction or ultrasonic-assisted extraction, followed by separation and purification through liquid-liquid partitioning, column chromatography, and other methods. High-performance liquid chromatography (HPLC) and mass spectrometry (LC-MS) are widely used for qualitative and quantitative analysis of acacia extracts. In recent years, green technologies such as supercritical fluid extraction and microwave-assisted extraction have gradually been applied to the efficient extraction of acacia extract, improving extraction efficiency and purity.

Pharmacological activity research

1. Cardiovascular protective effects

Acacia extract, as a selective atrial drug, can significantly prolong the effective atrial refractory period (AERP) without affecting the corrected QT interval, demonstrating good antiarrhythmic potential. In animal experiments, acacia extract was effective in preventing atrial fibrillation (AF) in anesthetized dogs through intradodecodal administration, suggesting its promising application in clinical arrhythmia prevention and treatment, especially atrial fibrillation.

2. Anti-cancer activity

Acacia extract exhibits significant anti-proliferative effects across various cancer cell lines. Its mechanisms include inducing cell cycle arrest, promoting apoptosis, and autophagy. At the molecular level, acacia protein inhibits the ATP-binding pocket of PI3Kγ, disrupting the PI3K/AKT signaling pathway and blocking cancer cell growth and survival signals. In addition, acacia extract also inhibits tumor cell migration and invasion, demonstrating multi-target anti-tumor potential.

3. Anti-inflammatory and antioxidant effects

Acacia extract can significantly inhibit the release of inflammatory mediators and the activation of inflammatory signaling pathways, such as NF-κB and MAPK pathways, thereby reducing tissue inflammatory responses. Its antioxidant activity includes scavenging free radicals, reducing lipid peroxide formation, and protecting cells from oxidative stress damage. These effects give acacia extract therapeutic potential in inflammatory diseases and oxidative stress-related conditions.

4. Anticonvulsant and neuroprotection

As a natural anticonvulsant, acacia extract can regulate neurotransmitter balance, suppress neuronal overexcitation, and reduce seizures. Its ability to penetrate the blood-brain barrier is moderate, supporting its application in central nervous system diseases. Related studies have also shown that acacia extract has protective effects against neuroinflammation and neurodegenerative diseases.

5. Other pharmacological effects

Acacia extract also exhibits multiple biological activities including anti-mutagenic, antiepileptic, and pain relief, indicating its broad potential application in various disease models.

Mechanism of action and molecular targets

The multi-target mechanism of acacia extract forms the basis of its multiple pharmacological effects. Through molecular docking and biochemical experiments, acacia extract has been found to bind to and regulate multiple key protein targets:

• PI3Kγ: Acacia extract remains in the ATP-binding pocket of PI3Kγ, inhibiting its kinase activity, blocking the PI3K/AKT signaling pathway, and inducing cancer cell cycle arrest and apoptosis.
• APP (amyloid precursor protein): Related to myocardial infarction, acacia extract may participate in myocardial protection by regulating APP expression or processing.
• PTPN1 (protein tyrosine phosphatase 1B): regulates cellular signal transduction, affecting metabolism and inflammatory responses.
• MAOA (Monoamine Oxidase A): Involved in neurotransmitter metabolism, affecting nervous system function.
• ABCB1 and ABCG2 (drug transporters): affect drug absorption, distribution, and resistance.
• SYNJ2 (phosphatidyl-inositol phosphatase): regulates cell membrane signaling and intracellular transport.
• ALOX5 (lipoxygenase 5): involved in the synthesis of inflammatory mediators.
• TRPV1 (Transient receptor potential vanillic acid receptor 1): a target related to pain perception.
• CNR1 (Cannabinoid Receptor 1): Regulates the nervous system and immune responses.
• SHBG (sex hormone-binding globulin): regulates hormone activity.

The diversity of these targets reflects the multiple regulatory roles of acacia extract in cardiovascular diseases, cancer, neurological disorders, and inflammation.

Druggability evaluation and pharmacokinetics

The druggability parameters of Acacia Extract indicate that it has promising potential for drug development. The molecular weight is moderate (284.26), meeting the Lipinski rule; a LogP value of 2.2 indicates moderate lipid solubility, which is beneficial for oral absorption. TPSA is approximately 87 Ų, supporting its excellent membrane permeability and target binding capability.

In terms of safety, acacia extract carries low hepatotoxicity risk, no cardiotoxicity or hERG channel inhibition, and a negative Ames test indicates low genotoxicity risk and good safety.

Pharmacokinetic studies show that acacia extract has good oral bioavailability and moderate blood-brain barrier penetration, making it suitable for treating central nervous system diseases. Its metabolism mainly passes through the liver enzyme system, where metabolites are stable and excretion pathways are diverse, supporting the maintenance of its effective efficacy in the body.

Prospects and outlooks for clinical applications

With its multi-target and multi-mechanism pharmacological effects, acacia extract demonstrates broad clinical application potential:

• Cardiovascular diseases: As a selective atrial antiarrhythmic drug, acacia extract has unique advantages in the prevention and treatment of atrial fibrillation, and may be developed into a novel antiarrhythmic drug in the future.
• Tumor Therapy: Its anti-cancer mechanisms are diverse, especially of great value in the development of PI3Kγ inhibitors, and can serve as candidate molecules for monotherapy or combination therapy.
• Inflammation and neurological diseases: Its anti-inflammatory, antioxidant, and neuroprotective effects give it potential in treating chronic inflammation, neurodegenerative diseases, and epilepsy.
• Pain management: By regulating targets such as TRPV1, acacia extract is expected to become a new type of analgesic drug.

Future research should focus on preclinical pharmacokinetic optimization, formulation development, and safety evaluation of acacia extract, while integrating modern molecular biology and medicinal chemistry techniques to deeply analyze its mechanisms of action and promote clinical translation.

Conclusion

As a monomethoxyflavonoid derived from natural plants, acacia extract has become an important subject in natural product pharmacology research due to its unique chemical structure and diverse biological activities. Its significant effects in cardiovascular protection, anti-cancer, anti-inflammation, and neuroprotection, combined with good druggability and safety, lay a solid foundation for it as a potential drug molecule. In the future, through systematic pharmacological mechanism research and clinical translational development, Acacia Extract is expected to become a new natural medicine for treating various diseases, contributing new strength to human health.