Acacetin (Flavone · Antiarrhythmic · Anti-inflammatory)

Compound	Acacetin (4′-Methoxyapigenin; 5,7-Dihydroxy-4′-methoxyflavone)
Chemical class	Polyphenol — Flavone (apigenin 4′-methyl ether; A-ring hydroxylated, B-ring monomethoxyated)
CAS	480-44-4
Primary source	Robinia pseudoacacia (black locust flowers), Populus spp. (poplar bud propolis), Chrysanthemum spp.
Key applications	Antiarrhythmic; anti-inflammatory; antioxidant; anticancer
Claim strength	Moderate
Typical form	Robinia flower extract; propolis extract (acacetin as minor flavone); Chrysanthemum extract
Buy from Herbuno	Availability on request — request bulk pricing →

Name origin: Acacetin is named after Acacia — the genus from which it was first isolated (though the taxonomy has shifted; Robinia pseudoacacia, the black locust, was historically classified as an Acacia). It is apigenin's 4′-methyl ether — the single methoxy group at the para-position of the B-ring distinguishes it from apigenin (4′-OH) and from genkwanin (7-O-methylapigenin) in the apigenin methylation series. Traditional use: Black locust (Robinia pseudoacacia) flowers are used in European folk medicine for spasmolytic and anti-inflammatory applications, and the flowers are consumed in Central and Eastern European cuisine. Propolis preparations — which contain acacetin as a minor flavone constituent alongside chrysin, pinocembrin, and caffeic acid phenethyl ester — have been used in folk medicine across Asia, Eastern Europe, and the Middle East for antimicrobial, wound-healing, and immunostimulatory applications. Research trajectory: Acacetin has attracted focused research attention for antiarrhythmic activity — specifically, inhibition of the ultrarapid delayed rectifier potassium current (IKur) in atrial cardiomyocytes, a target relevant to atrial fibrillation (AF) without the ventricular proarrhythmic risk associated with non-selective K⁺ channel blockers. This atrial-selective antiarrhythmic mechanism positions acacetin as a potentially safer AF treatment candidate. Commercial source: Acacetin is not currently available as a standalone standardised extract in the Herbuno catalogue; availability on request.

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Evidence for Acacetin Applications

Antiarrhythmic activity: Acacetin selectively inhibits IKur (Kv1.5 channels), the ultrarapid delayed rectifier K⁺ current expressed predominantly in atrial (not ventricular) cardiomyocytes. This atrial selectivity is clinically important — ventricular K⁺ channel blockade causes QT prolongation and torsades de pointes risk, while atrial-selective IKur block converts AF without this hazard. In canine AF models, acacetin (oral and IV) effectively terminates and prevents AF without QT prolongation or ventricular arrhythmia induction. Phase I pharmacokinetic studies in healthy volunteers have been reported. Claim strength: Moderate.

Anti-inflammatory: Acacetin inhibits COX-2, 5-LOX, and iNOS expression in LPS-stimulated macrophage models via NF-κB and MAPK pathway suppression. At 10–50 μM, it reduces prostaglandin E₂ and leukotriene B₄ production more potently than its parent aglycone apigenin in comparative studies. Claim strength: Moderate.

Antioxidant: Acacetin scavenges DPPH, ABTS, and superoxide radicals with activity comparable to quercetin in some assays. Nrf2/HO-1 pathway induction provides indirect antioxidant cytoprotection in hepatocyte and neuronal models. Claim strength: Moderate.

Antiproliferative: Acacetin demonstrates selective cytotoxicity in multiple cancer cell lines (breast, lung, hepatocellular) via G1/S arrest, PARP cleavage, and mitochondrial pathway apoptosis at 20–80 μM concentrations. PI3K/Akt and mTOR pathway inhibition are mechanistically documented. Research is preclinical. Claim strength: Emerging.

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Dosage & Formulator Specification

No human supplement dosing data exist for acacetin. Pharmacokinetic studies in healthy volunteers have used single-dose IV or oral administration for PK characterisation rather than therapeutic dosing. Preclinical antiarrhythmic efficacy was demonstrated at 5–30 mg/kg in canine models; human equivalent dose estimation is premature without Phase II trial data.

For formulators interested in the flavone antiarrhythmic class, acacetin is more accessible as a component of propolis or Robinia flower extracts than as an isolated compound. Propolis extract (standardised to total flavonoids ≥15%) delivers acacetin alongside chrysin, pinocembrin, and caffeic acid esters. Black locust flower extract is available from some Eastern European botanical suppliers.

Acacetin's lipophilicity (logP ~2.5) is higher than apigenin (logP ~2.0), improving membrane penetration for intracellular anti-inflammatory targets. Aqueous solubility is low; lipid-based or phospholipid-complexed delivery formats are appropriate for oral supplement applications.

No clinically significant drug interactions are documented for acacetin in supplement contexts. Given the antiarrhythmic mechanism (K⁺ channel modulation), formulators should note that high-dose acacetin isolate co-administration with antiarrhythmic drugs requires professional oversight, though this risk is theoretical at typical botanical extract exposure levels.

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Frequently Asked Questions — Acacetin

What makes acacetin's antiarrhythmic mechanism atrial-selective?
The ultrarapid delayed rectifier K⁺ current (IKur), mediated by Kv1.5 channels, is expressed predominantly in human atrial cardiomyocytes with minimal ventricular expression. Drugs blocking IKur therefore shorten atrial action potential duration and refractory period selectively, suppressing AF without prolonging ventricular QT interval — the mechanism responsible for the lethal arrhythmia torsades de pointes that limits non-selective K⁺ channel blockers like sotalol and quinidine.

How does acacetin differ from apigenin?
Acacetin is apigenin's 4′-methyl ether — one hydroxyl group is methylated at the para-position of the B-ring. This increases lipophilicity and metabolic stability while shifting pharmacological selectivity: acacetin has stronger Kv1.5 channel affinity and enhanced anti-inflammatory potency in some assays, while apigenin has stronger 5-HT1A binding and better-characterised anxiolytic activity. Both share the 5,7-dihydroxy A-ring template.

Is acacetin present in standard propolis extracts?
Yes — propolis typically contains acacetin alongside chrysin, pinocembrin, kaempferol, quercetin, and caffeic acid phenethyl ester (CAPE) as its principal flavone/flavonoid constituents. Acacetin concentration varies by propolis geographic origin; temperate European and Chinese propolis contains higher flavonoid content than tropical propolis. Propolis extracts standardised to ≥15% total flavonoids will deliver acacetin as a minor constituent.

What is the current clinical development status of acacetin as an antiarrhythmic?
Acacetin has completed Phase I pharmacokinetic studies in healthy volunteers, demonstrating oral bioavailability and acceptable safety profile. As of the HerbIQ knowledge reference date, Phase II efficacy trials for atrial fibrillation conversion have not been publicly reported. The compound is an active pharmaceutical investigation candidate but is not an approved antiarrhythmic drug in any jurisdiction.

Related compounds: Apigenin, Chrysin, Diosmetin, Tangeretin

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Claim-strength scale – High = multiple human RCTs; Moderate = limited trials or strong preclinical convergence; Emerging = early-stage lab or animal data.

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