Amorfrutin A

Amorfrutin A at a Glance

Amorfrutin A is a prenylated benzoic acid — structurally a bibenzyl carrying a prenyl group and a free carboxylic acid, and formally one of the amorfrutin-type phytocannabinoids, a scaffold that resembles the cannabinoids without acting at their receptors. It was isolated in 1981 from the fruits of Amorpha fruticosa, which is where its name comes from, and described then simply as an antimicrobial ^{14Reference 14Mitscher LA et al. · 1981Amorfrutin A and B, bibenzyl antimicrobial agents from Amorpha fruticosaView study →}.

Thirty years later it turned out to be something more interesting: a selective PPARγ agonist. In diet-induced obese and db/db mice, amorfrutins improved insulin resistance and inflammatory markers without the fat gain or hepatotoxicity that characterise the glitazone drugs acting at the same receptor ^{1Reference 1Weidner C et al. · 2012AnimalAmorfrutins are potent antidiabetic dietary natural products — animal study in miceView study →}. That is the finding the molecule is known for, and it is the reason anyone looks at this shrub.

It has since accumulated a scattered second literature — NF-κB and JAK/STAT3 inhibition in cancer cells, neuroprotection in a rat stroke model, and membrane-disrupting activity against multidrug-resistant Staphylococcus aureus ^{2,3,4,5Reference 2Shi H et al. · 2014In vitroAmorfrutin A inhibits TNF-α-induced NF-κB activation and NF-κB-regulated target gene products — in vitroView study →Reference 3Mi C et al. · 2017In vitroAmorfrutin A inhibits TNF-α induced JAK/STAT signaling, cell survival and proliferation of human cancer cells — in vitro with mouse xenograftView study →Reference 4Yang Y et al. · 2025In vitroAmorfrutin A ameliorates cerebral ischemia/reperfsion injury in vivo and in vitro via modulating Nrf2/HO-1 signaling pathway — animal model in ratsView study →Reference 5Lucidi M et al. · 2026In vitroAmorfrutin-A, a membrane-targeting phytochemical active against multidrug-resistant Staphylococcus aureus: In vitro and in vivo activity and mechanism of actionView study →}. None of it has reached a person. And the source question runs through all of it: several of these studies used amorfrutin purified from a licorice species, not from Amorpha.

Which Plant Was Actually Tested

Amorfrutins occur in two unrelated legumes — Amorpha fruticosa (false indigo bush) and Glycyrrhiza foetida, a wild licorice — and the flagship papers are split between them ^{1Reference 1Weidner C et al. · 2012AnimalAmorfrutins are potent antidiabetic dietary natural products — animal study in miceView study →}. Attributing a result to the wrong plant is the standard error with this molecule, so each claim below names its source. Three points make the distinction load-bearing:

The licorice in question is not the licorice on a shelf. When the quantitative HPLC method was applied across both genera, amorfrutins were detected only in the fruits of A. fruticosa. None was found in Amorpha canescens, and none in the roots of Glycyrrhiza uralensis, G. inflata or G. glabra — the three species that supply essentially all commercial licorice ^{7Reference 7Chen C et al. · 2016Qualitative and quantitative analysis of amorfrutins, novel antidiabetic dietary natural products, by HPLCView study →}. G. foetida is a distinct wild species; a licorice root extract or confection carries no amorfrutins.

The antibacterial work is licorice work. The ten amorfrutins screened for activity against Staphylococcus aureus, including amorfrutin A itself, were purified from G. foetida ^{5Reference 5Lucidi M et al. · 2026In vitroAmorfrutin-A, a membrane-targeting phytochemical active against multidrug-resistant Staphylococcus aureus: In vitro and in vivo activity and mechanism of actionView study →}. So was amorfrutin C — a sibling that barely activates PPARγ and kills cells by depolarising mitochondria instead, and that has never been reported from Amorpha at all ^{12Reference 12Weidner C et al. · 2016In vitroAmorfrutin C Induces Apoptosis and Inhibits Proliferation in Colon Cancer Cells through Targeting Mitochondria — in vitroView study →} — and so were the phytocannabinoid analogues in the 2023 structure–activity study ^{13Reference 13Serino E et al. · 2023In vitroPPARα/γ-Targeting Amorfrutin Phytocannabinoids from Aerial Parts of Glycyrrhiza foetida — in vitroView study →}.

The metabolic work spans both. The 2012 study that established the amorfrutins as antidiabetic drew them from the edible parts of both species and treated them as one chemical family ^{1Reference 1Weidner C et al. · 2012AnimalAmorfrutins are potent antidiabetic dietary natural products — animal study in miceView study →}. That is defensible for a shared scaffold, but it means the mouse data belong to amorfrutins, plural, rather than to amorfrutin A as an isolate.

What It's Used For

Five separate lines of work, four of them from single laboratories, and one of them — the PPARγ metabolic story — genuinely substantial. There is also an isolated report that amorfrutin-A at 0.5–1.0 µM extended the growth span and stress tolerance of serially passaged human skin fibroblasts, slowing telomere and methylation loss, which the authors read as mild-stress hormesis rather than as a drug effect ^{11Reference 11Sodagam L et al. · 2019In vitroPhytochemicals Rosmarinic Acid, Ampelopsin, and Amorfrutin-A Can Modulate Age-Related Phenotype of Serially Passaged Human Skin Fibroblasts in vitroView study →}.

Evidence by IndicationStrength of support · Beta

01PPARγ Agonism and Metabolic EffectsShaky42%Receptor binding, selective gene profile, and two mouse models of insulin resistance — dosed as amorfrutins, not the single isolate ^{1,13Reference 1Weidner C et al. · 2012AnimalAmorfrutins are potent antidiabetic dietary natural products — animal study in miceView study →Reference 13Serino E et al. · 2023In vitroPPARα/γ-Targeting Amorfrutin Phytocannabinoids from Aerial Parts of Glycyrrhiza foetida — in vitroView study →}

02Anti-Inflammatory and NF-κB InhibitionShaky32%Mechanistically detailed in-vitro work in TNF-α-stimulated cells, plus PPARγ-dependent suppression in colon cells ^{2,6Reference 2Shi H et al. · 2014In vitroAmorfrutin A inhibits TNF-α-induced NF-κB activation and NF-κB-regulated target gene products — in vitroView study →Reference 6Fuhr L et al. · 2015In vitroAmorfrutins Are Natural PPARγ Agonists with Potent Anti-inflammatory Properties — in vitroView study →}

03Antibacterial Activity Against MRSAShaky30%MICs, a defined membrane mechanism, biofilm and persister data, and an insect infection model — licorice-sourced ^{5Reference 5Lucidi M et al. · 2026In vitroAmorfrutin-A, a membrane-targeting phytochemical active against multidrug-resistant Staphylococcus aureus: In vitro and in vivo activity and mechanism of actionView study →}

04Antiproliferative and STAT3 InhibitionShaky24%One laboratory: JAK1/JAK2/Src and STAT3 blockade in four cell lines, with a HeLa xenograft ^{3Reference 3Mi C et al. · 2017In vitroAmorfrutin A inhibits TNF-α induced JAK/STAT signaling, cell survival and proliferation of human cancer cells — in vitro with mouse xenograftView study →}

05Neuroprotection in Cerebral IschaemiaShaky20%A single rat MCAO/reperfusion study with matched cell work, attributed to Nrf2/HO-1 signalling ^{4Reference 4Yang Y et al. · 2025In vitroAmorfrutin A ameliorates cerebral ischemia/reperfsion injury in vivo and in vitro via modulating Nrf2/HO-1 signaling pathway — animal model in ratsView study →}

Mechanisms

Two of these are receptor pharmacology and one is a detergent-like physical effect. They will not scale together: the concentration that disrupts a bacterial membrane has no necessary relationship to the one that occupies PPARγ.

Pharmacokinetics

None published. There is no absorption, distribution, metabolism, half-life or bioavailability study for amorfrutin A in any species. That is the largest hole in what is known: a free carboxylic acid on a lipophilic prenylated scaffold is exactly the structure whose oral behaviour cannot be guessed, and both in-vivo results — the mouse metabolic work and the rat stroke model — rest on an unmeasured exposure. Work on the closely related amorfrutin B has gone as far as PEG modification to raise gastric absorption and circulating half-life ^{15Reference 15Samad MB et al. · 2017PEG modification of Amorfrutin B from Amorpha fructicosa increases gastric absorption, circulation half-life and glucose uptake by T3T-L1 adipocytes — animal studyView study →}, which is itself an indication that the unmodified molecules are not well behaved.

Clinical Trials

None. No registered trial of amorfrutin A or of an amorfrutin preparation in humans.

Last checked: September 2026.

Isolate vs. Plant Studies

Unusually for a plant constituent, this is isolate evidence almost throughout — and the problem is not extract-versus-molecule but which molecule and which plant. The mouse metabolic work dosed a mixture of amorfrutins drawn from two species, so its conclusions belong to the family rather than to amorfrutin A ^{1Reference 1Weidner C et al. · 2012AnimalAmorfrutins are potent antidiabetic dietary natural products — animal study in miceView study →}. The antibacterial and structure–activity work used purified single compounds, but from Glycyrrhiza foetida ^{5,13Reference 5Lucidi M et al. · 2026In vitroAmorfrutin-A, a membrane-targeting phytochemical active against multidrug-resistant Staphylococcus aureus: In vitro and in vivo activity and mechanism of actionView study →Reference 13Serino E et al. · 2023In vitroPPARα/γ-Targeting Amorfrutin Phytocannabinoids from Aerial Parts of Glycyrrhiza foetida — in vitroView study →}. The NF-κB study has the cleanest attribution of the set: a single molecule, purified from Amorpha fruticosa fruit, tested alone ^{2Reference 2Shi H et al. · 2014In vitroAmorfrutin A inhibits TNF-α-induced NF-κB activation and NF-κB-regulated target gene products — in vitroView study →}.

There is no whole-plant human evidence on either side, because neither plant has a materia-medica tradition that would produce it. A. fruticosa is not used internally, and G. foetida is not the licorice of commerce or of herbal practice ^{7Reference 7Chen C et al. · 2016Qualitative and quantitative analysis of amorfrutins, novel antidiabetic dietary natural products, by HPLCView study →}. So there is no extract literature to weigh the isolate against — an absence, not a reassurance.

Prevalence in Nature

Amorfrutin A is a Fabaceae molecule with a narrow distribution, and the quantitative picture is unusually clean because someone went and measured it.

In Amorpha fruticosa the amorfrutins are fruit constituents: validated HPLC put amorfrutin A at 0.54–3.52 mg/g and amorfrutin B at 0.64–4.63 mg/g across batches, with 2-carboxy-3,5-dihydroxy-4-geranylbibenzyl at 1.31–7.43 mg/g — ranges wide enough that provenance and season move the content several-fold ^{7Reference 7Chen C et al. · 2016Qualitative and quantitative analysis of amorfrutins, novel antidiabetic dietary natural products, by HPLCView study →}. Counter-current chromatography recovers them readily from the hexane-soluble fraction of the fruit, alongside 5,7-dihydroxy-8-geranylflavanone ^{8Reference 8Chen C et al. · 2015Isolation and purification of prenylated phenolics from Amorpha fruticosa by high-speed counter-current chromatographyView study →}.

The same assay found no amorfrutins in Amorpha canescens and none in the roots of Glycyrrhiza uralensis, G. inflata or G. glabra ^{7Reference 7Chen C et al. · 2016Qualitative and quantitative analysis of amorfrutins, novel antidiabetic dietary natural products, by HPLCView study →}. Occurrence in the genus Glycyrrhiza is specific to G. foetida, whose aerial parts carry a substantial amorfrutin series — six new members plus six known ones were characterised in a single 2023 analysis, alongside alkyl-type phytocannabinoids ^{13Reference 13Serino E et al. · 2023In vitroPPARα/γ-Targeting Amorfrutin Phytocannabinoids from Aerial Parts of Glycyrrhiza foetida — in vitroView study →}.

Outside the legumes, amorfrutin-type phytocannabinoids have been reported from Helichrysum umbraculigerum, a South African daisy ^{10Reference 10Pollastro F et al. · 2017Amorfrutin-type phytocannabinoids from Helichrysum umbraculigerumView study →} — placing the scaffold in the small group of cannabinoid-like structures that plants arrive at independently of Cannabis.

Discovery & Synthesis

Amorfrutin A was isolated in 1981 from Amorpha fruticosa, together with amorfrutin B, and described as a pair of bibenzyl antimicrobial agents — the name is built from the plant’s ^{14Reference 14Mitscher LA et al. · 1981Amorfrutin A and B, bibenzyl antimicrobial agents from Amorpha fruticosaView study →}. For three decades that was the whole of it. The molecule’s metabolic pharmacology arrived in 2012, when a screen of edible legume material identified the amorfrutins as selective PPARγ agonists ^{1Reference 1Weidner C et al. · 2012AnimalAmorfrutins are potent antidiabetic dietary natural products — animal study in miceView study →}, and the antimicrobial claim of the original paper was not mechanistically resolved until 2026 ^{5Reference 5Lucidi M et al. · 2026In vitroAmorfrutin-A, a membrane-targeting phytochemical active against multidrug-resistant Staphylococcus aureus: In vitro and in vivo activity and mechanism of actionView study →}.

Preparative access is by extraction — high-speed counter-current chromatography delivers amorfrutins A and B at >96% purity from the hexane-soluble fruit extract in a single step ^{8Reference 8Chen C et al. · 2015Isolation and purification of prenylated phenolics from Amorpha fruticosa by high-speed counter-current chromatographyView study →} — or by total synthesis. A unified route to amorfrutins A and C from commercially available 3,5-dimethoxybenzaldehyde was published in 2019, taking nine steps to amorfrutin A in 38% overall yield; the key step is a Claisen rearrangement of a mono-O-(1,1-dimethylallyl)resorcinol derivative to install the prenyl group at C3 ^{9Reference 9Fujita T et al. · 2019Unified total synthesis of amorfrutins A and C via the Claisen rearrangementView study →}.

There is no commercial production. Amorfrutin A is a research chemical.

Patents: not yet researched.

Toxicity & Safety

Amorfrutin A carries a low flag, which reflects an absence of adverse findings rather than a completed safety assessment.

Safety at a Glance

✅ Low / no toxicity

• No cytotoxicity at antibacterial concentrations. Screened against human cell lines alongside its MIC determination, amorfrutin A showed no detectable cytotoxicity, and no toxicity in the Galleria mellonella infection model ^{5Reference 5Lucidi M et al. · 2026In vitroAmorfrutin-A, a membrane-targeting phytochemical active against multidrug-resistant Staphylococcus aureus: In vitro and in vivo activity and mechanism of actionView study →}.
• No hepatotoxicity or fat gain in the mouse metabolic work — the specific liabilities of the synthetic PPARγ drugs were looked for and not found ^{1Reference 1Weidner C et al. · 2012AnimalAmorfrutins are potent antidiabetic dietary natural products — animal study in miceView study →}.
• PPARγ agonism is a systemic hormonal action. The receptor governs adipocyte differentiation, glucose handling, fluid balance and bone turnover; a selective profile in mice is not a demonstration that the human consequences of activating it are avoided.
• Membrane-active compounds warrant a selectivity check at systemic exposure. The anti-staphylococcal mechanism is physical disruption of a lipid bilayer, and the reassurance so far is culture-based ^{5Reference 5Lucidi M et al. · 2026In vitroAmorfrutin-A, a membrane-targeting phytochemical active against multidrug-resistant Staphylococcus aureus: In vitro and in vivo activity and mechanism of actionView study →}.
• No toxicology package exists. No genotoxicity, repeat-dose, reproductive or developmental study of the isolated molecule in any species.

Full Safety & Interactions Detail

What has been looked at. The antibacterial study assessed cytotoxicity in human cell lines and found none at active concentrations, and reported no in-vivo toxicity in Galleria mellonella ^{5Reference 5Lucidi M et al. · 2026In vitroAmorfrutin-A, a membrane-targeting phytochemical active against multidrug-resistant Staphylococcus aureus: In vitro and in vivo activity and mechanism of actionView study →}. The metabolic study specifically checked for the adverse effects that define the thiazolidinedione class — fat storage and hepatotoxicity — and reported neither in diet-induced obese or db/db mice ^{1Reference 1Weidner C et al. · 2012AnimalAmorfrutins are potent antidiabetic dietary natural products — animal study in miceView study →}. In serially passaged human skin fibroblasts, sub-micromolar amorfrutin-A improved rather than impaired long-term growth and stress tolerance ^{11Reference 11Sodagam L et al. · 2019In vitroPhytochemicals Rosmarinic Acid, Ampelopsin, and Amorfrutin-A Can Modulate Age-Related Phenotype of Serially Passaged Human Skin Fibroblasts in vitroView study →}.

What has not. There is no dedicated toxicology of any kind: no acute or repeat-dose study, no genotoxicity assay, no reproductive or developmental work, and no pharmacokinetics. Nothing here should be read as a safety clearance; it is a record of studies that were not looking for toxicity and did not stumble over any.

Interactions. No interaction study exists, and no cytochrome-P450 or transporter data have been published for amorfrutin A. The theoretical concern is pharmacodynamic rather than pharmacokinetic: a PPARγ agonist would be expected to add to the effects of glitazones and of glucose-lowering drugs generally.

Reproductive note. No reproductive or developmental toxicity data exist for the isolated molecule.

Source caveat as a safety point. Because the amorfrutins occur in a wild licorice, it is worth stating plainly that the caution attaching to ordinary licorice — the mineralocorticoid effect of glycyrrhizin — has nothing to do with this molecule and does not transfer. The commercial licorice species contain no amorfrutins, and amorfrutins are not glycyrrhizin ^{7Reference 7Chen C et al. · 2016Qualitative and quantitative analysis of amorfrutins, novel antidiabetic dietary natural products, by HPLCView study →}.

Dosage

There is no human dose. No amorfrutin preparation has been given to a person in a trial, and no supplement contains a standardised amount. The figures worth knowing are the research concentrations:

These are research figures, not a personal recommendation, and there is no established preparation of the source plant that would deliver a known amount.

References

1. Weidner C, de Groot JC, Prasad A, et al. (2012). Amorfrutins are potent antidiabetic dietary natural products — animal study in mice. Proc Natl Acad Sci U S A. https://pubmed.ncbi.nlm.nih.gov/22509006/
2. Shi H, Ma J, Mi C, et al. (2014). Amorfrutin A inhibits TNF-α-induced NF-κB activation and NF-κB-regulated target gene products — in vitro. Int Immunopharmacol. https://pubmed.ncbi.nlm.nih.gov/24785328/
3. Mi C, Ma J, Wang KS, et al. (2017). Amorfrutin A inhibits TNF-α induced JAK/STAT signaling, cell survival and proliferation of human cancer cells — in vitro with mouse xenograft. Immunopharmacol Immunotoxicol. https://pubmed.ncbi.nlm.nih.gov/28879797/
4. Yang Y, Shi L, Xu X, et al. (2025). Amorfrutin A ameliorates cerebral ischemia/reperfsion injury in vivo and in vitro via modulating Nrf2/HO-1 signaling pathway — animal model in rats. Korean J Physiol Pharmacol. https://pubmed.ncbi.nlm.nih.gov/40368848/
5. Lucidi M, Imperi F, Turi M, et al. (2026). Amorfrutin-A, a membrane-targeting phytochemical active against multidrug-resistant Staphylococcus aureus: In vitro and in vivo activity and mechanism of action. Phytomedicine. https://pubmed.ncbi.nlm.nih.gov/42235358/
6. Fuhr L, Rousseau M, Plauth A, et al. (2015). Amorfrutins Are Natural PPARγ Agonists with Potent Anti-inflammatory Properties — in vitro. J Nat Prod. https://pubmed.ncbi.nlm.nih.gov/25938459/
7. Chen C, Wu Y, Du L (2016). Qualitative and quantitative analysis of amorfrutins, novel antidiabetic dietary natural products, by HPLC. Pharm Biol. https://pubmed.ncbi.nlm.nih.gov/26004584/
8. Chen C, Wu Y, Chen Y, et al. (2015). Isolation and purification of prenylated phenolics from Amorpha fruticosa by high-speed counter-current chromatography. J Sep Sci. https://pubmed.ncbi.nlm.nih.gov/26041477/
9. Fujita T, Kuwahara S, Ogura Y (2019). Unified total synthesis of amorfrutins A and C via the Claisen rearrangement. Biosci Biotechnol Biochem. https://pubmed.ncbi.nlm.nih.gov/31130067/
10. Pollastro F, De Petrocellis L, Schiano-Moriello A, et al. (2017). Amorfrutin-type phytocannabinoids from Helichrysum umbraculigerum. Fitoterapia. https://pubmed.ncbi.nlm.nih.gov/28941742/
11. Sodagam L, Lewinska A, Kwasniewicz E, et al. (2019). Phytochemicals Rosmarinic Acid, Ampelopsin, and Amorfrutin-A Can Modulate Age-Related Phenotype of Serially Passaged Human Skin Fibroblasts in vitro. Front Genet. https://pubmed.ncbi.nlm.nih.gov/30847003/
12. Weidner C, Rousseau M, Micikas RJ, et al. (2016). Amorfrutin C Induces Apoptosis and Inhibits Proliferation in Colon Cancer Cells through Targeting Mitochondria — in vitro. J Nat Prod. https://pubmed.ncbi.nlm.nih.gov/26731300/
13. Serino E, Iannotti FA, Al-Hmadi HB, et al. (2023). PPARα/γ-Targeting Amorfrutin Phytocannabinoids from Aerial Parts of Glycyrrhiza foetida — in vitro. J Nat Prod. https://pubmed.ncbi.nlm.nih.gov/37940359/
14. Mitscher LA, Park YH, Alshamma A, et al. (1981). Amorfrutin A and B, bibenzyl antimicrobial agents from Amorpha fruticosa. Phytochemistry. https://doi.org/10.1016/0031-9422(81)85174-6
15. Samad MB, Hasan MN, Banarjee S, et al. (2017). PEG modification of Amorfrutin B from Amorpha fructicosa increases gastric absorption, circulation half-life and glucose uptake by T3T-L1 adipocytes — animal study. Biomed Pharmacother. https://pubmed.ncbi.nlm.nih.gov/28866418/

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