Maackiain

Maackiain at a Glance

Maackiain is a pterocarpan — an isoflavonoid-derived compound whose primary, best-understood role is as a phytoalexin: an antimicrobial defence molecule that legumes make (or accumulate) to resist fungal attack. It occurs in Sophora (the source of the Chinese herbs kushen and sanzukon), in Maackia — the genus it is named after — and in familiar legumes such as red clover and chickpea, often stored as its glucoside trifolirhizin.

Structurally it is the methylenedioxy analogue of medicarpin: the two molecules share the same pterocarpan skeleton, but where medicarpin carries a methoxy group, maackiain closes a methylenedioxy bridge across the same ring positions. That single distinction is what separates the two most-studied legume pterocarpan phytoalexins.

Its human pharmacology is worth stating plainly: all of it is preclinical. A steady stream of cell-culture and rodent studies report anti-inflammatory, anticancer, neuroprotective and antiallergic effects, but there are no clinical trials of maackiain, and its natural role — a plant antifungal — is not a human use. This page keeps the isolate-versus-plant line honest throughout.

Maackiain vs. Medicarpin

The compound-defining comparison is with medicarpin, the other archetypal legume pterocarpan phytoalexin. Both are built on the same tetracyclic pterocarpan core and both function as inducible antifungal defence compounds in legumes; the difference is one substitution pattern on the D-ring.

• Medicarpin carries a methoxy group (a 3-hydroxy-9-methoxy pattern) — the dominant phytoalexin of alfalfa and other Medicago species.
• Maackiain replaces that arrangement with a methylenedioxy bridge (a dioxole ring fused across the equivalent positions), the same benzodioxole motif seen in many plant natural products.

Biosynthetically the two diverge late in the pterocarpan pathway, and the extra ring changes maackiain’s antifungal spectrum and how pathogenic fungi metabolise it ^{6,12Reference 6Covert SF et al. · 1996A gene for maackiain detoxification from a dispensable chromosome of Nectria haematococcaView study →Reference 12Soby S et al. · 1997Oxidation of the phytoalexin maackiain to 6,6-dihydroxy-maackiain by Colletotrichum gloeosporioidesView study →}. Because they co-occur and interconvert conceptually in the same defence chemistry, the two are best read as a pair — maackiain being the “methylenedioxy medicarpin.”

What It's Used For

Maackiain’s native activity — antifungal defence — is the part of its pharmacology with a mechanistic, ecologically grounded story. Everything reported in a medical frame is early-stage: isolated-compound assays and animal models, with no human data.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. Every row here rests on preclinical work only; the antifungal row scores highest because it reflects maackiain’s documented biological function, not a human use.

01Antifungal / phytoalexin (plant defence)Shaky40%Documented legume defence role + fungal detoxification genes ^{6,12Reference 6Covert SF et al. · 1996A gene for maackiain detoxification from a dispensable chromosome of Nectria haematococcaView study →Reference 12Soby S et al. · 1997Oxidation of the phytoalexin maackiain to 6,6-dihydroxy-maackiain by Colletotrichum gloeosporioidesView study →}

02Anti-inflammatory / immunomodulatoryShaky33%Rodent sepsis, osteoclast, diabetic-kidney models (NF-κB, Nrf2/HO-1) ^{3,4,5Reference 3Liu Y et al. · 2020Maackiain dampens osteoclastogenesis via attenuating RANKL-stimulated NF-κB signalling pathway and NFATc1 activityView study →Reference 4Bai X et al. · 2022Maackiain protects against sepsis via activating AMPK/Nrf2/HO-1 pathwayView study →Reference 5Guo J et al. · 2021AnimalMaackiain protects the kidneys of type 2 diabetic rats via modulating the Nrf2/HO-1 and TLR4/NF-κB/caspase-3 pathwaysView study →}

03Anticancer (preclinical)Shaky29%In-vitro apoptosis (leukaemia) + cell/animal cancer models ^{2,7,8,10Reference 2Aratanechemuge Y et al. · 2004Induction of apoptosis by maackiain and trifolirhizin (maackiain glycoside) isolated from sanzukon in human promyelotic leukemia HL-60 cellsView study →Reference 7He J et al. · 2024Maackiain suppresses the development of cervical cancer via AMPK priming autophagyView study →Reference 8Peng F et al. · 2022Maackiain modulates miR-374a/GADD45A axis to inhibit triple-negative breast cancer initiation and progressionView study →Reference 10Kuo YH et al. · 2022A novel splice variant of BCAS1 inhibits β-arrestin 2 to promote the proliferation and migration of glioblastoma cells, and this effect was blocked by maackiainView study →}

04Neuroprotective (preclinical)Shaky25%Cell/rodent Parkinson’s and amyloid-beta models ^{9,11Reference 9Tsai RT et al. · 2020Maackiain ameliorates 6-hydroxydopamine and SNCA pathologies by modulating the PINK1/Parkin pathway in models of Parkinson’s diseaseView study →Reference 11Lu N et al. · 2022Maackiain prevents amyloid-beta-induced cellular injury via priming PKC-Nrf2 pathwayView study →}

05Antiallergic (preclinical)Shaky22%Cell-based H1-receptor / IL-4 suppression via Hsp90–PKCδ ^{13,14Reference 13Mizuguchi H et al. · 2015Maackiain is a novel antiallergic compound that suppresses transcriptional upregulation of the histamine H1 receptor and interleukin-4 genesView study →Reference 14Nariai Y et al. · 2015Disruption of heat shock protein 90 (Hsp90)–protein kinase Cδ (PKCδ) interaction by (-)-maackiain suppresses histamine H1 receptor gene transcriptionView study →}

Mechanisms

The through-line is a set of generic cytoprotective/inflammatory hubs (NF-κB, Nrf2, AMPK) hit by an isolated compound in disparate models — a common signature of an under-characterised natural product, not a validated drug mechanism.

Pharmacokinetics

Maackiain has low oral bioavailability, poor absorption and rapid elimination ^{15,17Reference 15Haider W et al. · 2025ReviewMaackiain: a comprehensive review of its pharmacology, synthesis, pharmacokinetics and toxicityView study →Reference 17Yoo H et al. · 2014AnimalSimultaneous determination of trifolirhizin, (-)-maackiain, (-)-sophoranone, and related compounds from Sophora tonkinensis in rat plasma by LC-MS/MSView study →}. In rat studies of Sophora tonkinensis extract, maackiain and its glycoside trifolirhizin showed non-linear (saturable) gastrointestinal absorption across escalating oral doses ^{16,17Reference 16Jang SM et al. · 2015AnimalPharmacokinetic properties of trifolirhizin, (-)-maackiain, (-)-sophoranone and 2-(2,4-dihydroxyphenyl)-5,6-methylenedioxybenzofuran after intravenous and oral administration of Sophora tonkinensis extract in ratsView study →Reference 17Yoo H et al. · 2014AnimalSimultaneous determination of trifolirhizin, (-)-maackiain, (-)-sophoranone, and related compounds from Sophora tonkinensis in rat plasma by LC-MS/MSView study →}, and — notably — maackiain was absorbed better from the whole extract than as the pure compound, attributed to increased solubility and reduced metabolism by co-occurring extract components ^{16,17Reference 16Jang SM et al. · 2015AnimalPharmacokinetic properties of trifolirhizin, (-)-maackiain, (-)-sophoranone and 2-(2,4-dihydroxyphenyl)-5,6-methylenedioxybenzofuran after intravenous and oral administration of Sophora tonkinensis extract in ratsView study →Reference 17Yoo H et al. · 2014AnimalSimultaneous determination of trifolirhizin, (-)-maackiain, (-)-sophoranone, and related compounds from Sophora tonkinensis in rat plasma by LC-MS/MSView study →}. Quantitative human PK is not established.

Clinical Trials

There are no clinical trials of maackiain. The entire evidence base is cell-culture and rodent work; the compound is not in human development as an isolate.

Last checked: July 2026.

Isolate vs. Plant Studies

Nearly all maackiain research uses the isolated molecule, typically purified from Sophora flavescens (kushen), Sophora tonkinensis or the crude drug sanzukon ^{2,9,13Reference 2Aratanechemuge Y et al. · 2004Induction of apoptosis by maackiain and trifolirhizin (maackiain glycoside) isolated from sanzukon in human promyelotic leukemia HL-60 cellsView study →Reference 9Tsai RT et al. · 2020Maackiain ameliorates 6-hydroxydopamine and SNCA pathologies by modulating the PINK1/Parkin pathway in models of Parkinson’s diseaseView study →Reference 13Mizuguchi H et al. · 2015Maackiain is a novel antiallergic compound that suppresses transcriptional upregulation of the histamine H1 receptor and interleukin-4 genesView study →}. That means the pharmacology is genuinely about maackiain rather than about a whole extract — but it also means there is no human whole-plant evidence tying these effects back to any traditional or clinical use. Sophora flavescens itself is a well-used herb, yet its activity is a composite of alkaloids (matrine, oxymatrine) and multiple flavonoids, so its effects cannot be attributed to maackiain. The one repeatedly noted plant-versus-isolate wrinkle is pharmacokinetic: maackiain is absorbed more efficiently from the extract matrix than as the pure compound ^{16,17Reference 16Jang SM et al. · 2015AnimalPharmacokinetic properties of trifolirhizin, (-)-maackiain, (-)-sophoranone and 2-(2,4-dihydroxyphenyl)-5,6-methylenedioxybenzofuran after intravenous and oral administration of Sophora tonkinensis extract in ratsView study →Reference 17Yoo H et al. · 2014AnimalSimultaneous determination of trifolirhizin, (-)-maackiain, (-)-sophoranone, and related compounds from Sophora tonkinensis in rat plasma by LC-MS/MSView study →} — a caveat that cuts against dosing it as a purified isolate.

Its Role in Plants

Maackiain is a phytoalexin — a compound that legumes synthesise or accumulate in response to fungal attack, and one of the classic model pterocarpans in plant-pathology research alongside medicarpin and pisatin. It is antifungal to a range of legume and non-legume pathogens, and appears both constitutively (in the heartwood of legume trees) and as an inducible defence in herbaceous species such as chickpea ^{6,12Reference 6Covert SF et al. · 1996A gene for maackiain detoxification from a dispensable chromosome of Nectria haematococcaView study →Reference 12Soby S et al. · 1997Oxidation of the phytoalexin maackiain to 6,6-dihydroxy-maackiain by Colletotrichum gloeosporioidesView study →}.

The molecular arms race around it is well documented: successful pathogens deploy specific detoxification enzymes, such as the Nectria haematococca MAK1 gene product that converts maackiain to a less-toxic form, and oxidative modification by Colletotrichum species ^{6,12Reference 6Covert SF et al. · 1996A gene for maackiain detoxification from a dispensable chromosome of Nectria haematococcaView study →Reference 12Soby S et al. · 1997Oxidation of the phytoalexin maackiain to 6,6-dihydroxy-maackiain by Colletotrichum gloeosporioidesView study →}. In the plant, maackiain is frequently stored as its 3-O-glucoside trifolirhizin (and as malonyl-glucoside conjugates), the inactive storage forms that are mobilised on demand ^{2,18Reference 2Aratanechemuge Y et al. · 2004Induction of apoptosis by maackiain and trifolirhizin (maackiain glycoside) isolated from sanzukon in human promyelotic leukemia HL-60 cellsView study →Reference 18Stocker P et al. · 2005Maackiain 3-O-(6’-O-malonyl-beta-D-glucopyranoside) from Oudneya africana, a powerful inhibitor of porcine kidney acylase IView study →}.

These are plant-biology functions and should not be read as human pharmacology — a molecule’s role as an antifungal phytoalexin does not predict what it does as a medicine.

Prevalence in Nature

Maackiain is distributed across the legume family (Fabaceae). It is a signature constituent of Sophora — richest in the xylem of Sophora flavescens (kushen) and present in Sophora tonkinensis (Vietnamese sophora / sanzukon) — and lends its name to the genus Maackia (e.g. Maackia amurensis) ^{9,17Reference 9Tsai RT et al. · 2020Maackiain ameliorates 6-hydroxydopamine and SNCA pathologies by modulating the PINK1/Parkin pathway in models of Parkinson’s diseaseView study →Reference 17Yoo H et al. · 2014AnimalSimultaneous determination of trifolirhizin, (-)-maackiain, (-)-sophoranone, and related compounds from Sophora tonkinensis in rat plasma by LC-MS/MSView study →}. It also occurs in red clover (Trifolium pratense) — alongside the estrogenic isoflavones formononetin, daidzein and biochanin A — in chickpea (Cicer arietinum) as an induced phytoalexin, and in Spatholobus suberectus, Caragana and Millettia species ^{6,8Reference 6Covert SF et al. · 1996A gene for maackiain detoxification from a dispensable chromosome of Nectria haematococcaView study →Reference 8Peng F et al. · 2022Maackiain modulates miR-374a/GADD45A axis to inhibit triple-negative breast cancer initiation and progressionView study →}.

In plants it is commonly present not as the free aglycone but as glycosides — chiefly trifolirhizin (maackiain 3-O-β-D-glucoside) — and as malonyl-glucoside conjugates such as the acylase-inhibitory maackiain 3-O-(6′-O-malonyl-glucoside) isolated from Oudneya africana ^{2,18Reference 2Aratanechemuge Y et al. · 2004Induction of apoptosis by maackiain and trifolirhizin (maackiain glycoside) isolated from sanzukon in human promyelotic leukemia HL-60 cellsView study →Reference 18Stocker P et al. · 2005Maackiain 3-O-(6’-O-malonyl-beta-D-glucopyranoside) from Oudneya africana, a powerful inhibitor of porcine kidney acylase IView study →}. Absolute concentrations across these sources are not well quantified in the literature, so no comparative content figures are given here.

Discovery & Synthesis

Maackiain was characterised as a legume pterocarpan in the mid-twentieth century — historically also called inermin in the Sophora literature — and takes its common name from the genus Maackia. Much of its early profile came not from drug discovery but from plant pathology, where it and medicarpin became reference phytoalexins for studying how legumes resist fungi and how fungi detoxify plant defences ^{6,12Reference 6Covert SF et al. · 1996A gene for maackiain detoxification from a dispensable chromosome of Nectria haematococcaView study →Reference 12Soby S et al. · 1997Oxidation of the phytoalexin maackiain to 6,6-dihydroxy-maackiain by Colletotrichum gloeosporioidesView study →}. The natural product is the levorotatory (-)-(6aR,11aR) enantiomer, and its biosynthesis proceeds through the isoflavonoid/pterocarpan pathway — the isoflavone formononetin is an upstream precursor — with the characteristic methylenedioxy bridge installed late to distinguish it from medicarpin.

Manufacture today is by extraction from Sophora and related legumes (often via hydrolysis of the abundant glycoside trifolirhizin) rather than by commercial total synthesis; pterocarpans of this type have been prepared synthetically, but maackiain is not produced industrially at scale, consistent with its research-only status.

Patents: not yet researched.

Toxicity & Safety

Maackiain carries a low toxicity flag. It is a dietary pterocarpan — humans ingest it incidentally in legumes such as chickpea and red clover — and no notable toxicity signal has been reported for it. That said, the low rating reflects an absence of dedicated human safety data as much as any positive evidence of safety: the compound has only ever been studied preclinically, so its rating should be read as “no signal of harm at dietary/experimental exposure,” not as a cleared safety profile.

Safety at a Glance

✅ Low / no toxicity

• Dietary pterocarpan. Consumed incidentally in legumes (chickpea, red clover) with no reported toxicity at food-level exposure.
• Preclinical-only compound. No human safety, drug-interaction or repeat-dose data exist; effects are known only from cell and rodent studies.
• Low oral bioavailability. Poor absorption and rapid elimination mean isolated-compound findings may not translate to meaningful human exposure.
• Reproductive/interaction data not assessed. No developmental-toxicity or CYP/transporter interaction studies have been done on isolated maackiain.

No comprehensive isolate genotoxicity, repeat-dose or reproductive-toxicity package has been characterised for maackiain, and no drug-interaction studies (CYP isoforms, transporters) have been reported. Pregnancy and lactation decisions belong to the herb or product a person actually takes, not to this molecule page; the finding here is simply that dedicated data do not exist.

Dosage

There is no established human dose for maackiain. It is not sold or used as a stand-alone therapeutic, and every reported effect comes from cell-culture or rodent studies where doses are given in mg/kg and do not translate to people. Its low oral bioavailability further complicates any attempt to infer a human dose from animal work ^{15,17Reference 15Haider W et al. · 2025ReviewMaackiain: a comprehensive review of its pharmacology, synthesis, pharmacokinetics and toxicityView study →Reference 17Yoo H et al. · 2014AnimalSimultaneous determination of trifolirhizin, (-)-maackiain, (-)-sophoranone, and related compounds from Sophora tonkinensis in rat plasma by LC-MS/MSView study →}. Dietary exposure — via legumes such as chickpea and red clover — is incidental and unquantified. These are experimental research parameters, not a personal recommendation.

References

1. Huh JW, et al. (2020). Maackiain, a compound derived from Sophora flavescens, increases IL-1β production by amplifying nigericin-mediated inflammasome activation. FEBS Open Bio. https://pubmed.ncbi.nlm.nih.gov/32428336/
2. Aratanechemuge Y, et al. (2004). Induction of apoptosis by maackiain and trifolirhizin (maackiain glycoside) isolated from sanzukon in human promyelotic leukemia HL-60 cells. Oncology Reports. https://pubmed.ncbi.nlm.nih.gov/15547735/
3. Liu Y, et al. (2020). Maackiain dampens osteoclastogenesis via attenuating RANKL-stimulated NF-κB signalling pathway and NFATc1 activity. Journal of Cellular and Molecular Medicine. https://pubmed.ncbi.nlm.nih.gov/32939977/
4. Bai X, et al. (2022). Maackiain protects against sepsis via activating AMPK/Nrf2/HO-1 pathway. International Immunopharmacology. https://pubmed.ncbi.nlm.nih.gov/35405595/
5. Guo J, et al. (2021). Maackiain protects the kidneys of type 2 diabetic rats via modulating the Nrf2/HO-1 and TLR4/NF-κB/caspase-3 pathways. Drug Design, Development and Therapy. https://pubmed.ncbi.nlm.nih.gov/34703210/
6. Covert SF, Enkerli J, Miao VP, VanEtten HD (1996). A gene for maackiain detoxification from a dispensable chromosome of Nectria haematococca. Molecular and General Genetics. https://pubmed.ncbi.nlm.nih.gov/8709942/
7. He J, et al. (2024). Maackiain suppresses the development of cervical cancer via AMPK priming autophagy. Journal of Pharmacy and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/37934902/
8. Peng F, et al. (2022). Maackiain modulates miR-374a/GADD45A axis to inhibit triple-negative breast cancer initiation and progression. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/35308218/
9. Tsai RT, et al. (2020). Maackiain ameliorates 6-hydroxydopamine and SNCA pathologies by modulating the PINK1/Parkin pathway in models of Parkinson’s disease. International Journal of Molecular Sciences. https://pubmed.ncbi.nlm.nih.gov/32585871/
10. Kuo YH, et al. (2022). A novel splice variant of BCAS1 inhibits β-arrestin 2 to promote the proliferation and migration of glioblastoma cells, and this effect was blocked by maackiain. Cancers. https://pubmed.ncbi.nlm.nih.gov/36010884/
11. Lu N, et al. (2022). Maackiain prevents amyloid-beta-induced cellular injury via priming PKC-Nrf2 pathway. BioMed Research International. https://pubmed.ncbi.nlm.nih.gov/35782063/
12. Soby S, Bates R, VanEtten H (1997). Oxidation of the phytoalexin maackiain to 6,6-dihydroxy-maackiain by Colletotrichum gloeosporioides. Phytochemistry. https://pubmed.ncbi.nlm.nih.gov/9214775/
13. Mizuguchi H, et al. (2015). Maackiain is a novel antiallergic compound that suppresses transcriptional upregulation of the histamine H1 receptor and interleukin-4 genes. Pharmacology Research & Perspectives. https://pubmed.ncbi.nlm.nih.gov/26516579/
14. Nariai Y, et al. (2015). Disruption of heat shock protein 90 (Hsp90)–protein kinase Cδ (PKCδ) interaction by (-)-maackiain suppresses histamine H1 receptor gene transcription. Journal of Biological Chemistry. https://pubmed.ncbi.nlm.nih.gov/26391399/
15. Haider W, et al. (2025). Maackiain: a comprehensive review of its pharmacology, synthesis, pharmacokinetics and toxicity. Chemico-Biological Interactions. https://pubmed.ncbi.nlm.nih.gov/39477181/
16. Jang SM, et al. (2015). Pharmacokinetic properties of trifolirhizin, (-)-maackiain, (-)-sophoranone and 2-(2,4-dihydroxyphenyl)-5,6-methylenedioxybenzofuran after intravenous and oral administration of Sophora tonkinensis extract in rats. Xenobiotica. https://pubmed.ncbi.nlm.nih.gov/26068519/
17. Yoo H, et al. (2014). Simultaneous determination of trifolirhizin, (-)-maackiain, (-)-sophoranone, and related compounds from Sophora tonkinensis in rat plasma by LC-MS/MS. Journal of Separation Science. https://pubmed.ncbi.nlm.nih.gov/25156071/
18. Stocker P, et al. (2005). Maackiain 3-O-(6’-O-malonyl-beta-D-glucopyranoside) from Oudneya africana, a powerful inhibitor of porcine kidney acylase I. Biochimie. https://pubmed.ncbi.nlm.nih.gov/15935275/

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