Casuarinin

Casuarinin at a Glance

Casuarinin is a C-glycosidic ellagitannin — a hydrolysable tannin in which the glucose core has been prised open from its usual ring form and bolted directly to a polyphenol ring by a carbon–carbon bond ^{1,4Reference 1Okuda T et al. · 1983Tannins of Casuarina and Stachyurus speciesView study →Reference 4Yoshida T et al. · 2010ReviewStructural features and biological properties of ellagitannins in some plant families of the order Myrtales — reviewView study →}. Its formula is C₄₁H₂₈O₂₆ and its molecular weight 936.6 Da ^{3Reference 3National Center for Biotechnology InformPubChem Compound Summary for CID 13834145, CasuarininView study →}, which makes it roughly half the size of sanguiin H-6 and a third the size of lambertianin C — still far too large to be absorbed, but small enough to be a discrete, synthesisable, testable molecule rather than a chromatographic smear.

Two things make it worth a page. The first is where it sits in raspberry. Our source herb is raspberry leaf, not fruit, and the ellagitannin the site has been describing — sanguiin H-6, the dimer that dominates the berry — has never been given a published figure in raspberry leaf. The one quantitative analysis of a raspberry-leaf polyphenol extract found casuarinin, not sanguiin H-6 and not lambertianin C, as the single largest component, at about 83% of all identified phenolics ^{5Reference 5Cyboran-Mikołajczyk S et al. · 2022Protection of erythrocytes and microvascular endothelial cells against oxidative damage by Fragaria vesca L. and Rubus idaeus L. leaves extracts — the mechanism of actionView study →}. If that assignment holds, the compound doing the astringent work in a cup of raspberry-leaf tea is this one.

The second is that casuarinin has more of its own pharmacology than any other molecule in this family. Where the Rubus oligomers offer cell-culture assays and hopeful attribution, casuarinin has a dose-dependent rat gastroprotection study using the purified compound ^{10Reference 10Al-Sayed E et al. · 2020AnimalProtective role of casuarinin from Melaleuca leucadendra against ethanol-induced gastric ulcer in ratsView study →}, a mouse chemotherapy-mucositis study using the purified compound ^{11Reference 11Chen KJ et al. · 2022AnimalProtective role of casuarinin from Melastoma malabathricum against a mouse model of 5-fluorouracil-induced intestinal mucositis — impact on inflammation and gut microbiota dysbiosisView study →}, a genuine antiviral selectivity index ^{7Reference 7Cheng HY et al. · 2002Antiherpes simplex virus type 2 activity of casuarinin from the bark of Terminalia arjuna LinnView study →}, an acetylcholinesterase IC₅₀ in the nanomolar range ^{15Reference 15Orabi MAA et al. · 2023Structural determination and anticholinesterase assay of C-glycosidic ellagitannins from Lawsonia inermis leaves — a study supported by DFT calculations and molecular dockingView study →}, and — most unusually for anything in this chemical class — two placebo-controlled human trials of an extract standardised to its content ^{13,14Reference 13Sawada S et al. · 2025RCTLemon myrtle extract enhances muscle hypertrophy induced by low-load bodyweight resistance training in older adults — findings from two independent randomized controlled trialsView study →Reference 14Mitsuhashi R et al. · 2026RCTLow-dose lemon myrtle supplementation enhances muscle hypertrophy in older adults undergoing low-load resistance training — a randomized controlled trialView study →}. Those trials are small, industry-funded and measure an extract rather than the molecule, and they are dealt with honestly below. But they exist, which is more than can be said for most of the hydrolysable tannins.

Casuarinin Is Not Casuarictin

This has to come first, because the two names are one letter apart, the two molecules have the same molecular formula and the same molecular weight, and they were named in the same 1983 paper, from the same plant, by the same four chemists ^{1Reference 1Okuda T et al. · 1983Tannins of Casuarina and Stachyurus speciesView study →}.

	Casuarinin	Casuarictin
Formula / mass	C41H28O26, 936.6 Da	C41H28O26, 936.6 Da
Glucose core	open-chain	pyranose ring (β-D-glucopyranose)
Linkage to glucose	one C-glycosidic (C–C) bond, plus ester bonds	ester bonds only
Groups carried	two (S)-HHDP + one galloyl	two (S)-HHDP + one galloyl
Family it belongs to	C-glycosidic ellagitannins — with castalagin, vescalagin, stachyurin, casuariin	simple monomeric ellagitannins — with pedunculagin, tellimagrandin II
What it leads to	castalagin and vescalagin (oxidative closure); the salicarinin dimers	sanguiin H-6 → lambertianin C (oligomerisation)

They are structural isomers with the same atoms arranged differently, and biogenetically they are parent and daughter: casuarictin’s glucose ring opens and forms the C-glycosidic bond, producing casuarinin and its C-1 epimer stachyurin ^{4,17Reference 4Yoshida T et al. · 2010ReviewStructural features and biological properties of ellagitannins in some plant families of the order Myrtales — reviewView study →Reference 17Kusuki R et al. · 2023Divergent synthesis of stachyurin and casuarinin focusing on C-glycosidic bond reactivityView study →}. That the two are epimers rather than synonyms is not a detail — a 2023 synthesis paper is devoted specifically to making both stereoisomers and exploring how the C-glycosidic bond’s reactivity differs between them ^{17Reference 17Kusuki R et al. · 2023Divergent synthesis of stachyurin and casuarinin focusing on C-glycosidic bond reactivityView study →}. Reference works that list casuarinin as “also known as stachyurin” are wrong; Okuda’s 1983 paper named casuarinin, casuariin and stachyurin as three separate compounds from one extract ^{1Reference 1Okuda T et al. · 1983Tannins of Casuarina and Stachyurus speciesView study →}.

The practical consequence is an analytical one, and it matters for every concentration figure here. Casuarinin and casuarictin are indistinguishable by mass. An LC-MS peak at m/z 935 in a plant extract, assigned by mass and retention time without an authentic standard, cannot tell them apart — and neither can it separate casuarinin from stachyurin, which is a true stereoisomer. Where you see a large casuarinin figure below, check what the study actually calibrated against.

The Raspberry-Leaf Question

Two pages here — sanguiin H-6 and lambertianin C — had to close with the same admission: Rubus idaeus leaf has no published figure for either compound. The fruit is well characterised, the young shoots have been quantified, but the leaf, which is the part actually made into tea, has not. Casuarinin partly closes that gap, and the way it closes it is worth setting out precisely, because the numbers are easy to misuse.

What was measured. A 2022 Polish study prepared purified polyphenol extracts from raspberry leaf and wild-strawberry leaf — water with 200 ppm SO₂, adsorbed onto Purolite AP400 resin, eluted with 80% ethanol, freeze-dried — and profiled them by HPLC-DAD and UPLC-ESI-MS. In the raspberry-leaf extract, the compound listed as “ellagitannins hex (casuarinin)” came in at 483.33 mg/g, against a total identified phenolic content of 581.88 mg/g. The authors state plainly that casuarinin is “the main component in both extracts”, making up approximately 83% of raspberry’s and 64% of wild strawberry’s identified phenolics ^{5Reference 5Cyboran-Mikołajczyk S et al. · 2022Protection of erythrocytes and microvascular endothelial cells against oxidative damage by Fragaria vesca L. and Rubus idaeus L. leaves extracts — the mechanism of actionView study →}. Lambertianin C was recorded at zero in raspberry leaf and 267.98 mg/g in wild strawberry leaf; sanguiin H-6 was not among the targets at all ^{5Reference 5Cyboran-Mikołajczyk S et al. · 2022Protection of erythrocytes and microvascular endothelial cells against oxidative damage by Fragaria vesca L. and Rubus idaeus L. leaves extracts — the mechanism of actionView study →}.

Three caveats, all load-bearing.

• This is milligrams per gram of extract, not of leaf. The material was concentrated on resin and stripped of everything that did not bind. Nothing in the paper converts it back to a leaf-content figure, and it must not be read as “raspberry leaf is 48% casuarinin”. The gap our other pages flagged is narrowed, not closed.
• The compound label is a mass assignment, not a standard. The row is headed “ellagitannins hex”, the identification method is the same laboratory’s earlier LC-MS protocol, and no calibration against authentic casuarinin is described ^{5Reference 5Cyboran-Mikołajczyk S et al. · 2022Protection of erythrocytes and microvascular endothelial cells against oxidative damage by Fragaria vesca L. and Rubus idaeus L. leaves extracts — the mechanism of actionView study →}. Given the isomer problem above, that is a real limit.
• The one dedicated raspberry-leaf polyphenol survey does not find it. A 2025 LC-MS/MS study of six raspberry-leaf samples quantified the ellagitannin fraction as ellagic acid after hydrolysis (155–394 mg/100 g) and does not report casuarinin among its targets ^{16Reference 16Alkhudaydi HMS et al. · 2025Determination of the polyphenol composition of raspberry leaf using LC-MS/MSView study →}.

What corroborates it. The same laboratory’s earlier survey of 26 wild Rubus (blackberry) leaf samples quantified casuarinin directly in dried plant material at 34.8–117.9 mg/g of dry matter, mean around 77 mg/g — alongside lambertianin C (5.7–123.4 mg/g) and sanguiin H-6 (not detected to 73.9 mg/g) ^{6Reference 6Oszmiański J et al. · 2015Determination of phenolic compounds and antioxidant activity in leaves from wild Rubus L. speciesView study →}. On those numbers casuarinin has the highest average of the three across wild Rubus leaf, even though the paper’s prose lists sanguiin H-6 first. Independently, in sea-buckthorn leaf — an unrelated genus in an unrelated family — stachyurin and casuarinin are the two most abundant ellagitannins ^{18,39Reference 18Suvanto J et al. · 2018Variability in foliar ellagitannins of Hippophaë rhamnoides L. and identification of a new ellagitannin, hippophaenin CView study →Reference 39Ma X et al. · 2019Phenolic compounds and antioxidant activities of tea-type infusions processed from sea buckthorn (Hippophaë rhamnoides) leavesView study →}, which is at least consistent with C-glycosidic ellagitannins being a leaf story rather than a fruit one.

The honest summary: in Rubus, the fruit is a sanguiin H-6 / lambertianin C material and the leaf appears to be a casuarinin material. That distinction has been reported by one laboratory, twice, using one analytical method, without an authentic standard — which is enough to change what we say about raspberry leaf, and not enough to state as settled.

What It's Used For

Unusually for a large polyphenol, the strongest evidence here is in vivo and uses the purified compound. Three separate rodent studies dosed isolated casuarinin orally; two of them are gut-surface models where a non-absorbed molecule can plausibly act.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume, and capped where the finding belongs to an extract rather than the pure molecule. A beta, not a validated metric. Note that the top two rows are held up by in-vivo work on the purified compound, which is unusual for a hydrolysable tannin and is the reason it scores higher than its oligomeric relatives.

01Gastroprotection & gut mucosaPromising46%Two rodent studies of the purified isolate, one with a clean 25/50/100 mg/kg dose–response ^{10,11Reference 10Al-Sayed E et al. · 2020AnimalProtective role of casuarinin from Melaleuca leucadendra against ethanol-induced gastric ulcer in ratsView study →Reference 11Chen KJ et al. · 2022AnimalProtective role of casuarinin from Melastoma malabathricum against a mouse model of 5-fluorouracil-induced intestinal mucositis — impact on inflammation and gut microbiota dysbiosisView study →}

02Muscle & satellite-cell activationShaky38%Three human RCT arms of a casuarinin-standardised extract + rat and cell mechanism, all one sponsor ^{12,13,14Reference 12Yamamoto A et al. · 2022In vitroLemon myrtle (Backhousia citriodora) extract and its active compound, casuarinin, activate skeletal muscle satellite cells in vitro and in vivoView study →Reference 13Sawada S et al. · 2025RCTLemon myrtle extract enhances muscle hypertrophy induced by low-load bodyweight resistance training in older adults — findings from two independent randomized controlled trialsView study →Reference 14Mitsuhashi R et al. · 2026RCTLow-dose lemon myrtle supplementation enhances muscle hypertrophy in older adults undergoing low-load resistance training — a randomized controlled trialView study →}

03Anti-inflammatory & skinShaky33%Isolate in vitro across keratinocytes, macrophages and colon epithelium; supporting in-vivo markers ^{10,19,20,21,24Reference 10Al-Sayed E et al. · 2020AnimalProtective role of casuarinin from Melaleuca leucadendra against ethanol-induced gastric ulcer in ratsView study →Reference 19Kwon DJ et al. · 2011Casuarinin suppresses TNF-α-induced ICAM-1 expression via blockade of NF-κB activation in HaCaT cellsView study →Reference 20Kwon DJ et al. · 2012Casuarinin suppresses TARC/CCL17 and MDC/CCL22 production via blockade of NF-κB and STAT1 activation in HaCaT cellsView study →Reference 21Yang GX et al. · 2014Chemical constituents from Melastoma dodecandrum and their inhibitory activity on interleukin-8 production in HT-29 cellsView study →Reference 24Ishii R et al. · 1999AnimalInhibitory effects of hydrolyzable tannins from Melastoma dodecandrum Lour. on nitric oxide production by a murine macrophage-like cell line, RAW264.7, activated with lipopolysaccharide and interferon-γView study →}

04AntiviralShaky28%One well-designed in-vitro study with CC₅₀, SI and time-of-addition data; never followed into an animal ^{7Reference 7Cheng HY et al. · 2002Antiherpes simplex virus type 2 activity of casuarinin from the bark of Terminalia arjuna LinnView study →}

05Enzyme inhibitionShaky24%Cell-free potency across AChE, elastase, α-glucosidase, carbonic anhydrase, LOX — mostly single reports ^{15,11,27,22,25Reference 15Orabi MAA et al. · 2023Structural determination and anticholinesterase assay of C-glycosidic ellagitannins from Lawsonia inermis leaves — a study supported by DFT calculations and molecular dockingView study →Reference 11Chen KJ et al. · 2022AnimalProtective role of casuarinin from Melastoma malabathricum against a mouse model of 5-fluorouracil-induced intestinal mucositis — impact on inflammation and gut microbiota dysbiosisView study →Reference 27Wubshet SG et al. · 2015High-resolution bioactivity profiling combined with HPLC-HRMS-SPE-NMR — α-glucosidase inhibitors and acetylated ellagic acid rhamnosides from Myrcia palustris DCView study →Reference 22Satomi H et al. · 1993Carbonic anhydrase inhibitors from the pericarps of Punica granatum LView study →Reference 25Yamada P et al. · 2012Inhibitory effect of tannins from galls of Carpinus tschonoskii on the degranulation of RBL-2H3 cellsView study →}

06Anticancer (in vitro)Shaky20%Cell culture only, no selectivity index, no animal tumour model ^{8,9,23,26Reference 8Kuo PL et al. · 2005Induction of cell cycle arrest and apoptosis in human non-small cell lung cancer A549 cells by casuarinin from the bark of Terminalia arjuna LinnView study →Reference 9Kuo PL et al. · 2005Casuarinin from the bark of Terminalia arjuna induces apoptosis and cell cycle arrest in human breast adenocarcinoma MCF-7 cellsView study →Reference 23Yang LL et al. · 2000Induction of apoptosis by hydrolyzable tannins from Eugenia jambos L. on human leukemia cellsView study →Reference 26Liu H et al. · 2009Fatty acid synthase inhibitors from Geum japonicum Thunb. var. chinenseView study →}

Mechanisms

The last row is the one to hold onto. Casuarinin’s two most convincing in-vivo results are both luminal — stomach lining and intestinal crypt — where a non-absorbed molecule reaches high local concentration by definition. The systemic results (rat myocardium, skeletal muscle) require an absorbed species that nobody has identified.

Pharmacokinetics

There is no pharmacokinetic study of casuarinin. No plasma concentration, no half-life, no oral bioavailability figure, and no identification of the compound or a conjugate in human blood or urine. What can be said is structural and inferential.

At 936 Da with 26 oxygens it is well outside the range for passive intestinal absorption — smaller than sanguiin H-6 (1,871 Da) and lambertianin C (2,806 Da), but not smaller in any way that changes the conclusion. Its C-glycosidic bond makes it more chemically robust than its ester-linked relatives: that carbon–carbon link cannot be hydrolysed, so the glucose stays attached, and only the ester-linked HHDP group can be released as ellagic acid. Casuarinin is therefore a partial ellagic acid donor, not a full one.

The downstream route is the class route. Ex-vivo culture of fifteen ellagitannins with human gut microbiota showed that those carrying HHDP groups are metabolised to urolithins, with the rate depending on the individual donor’s microbiota ^{37Reference 37Piwowarski JP et al. · 2016Differences in metabolism of ellagitannins by human gut microbiota ex vivo culturesView study →}; the closest structural analogues to casuarinin — castalagin and vescalagin, also C-glycosidic — are converted to urolithins A and C in the same system ^{38Reference 38Granica S et al. · 2020Lythrum salicaria ellagitannins stimulate IPEC-J2 cells monolayer formation and inhibit enteropathogenic Escherichia coli growth and adhesionView study →}; and a raspberry-leaf infusion incubated with human faecal microbiota yields urolithins A, B and C ^{40Reference 40Piwowarski JP et al. · 2014Role of human gut microbiota metabolism in the anti-inflammatory effect of traditionally used ellagitannin-rich plant materialsView study →}. Humans sort into urolithin metabotypes A, B and 0, so the same herbal dose produces very different systemic exposure in different people ^{41Reference 41Tomás-Barberán FA et al. · 2014Ellagic acid metabolism by human gut microbiota — consistent observation of three urolithin phenotypes in intervention trials, independent of food source, age and health statusView study →}. Nobody has fed casuarinin, alone, to anything and looked for what came out.

The practical reading: casuarinin’s demonstrated actions in the stomach and intestine are pharmacologically reachable at herbal doses. Its demonstrated actions anywhere else are not — unless a metabolite is doing the work, and no one has shown which.

Clinical Trials

No trial has administered isolated casuarinin to a human being. Three published randomised, placebo-controlled, double-blind arms have administered a lemon-myrtle leaf extract standardised to casuarinin content to Japanese adults aged 65 and over, paired with low-load bodyweight resistance training ^{13,14Reference 13Sawada S et al. · 2025RCTLemon myrtle extract enhances muscle hypertrophy induced by low-load bodyweight resistance training in older adults — findings from two independent randomized controlled trialsView study →Reference 14Mitsuhashi R et al. · 2026RCTLow-dose lemon myrtle supplementation enhances muscle hypertrophy in older adults undergoing low-load resistance training — a randomized controlled trialView study →}.

Trial	n	Dose	Duration	Primary result
Sawada 2025, study 1	47	2.5 mg/day casuarinin (extract)	12 wk	Thigh thickness +14.9% vs +9.7%; p = 0.082, null
Sawada 2025, study 2	41	2.5 mg/day casuarinin (extract)	12 wk	+11.5% vs +5.4%; difference 1.59 mm, p < 0.05
Mitsuhashi 2026	60	1.25 mg/day casuarinin (extract)	12 wk + 6 wk detraining	Significantly greater thigh thickness gain; benefit lost during detraining

All three were funded by Kaneka Corporation, which supplied the product and employed three co-authors ^{13,14Reference 13Sawada S et al. · 2025RCTLemon myrtle extract enhances muscle hypertrophy induced by low-load bodyweight resistance training in older adults — findings from two independent randomized controlled trialsView study →Reference 14Mitsuhashi R et al. · 2026RCTLow-dose lemon myrtle supplementation enhances muscle hypertrophy in older adults undergoing low-load resistance training — a randomized controlled trialView study →}. Casuarinin was quantified by manufacturer specification and never measured in a participant. Secondary functional outcomes — walking speed, chair-stand — were flat throughout ^{13Reference 13Sawada S et al. · 2025RCTLemon myrtle extract enhances muscle hypertrophy induced by low-load bodyweight resistance training in older adults — findings from two independent randomized controlled trialsView study →}.

Last checked: August 2026.

Isolate vs. Plant Studies

Casuarinin sits on the better side of this divide than most of its family, and the reason is that several groups isolated it in order to test it, not merely to measure it.

The purified-compound work is substantial: the ethanol-ulcer dose–response in rats ^{10Reference 10Al-Sayed E et al. · 2020AnimalProtective role of casuarinin from Melaleuca leucadendra against ethanol-induced gastric ulcer in ratsView study →}, the 5-FU mucositis mouse study with a bioactivity-guided isolation behind it ^{11Reference 11Chen KJ et al. · 2022AnimalProtective role of casuarinin from Melastoma malabathricum against a mouse model of 5-fluorouracil-induced intestinal mucositis — impact on inflammation and gut microbiota dysbiosisView study →}, the HSV-2 study with full cytotoxicity and time-of-addition controls ^{7Reference 7Cheng HY et al. · 2002Antiherpes simplex virus type 2 activity of casuarinin from the bark of Terminalia arjuna LinnView study →}, the A549 and MCF-7 mechanism papers ^{8,9Reference 8Kuo PL et al. · 2005Induction of cell cycle arrest and apoptosis in human non-small cell lung cancer A549 cells by casuarinin from the bark of Terminalia arjuna LinnView study →Reference 9Kuo PL et al. · 2005Casuarinin from the bark of Terminalia arjuna induces apoptosis and cell cycle arrest in human breast adenocarcinoma MCF-7 cellsView study →}, the AChE assay ^{15Reference 15Orabi MAA et al. · 2023Structural determination and anticholinesterase assay of C-glycosidic ellagitannins from Lawsonia inermis leaves — a study supported by DFT calculations and molecular dockingView study →}, the keratinocyte chemokine work ^{19,20Reference 19Kwon DJ et al. · 2011Casuarinin suppresses TNF-α-induced ICAM-1 expression via blockade of NF-κB activation in HaCaT cellsView study →Reference 20Kwon DJ et al. · 2012Casuarinin suppresses TARC/CCL17 and MDC/CCL22 production via blockade of NF-κB and STAT1 activation in HaCaT cellsView study →}, and the satellite-cell activation study, which tested the isolate both in culture and orally in rats ^{12Reference 12Yamamoto A et al. · 2022In vitroLemon myrtle (Backhousia citriodora) extract and its active compound, casuarinin, activate skeletal muscle satellite cells in vitro and in vivoView study →}. That is a genuine isolate literature.

Three things pull the other way. First, the human evidence is entirely extract-level — three trial arms of a standardised lemon-myrtle preparation whose casuarinin content came from a manufacturer’s spec sheet ^{13,14Reference 13Sawada S et al. · 2025RCTLemon myrtle extract enhances muscle hypertrophy induced by low-load bodyweight resistance training in older adults — findings from two independent randomized controlled trialsView study →Reference 14Mitsuhashi R et al. · 2026RCTLow-dose lemon myrtle supplementation enhances muscle hypertrophy in older adults undergoing low-load resistance training — a randomized controlled trialView study →}. Second, the source plants are all different: Melaleuca leucadendra, Melastoma malabathricum, Terminalia arjuna, Hippophae rhamnoides, Lawsonia inermis, Backhousia citriodora, Osbeckia octandra. Nothing has been replicated within a single plant or a single laboratory, so the picture is broad and shallow rather than deep. Third — and this is the quiet one — the plant most relevant to this site, raspberry leaf, contributes no pharmacology at all. Every raspberry-leaf finding on the site rests on the whole leaf or on other ellagitannins; casuarinin’s role there is compositional. If casuarinin really is the dominant leaf ellagitannin ^{5,6Reference 5Cyboran-Mikołajczyk S et al. · 2022Protection of erythrocytes and microvascular endothelial cells against oxidative damage by Fragaria vesca L. and Rubus idaeus L. leaves extracts — the mechanism of actionView study →Reference 6Oszmiański J et al. · 2015Determination of phenolic compounds and antioxidant activity in leaves from wild Rubus L. speciesView study →}, then the herb’s astringency and its luminal anti-inflammatory behaviour are plausibly its work — but that is an inference from two chemistry papers, not a demonstrated attribution.

Its Role in Plants

Casuarinin is a defence tannin, and specifically a leaf one. Its biosynthesis follows the standard hydrolysable-tannin route — gallic acid esterified onto glucose to give β-pentagalloylglucose, then oxidative coupling of adjacent galloyl groups to form HHDP units, giving tellimagrandin II and then casuarictin ^{4Reference 4Yoshida T et al. · 2010ReviewStructural features and biological properties of ellagitannins in some plant families of the order Myrtales — reviewView study →}. What happens next is the branch point of the whole class: casuarictin’s glucopyranose ring opens and one HHDP unit forms a carbon–carbon bond to C-1, producing casuarinin and its epimer stachyurin ^{4,17Reference 4Yoshida T et al. · 2010ReviewStructural features and biological properties of ellagitannins in some plant families of the order Myrtales — reviewView study →Reference 17Kusuki R et al. · 2023Divergent synthesis of stachyurin and casuarinin focusing on C-glycosidic bond reactivityView study →}. Further oxidative coupling closes that unit into a nonahydroxytriphenoyl group and yields castalagin and vescalagin ^{4Reference 4Yoshida T et al. · 2010ReviewStructural features and biological properties of ellagitannins in some plant families of the order Myrtales — reviewView study →}. The ester-linked branch, meanwhile, oligomerises into sanguiin H-6 and lambertianin C.

Functionally the point is protein precipitation. Casuarinin binds and cross-links proteins — this is what astringency is, what deters herbivores, and what shows up in the laboratory as anti-adhesion against Candida albicans and as changes in fungal cell-wall porosity and mannan density rather than as clean growth inhibition ^{32,36Reference 32Souza-Moreira TM et al. · 2013In vitroAnti-Candida targets and cytotoxicity of casuarinin isolated from Plinia cauliflora leaves in an in vitro studyView study →Reference 36Glasenapp Y et al. · 2019Anti-adhesion activity of tannins isolated from the mangrove Laguncularia racemosaView study →}. Its distribution matches that role: it concentrates in leaves (raspberry, blackberry, sea buckthorn, henna, lemon myrtle, Casuarina), in bark (arjuna, Melaleuca, oak) and in fruit pericarp (pomegranate) — the surfaces a plant most needs to defend. In sea-buckthorn leaf, total ellagitannin content across 58 individuals ranged 42.5–109.1 mg/g dry weight, with stachyurin and casuarinin among the three most abundant ^{18Reference 18Suvanto J et al. · 2018Variability in foliar ellagitannins of Hippophaë rhamnoides L. and identification of a new ellagitannin, hippophaenin CView study →}, a several-fold within-species variation that is itself evidence of an inducible defence rather than a structural constituent.

Prevalence in Nature

Casuarinin is a Myrtales molecule that also turns up strongly in Rosaceae leaf, and it is far more widely distributed than its Casuarina name suggests.

In Myrtales, the order it was reviewed under, it has been reported from Combretaceae, Lythraceae, Melastomataceae, Myrtaceae, Punicaceae and Trapaceae ^{4Reference 4Yoshida T et al. · 2010ReviewStructural features and biological properties of ellagitannins in some plant families of the order Myrtales — reviewView study →}. Named sources include arjuna bark (Terminalia arjuna) ^{7,8,9Reference 7Cheng HY et al. · 2002Antiherpes simplex virus type 2 activity of casuarinin from the bark of Terminalia arjuna LinnView study →Reference 8Kuo PL et al. · 2005Induction of cell cycle arrest and apoptosis in human non-small cell lung cancer A549 cells by casuarinin from the bark of Terminalia arjuna LinnView study →Reference 9Kuo PL et al. · 2005Casuarinin from the bark of Terminalia arjuna induces apoptosis and cell cycle arrest in human breast adenocarcinoma MCF-7 cellsView study →}, chebulic myrobalan fruit (Terminalia chebula) ^{42Reference 42Juang LJ et al. · 2004Determination of hydrolyzable tannins in the fruit of Terminalia chebula Retz. by high-performance liquid chromatography and capillary electrophoresisView study →}, pomegranate pericarp (Punica granatum) ^{22Reference 22Satomi H et al. · 1993Carbonic anhydrase inhibitors from the pericarps of Punica granatum LView study →}, Melaleuca leucadendra and M. styphelioides ^{10Reference 10Al-Sayed E et al. · 2020AnimalProtective role of casuarinin from Melaleuca leucadendra against ethanol-induced gastric ulcer in ratsView study →}, lemon myrtle (Backhousia citriodora) ^{12Reference 12Yamamoto A et al. · 2022In vitroLemon myrtle (Backhousia citriodora) extract and its active compound, casuarinin, activate skeletal muscle satellite cells in vitro and in vivoView study →}, allspice leaf (Pimenta dioica), jaboticaba leaf (Plinia cauliflora) ^{32Reference 32Souza-Moreira TM et al. · 2013In vitroAnti-Candida targets and cytotoxicity of casuarinin isolated from Plinia cauliflora leaves in an in vitro studyView study →}, Melastoma dodecandrum and M. malabathricum ^{11,24Reference 11Chen KJ et al. · 2022AnimalProtective role of casuarinin from Melastoma malabathricum against a mouse model of 5-fluorouracil-induced intestinal mucositis — impact on inflammation and gut microbiota dysbiosisView study →Reference 24Ishii R et al. · 1999AnimalInhibitory effects of hydrolyzable tannins from Melastoma dodecandrum Lour. on nitric oxide production by a murine macrophage-like cell line, RAW264.7, activated with lipopolysaccharide and interferon-γView study →}, Osbeckia octandra ^{29,33Reference 29Perera HDSM et al. · 2025In vitroInvestigating the antioxidant, pro-inflammatory enzyme inhibitory, neuroprotective, and antineuroinflammatory bioactives of Osbeckia octandra using in vitro and in silico approachesView study →Reference 33Bogahawaththa S et al. · 2023Identification and mechanistic investigation of ellagitannins from Osbeckia octandra that attenuate liver fibrosis via the TGF-β/SMAD signaling pathwayView study →}, Myrcia palustris ^{27Reference 27Wubshet SG et al. · 2015High-resolution bioactivity profiling combined with HPLC-HRMS-SPE-NMR — α-glucosidase inhibitors and acetylated ellagic acid rhamnosides from Myrcia palustris DCView study →}, Lagerstroemia speciosa ^{30Reference 30Bai N et al. · 2008Active compounds from Lagerstroemia speciosa, insulin-like glucose uptake-stimulatory/inhibitory and adipocyte differentiation-inhibitory activities in 3T3-L1 cellsView study →} and the mangrove Laguncularia racemosa ^{36Reference 36Glasenapp Y et al. · 2019Anti-adhesion activity of tannins isolated from the mangrove Laguncularia racemosaView study →}. In purple loosestrife (Lythrum salicaria, the pharmacopoeial Lythri herba) casuarinin appears not free but locked into the dimeric salicarinins B and C, joined to vescalagin and castalagin units ^{43Reference 43Piwowarski JP · 2013C-glucosidic ellagitannins from Lythri herba (European Pharmacopoeia) — chromatographic profile and structure determinationView study →}.

In Rosaceae it is a leaf and root compound. It was quantified across 26 wild Rubus (blackberry) leaf samples at 34.8–117.9 mg/g dry matter ^{6Reference 6Oszmiański J et al. · 2015Determination of phenolic compounds and antioxidant activity in leaves from wild Rubus L. speciesView study →}, reported as the dominant phenolic of raspberry-leaf and wild-strawberry-leaf polyphenol extracts ^{5Reference 5Cyboran-Mikołajczyk S et al. · 2022Protection of erythrocytes and microvascular endothelial cells against oxidative damage by Fragaria vesca L. and Rubus idaeus L. leaves extracts — the mechanism of actionView study →}, and identified in avens root (Geum urbanum) alongside stenophyllanin, stachyurin and pedunculagin ^{44Reference 44Günther I et al. · 2021Avens root (Geum urbanum L.) extract discovered by target-based screening exhibits antidiabetic activity in the hen’s egg test model and Drosophila melanogasterView study →} and in Geum japonicum ^{26Reference 26Liu H et al. · 2009Fatty acid synthase inhibitors from Geum japonicum Thunb. var. chinenseView study →}.

Elsewhere: sea-buckthorn leaf (Hippophae rhamnoides, Elaeagnaceae), where it and stachyurin are the most abundant ellagitannins in both fresh leaf and tea-type infusions ^{18,39Reference 18Suvanto J et al. · 2018Variability in foliar ellagitannins of Hippophaë rhamnoides L. and identification of a new ellagitannin, hippophaenin CView study →Reference 39Ma X et al. · 2019Phenolic compounds and antioxidant activities of tea-type infusions processed from sea buckthorn (Hippophaë rhamnoides) leavesView study →}; henna leaf (Lawsonia inermis) ^{15Reference 15Orabi MAA et al. · 2023Structural determination and anticholinesterase assay of C-glycosidic ellagitannins from Lawsonia inermis leaves — a study supported by DFT calculations and molecular dockingView study →}; sawtooth oak bark (Quercus acutissima) ^{28Reference 28Kim EB et al. · 2022Antiacne and anti-inflammatory effects of phenolic compounds from Quercus acutissimaView study →}; walnut pellicle, where it serves as an origin-authentication marker ^{45Reference 45Liu C et al. · 2026Classification and metabolomic profiling of walnut pellicle polyphenols using pseudotargeted metabolomicsView study →}; and the original Casuarina stricta and Stachyurus praecox ^{1Reference 1Okuda T et al. · 1983Tannins of Casuarina and Stachyurus speciesView study →}.

A caveat that applies to this whole section. Most of these are LC-MS identifications. Given that casuarinin, casuarictin and stachyurin share a mass and casuarinin and stachyurin share a formula and a connectivity, a report of “casuarinin” in a plant extract is only as good as the standard it was matched against.

Major Natural Sources

Source	Part	Reported level	Basis
Wild blackberry (Rubus spp., 26 species)	leaf	34.8–117.9 mg/g 6Reference 6Oszmiański J et al. · 2015Determination of phenolic compounds and antioxidant activity in leaves from wild Rubus L. speciesView study →	dry plant matter — the cleanest quantitation available
Wild strawberry (Fragaria vesca)	leaf	592.6 mg/g 5Reference 5Cyboran-Mikołajczyk S et al. · 2022Protection of erythrocytes and microvascular endothelial cells against oxidative damage by Fragaria vesca L. and Rubus idaeus L. leaves extracts — the mechanism of actionView study →	purified polyphenol extract, not leaf
Raspberry leaf (Rubus idaeus)	leaf	483.3 mg/g 5Reference 5Cyboran-Mikołajczyk S et al. · 2022Protection of erythrocytes and microvascular endothelial cells against oxidative damage by Fragaria vesca L. and Rubus idaeus L. leaves extracts — the mechanism of actionView study →	purified polyphenol extract, not leaf; ~83% of identified phenolics
Sea buckthorn (Hippophae rhamnoides)	leaf	among the 3 most abundant of 42.5–109.1 mg/g total ellagitannins 18Reference 18Suvanto J et al. · 2018Variability in foliar ellagitannins of Hippophaë rhamnoides L. and identification of a new ellagitannin, hippophaenin CView study →	dry weight; casuarinin not resolved separately
Lemon myrtle (Backhousia citriodora)	leaf extract	1.25 mg per 125 mg tablet — 1% w/w 14Reference 14Mitsuhashi R et al. · 2026RCTLow-dose lemon myrtle supplementation enhances muscle hypertrophy in older adults undergoing low-load resistance training — a randomized controlled trialView study →	commercial supplement specification
Arjuna (Terminalia arjuna)	bark	qualitative 7,8,9Reference 7Cheng HY et al. · 2002Antiherpes simplex virus type 2 activity of casuarinin from the bark of Terminalia arjuna LinnView study →Reference 8Kuo PL et al. · 2005Induction of cell cycle arrest and apoptosis in human non-small cell lung cancer A549 cells by casuarinin from the bark of Terminalia arjuna LinnView study →Reference 9Kuo PL et al. · 2005Casuarinin from the bark of Terminalia arjuna induces apoptosis and cell cycle arrest in human breast adenocarcinoma MCF-7 cellsView study →	isolated for study; no content figure
Pomegranate (Punica granatum)	pericarp	qualitative 22Reference 22Satomi H et al. · 1993Carbonic anhydrase inhibitors from the pericarps of Punica granatum LView study →	isolated as one of seven active tannins
Chebulic myrobalan (Terminalia chebula)	fruit	qualitative 42Reference 42Juang LJ et al. · 2004Determination of hydrolyzable tannins in the fruit of Terminalia chebula Retz. by high-performance liquid chromatography and capillary electrophoresisView study →	one of fourteen tannins in an HPLC/CE method
Raspberry leaf (Rubus idaeus)	leaf, as dried plant material	no published figure	see gaps note

Discovery & Synthesis

Casuarinin was first isolated in 1983 by Takuo Okuda, Takashi Yoshida, Masashi Ashida and Kunio Yazaki at Okayama University, from the leaves of Casuarina stricta — the Australian she-oak — in Part 1 of their Tannins of Casuarina and Stachyurus Species series ^{1Reference 1Okuda T et al. · 1983Tannins of Casuarina and Stachyurus speciesView study →}. The paper reported seven ellagitannins at once and named four of them for the first time: the three C-glucosidic compounds casuarinin, casuariin and stachyurin, and the ester-linked monomer casuarictin, plus strictinin. All seven were subsequently found in Stachyurus praecox as well ^{1Reference 1Okuda T et al. · 1983Tannins of Casuarina and Stachyurus speciesView study →}. The name is botanical: it commemorates the genus, not a person or a property — and it is shared with casuarictin, which is precisely why the two get mixed up.

Unlike its oligomeric cousins, casuarinin has been made in a laboratory. Shinnosuke Wakamori, Shintaro Matsumoto, Reina Kusuki, Kazutada Ikeuchi and Hidetoshi Yamada at Kwansei Gakuin University published the first total synthesis in 2020 ^{2Reference 2Wakamori S et al. · 2020Total synthesis of casuarininView study →}. The hard part was the C-glycosidic bond, which they built with complete stereoselectivity using a benzyl oxime group to open the glucopyranose ring and serve as the scaffold for C-glycoside formation ^{2Reference 2Wakamori S et al. · 2020Total synthesis of casuarininView study →}. A 2023 follow-up developed a divergent route to both stachyurin and casuarinin, using α-selective C-glycosylation and β-selective oxygen functionalisation to reach either epimer at will and confirming that the two stereoisomers behave differently at that bond ^{17Reference 17Kusuki R et al. · 2023Divergent synthesis of stachyurin and casuarinin focusing on C-glycosidic bond reactivityView study →}. Synthetic access has since been used to make non-natural casuarinin analogues for structure–activity work.

For research use, casuarinin is nonetheless still an extraction product — pulled from arjuna bark, Melaleuca leaf, sea-buckthorn leaf or Melastoma root by resin adsorption and preparative HPLC — and sold as an expensive reagent rather than an article of commerce. The only casuarinin most people will ever buy is the fraction of a milligram inside a lemon-myrtle tablet.

Patents: not yet researched.

Toxicity & Safety

Casuarinin carries a low flag, and unusually for this family the flag rests on something more than dietary history. It is a normal constituent of teas, fruits and barks in long human use; it has been given orally to rats and mice at 25–100 mg/kg/day in three separate studies with protective rather than harmful outcomes ^{10,11,12,46Reference 10Al-Sayed E et al. · 2020AnimalProtective role of casuarinin from Melaleuca leucadendra against ethanol-induced gastric ulcer in ratsView study →Reference 11Chen KJ et al. · 2022AnimalProtective role of casuarinin from Melastoma malabathricum against a mouse model of 5-fluorouracil-induced intestinal mucositis — impact on inflammation and gut microbiota dysbiosisView study →Reference 12Yamamoto A et al. · 2022In vitroLemon myrtle (Backhousia citriodora) extract and its active compound, casuarinin, activate skeletal muscle satellite cells in vitro and in vivoView study →Reference 46Hassan HM et al. · 2025AnimalCasuarinin modulates renin-angiotensin-aldosterone system to counter ephedrine-induced myocardial damage in ratsView study →}; and a casuarinin-standardised extract has been through three placebo-controlled human trial arms in adults over 65 without reported adverse events ^{13,14Reference 13Sawada S et al. · 2025RCTLemon myrtle extract enhances muscle hypertrophy induced by low-load bodyweight resistance training in older adults — findings from two independent randomized controlled trialsView study →Reference 14Mitsuhashi R et al. · 2026RCTLow-dose lemon myrtle supplementation enhances muscle hypertrophy in older adults undergoing low-load resistance training — a randomized controlled trialView study →}. What it does not have is any dedicated toxicology package, and the human doses involved were milligram-scale, so the tolerability data are thin as well as favourable.

Safety at a Glance

✅ Low / no toxicity

• Real dietary and herbal exposure with no signal of harm. Present in pomegranate peel, raspberry- and sea-buckthorn-leaf tea, arjuna bark and Myrtaceae leaf; at 936 Da it is not meaningfully absorbed, which caps systemic risk.
• Repeat oral dosing in rodents was protective. 25–100 mg/kg/day in three models produced gastroprotection, mucosal repair and cardioprotection, not toxicity.
• Casuarinin is one of the C-glucosidic tannins of plants that poison cattle. It was isolated with vescalagin, castalagin and stachyurin from Thiloa glaucocarpa, a Brazilian plant associated with cattle poisoning whose symptomatology parallels oak (Quercus) toxicosis — a syndrome attributed to hydrolysable tannin content.
• Tannin-class effects at the gut surface. Non-specific protein binding is its mechanism of action as well as its astringency: expect the usual class cautions about concentrated tannin preparations, non-haem iron and mineral absorption, and digestive-enzyme inhibition.
• No toxicology, no interaction data, no reproductive data on the isolate. The human tolerability evidence covers 1.25–2.5 mg/day of a standardised extract, which is not a test of the molecule at any pharmacological dose.

Full Safety & Interactions Detail

The ruminant tannin question. In 1987 Itakura, Habermehl and Mebs isolated four ellagic C-glucosyl tannins — vescalagin, castalagin, stachyurin and casuarinin — from the dried leaves of Thiloa glaucocarpa, a Brazilian plant associated with cattle poisoning. Their point was comparative: vescalagin and castalagin are also the principal tannins of oak (Quercus spp.), whose toxicity in cattle is attributed to tannin content, and the shared chemistry explains the shared symptomatology ^{47Reference 47Itakura Y et al. · 1987Tannins occurring in the toxic Brazilian plant Thiloa glaucocarpaView study →}. This is worth recording and worth not over-reading. Nothing in that paper attributes toxicity to casuarinin specifically; hydrolysable-tannin toxicosis in ruminants is a high-dose, whole-forage, species-specific phenomenon (rumen microbiology converts tannins to gallic-acid derivatives that are nephrotoxic in cattle in a way they are not in monogastrics), and there is no analogous human syndrome from tannin-containing foods or teas. It is a warn, not a caution against use — but it is the only positive toxicity association this molecule has, and pretending otherwise would be dishonest.

What the rodent record shows. Three oral studies used the purified compound. Rats given 25, 50 and 100 mg/kg showed dose-dependent gastroprotection with improved antioxidant and anti-apoptotic markers and no reported adverse effects ^{10Reference 10Al-Sayed E et al. · 2020AnimalProtective role of casuarinin from Melaleuca leucadendra against ethanol-induced gastric ulcer in ratsView study →}. Mice given 50 and 100 mg/kg/day for five days alongside 5-fluorouracil had less weight loss and better intestinal integrity than 5-FU controls ^{11Reference 11Chen KJ et al. · 2022AnimalProtective role of casuarinin from Melastoma malabathricum against a mouse model of 5-fluorouracil-induced intestinal mucositis — impact on inflammation and gut microbiota dysbiosisView study →}. Rats given casuarinin 25 mg/kg alongside ephedrine were protected against myocardial oxidative, inflammatory and apoptotic damage; the study also ran a casuarinin-alone arm, which is the closest thing to a toxicity control in the literature ^{46Reference 46Hassan HM et al. · 2025AnimalCasuarinin modulates renin-angiotensin-aldosterone system to counter ephedrine-induced myocardial damage in ratsView study →}. None of these is a toxicology study — none used a maximum tolerated dose design, histopathology across organ systems, or repeat dosing beyond days — but their direction is consistent.

Human tolerability. Three RCT arms (n = 47, 41, 60) in Japanese adults aged 65+ gave a lemon-myrtle extract standardised to 1.25–2.5 mg/day casuarinin for 12 weeks with no adverse events reported ^{13,14Reference 13Sawada S et al. · 2025RCTLemon myrtle extract enhances muscle hypertrophy induced by low-load bodyweight resistance training in older adults — findings from two independent randomized controlled trialsView study →Reference 14Mitsuhashi R et al. · 2026RCTLow-dose lemon myrtle supplementation enhances muscle hypertrophy in older adults undergoing low-load resistance training — a randomized controlled trialView study →}. The doses are two to three orders of magnitude below the rodent doses on a body-weight basis, so this is evidence of tolerability at supplement levels, not of safety at pharmacological ones.

Tannin-class cautions. Casuarinin binds and precipitates proteins — the property behind its astringency, its anti-adhesion activity against Candida and, arguably, several of its enzyme IC₅₀ values ^{32,36Reference 32Souza-Moreira TM et al. · 2013In vitroAnti-Candida targets and cytotoxicity of casuarinin isolated from Plinia cauliflora leaves in an in vitro studyView study →Reference 36Glasenapp Y et al. · 2019Anti-adhesion activity of tannins isolated from the mangrove Laguncularia racemosaView study →}. The class cautions apply to concentrated preparations: pronounced dryness, potential gastric irritation, reduced non-haem iron and mineral absorption when taken with meals, and non-specific digestive-enzyme inhibition. None has been quantified for this molecule.

Interactions. No drug-interaction study of casuarinin exists — nothing on CYP isoforms, P-glycoprotein or any transporter. Because it is not absorbed, a systemic interaction is mechanistically implausible; a luminal one — binding a co-ingested drug or mineral in the gut — is plausible and untested. Two theoretical notes without overstating them: a cell-free acetylcholinesterase IC₅₀ of 34 nM ^{15Reference 15Orabi MAA et al. · 2023Structural determination and anticholinesterase assay of C-glycosidic ellagitannins from Lawsonia inermis leaves — a study supported by DFT calculations and molecular dockingView study →} would matter enormously if the compound reached a synapse, which it does not; and because the systemically active species in this class are microbial urolithins, anything that reshapes the colonic microbiota (antibiotics above all) will change real exposure more than any pharmacokinetic interaction ^{37,41Reference 37Piwowarski JP et al. · 2016Differences in metabolism of ellagitannins by human gut microbiota ex vivo culturesView study →Reference 41Tomás-Barberán FA et al. · 2014Ellagic acid metabolism by human gut microbiota — consistent observation of three urolithin phenotypes in intervention trials, independent of food source, age and health statusView study →}.

Reproductive note. No reproductive or developmental toxicity study has been performed on isolated casuarinin. Raspberry-leaf preparations have their own pregnancy literature; that discussion belongs to the raspberry leaf monograph, where intake is actually decided, not to a molecule page.

Dosage

There is no dose for isolated casuarinin. It has never been given to a human as a purified compound, and at 936 Da a systemic dose is not a coherent concept for it. What exists is one standardised-extract exposure and a set of research figures.

The gap between the human column and the rodent column is the story: a 70 kg human would need roughly 1.75–7 g/day to match the rodent gastroprotection doses, against the 1.25–2.5 mg/day that has actually been given to people. Nothing here has been tested in a human at a dose where its rodent pharmacology would be expected to appear. These are figures from research and product specifications, not a personal recommendation.

References

1. Okuda T, Yoshida T, Ashida M, Yazaki K (1983). Tannins of Casuarina and Stachyurus species. Part 1. Structures of pedunculagin, casuarictin, strictinin, casuarinin, casuariin, and stachyurin. Journal of the Chemical Society, Perkin Transactions 1, 1765-1772. https://doi.org/10.1039/P19830001765
2. Wakamori S, Matsumoto S, Kusuki R, Ikeuchi K, Yamada H (2020). Total synthesis of casuarinin. Organic Letters, 22(9), 3392-3396. https://pubmed.ncbi.nlm.nih.gov/32275157/
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5. Cyboran-Mikołajczyk S, Męczarska K, Solarska-Ściuk K, Ratajczak-Wielgomas K, Oszmiański J, Jencova V, Bonarska-Kujawa D (2022). Protection of erythrocytes and microvascular endothelial cells against oxidative damage by Fragaria vesca L. and Rubus idaeus L. leaves extracts — the mechanism of action. Molecules, 27(18), 5865. https://pubmed.ncbi.nlm.nih.gov/36144602/
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8. Kuo PL, Hsu YL, Lin TC, Chang JK, Lin CC (2005). Induction of cell cycle arrest and apoptosis in human non-small cell lung cancer A549 cells by casuarinin from the bark of Terminalia arjuna Linn. Anti-Cancer Drugs, 16(4), 409-415. https://pubmed.ncbi.nlm.nih.gov/15746577/
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