Rugosin D

Rugosin D at a Glance

Rugosin D is a dimeric ellagitannin — a hydrolysable tannin built from two smaller tannin units joined together, with a molecular weight near 1,875 daltons. It was isolated in 1982 from the petals of the rugosa rose, Rosa rugosa, which is where the whole rugosin family gets its name ^{5Reference 5Okuda T et al. · 1982Rugosin D, E, F and G, dimeric and trimeric hydrolyzable tanninsView study →}. Chemically it is two tellimagrandin II units bridged by a valoneoyl group, and that dimeric architecture is the reason the molecule matters pharmacologically.

Its claim to attention is narrow but genuinely interesting. Rugosin D is the most potent natural inhibitor of histidine decarboxylase (HDC) yet reported — the enzyme that decarboxylates the amino acid histidine into histamine, including the histamine that drives gastric-acid secretion ^{1,2Reference 1Nitta Y et al. · 2013Inhibitory activity of Filipendula ulmaria constituents on recombinant human histidine decarboxylaseView study →Reference 2Nitta Y et al. · 2016Inhibition of Morganella morganii histidine decarboxylase activity and histamine accumulation in mackerel muscle derived from Filipendula ulmaria extractsView study →}. That single fact is the leading mechanistic explanation for one of herbal medicine’s better paradoxes: meadowsweet is the plant that gave salicylic acid its name, yet it has been used for the stomach rather than causing the gastric harm that is aspirin’s signature side effect.

The load-bearing caveat is size. At nearly 1,900 daltons with more than fifty oxygen atoms, rugosin D is far outside the range of molecules that cross the gut wall intact. Like other hydrolysable tannins it is expected to be hydrolysed in the gut and converted by colonic bacteria toward ellagic acid and then urolithins, with large person-to-person variation ^{14,15,16Reference 14Tomás-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 →Reference 15Espín JC et al. · 2013Biological significance of urolithins, the gut microbial ellagic-acid-derived metabolites — the evidence so farView study →Reference 16Seeram NP et al. · 2004Bioavailability of ellagic acid in human plasma after consumption of ellagitannins from pomegranate (Punica granatum L.) juiceView study →}. So the micromolar enzyme constants below are concentrations reachable in the gut lumen, not in plasma. Whether the HDC mechanism actually operates in a person drinking meadowsweet tea is the open question — not its conclusion.

The Salicylate Paradox

This is the reason rugosin D has a page at all, so it is worth stating precisely — including where the evidence runs out.

The paradox. Meadowsweet (Filipendula ulmaria) is the plant salicin and salicylic acid were named after — Spiraea, its old genus, is the “spir” in aspirin. Yet the herb’s traditional and experimental reputation is gastroprotective. In classic rat work a flower decoction reduced ulceration from several ulcerogenic procedures and, pointedly, prevented acetylsalicylic-acid-induced gastric lesions ^{11Reference 11Barnaulov OD · 1980Anti-ulcer action of a decoction of the flowers of the dropwort, Filipendula ulmariaView study →}; a modern study confirmed protection against ethanol-induced acute gastric injury with lyophilised flower infusions at 100–300 mg/kg orally ^{12Reference 12Samardžić S et al. · 2018Antioxidant, anti-inflammatory and gastroprotective activity of Filipendula ulmaria (L.) Maxim. and Filipendula vulgaris MoenchView study →}. A salicylate-bearing plant that guards the stomach is the opposite of what the pharmacology of aspirin would predict.

The proposed resolution. Gastric acid secretion is driven substantially by histamine acting on parietal-cell H2 receptors, and that histamine is made on demand by histidine decarboxylase. Inhibit HDC and you reduce the histamine supply upstream of the receptor — a different point of attack from the H2 blockers and proton-pump inhibitors used clinically. Nitta and colleagues fractionated the ethyl-acetate extract of meadowsweet petals and found the activity concentrated in four ellagitannins: rugosin D, rugosin A, rugosin A methyl ester (a compound not previously described) and tellimagrandin II. All four inhibited recombinant human HDC non-competitively, with inhibition constants of roughly 0.35–1 µM — comparable to purpose-designed substrate-analogue inhibitors, and a big step up from the best dietary HDC inhibitor previously known, epicatechin gallate, which is competitive with a Ki near 10 µM ^{1,4Reference 1Nitta Y et al. · 2013Inhibitory activity of Filipendula ulmaria constituents on recombinant human histidine decarboxylaseView study →Reference 4Nitta Y et al. · 2007Food components inhibiting recombinant human histidine decarboxylase activityView study →}.

Where it stops being demonstrated. Three gaps, in order of importance:

It is an enzyme assay. Nitta 2013 used recombinant human HDC in vitro — not cells, not stomach tissue, not an animal ^{1Reference 1Nitta Y et al. · 2013Inhibitory activity of Filipendula ulmaria constituents on recombinant human histidine decarboxylaseView study →}. No study has shown rugosin D lowering gastric histamine, gastric acid or ulcer scores in a living animal.
A µM constant on a 1,875-dalton molecule is not a systemic effect. Hydrolysable tannins of this size are not meaningfully absorbed intact; a low-micromolar Ki is achievable in the stomach and gut lumen but not in plasma ^{14,15,16,19Reference 14Tomás-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 →Reference 15Espín JC et al. · 2013Biological significance of urolithins, the gut microbial ellagic-acid-derived metabolites — the evidence so farView study →Reference 16Seeram NP et al. · 2004Bioavailability of ellagic acid in human plasma after consumption of ellagitannins from pomegranate (Punica granatum L.) juiceView study →Reference 19Virtanen V · 2020Partition coefficients (logP) of hydrolysable tanninsView study →}. If the mechanism works at all in a person, it works locally — which happens to be where gastric HDC is, so the argument is not absurd, only unproven.
The closest in-vivo evidence is for the monomer, not for rugosin D. In the ethanol-injury rat model, tellimagrandin II at 40 mg/kg orally showed ulcer-preventive ability ^{12Reference 12Samardžić S et al. · 2018Antioxidant, anti-inflammatory and gastroprotective activity of Filipendula ulmaria (L.) Maxim. and Filipendula vulgaris MoenchView study →} — tellimagrandin II being precisely the unit rugosin D is built from. That is the best bridge in the literature, and it is still one step to the side: the study tested a different (smaller) molecule and did not test the HDC mechanism.

No animal or human gastroprotection study of isolated rugosin D, or of a rugosin-standardised extract, exists. The honest summary is that HDC inhibition is a well-measured enzyme-level property of the right molecule from the right plant, plausibly acting at the right anatomical site, that has never been tested in a stomach.

A Dimer of Tellimagrandin II

Rugosin D is not a dimer of rugosin A, despite the shared name. The rugosin series was named for its source plant, not for a shared build.

Rugosin D consists of two tellimagrandin II units linked by a single valoneoyl (m-depside, m-DOG) bond ^{5,3Reference 5Okuda T et al. · 1982Rugosin D, E, F and G, dimeric and trimeric hydrolyzable tanninsView study →Reference 3Nitta Y et al. · 2019The ellagitannin trimer rugosin G inhibits recombinant human histidine decarboxylaseView study →}. A valoneoyl group is a trigalloyl-derived unit in which one galloyl ring is joined through a diaryl ether to a hexahydroxydiphenoyl (HHDP) group; when that linkage forms between two tannin molecules rather than within one, a monomer becomes a dimer. Rugosin D is the linear, singly-bridged case. Its siblings from the same 1982 isolation illustrate the variations: rugosins D, E and F are dimers differing in the orientation of the valoneoyl group, and rugosin G is a trimer carrying two of them ^{5Reference 5Okuda T et al. · 1982Rugosin D, E, F and G, dimeric and trimeric hydrolyzable tanninsView study →}. Formula C82H58O52, MW ≈ 1,875.

Dimerisation is the structure–activity story. Against bacterial HDC from Morganella morganii, the four meadowsweet ellagitannins line up in a clear order — rugosin D (dimer) IC50 1.5 µM > rugosin A methyl ester 4.4 µM > tellimagrandin II 6.1 µM > rugosin A 6.8 µM ^{2Reference 2Nitta Y et al. · 2016Inhibition of Morganella morganii histidine decarboxylase activity and histamine accumulation in mackerel muscle derived from Filipendula ulmaria extractsView study →}. The dimer is roughly four times more potent than either monomer. Extending the chain extends the trend: the trimer rugosin G inhibits recombinant human HDC more strongly than the monomers and more strongly than oenothein B, a dimer with a macrocyclic rather than linear structure — from which Nitta’s group concluded that potency tracks a linear oligomeric conformation, not merely molecular size ^{3Reference 3Nitta Y et al. · 2019The ellagitannin trimer rugosin G inhibits recombinant human histidine decarboxylaseView study →}. A separate metabolomic study reached a compatible conclusion from a different direction, finding rugosin D the most growth-inhibitory of the hydrolysable tannins tested against E. coli and S. aureus and arguing that effective tannins need both hydrophobic and hydrophilic regions — a balance a linear dimer supplies and a small monomer does not ^{8Reference 8Virtanen V et al. · 2023NMR metabolomics and DNA sequencing of Escherichia coli and Staphylococcus aureus cultures treated with hydrolyzable tanninsView study →}.

The catch is that the same property cuts both ways: the extended, multivalent surface that makes rugosin D a better enzyme inhibitor is exactly what makes it a worse drug candidate. Bigger, more polar, more protein-binding, less absorbable.

What It's Used For

The literature on rugosin D is small — a PubMed search for the molecule by name returns single digits — and it is entirely in vitro apart from a whole-extract food-safety experiment. What exists is unusually clean, though: several papers test the purified molecule rather than a crude tannin fraction, which is rare in this field.

The strongest natural HDC inhibitor found so far.Non-competitive inhibition of recombinant human histidine decarboxylase at Ki ≈ 0.35–1 µM, alongside three sibling ellagitannins from the same meadowsweet petal fraction, and roughly an order of magnitude better than the previous dietary benchmark (epicatechin gallate) ^{1,4Reference 1Nitta Y et al. · 2013Inhibitory activity of Filipendula ulmaria constituents on recombinant human histidine decarboxylaseView study →Reference 4Nitta Y et al. · 2007Food components inhibiting recombinant human histidine decarboxylase activityView study →}.

Dimerisation buys potency.Rugosin D outperforms its own monomer units against bacterial HDC (1.5 µM vs 6.1–6.8 µM), and the trimer rugosin G outperforms it again — the effect tracks a linear oligomeric shape ^{2,3Reference 2Nitta Y et al. · 2016Inhibition of Morganella morganii histidine decarboxylase activity and histamine accumulation in mackerel muscle derived from Filipendula ulmaria extractsView study →Reference 3Nitta Y et al. · 2019The ellagitannin trimer rugosin G inhibits recombinant human histidine decarboxylaseView study →}.

Also a gut-luminal enzyme inhibitor more generally.It inhibits mammalian α-amylase (human pancreatic IC50 ≈ 31 µg/mL, ~16 µM) and, in a simulated digestion model, suppressed amylase activity comparably to acarbose ^{6Reference 6Olennikov DN et al. · 2021Metabolites of prickly rose — chemodiversity and digestive-enzyme-inhibiting potential of Rosa acicularis and the main ellagitannin rugosin DView study →}; it inhibits diacylglycerol acyltransferase by 82% at 10 µM ^{7Reference 7Kondo H et al. · 2011Identification of diacylglycerol acyltransferase inhibitors from Rosa centifolia petalsView study →}; and it is the most potent of a panel of hydrolysable tannins at inhibiting E. coli and S. aureus growth ^{8Reference 8Virtanen V et al. · 2023NMR metabolomics and DNA sequencing of Escherichia coli and Staphylococcus aureus cultures treated with hydrolyzable tanninsView study →}.

The honest headline:every one of these numbers is an isolated-enzyme or isolated-cell result at concentrations a ~1,875-dalton tannin will never reach in blood. There is no animal or human study of rugosin D itself — the gastroprotection evidence belongs to whole meadowsweet infusions and, at one remove, to its monomer tellimagrandin II ^{11,12Reference 11Barnaulov OD · 1980Anti-ulcer action of a decoction of the flowers of the dropwort, Filipendula ulmariaView study →Reference 12Samardžić S et al. · 2018Antioxidant, anti-inflammatory and gastroprotective activity of Filipendula ulmaria (L.) Maxim. and Filipendula vulgaris MoenchView study →}.

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 is capped low because no application has been tested in an animal or a person using the isolated molecule.

The marquee finding, and the reason this molecule appears in the meadowsweet monograph. Screening the ethyl-acetate fraction of Filipendula ulmaria petals against recombinant human HDC, Nitta and colleagues identified four ellagitannins as the active principles — rugosin D, rugosin A, rugosin A methyl ester and tellimagrandin II — all inhibiting non-competitively with Ki ≈ 0.35–1 µM, values the authors describe as comparable to designed substrate-analogue inhibitors ^{1Reference 1Nitta Y et al. · 2013Inhibitory activity of Filipendula ulmaria constituents on recombinant human histidine decarboxylaseView study →}.

For context, the same group’s earlier survey of dietary phenolics found epicatechin gallate the best of the food compounds at Ki = 10 µM, and competitive ^{4Reference 4Nitta Y et al. · 2007Food components inhibiting recombinant human histidine decarboxylase activityView study →}; the ellagitannins are both more potent and mechanistically different. A follow-up against the bacterial HDC of Morganella morganii — the enzyme behind scombroid histamine poisoning — ranked the same four compounds and put rugosin D first at IC50 1.5 µM; a 2% meadowsweet extract applied to mackerel muscle significantly reduced histamine accumulation ^{2Reference 2Nitta Y et al. · 2016Inhibition of Morganella morganii histidine decarboxylase activity and histamine accumulation in mackerel muscle derived from Filipendula ulmaria extractsView study →}.

Because parietal-cell histamine drives gastric acid secretion, HDC inhibition is a coherent upstream explanation for meadowsweet’s anti-ulcer behaviour ^{11,12Reference 11Barnaulov OD · 1980Anti-ulcer action of a decoction of the flowers of the dropwort, Filipendula ulmariaView study →Reference 12Samardžić S et al. · 2018Antioxidant, anti-inflammatory and gastroprotective activity of Filipendula ulmaria (L.) Maxim. and Filipendula vulgaris MoenchView study →}.

Gap: enzyme assays only. Nothing has been measured in a stomach — no gastric histamine, acid-output or ulcer-score data for rugosin D in any animal, and no human data of any kind. The nearest in-vivo evidence is that its monomer tellimagrandin II at 40 mg/kg p.o. prevented ethanol-induced gastric ulceration in rats, in a study that tested outcome and not mechanism ^{12Reference 12Samardžić S et al. · 2018Antioxidant, anti-inflammatory and gastroprotective activity of Filipendula ulmaria (L.) Maxim. and Filipendula vulgaris MoenchView study →}. The mackerel result is a food-preservation finding using a whole extract, not a gastric one.

Mechanisms

Target / pathway	Effect	Relevant to
Histidine decarboxylase (human, recombinant)	non-competitive inhibition, Ki ≈ 0.35–1 µM → less histidine converted to histamine	gastroprotection; histamine-mediated symptoms
Histidine decarboxylase (Morganella morganii)	IC50 1.5 µM — most potent of the four meadowsweet ellagitannins	food-borne histamine (scombroid)SAR ranking
α-Amylase (human pancreatic / salivary; porcine)	IC50 ≈ 31 / 68 / 32 µg/mL — starch digestion slowed in the lumen	carbohydrate digestion
Diacylglycerol acyltransferase (DGAT)	82% inhibition at 10 µM	triglyceride synthesis (screen-level)
Bacterial growth / metabolome (E. coli, S. aureus)	most inhibitory tannin of its panel; requires balanced hydrophobic + hydrophilic surface	antibacterial
Non-specific protein binding (astringency)	multivalent polyphenol–protein complexation — the general tannin action	astringent effectiron chelationmouthfeel

The pattern is consistent: rugosin D is a promiscuous, high-affinity protein binder whose large linear surface lets it inhibit structurally unrelated enzymes. That explains both the impressive potency numbers and why they should not be over-read — an inhibitor this indiscriminate at micromolar concentrations in a test tube tells you less about physiology than a weaker, more selective one would.

Pharmacokinetics

There is no pharmacokinetic study of rugosin D — no absorption, distribution or metabolite data for the molecule in any species. What can be said is inferential, and it is the most important thing on the page.

At MW ≈ 1,875 with 52 oxygens, rugosin D sits at the far end of the hydrolysable-tannin size range and well outside the physicochemical window for passive intestinal absorption; measured partition coefficients for hydrolysable tannins confirm the class is highly hydrophilic and size-penalised ^{19Reference 19Virtanen V · 2020Partition coefficients (logP) of hydrolysable tanninsView study →}. The established fate of dietary ellagitannins is hydrolysis in the gut releasing HHDP units that lactonise to ellagic acid, followed by colonic microbial conversion to urolithins (A, B, C, D) — and even free ellagic acid barely reaches plasma, peaking near 0.06 µmol/L after pomegranate juice ^{16Reference 16Seeram NP et al. · 2004Bioavailability of ellagic acid in human plasma after consumption of ellagitannins from pomegranate (Punica granatum L.) juiceView study →}. Urolithin production is strongly person-dependent: people fall into reproducible metabotypes A, B and 0, so two people drinking the same infusion get very different internal exposures ^{14,15Reference 14Tomás-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 →Reference 15Espín JC et al. · 2013Biological significance of urolithins, the gut microbial ellagic-acid-derived metabolites — the evidence so farView study →}.

The practical consequence: a 0.35–1 µM Ki is a luminal concentration, not a systemic one. Any real effect of rugosin D is most likely exerted in the gastrointestinal tract itself — on gastric HDC, on digestive enzymes, on gut bacteria — with anything downstream belonging to ellagic acid and urolithins rather than to this molecule. Notably, the two studies that have modelled meadowsweet’s gut biotransformation both tracked the flavonoid side of the extract (rutin, spiraeoside and isoquercitrin losing their sugars to quercetin and kaempferol) and did not follow the ellagitannins at all ^{13,17Reference 13Van der Auwera A et al. · 2023In vitroIn vitro biotransformation and anti-inflammatory activity of constituents and metabolites of Filipendula ulmariaView study →Reference 17Popowski D et al. · 2022Gut microbiota of pigs metabolizes extracts of Filipendula ulmaria and Orthosiphon aristatus — herbal remedies used in urinary tract disordersView study →}, so even the descriptive picture for rugosin D specifically is missing.

Clinical Trials

None. There are no clinical trials of rugosin D, no trials of a rugosin-standardised extract, and no human data of any kind for the isolated molecule. Human-adjacent evidence exists only at the level of the whole herb, where the EU herbal monograph for meadowsweet rests on traditional use rather than trial efficacy.

Completed	Planned	Terminated	Preclinical
—	—	—	Enzyme kinetics (HDC, α-amylase, DGAT), antibacterial in vitro; animal data only for whole meadowsweet infusion or the monomer tellimagrandin II

Last checked: August 2026.

Isolate vs. Plant Studies

Unusually for a tannin, the enzyme work here is genuine isolate work — Nitta’s group purified four individual ellagitannins from the petal fraction and ran kinetics on each, and Olennikov’s α-amylase IC50s are for purified rugosin D ^{1,2,6Reference 1Nitta Y et al. · 2013Inhibitory activity of Filipendula ulmaria constituents on recombinant human histidine decarboxylaseView study →Reference 2Nitta Y et al. · 2016Inhibition of Morganella morganii histidine decarboxylase activity and histamine accumulation in mackerel muscle derived from Filipendula ulmaria extractsView study →Reference 6Olennikov DN et al. · 2021Metabolites of prickly rose — chemodiversity and digestive-enzyme-inhibiting potential of Rosa acicularis and the main ellagitannin rugosin DView study →}. That is a real strength and lets the SAR conclusion (dimer beats monomer) stand.

The weakness is on the other side of the ledger: every outcome-level result belongs to something else. The anti-ulcer evidence is for a meadowsweet flower decoction and lyophilised flower infusions ^{11,12Reference 11Barnaulov OD · 1980Anti-ulcer action of a decoction of the flowers of the dropwort, Filipendula ulmariaView study →Reference 12Samardžić S et al. · 2018Antioxidant, anti-inflammatory and gastroprotective activity of Filipendula ulmaria (L.) Maxim. and Filipendula vulgaris MoenchView study →}; the histamine-suppression demonstration is a 2% whole extract applied to fish ^{2Reference 2Nitta Y et al. · 2016Inhibition of Morganella morganii histidine decarboxylase activity and histamine accumulation in mackerel muscle derived from Filipendula ulmaria extractsView study →}; the gut-flora selectivity is for whole rose-petal tannin ^{18Reference 18Kamijo M et al. · 2008Effects of Rosa rugosa petals on intestinal bacteriaView study →}; and the antitumour/IL-1β pattern is a class result from which rugosin D was absent ^{9Reference 9Miyamoto K et al. · 1993Antitumor activity and interleukin-1 induction by tanninsView study →}. So the page has an isolate mechanism and a plant outcome with nothing connecting them. Anyone crediting meadowsweet’s stomach-friendliness to rugosin D is chaining two solid but unjoined pieces of evidence — which is a reasonable hypothesis and not a demonstrated fact.

Prevalence in Nature

Rugosin D is a Rosaceae molecule. It was first found in, and named after, the petals of Rosa rugosa ^{5Reference 5Okuda T et al. · 1982Rugosin D, E, F and G, dimeric and trimeric hydrolyzable tanninsView study →}, and it recurs across the ornamental and medicinal roses — R. gallica (French rose), R. centifolia (cabbage rose) and R. acicularis (prickly rose) — and in Filipendula ulmaria, meadowsweet, the same family ^{1,6,7Reference 1Nitta Y et al. · 2013Inhibitory activity of Filipendula ulmaria constituents on recombinant human histidine decarboxylaseView study →Reference 6Olennikov DN et al. · 2021Metabolites of prickly rose — chemodiversity and digestive-enzyme-inhibiting potential of Rosa acicularis and the main ellagitannin rugosin DView study →Reference 7Kondo H et al. · 2011Identification of diacylglycerol acyltransferase inhibitors from Rosa centifolia petalsView study →}.

Its distribution within a plant is strongly tissue- and season-dependent. In prickly rose it is overwhelmingly a leaf compound, peaking during flowering: 41.15 mg/g dry weight in July leaf, falling to 32.67 mg/g in September and 18.35 mg/g in May, against only 4.06 mg/g in the flowers — and undetectable in roots and fruits ^{6Reference 6Olennikov DN et al. · 2021Metabolites of prickly rose — chemodiversity and digestive-enzyme-inhibiting potential of Rosa acicularis and the main ellagitannin rugosin DView study →}. That roughly ten-fold leaf-to-flower gradient is worth holding onto, because the herbal preparations people actually use are made from flowers (meadowsweet flowering tops, rose petals), which in the one plant where this has been mapped is the tissue with the least.

A caution about the name: several unrelated things are called “rugosin”. The rugosins A, B and C of the frog Rana rugosa are antimicrobial peptides with no relation to these tannins, and isorugosin D from Liquidambar formosana is a distinct compound differing in the orientation of the valoneoyl group. Attribution to Eucalyptus and Rubus also does not hold up for this molecule specifically: those genera carry their own valoneoyl-type oligomeric ellagitannins (eucarpanins, rubusuaviins) rather than rugosin D itself.

Major Natural Sources

Source	Part	Status of the figure
Meadowsweet (Filipendula ulmaria)	Flower petal	Identified as one of four principal ellagitannins of the ethyl-acetate petal fraction; not quantified — and the comprehensive LC-MS profile of the herb does not supply a figure either ^{1,10Reference 1Nitta Y et al. · 2013Inhibitory activity of Filipendula ulmaria constituents on recombinant human histidine decarboxylaseView study →Reference 10Bijttebier S et al. · 2016A first step in the quest for the active constituents in Filipendula ulmaria (meadowsweet) — comprehensive phytochemical identification by liquid chromatography coupled to quadrupole-orbitrap mass spectrometryView study →}
Prickly rose (Rosa acicularis)	Leaf (and flower)	The best-quantified source: 18–41 mg/g dry wt leaf, 4 mg/g flower ^{6Reference 6Olennikov DN et al. · 2021Metabolites of prickly rose — chemodiversity and digestive-enzyme-inhibiting potential of Rosa acicularis and the main ellagitannin rugosin DView study →}
Rugosa rose (Rosa rugosa)	Flower petal	Type source of the 1982 isolation; qualitative ^{5Reference 5Okuda T et al. · 1982Rugosin D, E, F and G, dimeric and trimeric hydrolyzable tanninsView study →}
French rose (Rosa gallica)	Petal / bud	Reported among the petal ellagitannins; qualitative ^{6Reference 6Olennikov DN et al. · 2021Metabolites of prickly rose — chemodiversity and digestive-enzyme-inhibiting potential of Rosa acicularis and the main ellagitannin rugosin DView study →}
Cabbage rose (Rosa centifolia)	Petal	Identified in the DGAT-inhibitor screen; qualitative ^{7Reference 7Kondo H et al. · 2011Identification of diacylglycerol acyltransferase inhibitors from Rosa centifolia petalsView study →}

Discovery & Synthesis

Rugosin D was described in 1982 by Takuo Okuda, Tsutomu Hatano and Noboru Ogawa at Okayama University, in a Chemical and Pharmaceutical Bulletin paper reporting four new hydrolysable tannins from Rosa rugosa flower petals: the dimers rugosin D, E and F, each carrying a valoneoyl group, and the trimer rugosin G carrying two — with the orientation of the valoneoyl groups established as part of the structural work ^{5Reference 5Okuda T et al. · 1982Rugosin D, E, F and G, dimeric and trimeric hydrolyzable tanninsView study →}. The paper sits inside Okuda’s long programme mapping the oligomeric ellagitannins, which produced much of the vocabulary this field still uses.

There is no total synthesis of rugosin D, and no commercial production. Molecules of this class are obtained by extraction and chromatographic purification from plant material — which is why the analytical papers cited here start from rose leaf or petal rather than from a bottle. Biosynthetically it arises the way ellagitannins generally do: galloyl esters of glucose (via pentagalloylglucose) undergo oxidative C–C coupling to form HHDP groups, and a further intermolecular oxidative coupling joins two tellimagrandin II units through the valoneoyl bridge that defines the dimer.

Patents: not yet researched.

Toxicity & Safety

Rugosin D carries a low flag. It is a dietary hydrolysable tannin from edible flowers and a long-used herbal tea plant, with no reported specific organ toxicity; its cautions are the generic tannin-class ones, and its very poor absorption caps systemic risk. No dedicated toxicology study of the isolated molecule exists.

Safety at a Glance

Low / no toxicity

Long dietary and herbal exposure. Consumed for centuries in meadowsweet infusion and rose-petal tea as part of the tannin fraction, with no specific toxicity attributed to it.
Very poorly absorbed. At ~1,875 daltons it is essentially confined to the gut lumen, which limits systemic exposure.
Tannin-class cautions. Astringent polyphenols bind dietary protein and reduce non-heme iron absorption; concentrated tannin intake can cause gastric irritation, nausea or constipation, and matters most for people managing iron-deficiency anaemia.
No isolate safety data. There is no toxicology, genotoxicity or reproductive dataset for purified rugosin D — the low rating is inferred from dietary use and class behaviour, not measured.

Full Safety & Interactions Detail

Class behaviour, not molecule data. Everything known about rugosin D’s safety is inherited from hydrolysable tannins generally: reversible protein precipitation (the astringency you taste), chelation of non-heme iron and other divalent cations, and — at high concentrated intakes rather than tea-level ones — gastrointestinal irritation. Because tannins bind proteins non-specifically, they can in principle reduce the absorption of co-ingested drugs and of dietary minerals; separating a tannin-rich infusion from iron supplements or iron-rich meals is the standard, conservative precaution.

Herb-level context. Rugosin D’s practical exposure route is meadowsweet, whose own safety profile carries the salicylate cautions (aspirin/salicylate allergy, salicylate sensitivity, the class Reye’s-syndrome caution in children with viral illness) and a reported heparin-like anticoagulant fraction. Those belong to the herb and to its salicylic acid/salicin content, not to this tannin — see the meadowsweet monograph, where the decision about intake is actually made.

A theoretical mechanism-side caution. If HDC inhibition did operate in vivo, the consequence would be less histamine, which is the direction of benefit for gastric acid and for histamine-mediated symptoms rather than a hazard. Histamine also has physiological roles in neurotransmission and immune signalling, so a systemically active HDC inhibitor would need a proper safety evaluation — but nothing suggests a poorly absorbed tannin achieves systemic HDC inhibition, and this remains hypothetical.

Reproductive note (prose only). No reproductive-toxicity data exist for isolated rugosin D. Pregnancy and lactation decisions belong to the herb or product page where intake is decided, not to this molecule page.

Dosage

There is no dose for rugosin D. It is not sold as an isolate, no preparation is standardised to it, and no human study has administered it. Every quantity in the literature is one of three things:

Kind of number	Typical values	What it is
Enzyme inhibition constants	Ki ≈ 0.35–1 µM (human HDC); IC50 1.5 µM (bacterial HDC)	Test-tube kinetics ^{1,2Reference 1Nitta Y et al. · 2013Inhibitory activity of Filipendula ulmaria constituents on recombinant human histidine decarboxylaseView study →Reference 2Nitta Y et al. · 2016Inhibition of Morganella morganii histidine decarboxylase activity and histamine accumulation in mackerel muscle derived from Filipendula ulmaria extractsView study →}
In-vitro concentrations	~31–68 µg/mL (α-amylase); 10 µM (DGAT)	Cell-free assay concentrations ^{6,7Reference 6Olennikov DN et al. · 2021Metabolites of prickly rose — chemodiversity and digestive-enzyme-inhibiting potential of Rosa acicularis and the main ellagitannin rugosin DView study →Reference 7Kondo H et al. · 2011Identification of diacylglycerol acyltransferase inhibitors from Rosa centifolia petalsView study →}
Plant content	4–41 mg/g dry weight (prickly rose flower → leaf)	How much is in the plant, not how much reaches you ^{6Reference 6Olennikov DN et al. · 2021Metabolites of prickly rose — chemodiversity and digestive-enzyme-inhibiting potential of Rosa acicularis and the main ellagitannin rugosin DView study →}

Real-world exposure comes from meadowsweet infusion and rose-petal preparations, where rugosin D is one member of the tannin fraction and where the dose that matters is the herb’s, not the molecule’s. Because it is large and poorly absorbed, whatever it does it almost certainly does in the gut. Treat the numbers above as research figures, not recommendations.

References

Nitta Y, Kikuzaki H, Azuma T, Ye Y, Sakaue M, Higuchi Y, Komori H, Ueno H. (2013). Inhibitory activity of Filipendula ulmaria constituents on recombinant human histidine decarboxylase. Food Chemistry, 138(2–3), 1551–1556. https://pubmed.ncbi.nlm.nih.gov/23411280/
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