Sanguiin H-6

Sanguiin H-6 at a Glance

Sanguiin H-6 is a dimeric ellagitannin — a hydrolysable tannin of 1,871 Da (C₈₂H₅₄O₅₂) built from two casuarictin-type units joined by a sanguisorboyl ester bridge ^{1,28Reference 1Nonaka G et al. · 1982A dimeric hydrolyzable tannin, sanguiin H-6 from Sanguisorba officinalis LView study →Reference 28Yamada H et al. · 2018ReviewStructural revisions in natural ellagitannins — reviewView study →}. It is the signature molecule of the genus Rubus: the largest single polyphenol in a raspberry, and the compound that makes raspberries, blackberries and cloudberries register as ellagitannin foods at all ^{3,4,27Reference 3Mullen W et al. · 2002In vitroEllagitannins, flavonoids, and other phenolics in red raspberries and their contribution to antioxidant capacity and vasorelaxation properties — in vitroView study →Reference 4Kähkönen M et al. · 2012In vitroAntioxidant activity of isolated ellagitannins from red raspberries and cloudberries — in vitroView study →Reference 27Gasperotti M et al. · 2010Profiling and accurate quantification of Rubus ellagitannins and ellagic acid conjugates using direct UPLC-Q-TOF HDMS and HPLC-DAD analysisView study →}.

Its pharmacology in a person is almost entirely a story about not being absorbed. The molecule is too large and too polar to cross the gut wall intact; it hydrolyses to ellagic acid in the stomach and small intestine, and whatever survives to the colon is converted by resident bacteria into urolithins — small metabolites that do circulate, in amounts that vary enormously between people ^{7,8Reference 7González-Barrio R et al. · 2010Clinical trialBioavailability of anthocyanins and ellagitannins following consumption of raspberries by healthy human volunteers and subjects with an ileostomyView study →Reference 8Piwowarski JP et al. · 2014In vitroRole of human gut microbiota metabolism in the anti-inflammatory effect of traditionally used ellagitannin-rich plant materials — in vitroView study →}. No intact or conjugated sanguiin H-6 has ever been detected in human plasma or urine ^{7Reference 7González-Barrio R et al. · 2010Clinical trialBioavailability of anthocyanins and ellagitannins following consumption of raspberries by healthy human volunteers and subjects with an ileostomyView study →}. Every micromolar result in the cell literature below therefore describes a concentration reachable in the gut lumen, not in blood.

Within that constraint there is a real body of work: it is a potent catalytic inhibitor of both DNA topoisomerases, a direct blocker of VEGF binding to its receptor, and a repeatedly-reproduced suppressor of NF-κB-driven inflammatory signalling ^{9,10,16,18Reference 9Bastow KF et al. · 1993In vitroInhibition of DNA topoisomerases by sanguiin H-6, a cytotoxic dimeric ellagitannin from Sanguisorba officinalis — in vitroView study →Reference 10Lee SJ · 2005In vitroSanguiin H-6 blocks endothelial cell growth through inhibition of VEGF binding to VEGF receptor — in vitroView study →Reference 16Sangiovanni E et al. · 2013In vitroEllagitannins from Rubus berries for the control of gastric inflammation — in vitro and in vivo rat studiesView study →Reference 18Yokozawa T et al. · 2002In vitroEffects of sanguiin H-6, a component of Sanguisorbae Radix, on lipopolysaccharide-stimulated nitric oxide production — in vitroView study →}. None of it has been tested in a human being as the isolated molecule.

Dimer, Trimer and the Rubus Ellagitannin Family

Rubus ellagitannins are an oligomeric series built from the same repeating unit, and the family relationships matter for reading the literature:

Compound	Form	Approx. mass	Where it leads
Casuarictin	monomer	~936 Da	the repeating unit; a minor raspberry constituent 4Reference 4Kähkönen M et al. · 2012In vitroAntioxidant activity of isolated ellagitannins from red raspberries and cloudberries — in vitroView study →
Sanguiin H-6	dimer	1,871 Da	the dominant ellagitannin of raspberry and Rubus generally 3,27Reference 3Mullen W et al. · 2002In vitroEllagitannins, flavonoids, and other phenolics in red raspberries and their contribution to antioxidant capacity and vasorelaxation properties — in vitroView study →Reference 27Gasperotti M et al. · 2010Profiling and accurate quantification of Rubus ellagitannins and ellagic acid conjugates using direct UPLC-Q-TOF HDMS and HPLC-DAD analysisView study →
Lambertianin C	trimer	~2,805 Da	the same unit extended once more; second-most abundant in raspberry, most abundant in blackberry 3,16Reference 3Mullen W et al. · 2002In vitroEllagitannins, flavonoids, and other phenolics in red raspberries and their contribution to antioxidant capacity and vasorelaxation properties — in vitroView study →Reference 16Sangiovanni E et al. · 2013In vitroEllagitannins from Rubus berries for the control of gastric inflammation — in vitro and in vivo rat studiesView study →

Sanguiin H-6 and lambertianin C are the dimer and trimer of one another’s building block, which is why they are almost always reported together, respond alike in assays, and behave alike in the gut. Their one consistent practical difference is size: in juice processing, ellagitannin transfer falls more than tenfold as molecular mass rises from 1,568 to 2,805 Da, so the smaller sanguiin H-6 travels into juice better while the trimer stays behind in the press cake ^{22Reference 22Sójka M et al. · 2016Transfer and mass balance of ellagitannins, anthocyanins, flavan-3-ols and flavonols during the processing of red raspberries (Rubus idaeus L.) to juiceView study →}.

Two attributions worth separating out. First, strawberry is not a sanguiin H-6 plant in the way raspberry is. A dedicated structural study established that the main ellagitannin of both Fragaria vesca and F. ananassa is agrimoniin, a different dimer; sanguiin H-6 is present in strawberry but “at a much lower concentration,” and the two had previously been confused by chromatography ^{6Reference 6Vrhovsek U et al. · 2012Clarifying the identity of the main ellagitannin in the fruit of the strawberry, Fragaria vesca and Fragaria ananassa DuchView study →}. Second, sanguiin H-6 is not a Rubus exclusive — it was first isolated from great burnet (Sanguisorba officinalis), which is where its name comes from ^{1Reference 1Nonaka G et al. · 1982A dimeric hydrolyzable tannin, sanguiin H-6 from Sanguisorba officinalis LView study →}.

The Urolithin Pathway — What Actually Reaches You

This is the load-bearing fact about the molecule, and the reason it should never be read as a systemically-acting drug.

An ileostomy study traced the whole route directly. After 300 g of raspberries, 23% of the ingested sanguiin H-6 was recovered intact in ileal fluid, while recovery of ellagic acid ran to 241% of intake — meaning ellagitannins were being hydrolysed to free ellagic acid before they ever reached the colon. In healthy volunteers, plasma contained no detectable raspberry polyphenolics or their metabolites, and no intact or conjugated ellagitannin appeared in urine from either group. What did appear, 7–48 hours later and only in the intact-colon subjects, were urolithin A-O-glucuronide, two isomers, and urolithin B-O-glucuronide — with, in the authors’ words, marked variation between individuals reflecting differences in the colonic microflora ^{7Reference 7González-Barrio R et al. · 2010Clinical trialBioavailability of anthocyanins and ellagitannins following consumption of raspberries by healthy human volunteers and subjects with an ileostomyView study →}.

Ex-vivo work confirms the disappearance step: incubate post-raspberry ileal fluid with a faecal inoculum for 24 hours and sanguiin H-6 falls significantly while microbial catabolites rise ^{30Reference 30Dobani S et al. · 2021Ex vivo fecal fermentation of human ileal fluid collected after raspberry consumption modifies (poly)phenolics and modulates genoprotective effects in colonic epithelial cellsView study →}. And the pathway is not raspberry-specific — faecal incubation of an aqueous raspberry-leaf infusion (alongside meadowsweet, tormentil, oak bark, avens and others) produces urolithins A, B and C, and it is those metabolites that carry anti-inflammatory activity, urolithin A inhibiting TNF-α production at 0.625 µM ^{8Reference 8Piwowarski JP et al. · 2014In vitroRole of human gut microbiota metabolism in the anti-inflammatory effect of traditionally used ellagitannin-rich plant materials — in vitroView study →}.

Three consequences follow, and they frame everything below:

• Concentration-reachability. A 20 µM in-vitro effect is achievable in the gut lumen after a bowl of raspberries. It is not achievable in plasma at any realistic intake.
• Metabotype variation. People fall into three reproducible groups: metabotype A produces urolithin A only; metabotype B produces isourolithin A and urolithin B in addition to urolithin A; and metabotype 0 produces essentially none. The same dose of the same berry is not the same exposure in two different people ^{7Reference 7González-Barrio R et al. · 2010Clinical trialBioavailability of anthocyanins and ellagitannins following consumption of raspberries by healthy human volunteers and subjects with an ileostomyView study →}.
• Attribution. Where a whole-berry or whole-leaf human effect is real, the molecule doing the work downstream is more likely a urolithin — or free ellagic acid acting locally in the gut — than sanguiin H-6 itself.

What It's Used For

The isolate literature is genuine and mechanistically specific, but it is almost entirely in vitro, with two small rodent studies and no human trials of any kind.

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. Scores are capped hard here: there are no human trials of the isolated molecule at all, and the bioavailability ceiling applies to every row. Each application links to its write-up.

01Anti-inflammatory and gastroprotectiveShaky40%Isolate in vitro (NF-κB/IL-8 at 2.5 µM; iNOS at 25 µM) + two rodent studies, one of them the isolate ^{16,18,19Reference 16Sangiovanni E et al. · 2013In vitroEllagitannins from Rubus berries for the control of gastric inflammation — in vitro and in vivo rat studiesView study →Reference 18Yokozawa T et al. · 2002In vitroEffects of sanguiin H-6, a component of Sanguisorbae Radix, on lipopolysaccharide-stimulated nitric oxide production — in vitroView study →Reference 19Yokozawa T et al. · 2002AnimalPotential of sanguiin H-6 against oxidative damage in renal mitochondria and apoptosis mediated by peroxynitrite in vivo — rat studyView study →}

02AntioxidantShaky38%Preparative fractionation of raspberry/cloudberry; isolate and ellagitannin-fraction assays, no human outcome ^{3,4Reference 3Mullen W et al. · 2002In vitroEllagitannins, flavonoids, and other phenolics in red raspberries and their contribution to antioxidant capacity and vasorelaxation properties — in vitroView study →Reference 4Kähkönen M et al. · 2012In vitroAntioxidant activity of isolated ellagitannins from red raspberries and cloudberries — in vitroView study →}

03Antimicrobial and antibiofilmShaky32%Purified isolate vs. MRSA with a mouse wound model; isolate antifungal MIC ^{20,21Reference 20Aguilera-Correa JJ et al. · 2021AnimalSanguiin H-6 fractionated from cloudberry (Rubus chamaemorus) seeds can prevent methicillin-resistant Staphylococcus aureus biofilm development during wound infection — mouse modelView study →Reference 21Klewicka E et al. · 2016In vitroEllagitannins from raspberry (Rubus idaeus L.) fruit as natural inhibitors of Geotrichum candidum — in vitroView study →}

04Anticancer (in vitro)Shaky30%Rich mechanism across breast, ovarian, lung and endothelial lines — all cell culture, at concentrations plasma never reaches ^{9,10,11,12,13,14Reference 9Bastow KF et al. · 1993In vitroInhibition of DNA topoisomerases by sanguiin H-6, a cytotoxic dimeric ellagitannin from Sanguisorba officinalis — in vitroView study →Reference 10Lee SJ · 2005In vitroSanguiin H-6 blocks endothelial cell growth through inhibition of VEGF binding to VEGF receptor — in vitroView study →Reference 11Park EJ et al. · 2017In vitroCytotoxic effect of sanguiin H-6 on MCF-7 and MDA-MB-231 human breast carcinoma cells — in vitroView study →Reference 12Park EH et al. · 2016In vitroAssessment of the anti-metastatic properties of sanguiin H-6 in HUVECs and MDA-MB-231 human breast cancer cells — in vitroView study →Reference 13Lee D et al. · 2016In vitroInhibition of A2780 human ovarian carcinoma cell proliferation by a Rubus component, sanguiin H-6 — in vitroView study →Reference 14Ko H et al. · 2015In vitroSanguiin H6 suppresses TGF-β induction of the epithelial-mesenchymal transition and inhibits migration and invasion in A549 lung cancer — in vitroView study →}

05Bone and osteoclast inhibitionShaky26%One laboratory: RANKL-induced osteoclastogenesis in vitro plus a TNF-α mouse model ^{17Reference 17Sakai E et al. · 2016In vitroSanguiin H-6, a constituent of Rubus parvifolius L., inhibits RANKL-induced osteoclastogenesis and bone resorption in vitro and prevents TNF-α-induced osteoclast formation in miceView study →}

Mechanisms

The last row governs the rest. The topoisomerase and VEGF numbers are among the most potent in the whole ellagitannin literature, and they are also the least translatable: a 0.01 µM cell-free IC₅₀ is meaningless for a compound whose plasma concentration is zero.

Pharmacokinetics

Sanguiin H-6 is a 1,871 Da polyphenol with 52 oxygen atoms — about as far from a drug-like absorbable molecule as a natural product gets, and its human kinetics reflect that exactly. In ileostomy subjects, 23% of ingested sanguiin H-6 was recovered unchanged in ileal fluid within 4 hours, while ellagic acid recovery reached 241% of intake, evidencing net hydrolysis of ellagitannins in the stomach and small intestine. Plasma from healthy volunteers contained no detectable native raspberry polyphenolics or metabolites, and no intact or conjugated ellagitannin appeared in the urine of either group; urinary ellagic acid and its O-glucuronide accounted for <1% of intake ^{7Reference 7González-Barrio R et al. · 2010Clinical trialBioavailability of anthocyanins and ellagitannins following consumption of raspberries by healthy human volunteers and subjects with an ileostomyView study →}. The compounds that do circulate are the colonic-microbial catabolites: urolithin A-O-glucuronide (plus two isomers) and urolithin B-O-glucuronide, excreted 7–48 hours post-ingestion, with pronounced between-subject variation in the profile ^{7Reference 7González-Barrio R et al. · 2010Clinical trialBioavailability of anthocyanins and ellagitannins following consumption of raspberries by healthy human volunteers and subjects with an ileostomyView study →}. Faecal fermentation reproduces the disappearance step directly — sanguiin H-6 and sanguiin H-10 fall significantly over 24 hours as phenolic catabolites rise ^{30Reference 30Dobani S et al. · 2021Ex vivo fecal fermentation of human ileal fluid collected after raspberry consumption modifies (poly)phenolics and modulates genoprotective effects in colonic epithelial cellsView study →} — and raspberry leaf infusion behaves the same way, yielding urolithins A, B and C on incubation with human faecal microbiota ^{8Reference 8Piwowarski JP et al. · 2014In vitroRole of human gut microbiota metabolism in the anti-inflammatory effect of traditionally used ellagitannin-rich plant materials — in vitroView study →}.

There is no half-life, no peak plasma concentration, no oral bioavailability figure for the parent compound, because it has never been measured in circulation. Practically, its distribution volume is the gut lumen; its pharmacologically relevant descendants are ellagic acid (locally, in the upper gut) and the urolithins (systemically, if your microbiota makes them).

Clinical Trials

None. Sanguiin H-6 has never been administered to human beings as a purified compound in any registered or published trial. The human data adjacent to it are all whole-food or whole-herb: a randomised crossover trial of raspberry-leaf tea (10 g infusion, 22 healthy adults) that blunted postprandial glucose and insulin after sucrose — an effect the authors attribute chiefly to ellagic acid inhibiting α-glucosidase and β-fructofuranosidase, not to the intact ellagitannin ^{26Reference 26Alkhudaydi HMS · 2025RCTEffects of raspberry leaf tea polyphenols on postprandial glucose and insulin responses in healthy adults — randomized crossover trialView study →} — and the raspberry-feeding bioavailability and ileostomy work described above ^{7,30Reference 7González-Barrio R et al. · 2010Clinical trialBioavailability of anthocyanins and ellagitannins following consumption of raspberries by healthy human volunteers and subjects with an ileostomyView study →Reference 30Dobani S et al. · 2021Ex vivo fecal fermentation of human ileal fluid collected after raspberry consumption modifies (poly)phenolics and modulates genoprotective effects in colonic epithelial cellsView study →}.

Last checked: August 2026.

Isolate vs. Plant Studies

This molecule sits at the awkward end of the isolate-vs-plant problem: the isolate work is good and the plant work is human, and the two do not join up.

On the isolate side, most of the mechanistic papers used genuinely purified sanguiin H-6 — Bastow’s topoisomerase assays, Lee’s VEGF-binding work, the breast and ovarian apoptosis studies, Sakai’s osteoclast work, and Aguilera-Correa’s MRSA experiments all tested the compound itself ^{9,10,11,13,17,20Reference 9Bastow KF et al. · 1993In vitroInhibition of DNA topoisomerases by sanguiin H-6, a cytotoxic dimeric ellagitannin from Sanguisorba officinalis — in vitroView study →Reference 10Lee SJ · 2005In vitroSanguiin H-6 blocks endothelial cell growth through inhibition of VEGF binding to VEGF receptor — in vitroView study →Reference 11Park EJ et al. · 2017In vitroCytotoxic effect of sanguiin H-6 on MCF-7 and MDA-MB-231 human breast carcinoma cells — in vitroView study →Reference 13Lee D et al. · 2016In vitroInhibition of A2780 human ovarian carcinoma cell proliferation by a Rubus component, sanguiin H-6 — in vitroView study →Reference 17Sakai E et al. · 2016In vitroSanguiin H-6, a constituent of Rubus parvifolius L., inhibits RANKL-induced osteoclastogenesis and bone resorption in vitro and prevents TNF-α-induced osteoclast formation in miceView study →Reference 20Aguilera-Correa JJ et al. · 2021AnimalSanguiin H-6 fractionated from cloudberry (Rubus chamaemorus) seeds can prevent methicillin-resistant Staphylococcus aureus biofilm development during wound infection — mouse modelView study →}. That is a strength, and it is why the mechanism table can name specific targets.

On the plant side, everything with a living subject used a mixture. The rat gastroprotection study dosed a crude Rubus ellagitannin extract, with the isolate tested only in cell culture ^{16Reference 16Sangiovanni E et al. · 2013In vitroEllagitannins from Rubus berries for the control of gastric inflammation — in vitro and in vivo rat studiesView study →}. The Caco-2 genotoxicity work ran a raspberry ellagitannin preparation alongside the two purified compounds ^{15Reference 15Nowak A et al. · 2017In vitroEllagitannins from Rubus idaeus L. exert geno- and cytotoxic effects against human colon adenocarcinoma cell line Caco-2 — in vitroView study →}. The human raspberry and raspberry-leaf studies dosed fruit and tea ^{7,26,30Reference 7González-Barrio R et al. · 2010Clinical trialBioavailability of anthocyanins and ellagitannins following consumption of raspberries by healthy human volunteers and subjects with an ileostomyView study →Reference 26Alkhudaydi HMS · 2025RCTEffects of raspberry leaf tea polyphenols on postprandial glucose and insulin responses in healthy adults — randomized crossover trialView study →Reference 30Dobani S et al. · 2021Ex vivo fecal fermentation of human ileal fluid collected after raspberry consumption modifies (poly)phenolics and modulates genoprotective effects in colonic epithelial cellsView study →}. And where the class-level activity of an ellagitannin plant material has been dissected, the active species turned out to be microbial metabolites the plant does not contain ^{8Reference 8Piwowarski JP et al. · 2014In vitroRole of human gut microbiota metabolism in the anti-inflammatory effect of traditionally used ellagitannin-rich plant materials — in vitroView study →}.

Two further caveats travel with this compound specifically. Purified sanguiin H-6, purified lambertianin C and the crude preparation gave identical antifungal MIC and MFC values ^{21Reference 21Klewicka E et al. · 2016In vitroEllagitannins from raspberry (Rubus idaeus L.) fruit as natural inhibitors of Geotrichum candidum — in vitroView study →} — a plain signal that some of its activity is generic hydrolysable-tannin chemistry rather than anything molecule-specific. And Rubus ellagitannin content varies severalfold with species, cultivar, harvest and processing ^{22,24,27Reference 22Sójka M et al. · 2016Transfer and mass balance of ellagitannins, anthocyanins, flavan-3-ols and flavonols during the processing of red raspberries (Rubus idaeus L.) to juiceView study →Reference 24Oszmiański J et al. · 2015In vitroDetermination of phenolic compounds and antioxidant activity in leaves from wild Rubus L. species — in vitroView study →Reference 27Gasperotti M et al. · 2010Profiling and accurate quantification of Rubus ellagitannins and ellagic acid conjugates using direct UPLC-Q-TOF HDMS and HPLC-DAD analysisView study →}, so a result obtained with one cultivar’s extract does not transfer cleanly to another’s.

Its Role in Plants

Sanguiin H-6 belongs to the oxidative branch of the hydrolysable-tannin pathway: β-pentagalloyl-D-glucose — itself assembled from gallic acid esterified onto glucose — is oxidatively coupled to form the hexahydroxydiphenoyl (HHDP) groups that define an ellagitannin, and further phenolic coupling then links monomers into dimers and larger oligomers ^{28Reference 28Yamada H et al. · 2018ReviewStructural revisions in natural ellagitannins — reviewView study →}. In Rubus the repeating unit is casuarictin; two of them joined through a sanguisorboyl (galloyl-O-galloyl) bridge give sanguiin H-6, and a third gives lambertianin C ^{4,27Reference 4Kähkönen M et al. · 2012In vitroAntioxidant activity of isolated ellagitannins from red raspberries and cloudberries — in vitroView study →Reference 27Gasperotti M et al. · 2010Profiling and accurate quantification of Rubus ellagitannins and ellagic acid conjugates using direct UPLC-Q-TOF HDMS and HPLC-DAD analysisView study →}.

Functionally these are defence polyphenols. Their astringency — the capacity to bind and precipitate proteins — is what deters herbivores and inhibits microbial and fungal growth on the plant surface, and it is the same chemistry that produces the antibacterial and antifungal MICs above ^{20,21Reference 20Aguilera-Correa JJ et al. · 2021AnimalSanguiin H-6 fractionated from cloudberry (Rubus chamaemorus) seeds can prevent methicillin-resistant Staphylococcus aureus biofilm development during wound infection — mouse modelView study →Reference 21Klewicka E et al. · 2016In vitroEllagitannins from raspberry (Rubus idaeus L.) fruit as natural inhibitors of Geotrichum candidum — in vitroView study →}. Concentration tracks that role: the compound is densest in the vegetative tissue a plant most needs to protect, with dried young raspberry shoots carrying 139–633 mg/100 g, several times the fresh fruit ^{5Reference 5Krauze-Baranowska M et al. · 2014In vitroChemical composition and biological activity of Rubus idaeus shoots — a traditional herbal remedy of Eastern Europe — in vitroView study →}.

Prevalence in Nature

Sanguiin H-6 is a Rosaceae molecule, concentrated in Rubus, where a review counts it in roughly 22 species of the genus ^{2Reference 2Gesek J et al. · 2021ReviewSanguiins — promising molecules with broad biological potential — reviewView study →}.

In Rubus fruit. It is the main ellagitannin of red raspberry: 76 mg/100 g fresh weight in the Glen Ample cultivar (with lambertianin C at 31 mg/100 g) ^{3Reference 3Mullen W et al. · 2002In vitroEllagitannins, flavonoids, and other phenolics in red raspberries and their contribution to antioxidant capacity and vasorelaxation properties — in vitroView study →}, and 0.4% w/w of a commercial freeze-dried raspberry powder ^{23Reference 23Marino M et al. · 2024Nutritional and phytochemical characterization of freeze-dried raspberry (Rubus idaeus) — a comprehensive analysisView study →}. Ellagitannins make up about 64% of raspberry’s total polyphenols, and they concentrate in the press cake — 98% of the residue’s polyphenols after juicing, with 68% of the fruit’s ellagitannins retained there ^{22Reference 22Sójka M et al. · 2016Transfer and mass balance of ellagitannins, anthocyanins, flavan-3-ols and flavonols during the processing of red raspberries (Rubus idaeus L.) to juiceView study →}. In an ellagitannin preparation from fresh fruit (155 mg total ellagitannins per 100 g raspberry, 343 mg per 100 g blackberry), sanguiin H-6 accounted for 19% of raspberry’s and 12% of blackberry’s ellagitannin fraction, with lambertianin C taking the larger share in blackberry ^{16Reference 16Sangiovanni E et al. · 2013In vitroEllagitannins from Rubus berries for the control of gastric inflammation — in vitro and in vivo rat studiesView study →}. In cloudberry it is likewise one of the two dominant ellagitannins with lambertianin C ^{4Reference 4Kähkönen M et al. · 2012In vitroAntioxidant activity of isolated ellagitannins from red raspberries and cloudberries — in vitroView study →}.

In Rubus leaf and shoot — the herbal exposure. This is where the source herb here sits, and the data are patchier than for fruit. Dried young raspberry shoots are a rich and directly quantified source at 139.2–633.1 mg/100 g, with ellagic acid at 26.1–106.8 mg/100 g ^{5Reference 5Krauze-Baranowska M et al. · 2014In vitroChemical composition and biological activity of Rubus idaeus shoots — a traditional herbal remedy of Eastern Europe — in vitroView study →}. Across 26 wild Rubus (blackberry) leaf samples, ellagic acid derivatives were the predominant phenolics — though that paper’s prose and its table disagree, and the table is what counts: sanguiin H-6 runs nd–73.9 mg/g dry matter against casuarinin’s 34.8–117.9 (the highest mean of the three) and lambertianin C’s 5.7–123.4 ^{24Reference 24Oszmiański J et al. · 2015In vitroDetermination of phenolic compounds and antioxidant activity in leaves from wild Rubus L. species — in vitroView study →}. In blackberry leaf, sanguiin H-6 is not the leading ellagitannin; it has also been identified in cloudberry leaf ^{2Reference 2Gesek J et al. · 2021ReviewSanguiins — promising molecules with broad biological potential — reviewView study →}. Raspberry leaf specifically has no published sanguiin H-6 figure. The one dedicated LC-MS/MS study of raspberry leaf reports ellagitannins as the predominant polyphenol class (155–394 mg/100 g) but quantifies them as ellagic acid and does not name sanguiin H-6 among its targets ^{25Reference 25Alkhudaydi HMS et al. · 2025Determination of the polyphenol composition of raspberry leaf using LC-MS/MSView study →} — so the leaf is confidently an ellagitannin material (its infusion yields urolithins on faecal incubation ^{8Reference 8Piwowarski JP et al. · 2014In vitroRole of human gut microbiota metabolism in the anti-inflammatory effect of traditionally used ellagitannin-rich plant materials — in vitroView study →}) without a molecule-level number. The shoot figures are the closest real quantitation, and are not a substitute.

Outside Rubus. The molecule takes its name from great burnet (Sanguisorba officinalis), from whose root it was first isolated and where it remains a characterised constituent of the traditional drug Sanguisorbae Radix ^{1,18Reference 1Nonaka G et al. · 1982A dimeric hydrolyzable tannin, sanguiin H-6 from Sanguisorba officinalis LView study →Reference 18Yokozawa T et al. · 2002In vitroEffects of sanguiin H-6, a component of Sanguisorbae Radix, on lipopolysaccharide-stimulated nitric oxide production — in vitroView study →}. In strawberry it is a genuine but minor constituent — the dominant Fragaria ellagitannin is agrimoniin, and the two were historically confused ^{6Reference 6Vrhovsek U et al. · 2012Clarifying the identity of the main ellagitannin in the fruit of the strawberry, Fragaria vesca and Fragaria ananassa DuchView study →}. It is also reported from Rubus coreanus (Korean black raspberry / bokbunja), the source used in much of the Korean anticancer work ^{10,11Reference 10Lee SJ · 2005In vitroSanguiin H-6 blocks endothelial cell growth through inhibition of VEGF binding to VEGF receptor — in vitroView study →Reference 11Park EJ et al. · 2017In vitroCytotoxic effect of sanguiin H-6 on MCF-7 and MDA-MB-231 human breast carcinoma cells — in vitroView study →}, and from Rubus parvifolius ^{17Reference 17Sakai E et al. · 2016In vitroSanguiin H-6, a constituent of Rubus parvifolius L., inhibits RANKL-induced osteoclastogenesis and bone resorption in vitro and prevents TNF-α-induced osteoclast formation in miceView study →}. Related Rosaceae berries that register as ellagitannin sources in food-composition surveys — cloudberry, raspberry, rose hip, strawberry, sea buckthorn — do so on total ellagitannin measured as ellagic-acid equivalents (1–330 mg/100 g), not on sanguiin H-6 assayed directly ^{31Reference 31Koponen JM et al. · 2007Contents of anthocyanins and ellagitannins in selected foods consumed in FinlandView study →}.

Discovery & Synthesis

Sanguiin H-6 was isolated and named in 1982 by Genichiro Nonaka, Takashi Tanaka, Meiko Nita and Itsuo Nishioka at Kyushu University, from the root of great burnet, Sanguisorba officinalis — hence the name, with “H” marking its place in the sanguiin series ^{1Reference 1Nonaka G et al. · 1982A dimeric hydrolyzable tannin, sanguiin H-6 from Sanguisorba officinalis LView study →}. The structure they published was not correct in two respects, and the same group revised it three years later: the sanguisorboyl bridge was reassigned from O-2/O-4 to O-4/O-6 (moving the HHDP group to O-2/O-3), and the axial chirality of the sanguisorboyl group was changed from R to S ^{28Reference 28Yamada H et al. · 2018ReviewStructural revisions in natural ellagitannins — reviewView study →}. It is a useful reminder for anyone reading pre-1985 ellagitannin literature.

Its identity as the dominant Rubus ellagitannin came later, through the berry-chemistry literature of the 2000s — Mullen’s HPLC-MS work on Glen Ample raspberries in 2002 ^{3Reference 3Mullen W et al. · 2002In vitroEllagitannins, flavonoids, and other phenolics in red raspberries and their contribution to antioxidant capacity and vasorelaxation properties — in vitroView study →} and the first accurate quantification using purified sanguiin H-6 and lambertianin C as external standards in 2010 ^{27Reference 27Gasperotti M et al. · 2010Profiling and accurate quantification of Rubus ellagitannins and ellagic acid conjugates using direct UPLC-Q-TOF HDMS and HPLC-DAD analysisView study →}.

No total synthesis of sanguiin H-6 has been reported. Ellagitannin total synthesis is a hard, active field — the monomeric sanguiin H-5 and corilagin have been made — but this dimer, with two macrocyclic glucose cores and an atropisomeric biaryl bridge, has not. Supply is therefore extraction only, and the practical sources are food-industry by-products: raspberry press cake extracted onto Amberlite XAD resin and purified by preparative HPLC ^{21Reference 21Klewicka E et al. · 2016In vitroEllagitannins from raspberry (Rubus idaeus L.) fruit as natural inhibitors of Geotrichum candidum — in vitroView study →}, or cloudberry seed ^{20Reference 20Aguilera-Correa JJ et al. · 2021AnimalSanguiin H-6 fractionated from cloudberry (Rubus chamaemorus) seeds can prevent methicillin-resistant Staphylococcus aureus biofilm development during wound infection — mouse modelView study →}. Since press cake retains 68% of the fruit’s ellagitannins and 98% of its residual polyphenols are tannins, the juice industry’s waste stream is the natural feedstock ^{22Reference 22Sójka M et al. · 2016Transfer and mass balance of ellagitannins, anthocyanins, flavan-3-ols and flavonols during the processing of red raspberries (Rubus idaeus L.) to juiceView study →}.

Patents: not yet researched.

Toxicity & Safety

Sanguiin H-6 carries a low flag: it is a constituent of foods eaten in quantity for as long as people have eaten berries, it is not absorbed intact, and no in-vivo toxicity signal exists — the one rodent study of the isolate (10 mg/kg/day for 30 days) was protective ^{19Reference 19Yokozawa T et al. · 2002AnimalPotential of sanguiin H-6 against oxidative damage in renal mitochondria and apoptosis mediated by peroxynitrite in vivo — rat studyView study →}. The caveats below are real but bounded, and two of them are hydrolysable-tannin class properties rather than anything specific to this molecule.

Safety at a Glance

✅ Low / no toxicity

• A well-established dietary compound. The largest polyphenol in a raspberry, consumed at tens of milligrams per serving with no signal of harm.
• Poorly absorbed, which cuts both ways. The same barrier that blocks systemic efficacy also blocks systemic toxicity.
• Genotoxic to colon cells in vitro at food-relevant concentrations. Purified sanguiin H-6 caused concentration-dependent DNA damage, double-strand breaks and base oxidation in Caco-2 cells — and the authors state the concentrations correspond to those found in raspberry-containing foods.
• Tannin astringency. Protein-binding is the mechanism of its antimicrobial and astringent action; heavy tannin intake is markedly drying and can hinder iron, mineral and protein absorption.
• No isolate safety data in humans. No dose-ranging, no repeat-dose toxicology, no interaction studies of the purified molecule.

Full Safety & Interactions Detail

The Caco-2 genotoxicity finding. This is the one flag worth taking seriously and the one most easily misread. A raspberry ellagitannin preparation (2.5–160 µg/mL) and the purified individual compounds — sanguiin H-6 at 12.8–256 µM and lambertianin C at 9.3–378 µM — produced strong concentration-dependent genotoxicity in human colon adenocarcinoma Caco-2 cells, inducing DNA damage from 7.3% to 56.8% with double-strand breaks and oxidation of DNA bases; at IC₅₀ (124 µg/mL) the preparation altered nuclear morphology and induced apoptosis. Crucially, the authors state the concentrations used correspond to those found in foodstuffs containing raspberry fruit — so this is a luminal-realistic exposure, not an artefact of extreme dosing ^{15Reference 15Nowak A et al. · 2017In vitroEllagitannins from Rubus idaeus L. exert geno- and cytotoxic effects against human colon adenocarcinoma cell line Caco-2 — in vitroView study →}. Two things temper it. First, the same authors frame the result as chemopreventive: Caco-2 is a colon cancer line, and killing transformed colonocytes is the intended reading. Second, ex-vivo work in the opposite direction exists — post-raspberry ileal fermentate reduced oxidative DNA damage by ~30% in the normal colonocyte line CCD 841 CoN and induced Nrf2-ARE cytoprotective genes ^{30Reference 30Dobani S et al. · 2021Ex vivo fecal fermentation of human ileal fluid collected after raspberry consumption modifies (poly)phenolics and modulates genoprotective effects in colonic epithelial cellsView study →}. No in-vivo genotoxicity signal has been reported for either compound, and no epidemiology links berry intake to colorectal harm. Treat it as an unresolved in-vitro finding that argues against megadosing concentrated ellagitannin extracts, not against eating raspberries.

Tannin-class effects. As a large hydrolysable tannin, sanguiin H-6 binds and precipitates proteins — the basis of its astringency, of the raspberry-leaf tradition of astringent use, and of the mg/mL antibacterial and antifungal MICs ^{20,21Reference 20Aguilera-Correa JJ et al. · 2021AnimalSanguiin H-6 fractionated from cloudberry (Rubus chamaemorus) seeds can prevent methicillin-resistant Staphylococcus aureus biofilm development during wound infection — mouse modelView study →Reference 21Klewicka E et al. · 2016In vitroEllagitannins from raspberry (Rubus idaeus L.) fruit as natural inhibitors of Geotrichum candidum — in vitroView study →}. The general tannin cautions apply to concentrated preparations: pronounced dryness and puckering, potential interference with non-haem iron and other mineral absorption, and reduced protein availability when intakes are high. These are class properties; they have not been quantified for this molecule.

Interactions. No drug-interaction study of sanguiin H-6 exists — nothing on CYP isoforms, P-glycoprotein, or any transporter. Silence here is absence of data, not evidence of safety. Two mechanistic considerations are worth stating without overstating: the compound is a catalytic topoisomerase I and II inhibitor in cell-free systems ^{9Reference 9Bastow KF et al. · 1993In vitroInhibition of DNA topoisomerases by sanguiin H-6, a cytotoxic dimeric ellagitannin from Sanguisorba officinalis — in vitroView study →} and a VEGF-receptor binding blocker ^{10Reference 10Lee SJ · 2005In vitroSanguiin H-6 blocks endothelial cell growth through inhibition of VEGF binding to VEGF receptor — in vitroView study →}, so a theoretical concern about concentrated extracts alongside topoisomerase-targeted chemotherapy or anti-angiogenic therapy is arguable — but the compound does not reach plasma, which makes the concern largely academic at dietary intakes. Because the active downstream species are microbial urolithins, anything that reshapes the colonic microbiota (antibiotics in particular) will change real exposure more than any pharmacokinetic interaction would ^{7,8Reference 7González-Barrio R et al. · 2010Clinical trialBioavailability of anthocyanins and ellagitannins following consumption of raspberries by healthy human volunteers and subjects with an ileostomyView study →Reference 8Piwowarski JP et al. · 2014In vitroRole of human gut microbiota metabolism in the anti-inflammatory effect of traditionally used ellagitannin-rich plant materials — in vitroView study →}.

Reproductive note (prose only). There is no reproductive or developmental toxicity dataset for isolated sanguiin H-6. This is relevant context for raspberry leaf, a herb with a strong late-pregnancy tradition, but pregnancy and lactation decisions belong to the raspberry leaf monograph, where intake is actually decided, not to a molecule page. Note also that no repeat-dose, carcinogenicity or reproductive package exists for the isolate at all — the safety position rests on dietary history and non-absorption.

Dosage

There is no dose. Sanguiin H-6 is not sold as a supplement, has never been given to a person as a purified compound, and has no established or studied human dose. What exists is dietary and research exposure:

The raspberry-leaf figure is worth holding onto, because the herbal literature rarely offers this: the 10 g infusion used in the human crossover trial is an ordinary cup of tea, so the ~38 mg of ellagitannins it delivers is a realistic real-world exposure rather than an extract-only number ^{26Reference 26Alkhudaydi HMS · 2025RCTEffects of raspberry leaf tea polyphenols on postprandial glucose and insulin responses in healthy adults — randomized crossover trialView study →}. Content varies severalfold with species, cultivar, harvest time and preparation ^{22,24Reference 22Sójka M et al. · 2016Transfer and mass balance of ellagitannins, anthocyanins, flavan-3-ols and flavonols during the processing of red raspberries (Rubus idaeus L.) to juiceView study →Reference 24Oszmiański J et al. · 2015In vitroDetermination of phenolic compounds and antioxidant activity in leaves from wild Rubus L. species — in vitroView study →}, so treat all of these as ranges. These are figures from research and food analysis, not a personal recommendation.

References

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