Punicalagin

Punicalagin at a Glance

Punicalagin is the largest and most abundant polyphenol in the pomegranate, and one of the largest single secondary metabolites routinely consumed by people. It is a gallagyl-type ellagitannin — a glucose core carrying a hexahydroxydiphenoyl (HHDP) group at positions 2 and 3 and a gallagyl group, an unusual four-ring dimer of gallic acid, bridging positions 4 and 6. The result is C₄₈H₂₈O₃₀, molecular weight 1084.7, with thirty oxygens and seventeen free phenolic hydroxyls. That size and that hydroxyl density explain nearly everything about the molecule: it is a phenomenal radical scavenger and protein binder in a test tube, and it is far too large and too polar to cross a gut wall.

The molecule has an outsized reputation because pomegranate has an outsized evidence base. Pomegranate juice and extract have been through real randomised trials in real numbers — blood pressure, lipids, oxidative-stress markers — and punicalagin is by far the biggest phenolic peak in the preparation those trials used. It is therefore constantly named as the active. That inference is where it has to be careful, because two facts sit in the way of it.

The first is bioavailability. When six healthy volunteers drank a litre of pomegranate juice a day for five days — 4.37 g/L of punicalagin isomers, so more than 4 g of the molecule daily — neither punicalagin nor ellagic acid was detected in plasma or urine at all ^{5Reference 5Cerdá B et al. · 2004In vitroThe potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy-6H-dibenzopyran-6-one derivatives by the colonic microflora of healthy humansView study →}. What appeared instead were dibenzopyranone metabolites (what we now call urolithins) reaching up to 18.6 µM, with urinary recovery varying between individuals from 0.7% to 52.7% of the dose. The same study found those metabolites were poor antioxidants relative to punicalagin itself — so the molecule that does the antioxidant chemistry stays in the gut, and the molecules that reach the blood mostly don’t do it.

The second is provenance. Punicalagin is concentrated in the peel, not the fruit you eat. Juice pressed from arils alone contains only traces of it; commercial juice contains grams per litre because industrial pressing squeezes the rind ^{3Reference 3Gil MI et al. · 2000Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processingView study →}. Most “pomegranate extract” sold as a supplement is a husk extract standardised to punicalagin. The compound’s dietary story is therefore a story about food processing as much as about botany.

The α & β Anomers

Punicalagin is almost never one compound. The glucose core’s anomeric centre is free, so the molecule exists as an interconverting pair of anomers — α-punicalagin and β-punicalagin, universally reported as “punicalagin A and B” or simply “punicalagin isomers”. They separate cleanly on HPLC as two peaks, which is why quantitative papers so often report two numbers for what buyers and reviewers treat as one substance.

The interconversion is fast and spontaneous in solution. When Gosset-Erard and colleagues purified both forms from pomegranate peel and tested them separately, they found the two converted readily into one another and settled at an α/β equilibrium ratio of about 3:7 — and, importantly, that both forms were antibacterially active ^{14Reference 14Gosset-Erard C et al. · 2021Identification of punicalagin as the bioactive compound behind the antimicrobial activity of pomegranate (Punica granatum L.) peelsView study →}. Preparative isolation of a single anomer is therefore a temporary achievement: leave it in solution and you get the mixture back.

Three practical consequences follow, and they are under-stated in the literature:

• Quantitation is ambiguous unless the paper says what it summed. A “punicalagin” figure may be the α peak, the β peak, or both. Which anomer dominates also depends on the material: one four-cultivar peel survey gave punicalagin A at 7,206 mg/kg against punicalagin B at 5,813 mg/kg in the same extract ^{45Reference 45Gigliobianco MR et al. · 2022Chemical, antioxidant, and antimicrobial properties of the peel and male flower by-products of four varieties of Punica granatum L. cultivated in the Marche region for their use in cosmetic productsView study →}, the reverse of the 3:7 equilibrium ratio measured in pure solution ^{14Reference 14Gosset-Erard C et al. · 2021Identification of punicalagin as the bioactive compound behind the antimicrobial activity of pomegranate (Punica granatum L.) peelsView study →}. The numbers here are α + β sums wherever the source allowed it.
• A “pure punicalagin” standard is a mixture. Commercial reference material is sold as “punicalagin A&B”. Bioassay results attributed to punicalagin are therefore anomer-mixture results, essentially always.
• Nobody has separated the pharmacology. No study here distinguishes an activity of α from an activity of β. Given how fast they equilibrate, it is not obvious the distinction is even experimentally accessible in a cell assay.

This is a real contrast with the other C-glycosidic and HHDP ellagitannins here. Castalagin and vescalagin are C-1 epimers whose activities genuinely diverge and do not interconvert, because a carbon–carbon bond locks their configuration. Punicalagin’s anomers are the opposite case: chemically distinguishable, biologically inseparable.

Peel, Juice and What “Pomegranate Extract” Means

The most decision-relevant fact about punicalagin supply is that the fruit’s edible part is the poor source. Fischer’s HPLC-MS survey of pomegranate tissues found punicalagin at 11–20 g per kilogram of dry matter in peel and mesocarp — one to two percent of the dry weight of the rind — against 4 to 565 mg/L across differently produced juices, a more than hundredfold spread that tracked directly with how much peel the pressing method involved ^{4Reference 4Fischer UA et al. · 2011Identification and quantification of phenolic compounds from pomegranate (Punica granatum L.) peel, mesocarp, aril and differently produced juices by HPLC-DAD-ESI/MSⁿView study →}.

Gil’s earlier work made the same point more starkly: commercial pomegranate juices contained 1,500–1,900 mg/L of punicalagin, while juice pressed in the laboratory from arils only contained mere traces — and the commercial juices were correspondingly more antioxidant ^{3Reference 3Gil MI et al. · 2000Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processingView study →}. The 2004 human bioavailability study used a juice at 4,370 mg/L, at the top of the commercial range ^{5Reference 5Cerdá B et al. · 2004In vitroThe potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy-6H-dibenzopyran-6-one derivatives by the colonic microflora of healthy humansView study →}.

So:

• Aril juice and fresh seeds deliver anthocyanins, sugars and a little ellagic acid, and almost no punicalagin.
• Commercial whole-fruit juice delivers grams per litre, because the rind is in the press.
• “Pomegranate extract” capsules are usually husk extracts standardised to punicalagin — the ingredient used in the human supplement trials here is a peel-derived extract standardised to 30% punicalagin ^{33Reference 33Quirós-Fernández R et al. · 2022RCTOral supplement containing hydroxytyrosol and punicalagin improves dyslipidemia in an adult population without co-adjuvant treatment — a randomized, double-blind, controlled and crossover trialView study →}.

That inversion is why the pomegranate industry’s largest waste stream is also its most valuable one, and why “pomegranate” on a supplement label almost always means the part of the fruit you throw away.

And the method decides the number as much as the tissue does. Fischer’s HPLC-DAD survey put peel and mesocarp at 11–20 g/kg dry matter — about 11–20 mg per gram ^{4Reference 4Fischer UA et al. · 2011Identification and quantification of phenolic compounds from pomegranate (Punica granatum L.) peel, mesocarp, aril and differently produced juices by HPLC-DAD-ESI/MSⁿView study →}. Optimised ultrasonic-assisted extraction of the same tissue, at 53% ethanol and 757 W for 25 minutes, returned a punicalagin yield of 505.89 ± 1.73 mg/g dry weight ^{16Reference 16Liu Y et al. · 2022Pomegranate peel-derived punicalagin — ultrasonic-assisted extraction, purification, and its α-glucosidase inhibitory mechanismView study →}. Both figures are real, both were measured properly, and they differ by roughly thirtyfold — because one is a survey of what is in the tissue and the other is the output of a process tuned to pull as much of it out as possible.

The practical consequence is that “standardised to punicalagin” means nothing without the method attached. A percentage on a label is a property of an extraction, not of a plant, and two products carrying the same number can be describing different things.

What It's Used For

Punicalagin’s pharmacology divides sharply into two piles that are constantly conflated. The larger pile is pomegranate: juice and extract trials, real randomised human data, punicalagin named as the presumed active. The smaller pile is punicalagin: purified-molecule assays, overwhelmingly in vitro, at micromolar-to-millimolar concentrations that plasma will never see. Almost every claim below belongs to one pile or the other, and the page labels which.

Evidence by IndicationStrength of support · Beta

01Cardiovascular — the pomegranate preparationPromising54%RCT meta-analyses of pomegranate juice/extract; punicalagin is the presumed but unproven active ^{30,31Reference 30Sahebkar A et al. · 2017Meta-analysisEffects of pomegranate juice on blood pressure — a systematic review and meta-analysis of randomized controlled trialsView study →Reference 31Bahari H et al. · 2024Meta-analysisThe effects of pomegranate consumption on blood pressure in adults — a systematic review and meta-analysisView study →}

02The punicalagin-dosed supplement trialsShaky42%Two crossover RCTs of 195 mg/day punicalagin + hydroxytyrosol, one group, industry-sponsored ^{32,33Reference 32Quirós-Fernández R et al. · 2019RCTSupplementation with hydroxytyrosol and punicalagin improves early atherosclerosis markers involved in the asymptomatic phase of atherosclerosis in the adult population — a randomized, placebo-controlled, crossover trialView study →Reference 33Quirós-Fernández R et al. · 2022RCTOral supplement containing hydroxytyrosol and punicalagin improves dyslipidemia in an adult population without co-adjuvant treatment — a randomized, double-blind, controlled and crossover trialView study →}

03Antiviral — blocking glycosaminoglycan-dependent entryShaky40%Purified punicalagin across six viruses in cell culture, with a defined mechanism; no in-vivo data ^{18,19,20Reference 18Lin LT et al. · 2011Hydrolyzable tannins (chebulagic acid and punicalagin) target viral glycoprotein–glycosaminoglycan interactions to inhibit herpes simplex virus 1 entry and cell-to-cell spreadView study →Reference 19Lin LT et al. · 2013Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entryView study →Reference 20Haidari M et al. · 2009Pomegranate (Punica granatum) purified polyphenol extract inhibits influenza virus and has a synergistic effect with oseltamivirView study →}

04Antibacterial and antibiotic potentiationShaky34%Isolate MICs, mec-operon suppression in MRSA, Enterobacteriaceae re-sensitisation — all in vitro, and the potency figures do not reconcile ^{14,23,24Reference 14Gosset-Erard C et al. · 2021Identification of punicalagin as the bioactive compound behind the antimicrobial activity of pomegranate (Punica granatum L.) peelsView study →Reference 23Mun SH et al. · 2018Punicalagin suppresses methicillin resistance of Staphylococcus aureus to oxacillinView study →Reference 24Kiran S et al. · 2024Punicalagin, a pomegranate polyphenol, sensitizes the activity of antibiotics against three MDR pathogens of the EnterobacteriaceaeView study →}

05Gut inflammationShaky32%Isolated punicalagin 100 mg/kg in DSS colitis, effect FMT-transferable; peel extract in infectious colitis ^{25,26Reference 25Liu H et al. · 2024AnimalGut microbiota and D-ribose mediate the anti-colitic effect of punicalagin in DSS-treated miceView study →Reference 26Smith AD et al. · 2020AnimalPomegranate peel extract reduced colonic damage and bacterial translocation in a mouse model of infectious colitis induced by Citrobacter rodentiumView study →}

06AntioxidantShaky30%Outstanding in vitro; undercut in humans by the finding that its circulating metabolites are poor antioxidants ^{3,5,27Reference 3Gil MI et al. · 2000Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processingView study →Reference 5Cerdá B et al. · 2004In vitroThe potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy-6H-dibenzopyran-6-one derivatives by the colonic microflora of healthy humansView study →Reference 27Chen B et al. · 2012Pomegranate juice and punicalagin attenuate oxidative stress and apoptosis in human placenta and in human placental trophoblastsView study →}

07Anticancer — in vitro onlyShaky20%Cell-line IC50s at 10–100 µM with one normal-cell comparison; no animal or human isolate data ^{28,29,42Reference 28Adaramoye O et al. · 2017Punicalagin, a polyphenol from pomegranate fruit, induces growth inhibition and apoptosis in human PC-3 and LNCaP cellsView study →Reference 29Chen LG et al. · 2009In vitroEllagitannins from Terminalia calamansanai induced apoptosis in HL-60 cellsView study →Reference 42Kasimsetty SG et al. · 2009Effects of pomegranate chemical constituents/intestinal microbial metabolites on CYP1B1 in 22Rv1 prostate cancer cellsView study →}

08Antiparasitic and enzyme-target leadsShaky16%Plasmodium N-myristoyltransferase inhibition; anti-trypanosomal activity at extract level ^{43,44Reference 43Apel C et al. · 2018N-myristoyltransferases inhibitory activity of ellagitannins from Terminalia bentzoë (L.) L. f. subsp. bentzoëView study →Reference 44Muganga R et al. · 2021In vitroIn vitro antileishmanial, antitrypanosomal, and anti-inflammatory-like activity of Terminalia mollis root barkView study →}

09Neuroprotective and cognitiveShaky14%Rodent models and a narrative review; no punicalagin trial in human cognition ^{35,36,37Reference 35Abu-Elfotuh K et al. · 2024AnimalNeuroprotective effects of punicalagin and/or micronized zeolite clinoptilolite on manganese-induced Parkinson’s disease in a rat model — involvement of multiple pathwaysView study →Reference 36Wang W et al. · 2024Pomegranate polyphenol punicalagin as a nutraceutical for mitigating mild cognitive impairment — an overview of beneficial propertiesView study →Reference 37Navale GR et al. · 2023Effect of cycloastragenol and punicalagin on PrP(106–126) and Aβ(25–35) oligomerization and fibrillizationView study →}

Mechanisms

Read this table with the exposure column in mind. Only the microbiota, α-glucosidase, luminal-antioxidant and topical/mucosal rows describe something that can happen in a person who swallows punicalagin. The rest describe what the molecule does when it is placed in a tube with a target it will never meet in vivo.

Pharmacokinetics

Punicalagin is not detectably absorbed by humans. In the only dedicated human study, six volunteers drank 1 L/day of pomegranate juice containing 4.37 g/L of punicalagin isomers for five days; neither punicalagin nor ellagic acid appeared in plasma or urine ^{5Reference 5Cerdá B et al. · 2004In vitroThe potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy-6H-dibenzopyran-6-one derivatives by the colonic microflora of healthy humansView study →}. What did appear were three microbial dibenzopyranone metabolites — the compounds now called urolithins — reaching up to 18.6 µM in plasma, detectable in urine from day one, with total urinary excretion ranging from 0.7% to 52.7% of the ingested punicalagin between individuals ^{5Reference 5Cerdá B et al. · 2004In vitroThe potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy-6H-dibenzopyran-6-one derivatives by the colonic microflora of healthy humansView study →}. That seventy-fold spread, recorded in 2004 before anyone had a name for it, is the phenomenon later formalised as the urolithin metabotypes.

The conversion runs: punicalagin → hydrolysis in the gut to gallagic acid and ellagic acid → stepwise microbial dehydroxylation to urolithin C, then urolithin A, and in some people isourolithin A and urolithin B. That this is microbial rather than mammalian chemistry was demonstrated directly, by incubating punicalagin with human faecal samples and recovering urolithin A — with “very different production rates and concentrations” between donors ^{10Reference 10Cerdá B et al. · 2005Identification of urolithin A as a metabolite produced by human colon microflora from ellagic acid and related compoundsView study →}. People sort into reproducible metabotypes: A (urolithin A only), B (also isourolithin A and urolithin B) and 0 (essentially no production), consistent across trials regardless of food source, and drifting with age toward metabotype B and non-production ^{11,12,13Reference 11Tomás-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 12Cortés-Martín A et al. · 2018The gut microbiota urolithin metabotypes revisited — the human metabolism of ellagic acid is mainly determined by agingView study →Reference 13García-Villalba R et al. · 2022Urolithins: a comprehensive update on their metabolism, bioactivity, and associated gut microbiotaView study →}. This is why the same glass of pomegranate juice produces very different internal exposure in different people, and it applies identically to every ellagitannin here.

The rat data differ in one respect worth stating, because it is often mis-cited as human data: in rats fed a 6% punicalagin diet (0.6–1.2 g/day) for 37 days, punicalagin was detected in plasma at around 30 µg/mL, and gallagic acid plus urolithin derivatives were found in liver and kidney ^{6Reference 6Cerdá B et al. · 2003AnimalEvaluation of the bioavailability and metabolism in the rat of punicalagin, an antioxidant polyphenol from pomegranate juiceView study →}. Only 3–6% of the ingested dose was recovered as identified metabolites in urine and faeces, so the bulk of it is either degraded past recognition or unaccounted for. Extreme dietary loading in a rodent is not a model of human juice-drinking, and the human study remains the governing one.

The practical read: assume plasma punicalagin is zero. Any in-vitro IC50 in the micromolar range is unreachable systemically. The molecule’s real venues are the gut lumen, mucosal surfaces, and — via the urolithins it becomes — a systemic exposure that is not punicalagin at all.

Clinical Trials

There is no completed clinical trial of isolated punicalagin for any indication. The human literature is of two kinds: many trials of pomegranate juice or extract in which punicalagin is the presumed active but is never dosed or measured, and two crossover RCTs of a punicalagin-plus-hydroxytyrosol supplement in which the punicalagin dose is stated (195 mg/day) but is not the only ingredient ^{32,33Reference 32Quirós-Fernández R et al. · 2019RCTSupplementation with hydroxytyrosol and punicalagin improves early atherosclerosis markers involved in the asymptomatic phase of atherosclerosis in the adult population — a randomized, placebo-controlled, crossover trialView study →Reference 33Quirós-Fernández R et al. · 2022RCTOral supplement containing hydroxytyrosol and punicalagin improves dyslipidemia in an adult population without co-adjuvant treatment — a randomized, double-blind, controlled and crossover trialView study →}.

Isolated punicalagin	Punicalagin-containing supplement	Pomegranate juice/extract	Bioavailability
None	2 crossover RCTs (n = 67 completers), one group, industry-sponsored	Many RCTs + meta-analyses (BP, lipids, oxidative markers)	1 human study (n = 6): parent molecule undetectable

Last checked: August 2026.

Isolate vs. Plant Studies

Punicalagin is one of the clearest isolate-versus-plant cases here, because for once the two literatures are both large.

Where the plant carries the evidence. All the meaningful human data — blood pressure, lipids, oxidative-stress markers — comes from pomegranate juice or peel extract ^{30,31Reference 30Sahebkar A et al. · 2017Meta-analysisEffects of pomegranate juice on blood pressure — a systematic review and meta-analysis of randomized controlled trialsView study →Reference 31Bahari H et al. · 2024Meta-analysisThe effects of pomegranate consumption on blood pressure in adults — a systematic review and meta-analysisView study →}. None of it isolates punicalagin’s contribution, and the bioavailability study makes that attribution actively difficult: the molecule the trials are crediting does not reach the bloodstream ^{5Reference 5Cerdá B et al. · 2004In vitroThe potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy-6H-dibenzopyran-6-one derivatives by the colonic microflora of healthy humansView study →}. Pomegranate’s clinical reputation is real; punicalagin’s claim on it is an inference, not a finding.

Where the isolate carries the evidence. The antiviral GAG mechanism ^{18,19Reference 18Lin LT et al. · 2011Hydrolyzable tannins (chebulagic acid and punicalagin) target viral glycoprotein–glycosaminoglycan interactions to inhibit herpes simplex virus 1 entry and cell-to-cell spreadView study →Reference 19Lin LT et al. · 2013Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entryView study →}, the influenza attribution ^{20Reference 20Haidari M et al. · 2009Pomegranate (Punica granatum) purified polyphenol extract inhibits influenza virus and has a synergistic effect with oseltamivirView study →}, the MRSA mec-operon result ^{23Reference 23Mun SH et al. · 2018Punicalagin suppresses methicillin resistance of Staphylococcus aureus to oxacillinView study →}, the DSS colitis result ^{25Reference 25Liu H et al. · 2024AnimalGut microbiota and D-ribose mediate the anti-colitic effect of punicalagin in DSS-treated miceView study →}, and the prostate-cell selectivity comparison ^{28Reference 28Adaramoye O et al. · 2017Punicalagin, a polyphenol from pomegranate fruit, induces growth inhibition and apoptosis in human PC-3 and LNCaP cellsView study →} were all done on purified compound. Two of them are model demonstrations of how this should be done: Haidari’s group tested four pomegranate polyphenols side by side and named punicalagin the active ^{20Reference 20Haidari M et al. · 2009Pomegranate (Punica granatum) purified polyphenol extract inhibits influenza virus and has a synergistic effect with oseltamivirView study →}, and Chen’s group showed punicalagin but not ellagic acid reproduced pomegranate juice’s protection of human trophoblasts ^{27Reference 27Chen B et al. · 2012Pomegranate juice and punicalagin attenuate oxidative stress and apoptosis in human placenta and in human placental trophoblastsView study →}. Both are genuine isolate results that discriminate against the obvious alternative.

Where the attribution goes wrong. Punicalagin’s name is regularly borrowed for whole-extract findings — the anti-adenoviral work is a good corrective, since in that study gallic acid and the n-butanol fraction, not punicalagin, carried the activity ^{38Reference 38Karimi A et al. · 2020In vitroIn vitro anti-adenoviral activities of ethanol extract, fractions, and main phenolic compounds of pomegranate (Punica granatum L.) peelView study →}. It is also borrowed across species: Terminalia mollis root’s antitrypanosomal activity survived tannin removal, so it is not the tannins doing it ^{44Reference 44Muganga R et al. · 2021In vitroIn vitro antileishmanial, antitrypanosomal, and anti-inflammatory-like activity of Terminalia mollis root barkView study →}. And the largest borrowing of all is the reverse direction — urolithin A’s genuinely impressive human muscle and mitochondrial trial data belongs to a metabolite produced by only some people from this molecule, and does not transfer to punicalagin supplementation.

Its Role in Plants

In the pomegranate, punicalagin is a structural defence tannin of the rind. Its distribution is the giveaway: one to two percent of the dry weight of peel and mesocarp, and near-absence from the arils ^{3,4Reference 3Gil MI et al. · 2000Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processingView study →Reference 4Fischer UA et al. · 2011Identification and quantification of phenolic compounds from pomegranate (Punica granatum L.) peel, mesocarp, aril and differently produced juices by HPLC-DAD-ESI/MSⁿView study →}. The peel is the barrier tissue — exposed to insects, fungi and desiccation for months while the fruit ripens — and it is loaded with a protein-precipitating polyphenol at concentrations that make it inedible to most herbivores. The arils, which the plant needs animals to eat and disperse, are not.

The astringency is the point. Punicalagin binds and precipitates proteins, including salivary proline-rich proteins and microbial and insect gut enzymes, and its antibacterial and antifungal activity against a broad panel of organisms ^{14Reference 14Gosset-Erard C et al. · 2021Identification of punicalagin as the bioactive compound behind the antimicrobial activity of pomegranate (Punica granatum L.) peelsView study →} is a plausible in-planta function rather than a laboratory artefact. Its metal-chelating capacity ^{37Reference 37Navale GR et al. · 2023Effect of cycloastragenol and punicalagin on PrP(106–126) and Aβ(25–35) oligomerization and fibrillizationView study →} may also serve iron sequestration against pathogens — the same trick many plant polyphenols use.

Biosynthetically it is built the ellagitannin way: gallic acid from the shikimate pathway is esterified onto glucose, and oxidative C–C coupling between adjacent galloyl groups creates first the hexahydroxydiphenoyl (HHDP) unit and then, by a further coupling, the four-ring gallagyl unit that is punicalagin’s defining feature and the reason it is so much larger than a typical ellagitannin. The related smaller tannin punicalin is the same gallagyl-glucose without the HHDP group, and is both a biosynthetic relative and a hydrolysis product — which is why the two are almost always reported together ^{1,2Reference 1Mayer W et al. · 1977Punicalagin und Punicalin, zwei Gerbstoffe aus den Schalen der GranatäpfelView study →Reference 2Tanaka T et al. · 1986Tannins and related compoundsView study →}.

Prevalence in Nature

Punicalagin has a narrow but deep distribution. It is overwhelmingly a Lythraceae compound, concentrated in pomegranate, with a genuine secondary presence in the Combretaceae genus Terminalia.

Pomegranate

The numbers are unusual for a single secondary metabolite. Peel and mesocarp run 11–20 g/kg dry matter — one to two percent of the tissue by dry weight ^{4Reference 4Fischer UA et al. · 2011Identification and quantification of phenolic compounds from pomegranate (Punica granatum L.) peel, mesocarp, aril and differently produced juices by HPLC-DAD-ESI/MSⁿView study →}. Juices span 4 to 565 mg/L in Fischer’s laboratory-produced series ^{4Reference 4Fischer UA et al. · 2011Identification and quantification of phenolic compounds from pomegranate (Punica granatum L.) peel, mesocarp, aril and differently produced juices by HPLC-DAD-ESI/MSⁿView study →} and 1,500–1,900 mg/L in Gil’s commercial samples ^{3Reference 3Gil MI et al. · 2000Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processingView study →}, with a human-trial juice at 4,370 mg/L ^{5Reference 5Cerdá B et al. · 2004In vitroThe potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy-6H-dibenzopyran-6-one derivatives by the colonic microflora of healthy humansView study →}; the variable is simply how much rind the pressing method extracts. Cultivar matters too — peel punicalagin varies severalfold across varieties, the cultivar richest in punicalagin was also the most antimicrobial ^{17Reference 17Rosas-Burgos EC et al. · 2017Antimicrobial activity of pomegranate peel extracts as affected by cultivarView study →}, and a four-variety survey found the punicalagin anomers and punicalin to be the most abundant polyphenols of both peel and male flower ^{45Reference 45Gigliobianco MR et al. · 2022Chemical, antioxidant, and antimicrobial properties of the peel and male flower by-products of four varieties of Punica granatum L. cultivated in the Marche region for their use in cosmetic productsView study →}. Punicalin travels with punicalagin everywhere it occurs. Extraction method adds a second axis of variation on top of tissue and cultivar: an optimised ultrasonic-assisted extraction of peel yielded 505.89 mg/g dry weight ^{16Reference 16Liu Y et al. · 2022Pomegranate peel-derived punicalagin — ultrasonic-assisted extraction, purification, and its α-glucosidase inhibitory mechanismView study →}, against Fischer’s 11–20 mg/g by survey HPLC-DAD ^{4Reference 4Fischer UA et al. · 2011Identification and quantification of phenolic compounds from pomegranate (Punica granatum L.) peel, mesocarp, aril and differently produced juices by HPLC-DAD-ESI/MSⁿView study →}.

Terminalia

Punicalagin is genuinely reported in several Terminalia species, and this site’s cross-references are sound. In haritaki (T. chebula), punicalagin is repeatedly identified in LC-MS profiling of the fruit alongside chebulagic acid, chebulinic acid, corilagin and ellagic acid ^{39,40Reference 39Yuan J et al. · 2025Multi-detector based at-line nanofractionation strategy accelerates discovery of influenza PA endonuclease inhibitors from Terminalia chebula RetzView study →Reference 40Wang X et al. · 2023Global profiling of the antioxidant constituents in Chebulae Fructus based on an integrative strategy of UHPLC/IM-QTOF-MS, MS/MS molecular networking, and spectrum-effect correlationView study →}, and the punicalagin used in the landmark HSV-1 entry study was purified from T. chebula fruit, not from pomegranate ^{18Reference 18Lin LT et al. · 2011Hydrolyzable tannins (chebulagic acid and punicalagin) target viral glycoprotein–glycosaminoglycan interactions to inhibit herpes simplex virus 1 entry and cell-to-cell spreadView study →}. It is also isolated from T. bentzoe bark ^{43Reference 43Apel C et al. · 2018N-myristoyltransferases inhibitory activity of ellagitannins from Terminalia bentzoë (L.) L. f. subsp. bentzoëView study →}, T. mollis root ^{44Reference 44Muganga R et al. · 2021In vitroIn vitro antileishmanial, antitrypanosomal, and anti-inflammatory-like activity of Terminalia mollis root barkView study →}, T. calamansanai leaf ^{29Reference 29Chen LG et al. · 2009In vitroEllagitannins from Terminalia calamansanai induced apoptosis in HL-60 cellsView study →} — and, consequentially, from T. oblongata, where it is the identified hepatotoxin (see below) ^{8Reference 8Filippich LJ et al. · 1991Hepatotoxic and nephrotoxic principles in Terminalia oblongataView study →}.

The distinction the Combretaceae and Lythraceae pages draw is therefore correct as written: it is a Lythraceae signature compound that also occurs across Combretaceae. Where Terminalia differs is quantitatively — no Terminalia source approaches pomegranate peel’s one-to-two-percent loading, and in haritaki punicalagin is one tannin among many rather than the dominant one.

Related Molecules Worth Distinguishing

• Punicalin — the gallagyl-glucose lacking the HHDP unit; a co-occurring tannin and a hydrolysis product of punicalagin. Frequently co-reported and occasionally conflated ^{1,2Reference 1Mayer W et al. · 1977Punicalagin und Punicalin, zwei Gerbstoffe aus den Schalen der GranatäpfelView study →Reference 2Tanaka T et al. · 1986Tannins and related compoundsView study →}.
• Gallagic acid — the free gallagyl acid released on hydrolysis; detected in rat liver and kidney after punicalagin feeding ^{7Reference 7Cerdá B et al. · 2003AnimalRepeated oral administration of high doses of the pomegranate ellagitannin punicalagin to rats for 37 days is not toxicView study →}.
• 2-O-Galloylpunicalin and 1-α-O-galloylpunicalagin — galloylated relatives from Terminalia calamansanai, more cytotoxic than punicalagin itself in HL-60 cells; do not read their results across ^{29Reference 29Chen LG et al. · 2009In vitroEllagitannins from Terminalia calamansanai induced apoptosis in HL-60 cellsView study →}.
• Castalagin and vescalagin — C-glycosidic ellagitannins of oak and chestnut, structurally distinct (open-chain glucose, non-hydrolysable C–C bond) and much poorer urolithin precursors.

Discovery & Synthesis

Punicalagin was isolated and named in 1977 by Wilhelm Mayer’s group at Heidelberg, reported together with punicalin as “two tannins from the peel of pomegranates” ^{1Reference 1Mayer W et al. · 1977Punicalagin und Punicalin, zwei Gerbstoffe aus den Schalen der GranatäpfelView study →}. It is the same laboratory, and the same run of work on the giant hydrolysable tannins, that had produced castalagin and vescalagin from oak and chestnut two decades earlier — Mayer’s group essentially founded the structural chemistry of this compound class.

The originally proposed structures did not survive. In 1986 Tanaka, Nonaka and Nishioka revised the structures of both punicalin and punicalagin, in the fortieth paper of their long Tannins and Related Compounds series, and simultaneously isolated 2-O-galloylpunicalin from Punica granatum ^{2Reference 2Tanaka T et al. · 1986Tannins and related compoundsView study →}. The accepted structure since then is 2,3-(S)-hexahydroxydiphenoyl-4,6-(S,S)-gallagyl-D-glucose — C₄₈H₂₈O₃₀, MW 1084.7, CAS 65995-63-3 — with the free anomeric centre that gives the α/β pair.

There is no synthesis. With thirty oxygens, two atropisomeric biaryl axes in the gallagyl unit and a free anomeric centre, punicalagin has never been made by total synthesis, and there is no economic reason to attempt one: pomegranate husk is an agricultural waste stream containing one to two percent of it by dry weight. Manufacture is entirely extractive — aqueous or hydroethanolic extraction of milled peel, then macroporous-resin cleanup and preparative chromatography. Published routes reach 92% purity by D101 resin plus prep-HPLC ^{16,17Reference 16Liu Y et al. · 2022Pomegranate peel-derived punicalagin — ultrasonic-assisted extraction, purification, and its α-glucosidase inhibitory mechanismView study →Reference 17Rosas-Burgos EC et al. · 2017Antimicrobial activity of pomegranate peel extracts as affected by cultivarView study →}, and medium-pressure liquid chromatography recovers the anomer pair in high purity from husk polyphenols ^{15Reference 15Aguilar-Zárate P et al. · 2017Characterisation of pomegranate-husk polyphenols and semi-preparative fractionation of punicalaginView study →}. Commercial “punicalagin standard” is supplied, correctly, as an A&B mixture.

Patents: not yet researched.

Toxicity & Safety

Punicalagin carries a moderate flag, and the reason is specific rather than precautionary: punicalagin is the identified hepatotoxic principle of a plant that kills livestock.

Terminalia oblongata — yellow-wood, of central Queensland — poisons cattle and sheep that browse it, and the losses were historically the region’s main cause of stock loss outside drought. When the toxic fraction was isolated and characterised, it was punicalagin, reproducing in mice the same liver lesion seen in ruminants ^{8Reference 8Filippich LJ et al. · 1991Hepatotoxic and nephrotoxic principles in Terminalia oblongataView study →}. A second, separate toxin in the same plant, terminalin, was later shown to cause renal rather than hepatic necrosis — the authors specifically noting that punicalagin “produces liver lesions but not kidney lesions” ^{9Reference 9Oelrichs PB et al. · 1994Isolation and structure determination of terminalin, a toxic condensed tannin from Terminalia oblongataView study →}. This is a positive, isolated-molecule toxicology finding with a clear target organ, and it is not something the pomegranate literature usually mentions.

Two things temper it. First, route matters enormously: the oral dose required to produce toxicity was at least twenty times the intraperitoneal dose ^{8Reference 8Filippich LJ et al. · 1991Hepatotoxic and nephrotoxic principles in Terminalia oblongataView study →} — consistent with a molecule that is barely absorbed. Second, the one deliberate oral toxicology study is reassuring: Sprague-Dawley rats fed a 6% punicalagin diet (0.6–1.2 g/day) for 37 days showed no significant change in any blood parameter except urea and triglycerides, no histopathological liver or kidney damage, and no deaths — though food intake and growth ran lower in the first fortnight, which the authors attributed to palatability ^{7Reference 7Cerdá B et al. · 2003AnimalRepeated oral administration of high doses of the pomegranate ellagitannin punicalagin to rats for 37 days is not toxicView study →}. Those authors’ own conclusion is the right one to carry: no toxic effect at that exposure in rats, but safety evaluation in humans at lower doses over longer periods has not been done.

Safety at a Glance

⚠️ Moderate toxicity

• Long dietary history. Commercial pomegranate juice supplies grams of punicalagin per litre and has been consumed at scale without a signal; a 37-day rat study at 6% of the diet found no toxicity.
• Very poor absorption is itself protective — human plasma punicalagin is undetectable, so systemic exposure to the parent molecule is essentially nil.
• A real hepatotoxicity finding exists on the isolated molecule. Punicalagin is the hepatotoxin of Terminalia oblongata, fatal to grazing ruminants and reproducing liver necrosis in mice. Oral toxicity requires ≥20× the injected dose, but this is a positive finding, not an absence.
• Tannin-class cautions. Astringency, protein binding, and reduced non-haem iron absorption at high intakes — relevant if iron status is marginal, and relevant to concentrated husk extracts rather than food.
• Response is microbiome-dependent, not dose-dependent. Urolithin metabotype (A / B / 0) sets what you actually get from any punicalagin dose, and roughly a tenth of people are non-producers.
• No human safety study of the isolate or of long-term concentrated extract use. Nothing here is a clearance.

Full Safety & Interactions Detail

The livestock hepatotoxicity, in proportion. Terminalia oblongata poisoning is a real veterinary syndrome and punicalagin is the isolated cause ^{8Reference 8Filippich LJ et al. · 1991Hepatotoxic and nephrotoxic principles in Terminalia oblongataView study →}, but the exposure is not comparable to eating pomegranate: browsing ruminants consume large quantities of tannin-dense leaf over days, and the mouse work that pinned the lesion used doses at which the oral:intraperitoneal potency ratio was ≥20:1. The finding matters for two reasons — it is the only positive toxicology on this molecule, and it establishes the liver as the target organ if a large systemic exposure ever occurred (for example from a concentrated extract in someone with unusually permeable gut).

Tannin-class effects. As a large protein-precipitating polyphenol punicalagin binds dietary protein, chelates metals, and contributes the astringency of pomegranate peel preparations. High habitual tannin intake is a recognised, modest inhibitor of non-haem iron absorption. The tannins class page carries the general picture.

Interactions. No human drug-interaction study exists. The documented signals are: punicalagins inhibit CYP1A1 with 5–10-fold selectivity over CYP1B1 in recombinant enzyme assay ^{42Reference 42Kasimsetty SG et al. · 2009Effects of pomegranate chemical constituents/intestinal microbial metabolites on CYP1B1 in 22Rv1 prostate cancer cellsView study →}; pomegranate peel extract showed pharmacodynamic and pharmacokinetic interaction with warfarin in rats, prolonging INR and inhibiting the CYPs that clear it ^{41Reference 41Alnaqeeb M et al. · 2019AnimalCritical pharmacokinetic and pharmacodynamic drug-herb interactions in rats between warfarin and pomegranate peel or guava leaves extractsView study →}. Neither is proven in people, but anyone on warfarin or another anticoagulant should treat concentrated pomegranate-peel supplements as a plausible additive bleeding-risk and CYP concern. The antibiotic-potentiation results ^{23,24Reference 23Mun SH et al. · 2018Punicalagin suppresses methicillin resistance of Staphylococcus aureus to oxacillinView study →Reference 24Kiran S et al. · 2024Punicalagin, a pomegranate polyphenol, sensitizes the activity of antibiotics against three MDR pathogens of the EnterobacteriaceaeView study →} are in vitro and are not a reason to combine anything.

Reproductive and developmental. No reproductive-toxicity study exists for isolated punicalagin. The one human-relevant datum runs the other way — a small randomised comparison of pomegranate juice versus apple juice in late pregnancy found reduced placental oxidative stress, and in cultured trophoblasts punicalagin (but not ellagic acid) reproduced the protective effect ^{27Reference 27Chen B et al. · 2012Pomegranate juice and punicalagin attenuate oxidative stress and apoptosis in human placenta and in human placental trophoblastsView study →}. That is a mechanistic observation on a food, not a safety clearance for a concentrated extract, and decisions about intake in pregnancy belong on the herb or product page where the intake is actually decided.

The honest summary. A food constituent with a very large safety margin by virtue of not being absorbed, one genuine target-organ toxicity finding at exposures no eater will reach, and no human toxicology on the isolate at all.

Dosage

There is no established dose of isolated punicalagin. The figures below are what research has used, for orientation only.

Two cautions on reading this table. The dietary numbers dwarf the supplement numbers — a glass of commercial pomegranate juice supplies more punicalagin than the daily dose used in the human supplement trials — which tells you that dose is not the limiting variable here. Absorption is, and after absorption, your microbiome is: the same intake produces urolithin exposure varying more than tenfold between people ^{5,11Reference 5Cerdá B et al. · 2004In vitroThe potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy-6H-dibenzopyran-6-one derivatives by the colonic microflora of healthy humansView study →Reference 11Tomás-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 →}. These are doses studied in research and are not a personal recommendation.

References

1. Mayer W, Görner A, Andrä K (1977). Punicalagin und Punicalin, zwei Gerbstoffe aus den Schalen der Granatäpfel. Justus Liebigs Annalen der Chemie, 1977(11–12), 1976–1986. https://doi.org/10.1002/jlac.197719771119
2. Tanaka T, Nonaka G, Nishioka I (1986). Tannins and related compounds. XL. Revision of the structures of punicalin and punicalagin, and isolation and characterization of 2-O-galloylpunicalin from Punica granatum L. Chemical and Pharmaceutical Bulletin, 34(2), 650–655. https://doi.org/10.1248/cpb.34.650
3. Gil MI, Tomás-Barberán FA, Hess-Pierce B, Holcroft DM, Kader AA (2000). Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. Journal of Agricultural and Food Chemistry, 48(10), 4581–4589. https://pubmed.ncbi.nlm.nih.gov/11052704/
4. Fischer UA, Carle R, Kammerer DR (2011). Identification and quantification of phenolic compounds from pomegranate (Punica granatum L.) peel, mesocarp, aril and differently produced juices by HPLC-DAD-ESI/MSⁿ. Food Chemistry, 127(2), 807–821. https://pubmed.ncbi.nlm.nih.gov/23140740/
5. Cerdá B, Espín JC, Parra S, Martínez P, Tomás-Barberán FA (2004). The potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy-6H-dibenzopyran-6-one derivatives by the colonic microflora of healthy humans. European Journal of Nutrition, 43(4), 205–220. https://pubmed.ncbi.nlm.nih.gov/15309440/
6. Cerdá B, Llorach R, Cerón JJ, Espín JC, Tomás-Barberán FA (2003). Evaluation of the bioavailability and metabolism in the rat of punicalagin, an antioxidant polyphenol from pomegranate juice. European Journal of Nutrition, 42(1), 18–28. https://pubmed.ncbi.nlm.nih.gov/12594538/
7. Cerdá B, Cerón JJ, Tomás-Barberán FA, Espín JC (2003). Repeated oral administration of high doses of the pomegranate ellagitannin punicalagin to rats for 37 days is not toxic. Journal of Agricultural and Food Chemistry, 51(11), 3493–3501. https://pubmed.ncbi.nlm.nih.gov/12744688/
8. Filippich LJ, Zhu J, Oelrichs P, Alsalami MT, Doig AJ, Cao GR, English PB (1991). Hepatotoxic and nephrotoxic principles in Terminalia oblongata. Research in Veterinary Science, 50(2), 170–177. https://pubmed.ncbi.nlm.nih.gov/2034896/
9. Oelrichs PB, Pearce CM, Zhu J, Filippich LJ (1994). Isolation and structure determination of terminalin, a toxic condensed tannin from Terminalia oblongata. Natural Toxins, 2(3), 144–150. https://pubmed.ncbi.nlm.nih.gov/8087436/
10. Cerdá B, Periago P, Espín JC, Tomás-Barberán FA (2005). Identification of urolithin A as a metabolite produced by human colon microflora from ellagic acid and related compounds. Journal of Agricultural and Food Chemistry, 53(14), 5571–5576. https://pubmed.ncbi.nlm.nih.gov/15998116/
11. Tomás-Barberán FA, García-Villalba R, González-Sarrías A, Selma MV, Espín JC (2014). Ellagic acid metabolism by human gut microbiota — consistent observation of three urolithin phenotypes in intervention trials, independent of food source, age and health status. Journal of Agricultural and Food Chemistry, 62(28), 6535–6538. https://pubmed.ncbi.nlm.nih.gov/24976365/
12. Cortés-Martín A, Selma MV, Espín JC, García-Villalba R (2018). The gut microbiota urolithin metabotypes revisited — the human metabolism of ellagic acid is mainly determined by aging. Food & Function, 9(8), 4100–4106. https://pubmed.ncbi.nlm.nih.gov/30004553/
13. García-Villalba R, Giménez-Bastida JA, Cortés-Martín A, et al. (2022). Urolithins: a comprehensive update on their metabolism, bioactivity, and associated gut microbiota. Molecular Nutrition & Food Research, 66(21), 2101019. https://pubmed.ncbi.nlm.nih.gov/35118817/
14. Gosset-Erard C, Zhao M, Lordel-Madeleine S, Ennahar S (2021). Identification of punicalagin as the bioactive compound behind the antimicrobial activity of pomegranate (Punica granatum L.) peels. Food Chemistry, 352, 129396. https://pubmed.ncbi.nlm.nih.gov/33652195/
15. Aguilar-Zárate P, Wong-Paz JE, Michel M, et al. (2017). Characterisation of pomegranate-husk polyphenols and semi-preparative fractionation of punicalagin. Phytochemical Analysis, 28(5), 433–438. https://pubmed.ncbi.nlm.nih.gov/28543801/
16. Liu Y, Kong KW, Wu DT, et al. (2022). Pomegranate peel-derived punicalagin — ultrasonic-assisted extraction, purification, and its α-glucosidase inhibitory mechanism. Food Chemistry, 374, 131635. https://pubmed.ncbi.nlm.nih.gov/34823934/
17. Rosas-Burgos EC, Burgos-Hernández A, Noguera-Artiaga L, et al. (2017). Antimicrobial activity of pomegranate peel extracts as affected by cultivar. Journal of the Science of Food and Agriculture, 97(3), 802–810. https://pubmed.ncbi.nlm.nih.gov/27173758/
18. Lin LT, Chen TY, Chung CY, et al. (2011). Hydrolyzable tannins (chebulagic acid and punicalagin) target viral glycoprotein–glycosaminoglycan interactions to inhibit herpes simplex virus 1 entry and cell-to-cell spread. Journal of Virology, 85(9), 4386–4398. https://pubmed.ncbi.nlm.nih.gov/21307190/
19. Lin LT, Chen TY, Lin SC, et al. (2013). Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entry. BMC Microbiology, 13, 187. https://pubmed.ncbi.nlm.nih.gov/23924316/
20. Haidari M, Ali M, Ward Casscells S, Madjid M (2009). Pomegranate (Punica granatum) purified polyphenol extract inhibits influenza virus and has a synergistic effect with oseltamivir. Phytomedicine, 16(12), 1127–1136. https://pubmed.ncbi.nlm.nih.gov/19586764/
21. Liu C, Cai D, Zhang L, et al. (2016). Identification of hydrolyzable tannins (punicalagin, punicalin and geraniin) as novel inhibitors of hepatitis B virus covalently closed circular DNA. Antiviral Research, 134, 97–107. https://pubmed.ncbi.nlm.nih.gov/27591143/
22. Nonaka G, Nishioka I, Nishizawa M, et al. (1990). Anti-AIDS agents, 2: inhibitory effects of tannins on HIV reverse transcriptase and HIV replication in H9 lymphocyte cells. Journal of Natural Products, 53(3), 587–595. https://pubmed.ncbi.nlm.nih.gov/1698933/
23. Mun SH, Kang OH, Kong R, et al. (2018). Punicalagin suppresses methicillin resistance of Staphylococcus aureus to oxacillin. Journal of Pharmacological Sciences, 137(4), 317–323. https://pubmed.ncbi.nlm.nih.gov/30150143/
24. Kiran S, Tariq A, Iqbal S, et al. (2024). Punicalagin, a pomegranate polyphenol, sensitizes the activity of antibiotics against three MDR pathogens of the Enterobacteriaceae. BMC Complementary Medicine and Therapies, 24(1), 93. https://pubmed.ncbi.nlm.nih.gov/38365729/
25. Liu H, Yan C, Teng Y, et al. (2024). Gut microbiota and D-ribose mediate the anti-colitic effect of punicalagin in DSS-treated mice. Food & Function, 15(13), 7108–7123. https://pubmed.ncbi.nlm.nih.gov/38874578/
26. Smith AD, George NS, Cheung L, et al. (2020). Pomegranate peel extract reduced colonic damage and bacterial translocation in a mouse model of infectious colitis induced by Citrobacter rodentium. Nutrition Research, 73, 27–37. https://pubmed.ncbi.nlm.nih.gov/31841745/
27. Chen B, Tuuli MG, Longtine MS, et al. (2012). Pomegranate juice and punicalagin attenuate oxidative stress and apoptosis in human placenta and in human placental trophoblasts. American Journal of Physiology — Endocrinology and Metabolism, 302(9), E1142–E1152. https://pubmed.ncbi.nlm.nih.gov/22374759/
28. Adaramoye O, Erguen B, Nitzsche B, Höpfner M, Jung K, Rabien A (2017). Punicalagin, a polyphenol from pomegranate fruit, induces growth inhibition and apoptosis in human PC-3 and LNCaP cells. Chemico-Biological Interactions, 274, 100–106. https://pubmed.ncbi.nlm.nih.gov/28709945/
29. Chen LG, Huang WT, Lee LT, Wang CC (2009). Ellagitannins from Terminalia calamansanai induced apoptosis in HL-60 cells. Toxicology in Vitro, 23(4), 603–609. https://pubmed.ncbi.nlm.nih.gov/19490839/
30. Sahebkar A, Ferri C, Giorgini P, Bo S, Nachtigal P, Grassi D (2017). Effects of pomegranate juice on blood pressure — a systematic review and meta-analysis of randomized controlled trials. Pharmacological Research, 115, 149–161. https://pubmed.ncbi.nlm.nih.gov/27888156/
31. Bahari H, Omidian K, Goudarzi K, et al. (2024). The effects of pomegranate consumption on blood pressure in adults — a systematic review and meta-analysis. Phytotherapy Research, 38(5), 2234–2248. https://pubmed.ncbi.nlm.nih.gov/38410857/
32. Quirós-Fernández R, López-Plaza B, Bermejo LM, Palma Milla S, Gómez-Candela C (2019). Supplementation with hydroxytyrosol and punicalagin improves early atherosclerosis markers involved in the asymptomatic phase of atherosclerosis in the adult population — a randomized, placebo-controlled, crossover trial. Nutrients, 11(3), 640. https://pubmed.ncbi.nlm.nih.gov/30884808/
33. Quirós-Fernández R, López-Plaza B, Bermejo LM, Palma Milla S, Zangara A, Gómez-Candela C (2022). Oral supplement containing hydroxytyrosol and punicalagin improves dyslipidemia in an adult population without co-adjuvant treatment — a randomized, double-blind, controlled and crossover trial. Nutrients, 14(9), 1879. https://pubmed.ncbi.nlm.nih.gov/35565844/
34. Hussein L, Gouda M, Buttar HS (2021). Pomegranate, its components, and modern deliverable formulations as potential botanicals in the prevention and treatment of various cancers. Current Drug Delivery, 18(10), 1391–1405. https://pubmed.ncbi.nlm.nih.gov/33538675/
35. Abu-Elfotuh K, Abbas AN, Najm MAA, et al. (2024). Neuroprotective effects of punicalagin and/or micronized zeolite clinoptilolite on manganese-induced Parkinson’s disease in a rat model — involvement of multiple pathways. CNS Neuroscience & Therapeutics, 30(10), e70008. https://pubmed.ncbi.nlm.nih.gov/39374157/
36. Wang W, Long P, He M, et al. (2024). Pomegranate polyphenol punicalagin as a nutraceutical for mitigating mild cognitive impairment — an overview of beneficial properties. European Journal of Pharmacology, 977, 176750. https://pubmed.ncbi.nlm.nih.gov/38897439/
37. Navale GR, Chauhan R, Saini S, Roy P, Ghosh K (2023). Effect of cycloastragenol and punicalagin on PrP(106–126) and Aβ(25–35) oligomerization and fibrillization. Biophysical Chemistry, 302, 107108. https://pubmed.ncbi.nlm.nih.gov/37734278/
38. Karimi A, Moradi MT, Rabiei M, Alidadi S (2020). In vitro anti-adenoviral activities of ethanol extract, fractions, and main phenolic compounds of pomegranate (Punica granatum L.) peel. Antiviral Chemistry and Chemotherapy, 28, 2040206620916571. https://pubmed.ncbi.nlm.nih.gov/32306749/
39. Yuan J, Chang Y, Gu R, et al. (2025). Multi-detector based at-line nanofractionation strategy accelerates discovery of influenza PA endonuclease inhibitors from Terminalia chebula Retz. Journal of Chromatography A, 1762, 466398. https://pubmed.ncbi.nlm.nih.gov/40992162/
40. Wang X, Xu J, Zhang LH, et al. (2023). Global profiling of the antioxidant constituents in Chebulae Fructus based on an integrative strategy of UHPLC/IM-QTOF-MS, MS/MS molecular networking, and spectrum-effect correlation. Antioxidants, 12(12), 2093. https://pubmed.ncbi.nlm.nih.gov/38136213/
41. Alnaqeeb M, Mansor KA, Mallah EM, et al. (2019). Critical pharmacokinetic and pharmacodynamic drug-herb interactions in rats between warfarin and pomegranate peel or guava leaves extracts. BMC Complementary and Alternative Medicine, 19(1), 29. https://pubmed.ncbi.nlm.nih.gov/30678660/
42. Kasimsetty SG, Bialonska D, Reddy MK, Thornton C, Willett KL, Ferreira D (2009). Effects of pomegranate chemical constituents/intestinal microbial metabolites on CYP1B1 in 22Rv1 prostate cancer cells. Journal of Agricultural and Food Chemistry, 57(22), 10636–10644. https://pubmed.ncbi.nlm.nih.gov/19919114/
43. Apel C, Bignon J, Garcia-Alvarez MC, et al. (2018). N-myristoyltransferases inhibitory activity of ellagitannins from Terminalia bentzoë (L.) L. f. subsp. bentzoë. Fitoterapia, 131, 91–95. https://pubmed.ncbi.nlm.nih.gov/30342177/
44. Muganga R, Bero J, Quetin-Leclercq J, et al. (2021). In vitro antileishmanial, antitrypanosomal, and anti-inflammatory-like activity of Terminalia mollis root bark. Planta Medica, 87(9), 724–731. https://pubmed.ncbi.nlm.nih.gov/33063302/
45. Gigliobianco MR, Cortese M, Nannini S, et al. (2022). Chemical, antioxidant, and antimicrobial properties of the peel and male flower by-products of four varieties of Punica granatum L. cultivated in the Marche region for their use in cosmetic products. Antioxidants, 11(4), 768. https://pubmed.ncbi.nlm.nih.gov/35453453/
46. Dell’Agli M, Galli GV, Bulgari M, et al. (2010). Ellagitannins of the fruit rind of pomegranate (Punica granatum) antagonize in vitro the host inflammatory response mechanisms involved in the onset of malaria — in vitro. Malaria Journal. https://pubmed.ncbi.nlm.nih.gov/20642847/

View all 46 references▾