Geraniin

Geraniin at a Glance

Geraniin is a hydrolysable tannin of the ellagitannin family — a large, intensely hydroxylated molecule (C₄₁H₂₈O₂₇, ~953 Da) named for Geranium thunbergii, the Japanese antidiarrhoeal herb gennoshōko from which it was first isolated in 1976 ^{1Reference 1Okuda T et al. · 1976Geraniin, a new ellagitannin from Geranium thunbergiiView study →}. It is also the marker ellagitannin of several Phyllanthus species, including the chanca piedra sold for kidney stones, and the dominant polyphenol of rambutan fruit peel ^{32Reference 32Li Y et al. · 2018Metal chelating, inhibitory DNA damage, and anti-inflammatory activities of phenolics from rambutan (Nephelium lappaceum) peel and the quantifications of geraniin and corilaginView study →}.

The single most important fact about geraniin is that it does not stay geraniin. It carries a dehydrohexahydroxydiphenoyl (DHHDP) group that exists as a hydrate equilibrium in solution, and it hydrolyses readily in hot water, weak acid and weak base to corilagin, and then on to ellagic acid and gallic acid ^{2,3,5Reference 2Okuda T et al. · 1982Constituents of Geranium thunbergii Sieb. et ZuccView study →Reference 3Okuda T et al. · 1979Constituents of Geranium thunbergii Sieb. et ZuccView study →Reference 5Elendran S et al. · 2019Permeability of the ellagitannin geraniin and its metabolites in a human colon adenocarcinoma Caco-2 cell culture modelView study →}. Boil a Geranium decoction briefly and geraniin is the major component; boil it longer and corilagin is ^{4Reference 4Bastian F et al. · 2018Simultaneous quantification of ellagitannins and related polyphenols in Geranium thunbergii using quantitative NMRView study →}. That instability runs through everything below — it determines what a preparation actually contains, what an assay is actually measuring, and which molecule deserves the credit.

The honest evidence posture is straightforward: geraniin has a substantial, genuinely isolate-based preclinical literature — more than most molecules here — across anti-inflammatory, antiviral, antihypertensive and antioxidant endpoints. It has no human trials at all, and no measurable intestinal permeability in a Caco-2 model ^{5Reference 5Elendran S et al. · 2019Permeability of the ellagitannin geraniin and its metabolites in a human colon adenocarcinoma Caco-2 cell culture modelView study →}, so its systemic effects are almost certainly delivered by gut-derived fragments and urolithins rather than by intact geraniin in plasma.

The Instability Problem

This is the section that matters most, and it is why it matters separately from corilagin.

The chemistry. Geraniin’s DHHDP moiety sits in a hydrate equilibrium — Okuda’s group needed a dedicated 1982 paper to pin down the hydrated stereostructure, because the molecule presents as multiple interconverting species rather than one clean peak ^{2Reference 2Okuda T et al. · 1982Constituents of Geranium thunbergii Sieb. et ZuccView study →}. Under decoction, acid or base it loses that group and becomes corilagin; further hydrolysis of the galloyl and HHDP esters yields gallic acid and ellagic acid ^{3,5Reference 3Okuda T et al. · 1979Constituents of Geranium thunbergii Sieb. et ZuccView study →Reference 5Elendran S et al. · 2019Permeability of the ellagitannin geraniin and its metabolites in a human colon adenocarcinoma Caco-2 cell culture modelView study →}.

It is measurable, not theoretical. Quantitative NMR of Geranium thunbergii showed geraniin as the major component of a short decoction and corilagin as the major component of a long one, with the ethyl acetate and butanol fractions of the long decoction dominated by corilagin ^{4Reference 4Bastian F et al. · 2018Simultaneous quantification of ellagitannins and related polyphenols in Geranium thunbergii using quantitative NMRView study →}. In other words, brewing time alone flips which molecule you are dosing. The same logic applies to extract age, drying method and solvent — a point rambutan-peel process papers make repeatedly ^{32Reference 32Li Y et al. · 2018Metal chelating, inhibitory DNA damage, and anti-inflammatory activities of phenolics from rambutan (Nephelium lappaceum) peel and the quantifications of geraniin and corilaginView study →}.

It contaminates the pharmacology. The cleanest demonstration comes from an amyloid study: geraniin inhibited Aβ42 aggregation in vitro, but saturation-transfer-difference NMR showed no binding of geraniin to Aβ42 — while its hydrolysates gallic acid and corilagin both bound. The authors concluded the activity of the extract was carried by hydrolysis products generated under the assay conditions, not by geraniin ^{29Reference 29Kubo K et al. · 2022Chemical analysis of amyloid β aggregation inhibitors derived from Geranium thunbergiiView study →}. Any long-incubation, aqueous, warm assay of geraniin is vulnerable to the same objection.

Formulators route around it. Because the free molecule is hard to isolate and store, some groups work with acetonylgeraniin, a stable acetone condensate, rather than geraniin itself ^{38Reference 38Gayosso-De-Lucio J et al. · 2014Chemical composition and hepatotoxic effect of Geranium schiedeanum in a thioacetamide-induced liver injury modelView study →}.

The practical reading: when a paper credits geraniin, ask whether the material was characterised at the point of assay, and whether corilagin, ellagic acid or gallic acid could have done the work instead. Several of the findings below survive that test — the dengue envelope-protein binding and the IL-1β binding are structure-specific — and several do not.

What It's Used For

The literature is unusually isolate-heavy for a tannin: purified geraniin (typically 95–99% pure, from rambutan rind or Geranium) has been run in cell models and in rats across five distinct areas. What it has never been run in is a human.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. Every row is preclinical, so all scores stay in the lower half by design. Each application links to its write-up.

01Anti-InflammatoryShaky42%Isolate macrophage mechanism + a direct IL-1β target + colitis mouse model ^{10,11,12Reference 10Wang P et al. · 2016Inhibitory effects of geraniin on LPS-induced inflammation via regulating NF-κB and Nrf2 pathways in RAW 264.7 cellsView study →Reference 11Lee HR et al. · 2024AnimalGeraniin alleviates inflammation in Caco-2 cells and dextran sulfate sodium-induced colitis mice by targeting IL-1βView study →Reference 12Fujiki H et al. · 2003New TNF-alpha releasing inhibitors as cancer preventive agents from traditional herbal medicineView study →}

02Antiviral (Flaviviruses)Shaky40%Isolate IC₅₀ 1.75 µM with a named viral target, plus mouse and zebrafish work ^{13,14,15Reference 13Abdul Ahmad SA et al. · 2017Geraniin extracted from the rind of Nephelium lappaceum binds to dengue virus type-2 envelope protein and inhibits early stage of virus replicationView study →Reference 14Abdul Ahmad SA et al. · 2019AnimalEfficacy of geraniin on dengue virus type-2 infected BALB/c miceView study →Reference 15Haddad JG et al. · 2020The geraniin-rich extract from Reunion Island endemic medicinal plant Phyllanthus phillyreifolius inhibits Zika and dengue virus infection at non-toxic effect doses in zebrafishView study →}

03Antihypertensive (ACE Inhibition)Shaky36%Isolate ACE IC₅₀, oral dosing in SHR and high-fat-diet rats ^{16,17,19Reference 16Ueno H et al. · 1988Chemical and pharmaceutical studies on medicinal plants in ParaguayView study →Reference 17Lin SY et al. · 2008Antioxidant, anti-semicarbazide-sensitive amine oxidase, and anti-hypertensive activities of geraniin isolated from Phyllanthus urinariaView study →Reference 19Phang SCW et al. · 2019AnimalEffects of geraniin (rambutan rind extract) on blood pressure and metabolic parameters in rats fed high-fat dietView study →}

04AntioxidantShaky34%Sub-micromolar radical-scavenging IC₅₀s + redox restoration in rats ^{17,22,34Reference 17Lin SY et al. · 2008Antioxidant, anti-semicarbazide-sensitive amine oxidase, and anti-hypertensive activities of geraniin isolated from Phyllanthus urinariaView study →Reference 22Chung APYS et al. · 2018AnimalGeraniin protects high-fat diet-induced oxidative stress in Sprague Dawley ratsView study →Reference 34Kumaran A · 2006Nitric oxide radical scavenging active components from Phyllanthus emblica LView study →}

05Metabolic (Insulin Sensitisation)Shaky30%Rat metabolic-syndrome models and 3T3-L1 adipocytes ^{19,20,21Reference 19Phang SCW et al. · 2019AnimalEffects of geraniin (rambutan rind extract) on blood pressure and metabolic parameters in rats fed high-fat dietView study →Reference 20Cheng HS et al. · 2020AnimalPleiotropic ameliorative effects of ellagitannin geraniin against metabolic syndrome induced by high-fat diet in ratsView study →Reference 21Perera A et al. · 2020The insulin-sensitising properties of the ellagitannin geraniin and its metabolites from Nephelium lappaceum rind in 3T3-L1 cellsView study →}

06Antiviral (Hepatitis B)Shaky22%In-vitro antigen/cccDNA suppression only, against a failed human whole-herb record ^{24,25,26,27Reference 24Li J et al. · 2008Anti-hepatitis B virus activities of Geranium carolinianum L. extracts and identification of the active componentsView study →Reference 25Huang RL et al. · 2003In vitroScreening of 25 compounds isolated from Phyllanthus species for anti-human hepatitis B virus in vitroView study →Reference 26Liu C et al. · 2016Identification of hydrolyzable tannins (punicalagin, punicalin and geraniin) as novel inhibitors of hepatitis B virus covalently closed circular DNAView study →Reference 27Milne A et al. · 1994Failure of New Zealand hepatitis B carriers to respond to Phyllanthus amarusView study →}

Mechanisms

The two mechanisms that survive the instability objection most cleanly are the DENV-envelope and IL-1β interactions, because both are structure-specific binding events rather than generic redox or protein-precipitation effects.

Pharmacokinetics

This is the load-bearing limitation, and it is unusually well characterised for a tannin. Geraniin is a ~953 Da, extremely polar molecule (log P −0.73) with poor solubility in simulated gastric fluid but good solubility in intestinal fluid — the physicochemical profile of something that dissolves but does not cross ^{6Reference 6Elendran S et al. · 2015The physicochemical properties of geraniin, a potential antihyperglycemic agentView study →}. In a Caco-2 monolayer, geraniin, corilagin and ellagic acid showed no apparent permeability at all; only gallic acid crossed (P_app 31.3 × 10⁻⁶ cm/s). Mass-balance work in the same study showed geraniin and corilagin were being hydrolysed in the transport buffer and metabolised during transport, with ellagic acid accumulating inside the cells ^{5Reference 5Elendran S et al. · 2019Permeability of the ellagitannin geraniin and its metabolites in a human colon adenocarcinoma Caco-2 cell culture modelView study →}.

What reaches the circulation is therefore fragments and microbial metabolites. After oral geraniin in rats, seven urinary and intestinal microbial metabolites were isolated and identified as dibenzopyran (urolithin-type) derivatives; four of them out-performed intact geraniin and corilagin in ORAC, and plasma antioxidant capacity rose in step with plasma metabolite concentration, not parent concentration ^{7Reference 7Ito H · 2011Metabolites of the ellagitannin geraniin and their antioxidant activitiesView study →}. Urolithin A — the same metabolite generated from pomegranate ellagitannins — is itself orally active and anti-inflammatory in carrageenan paw oedema ^{8Reference 8Ishimoto H et al. · 2011AnimalIn vivo anti-inflammatory and antioxidant properties of ellagitannin metabolite urolithin AView study →}. This places geraniin squarely inside the ellagitannin class picture, where conversion to ellagic acid and then to urolithins by colonic microbiota, with large inter-individual metabotype variation, governs what a person actually gets ^{37Reference 37Mihaylova R et al. · 2025ReviewUnlocking the therapeutic potential of ellagitannins: a comprehensive review of key representativesView study →}.

The one direct pharmacokinetic dataset is intravenous, not oral: a rat UPLC study reported a terminal half-life of 7.20 ± 2.20 h, clearance of 0.03 L/h/kg and an apparent volume of distribution of 0.05 L/kg — a very small distribution volume consistent with a molecule confined to plasma and extracellular water ^{9Reference 9Yi Z et al. · 2017AnimalAn UPLC method for determination of geraniin in rat plasma and its application to pharmacokinetic studiesView study →}. There is no human ADME study of geraniin.

Clinical Trials

There are no human trials of geraniin, of any design. A PubMed search returns none, and the compound’s entire evidence base is in vitro and rodent. Human exposure is incidental — as a tannin in Phyllanthus decoctions, amla preparations and rambutan peel products — and the one human Phyllanthus hepatitis-B result in this literature was negative ^{27Reference 27Milne A et al. · 1994Failure of New Zealand hepatitis B carriers to respond to Phyllanthus amarusView study →}.

Last checked: August 2026.

Isolate vs. Plant Studies

Geraniin scores better than most tannins here, with an important asterisk.

The isolate work is real. Unusually for this class, most of the pharmacology above used purified geraniin — 95–99% pure material from rambutan rind or Geranium — dosed as a single compound in cells and orally in rats ^{13,17,19,20,22Reference 13Abdul Ahmad SA et al. · 2017Geraniin extracted from the rind of Nephelium lappaceum binds to dengue virus type-2 envelope protein and inhibits early stage of virus replicationView study →Reference 17Lin SY et al. · 2008Antioxidant, anti-semicarbazide-sensitive amine oxidase, and anti-hypertensive activities of geraniin isolated from Phyllanthus urinariaView study →Reference 19Phang SCW et al. · 2019AnimalEffects of geraniin (rambutan rind extract) on blood pressure and metabolic parameters in rats fed high-fat dietView study →Reference 20Cheng HS et al. · 2020AnimalPleiotropic ameliorative effects of ellagitannin geraniin against metabolic syndrome induced by high-fat diet in ratsView study →Reference 22Chung APYS et al. · 2018AnimalGeraniin protects high-fat diet-induced oxidative stress in Sprague Dawley ratsView study →}. The dengue, ACE, colitis and metabolic-syndrome results are molecule-level findings, not extract-level ones. That is a genuine strength.

The asterisk is the instability, not the plant. The usual isolate-vs-plant caveat is replaced by an isolate-vs-fragment caveat: purity at the start of an experiment does not guarantee identity at the end of it ^{4,5,29Reference 4Bastian F et al. · 2018Simultaneous quantification of ellagitannins and related polyphenols in Geranium thunbergii using quantitative NMRView study →Reference 5Elendran S et al. · 2019Permeability of the ellagitannin geraniin and its metabolites in a human colon adenocarcinoma Caco-2 cell culture modelView study →Reference 29Kubo K et al. · 2022Chemical analysis of amyloid β aggregation inhibitors derived from Geranium thunbergiiView study →}. Where the isolate and its metabolites have been tested side by side, the metabolites sometimes win — ellagic acid on ACE ^{18Reference 18Looi D et al. · 2021In vitroMetabolites of the ellagitannin, geraniin inhibit human ACE; in vitro and in silico evidenceView study →}, the urolithin-type metabolites on ORAC ^{7Reference 7Ito H · 2011Metabolites of the ellagitannin geraniin and their antioxidant activitiesView study →}.

Where the plant does the work. The whole-Phyllanthus anti-inflammatory and immunomodulatory literature is extract-based, with geraniin quantified as one of several HPLC markers alongside phyllanthin, hypophyllanthin, corilagin, ellagic acid and gallic acid ^{36Reference 36Harikrishnan H et al. · 2018Anti-inflammatory effects of Phyllanthus amarus Schum. & Thonn. through inhibition of NF-κB, MAPK, and PI3K-Akt signaling pathways in LPS-induced human macrophagesView study →}. Those extract results belong to the extract. Likewise the Phyllanthus hepatitis-B reputation is a whole-decoction story with a negative human trial in it ^{27Reference 27Milne A et al. · 1994Failure of New Zealand hepatitis B carriers to respond to Phyllanthus amarusView study →}, not a geraniin story.

Its Role in Plants

Geraniin is a defensive hydrolysable tannin — an astringent, protein-precipitating polyphenol concentrated in the tissues most exposed to herbivory and microbial attack: fruit peel (rambutan), seed coat (longan) and aerial parts (Geranium, Phyllanthus). Its distinctive dehydrohexahydroxydiphenoyl group makes it chemically reactive as well as astringent, and it acts as a biosynthetic hub: related Phyllanthus ellagitannins such as elaeocarpusin and phyllanthusiin D are geraniin derivatives, and they co-occur with it in the same extracts ^{35Reference 35Grauzdytė D et al. · 2020Antioxidant potential and phytochemical composition of extracts obtained from Phyllanthus phillyreifolius by different extraction methodsView study →}. The instability that frustrates chemists is, from the plant’s point of view, part of the point — a tannin that fragments into further reactive phenolics on wounding.

Prevalence in Nature

Geraniin is distributed across three unrelated plant families, which is why its literature is scattered.

Geraniaceae is the type genus. It is the principal ellagitannin of Geranium thunbergii (the Japanese antidiarrhoeal gennoshōko), where quantitative NMR across six Japanese and three Chinese collection sites found Japanese material consistently richer than Chinese ^{4Reference 4Bastian F et al. · 2018Simultaneous quantification of ellagitannins and related polyphenols in Geranium thunbergii using quantitative NMRView study →}. It also occurs in G. carolinianum ^{24Reference 24Li J et al. · 2008Anti-hepatitis B virus activities of Geranium carolinianum L. extracts and identification of the active componentsView study →}, G. sibiricum ^{10Reference 10Wang P et al. · 2016Inhibitory effects of geraniin on LPS-induced inflammation via regulating NF-κB and Nrf2 pathways in RAW 264.7 cellsView study →} and G. schiedeanum ^{38Reference 38Gayosso-De-Lucio J et al. · 2014Chemical composition and hepatotoxic effect of Geranium schiedeanum in a thioacetamide-induced liver injury modelView study →}, and in a 46-sample survey of thirty-one Geranium and Erodium species, geraniin and ellagic acid were the major compounds identified in the most enzyme-inhibitory extracts ^{39Reference 39Özüpek B et al. · 2025Enzyme inhibitory activities and RP-HPLC analysis of Geranium and Erodium speciesView study →}.

Phyllanthaceae/Euphorbiaceae is the medicinal cluster. Geraniin appears in Phyllanthus niruri ^{16Reference 16Ueno H et al. · 1988Chemical and pharmaceutical studies on medicinal plants in ParaguayView study →}, P. amarus ^{36Reference 36Harikrishnan H et al. · 2018Anti-inflammatory effects of Phyllanthus amarus Schum. & Thonn. through inhibition of NF-κB, MAPK, and PI3K-Akt signaling pathways in LPS-induced human macrophagesView study →}, P. urinaria ^{17Reference 17Lin SY et al. · 2008Antioxidant, anti-semicarbazide-sensitive amine oxidase, and anti-hypertensive activities of geraniin isolated from Phyllanthus urinariaView study →}, P. emblica (amla) fruit rind ^{34Reference 34Kumaran A · 2006Nitric oxide radical scavenging active components from Phyllanthus emblica LView study →} and — as the single main constituent — P. phillyreifolius from Réunion ^{35Reference 35Grauzdytė D et al. · 2020Antioxidant potential and phytochemical composition of extracts obtained from Phyllanthus phillyreifolius by different extraction methodsView study →}.

Sapindaceae holds the richest documented source. In rambutan (Nephelium lappaceum) fruit peel, a phenolic extract assayed 140.02 mg/g geraniin against 7.87 mg/g corilagin by UPLC-QQQ-MS ^{32Reference 32Li Y et al. · 2018Metal chelating, inhibitory DNA damage, and anti-inflammatory activities of phenolics from rambutan (Nephelium lappaceum) peel and the quantifications of geraniin and corilaginView study →} — an ~18:1 ratio, and the reason nearly all modern geraniin pharmacology comes out of Malaysian groups working with rambutan processing waste. Longan (Dimocarpus longan) seed carries 5.79 g/kg dry weight within an 80.90 g/kg polyphenolic fraction ^{33Reference 33Sudjaroen Y et al. · 2012Isolation and characterization of ellagitannins as the major polyphenolic components of Longan (Dimocarpus longan Lour) seedsView study →}.

Major Natural Sources

Source	Part	Geraniin reported	Basis	Ref
Rambutan (Nephelium lappaceum)	fruit peel	140.02 mg/g	phenolic extract, dry wt	32Reference 32Li Y et al. · 2018Metal chelating, inhibitory DNA damage, and anti-inflammatory activities of phenolics from rambutan (Nephelium lappaceum) peel and the quantifications of geraniin and corilaginView study →
Longan (Dimocarpus longan)	seed	5.79 g/kg	seed dry wt	33Reference 33Sudjaroen Y et al. · 2012Isolation and characterization of ellagitannins as the major polyphenolic components of Longan (Dimocarpus longan Lour) seedsView study →
Geranium thunbergii	aerial parts	major component of a short decoction; corilagin overtakes it in a long one	qNMR of decoction	4Reference 4Bastian F et al. · 2018Simultaneous quantification of ellagitannins and related polyphenols in Geranium thunbergii using quantitative NMRView study →
Phyllanthus phillyreifolius	aerial parts	main constituent of the hydrophilic extract	UPLC-MS, qualitative rank	35Reference 35Grauzdytė D et al. · 2020Antioxidant potential and phytochemical composition of extracts obtained from Phyllanthus phillyreifolius by different extraction methodsView study →
Chanca piedra (Phyllanthus niruri)	whole plant	present; no quantified figure located	—	16Reference 16Ueno H et al. · 1988Chemical and pharmaceutical studies on medicinal plants in ParaguayView study →
Amla (Phyllanthus emblica)	fruit rind	present; strongest NO scavenger of the isolates	—	34Reference 34Kumaran A · 2006Nitric oxide radical scavenging active components from Phyllanthus emblica LView study →

The two numeric rows are on different bases — one is per gram of a phenolic extract, the other per gram of dry seed — so they are not directly comparable, and no like-for-like dry-weight series exists across these sources.

The Phyllanthus Species Problem

This matters for anyone matching the chemistry to chanca piedra. A targeted search for geraniin AND "Phyllanthus niruri" returns just two records; geraniin AND "Phyllanthus amarus" returns 23, and "Phyllanthus urinaria" eight. The attribution to P. niruri is nonetheless sound — it rests on the 1988 Paraguayan study that isolated geraniin from genuinely American P. niruri material sold as paraparai mi ^{16Reference 16Ueno H et al. · 1988Chemical and pharmaceutical studies on medicinal plants in ParaguayView study →} — but the bulk of the geraniin data attached to “chanca piedra” was generated on P. amarus or P. urinaria, the Asian look-alikes routinely sold and published under the P. niruri name. The three are widely conflated, and they differ chemically. Read a geraniin claim about chanca piedra as a genus-level claim unless the paper says otherwise.

Discovery & Synthesis

Geraniin was isolated and named in 1976 by Takuo Okuda, Takashi Yoshida and Hiroshi Nayeshiro at Okayama University, from Geranium thunbergii — hence the name ^{1Reference 1Okuda T et al. · 1976Geraniin, a new ellagitannin from Geranium thunbergiiView study →}. Its structure was assigned the following year, but the molecule resisted a clean description for another five: the dehydrohexahydroxydiphenoyl group exists as a hydrate in equilibrium, and Okuda’s group needed a further paper in 1982 to establish the hydrated stereostructure and equilibration ^{2Reference 2Okuda T et al. · 1982Constituents of Geranium thunbergii Sieb. et ZuccView study →}. The same laboratory published the decoction-transformation study that first documented geraniin’s conversion on boiling ^{3Reference 3Okuda T et al. · 1979Constituents of Geranium thunbergii Sieb. et ZuccView study →} — instability was recognised as a defining property from the beginning.

No total synthesis of geraniin is reported in the literature reviewed here. That is unsurprising: with 27 oxygens, a strained DHHDP bridge and a hydrate equilibrium, it is a hard target with no commercial incentive, since the natural material is abundant.

Manufacture today is extraction, not synthesis. The dominant route is purification from rambutan fruit peel, a food-processing waste stream: reverse-phase C18 chromatography of N. lappaceum rind extract gives 97–99% pure geraniin at a purification yield around 10.8% ^{6Reference 6Elendran S et al. · 2015The physicochemical properties of geraniin, a potential antihyperglycemic agentView study →}. Where the free molecule’s instability is prohibitive, chemists have worked instead with acetonylgeraniin, a stable acetone condensate ^{38Reference 38Gayosso-De-Lucio J et al. · 2014Chemical composition and hepatotoxic effect of Geranium schiedeanum in a thioacetamide-induced liver injury modelView study →}.

Patents: not yet researched.

Toxicity & Safety

Geraniin carries a low flag: the one formal toxicology study found no meaningful haematological or biochemical change after a single high oral dose, and rats tolerated four weeks of 10–100 mg/kg without reported toxicity ^{19,22,30Reference 19Phang SCW et al. · 2019AnimalEffects of geraniin (rambutan rind extract) on blood pressure and metabolic parameters in rats fed high-fat dietView study →Reference 22Chung APYS et al. · 2018AnimalGeraniin protects high-fat diet-induced oxidative stress in Sprague Dawley ratsView study →Reference 30Moorthy M et al. · 2019AnimalAcute oral toxicity of the ellagitannin geraniin and a geraniin-enriched extract from Nephelium lappaceum L rind in Sprague Dawley ratsView study →}. “Low” here means no signal found in a thin dataset, not characterised as safe — there is no human toxicology, no repeat-dose package and no reproductive dataset for the isolated molecule.

Safety at a Glance

✅ Low / no toxicity

• No acute toxicity signal. In an OECD 423 study, blood counts, biochemistry and histopathology were unchanged versus control, and the LD₅₀ cut-off was set at 2000 mg/kg for both geraniin and a geraniin-enriched rambutan extract.
• Tolerated in repeat-dose rodent work. Four weeks at 10–50 mg/kg and dose-ranging to 100 mg/kg produced benefit without reported harm.
• Liver histology at the top dose. Hepatocytes in three geraniin-dosed rats showed a “foamy appearance”, so the no-observed-adverse-effect level for pure geraniin was set below 2000 mg/kg — lower than for the enriched extract.
• Binds non-heme iron and proteins. A tannin-class effect; relevant if you supplement iron or are iron-deficient, and the reason high tannin intakes are astringent and can irritate the gut.
• A chromosome-instability mechanism exists. Geraniin weakens the spindle assembly checkpoint in colon cancer cells (the proposed basis of its selective anticancer effect) while strengthening it in normal cells — a mechanism worth naming rather than ignoring.
• No human data of any kind. No trial, no ADME study, no reproductive or developmental dataset for the isolate.

Full Safety & Interactions Detail

Acute oral toxicity. The only dedicated study followed OECD 423 in Sprague Dawley rats with a single oral dose of geraniin or a geraniin-enriched N. lappaceum rind extract, followed by 14 days of observation, full blood count, blood biochemistry and organ histopathology. All parameters were statistically indistinguishable from control, and the LD₅₀ cut-off was established at 2000 mg/kg for both. The one finding was a “foamy appearance” of hepatocytes in three geraniin-treated rats, on the strength of which the authors set the NOAEL for pure geraniin below 2000 mg/kg while allowing up to 2000 mg/kg for the enriched extract — a notable inversion, and they explicitly called for further toxicity work before human use ^{30Reference 30Moorthy M et al. · 2019AnimalAcute oral toxicity of the ellagitannin geraniin and a geraniin-enriched extract from Nephelium lappaceum L rind in Sprague Dawley ratsView study →}. Repeat-dose rodent studies at 10–100 mg/kg for four weeks reported no toxicity ^{19,22Reference 19Phang SCW et al. · 2019AnimalEffects of geraniin (rambutan rind extract) on blood pressure and metabolic parameters in rats fed high-fat dietView study →Reference 22Chung APYS et al. · 2018AnimalGeraniin protects high-fat diet-induced oxidative stress in Sprague Dawley ratsView study →}.

Cell-cycle and chromosome effects. Geraniin’s proposed selective anticancer mechanism is abrogation of the spindle assembly checkpoint: in HCT116 colon cancer cells it lowered transcription of SAC kinases (notably Mad2 and Bub1), forcing premature anaphase, mitotic aberrations and catastrophic chromosome instability, while in non-cancerous CCD841 colon epithelium it raised Mad1 and BubR1 and reduced chromosome instability ^{31Reference 31Guo X et al. · 2019Geraniin differentially modulates chromosome stability of colon cancer and noncancerous cells by oppositely regulating their spindle assembly checkpointView study →}. The opposite-direction effect in normal cells is reassuring, but a molecule that manipulates mitotic checkpoints is not one to treat as an inert dietary polyphenol.

Tannin-class interactions. As a large hydrolysable tannin, geraniin binds and precipitates proteins and chelates metal ions — rambutan peel phenolics chelate Fe²⁺ and Cu²⁺ with EC₅₀ values of 0.80 and 0.13 mg/mL ^{32Reference 32Li Y et al. · 2018Metal chelating, inhibitory DNA damage, and anti-inflammatory activities of phenolics from rambutan (Nephelium lappaceum) peel and the quantifications of geraniin and corilaginView study →}. The practical consequences are the class ones: reduced non-heme iron absorption, astringency and possible gastrointestinal irritation at high oral intakes, and the potential to complex co-administered drugs in the gut. No specific cytochrome-P450 or transporter interaction has been characterised for geraniin itself, which is a gap rather than a clean bill.

Reproductive note (prose only). No reproductive or developmental toxicity data exist for isolated geraniin, and its mitotic-checkpoint mechanism ^{31Reference 31Guo X et al. · 2019Geraniin differentially modulates chromosome stability of colon cancer and noncancerous cells by oppositely regulating their spindle assembly checkpointView study →} is an unfavourable unknown in that context. Pregnancy and lactation decisions belong to the herb or product page where intake is actually decided, not to a molecule page.

What is not known. Interactions, genotoxicity, carcinogenicity and repeat-dose toxicology have not been formally assessed for this compound in humans. Absence of findings here reflects absence of studies.

Dosage

There is no human dose for geraniin, and nothing below is a recommendation. Every figure is a research quantity.

Real-world exposure is entirely indirect — as one tannin among many in a Phyllanthus decoction, an amla preparation, or a rambutan-peel extract. Preparation matters more here than for most molecules: a brief infusion favours geraniin, while a long decoction or an aged extract converts it to corilagin and onward to gallic acid and ellagic acid ^{3,4Reference 3Okuda T et al. · 1979Constituents of Geranium thunbergii Sieb. et ZuccView study →Reference 4Bastian F et al. · 2018Simultaneous quantification of ellagitannins and related polyphenols in Geranium thunbergii using quantitative NMRView study →}. These are doses studied in research and are not a personal recommendation.

References

1. Okuda T, Yoshida T, Nayeshiro H (1976). Geraniin, a new ellagitannin from Geranium thunbergii. Tetrahedron Letters. https://doi.org/10.1016/S0040-4039(00)93091-0
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