Compound Monograph
Glucofrangulin A
Glucofrangulin A (emodin-6-O-rhamnosyl-8-O-glucoside) is the dominant emodin diglycoside of alder buckthorn (Frangula alnus) bark and the marker the European Pharmacopoeia standardises Frangula bark against. It is a laxative prodrug — colonic bacteria strip its sugars to release active emodin anthrone — with almost no isolate-level human data of its own, and it sits inside the EU-restricted hydroxyanthracene class.
Sources · 2
Where Does It Come From?
Glucofrangulin A is a naturally occurring anthraquinone diglycoside (emodin glycoside), found in Alder buckthorn and Other Rhamnus and Frangula species. It is flagged as moderately toxic.
Concentration
Content by Source
Concentrations not reported. No percent-dry-weight or mg/g figures have been published for this compound in its source plants.
Glucofrangulin A at a Glance
Glucofrangulin A is the main anthraquinone diglycoside of alder buckthorn (Frangula alnus, syn. Rhamnus frangula) bark. Chemically it is emodin bearing a rhamnose at the 6-position and a glucose at the 8-position — that is, it is emodin with two sugars attached. It matters less as a molecule with its own pharmacology than as the pharmacopoeial marker the European Pharmacopoeia uses to standardise Frangula bark 8Reference 8ReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →.
Its biological role is that of a laxative prodrug. The diglycoside is too polar to be absorbed in the upper gut; it travels intact to the colon, where bacterial enzymes cleave the sugars to release the active emodin anthrone, which stimulates colonic motility and secretion 4Reference 4The metabolism of anthranoid laxativesView study →. This is the same anthranoid mechanism that runs through senna, cascara and rhubarb — glucofrangulin A is simply the more-glycosylated end of Frangula’s own prodrug ladder.
The honest posture: almost all of the data are analytical and standardisation work, not clinical trials of the isolated molecule. Where efficacy and safety are discussed, they belong to whole standardised Frangula bark and to the hydroxyanthracene class — including the emodin genotoxicity signal and the EU restriction on hydroxyanthracene derivatives 5Reference 5Safety of hydroxyanthracene derivatives for use in foodView study →.
The Frangula Bark Marker
Glucofrangulin A is the number the pharmacopoeia points at. The European Pharmacopoeia monograph for Frangula bark requires a minimum of 7.0% glucofrangulins, expressed as glucofrangulin A (C27H30O14; Mr 578.5), calculated on the dried drug 8Reference 8ReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →. In practice glucofrangulin A is usually the dominant single anthraquinone in commercial bark and Frangula phytopharmaceuticals — a 2024 supercritical-fluid-chromatography survey found “glucofrangulin A always was the dominating compound” in commercial material, even where wild-collected samples varied 3Reference 3Determination of anthraquinones in Frangula alnus by supercritical fluid chromatographyView study →. Validated HPLC and UHPLC methods now resolve glucofrangulins A/B and frangulins A/B in a single run for exactly this quality-control purpose 2Reference 2Validated method for the analysis of frangulins A and B and glucofrangulins A and B using HPLC and UHPLCView study →.
Inside the bark, the anthraquinones sit on a hydrolysis ladder defined by how many sugars are attached:
glucofrangulin A (emodin + rhamnose + glucose) → frangulin A (emodin + rhamnose) → emodin (aglycone) → emodin anthrone (the reduced, colon-active form)
Losing the glucose converts the diglycoside glucofrangulin A into the monoglycoside frangulin A; losing the rhamnose too gives free emodin. The pharmacopoeial assay counts the diglycosides because they are the intact, storage-stable prodrug pool — the fraction that survives to the colon to do the work 4,
Glucofrangulin vs. Frangulin
The two names are a di- vs. mono-glycoside distinction on the same emodin core:
| Compound | Sugars on emodin | Type |
|---|---|---|
| Glucofrangulin A | 6-O-rhamnose and 8-O-glucose | diglycoside |
| Frangulin A | 6-O-rhamnose only | monoglycoside |
| Emodin | none | aglycone |
(The “B” series — glucofrangulin B and frangulin B — is the same pattern built on apiose instead of rhamnose at the 6-position.) The practical consequence of the extra sugar is twofold. First, more sugars mean more polarity, so the diglycoside is even less likely to be absorbed before the colon — good prodrug behaviour. Second, glycosylation blunts the intrinsic toxicity of the anthranoid: a structure–toxicity study of diverse anthranoids found that “the presence of glucose moieties in the chemical structure reduced the toxicity,” so the sugared prodrugs are gentler than the free aglycone they eventually release 6Reference 6Cytotoxicity of structurally diverse anthranoids and correlation with mechanism of action and side effectsView study →. The activity — and the genotoxicity concern — really belong to the emodin unmasked at the end of the ladder, not to the diglycoside carrying it there.
What It's Used For
There is no meaningful body of pharmacology on isolated glucofrangulin A beyond its behaviour as a Frangula-bark prodrug and its contribution to the antioxidant/antimicrobial activity of Frangula extracts. The evidence is thin by nature, and the honest read is below.
Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. Glucofrangulin A has almost no isolate-level data, so scores are low and reflect whole-bark/class evidence.
Glucofrangulin A is the diglycoside form of Frangula’s laxative principle. As an O-diglycoside it is not split by human digestive enzymes in the upper gut; it reaches the large intestine intact, where bacterial β-glycosidases strip the sugars and bacterial reductases convert the freed emodin to the active emodin anthrone, which drives colonic water/electrolyte secretion and peristalsis 4Reference 4The metabolism of anthranoid laxativesView study →.
This is the same prodrug logic as senna’s sennosides and cascara’s cascarosides. The application is real and pharmacopoeially recognised — but the evidence is for standardised whole Frangula bark, not for the purified diglycoside dosed on its own.
Gap: no clinical trial doses isolated glucofrangulin A; efficacy is inferred from standardised bark and the shared anthranoid mechanism, and the class is restricted by EU regulators (see Toxicity) 5,
Frangula bark extract shows in-vitro antioxidant (DPPH radical scavenging, reducing power) and antimicrobial activity, with glucofrangulins and frangulins among the anthraquinone constituents contributing to the profile; reported minimum inhibitory concentrations for the bark extracts were in the low-mg/mL range 9Reference 9Anthraquinone profiles, antioxidant and antimicrobial properties of Frangula rupestris (Scop.) Schur and Frangula alnus Mill. barkView study →. These are whole-extract assays in which glucofrangulin A is one anthraquinone among several (physcion, emodin, frangulins), rarely isolated and tested alone.
Gap: in-vitro, extract-level data only — no isolate potency, no in-vivo or human antioxidant/antimicrobial outcome attributable to glucofrangulin A specifically 9Reference 9Anthraquinone profiles, antioxidant and antimicrobial properties of Frangula rupestris (Scop.) Schur and Frangula alnus Mill. barkView study →.
Mechanisms
| Target / pathway | Effect | Relevant to |
|---|---|---|
| Colonic bacterial β-glycosidase | hydrolyses the rhamnose/glucose → releases emodin aglycone | laxative prodrug activation |
| Colonic bacterial reductase | reduces emodin → active emodin-9-anthrone | laxative prodrug activation |
| Colonic enterocyte water/electrolyte transport | anthrone stimulates secretion + inhibits reabsorption → ↑ luminal volume | laxative effect |
| Colonic myenteric stimulation | ↑ propulsive motility / peristalsis | laxative effect |
| Phenolic/anthraquinone radical scavenging | contributes to extract antioxidant capacity | antioxidant (extractin vitro) |
The load-bearing point is that glucofrangulin A does nothing until its sugars come off in the colon — it is a delivery form for emodin anthrone, and both the therapeutic effect and the class safety concern track the emodin it releases, not the intact diglycoside.
Pharmacokinetics
The pharmacokinetics are the whole story of an anthranoid prodrug. Being a polar diglycoside, glucofrangulin A is poorly absorbed in the stomach and small intestine and passes largely intact to the colon — this is the design feature that makes it a laxative rather than a systemically-absorbed drug 4Reference 4The metabolism of anthranoid laxativesView study →. Colonic flora then perform the two-step activation (deglycosylation, then reduction to the anthrone). The released emodin has poor oral bioavailability (~3–5% in rodents) owing to extensive glucuronidation and efflux, so systemic exposure to free aglycone stays low even after activation 7Reference 7ReviewEmodin: a review of its pharmacology, toxicity and pharmacokineticsView study →. Absorbed anthranoids are excreted mainly as glucuronide and sulfate conjugates in urine and bile 4Reference 4The metabolism of anthranoid laxativesView study →. No dedicated human pharmacokinetic dataset exists for isolated glucofrangulin A.
Clinical Trials
There are no clinical trials of isolated glucofrangulin A. Human evidence in this space is for standardised Frangula bark as a short-term laxative (the basis of the EMA herbal monograph), a multi-constituent preparation in which glucofrangulin A is the assay marker rather than an isolated intervention 8Reference 8ReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →. Treat all human data as bark-level.
| Completed | Planned | Terminated | Preclinical |
|---|---|---|---|
| —(isolate); standardised Frangula bark only | — | — | Analytical / mechanistic (class) |
Last checked: July 2026.
Isolate vs. Plant Studies
This molecule sits almost entirely on the plant/extract side of the ledger. Glucofrangulin A is studied overwhelmingly as a constituent and quality marker of Frangula bark — quantified by HPLC/UHPLC and supercritical-fluid chromatography 2,
Prevalence in Nature
Glucofrangulin A is the characteristic anthraquinone of alder buckthorn (Frangula alnus / Rhamnus frangula) bark, where it is usually the dominant single anthraquinone and the compound the pharmacopoeial assay is built around 3,
Two provenance points shape the real-world content. First, fresh bark is unsuitable: it carries reduced, harsh anthrones and anthranols and must be aged (dried and stored ~1 year, or heat-treated) before use, during which the violently purgative reduced forms oxidise toward the gentler stable glycosides 8Reference 8ReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →. Second, absolute anthraquinone content varies widely with source and processing — one survey spanned roughly 2–51 mg total anthraquinones across samples 3Reference 3Determination of anthraquinones in Frangula alnus by supercritical fluid chromatographyView study → — which is precisely why standardisation to glucofrangulin A exists.
Discovery & Synthesis
Frangula’s anthraquinone glycosides were isolated and named in the nineteenth-century wave of anthranoid chemistry (frangulin, then the more-glycosylated “glucofrangulin”). The definitive structure of frangulin and glucofrangulin was established by Hans Wagner and H. P. Hörhammer in 1966, who confirmed the assignments by synthesis and spectroscopic analysis 1Reference 1Wagner H, Hörhammer HP (1966). [Synthesis and definitive structural analysis of frangulin and glucofrangulin from Rhamnus frangula L.]. Naturwissenschaften. https://pubmed.ncbi.nlm.nih.gov/5992817/View study →. The name encodes the chemistry: frangulin from Frangula, with the gluco- prefix marking the extra glucose that distinguishes the diglycoside from the monoglycoside.
Manufacture today is by extraction from Frangula bark, not synthesis — glucofrangulin A is obtained (and purified as an analytical reference standard) from alder buckthorn bark rather than made industrially, and it reaches people through standardised bark preparations rather than as a discrete drug substance.
Patents: not yet researched.
Toxicity & Safety
Glucofrangulin A carries a moderate flag. The diglycoside itself is the gentler, sugared end of the anthranoid series — glycosylation lowers intrinsic anthranoid toxicity 6Reference 6Cytotoxicity of structurally diverse anthranoids and correlation with mechanism of action and side effectsView study → — but it is a prodrug for emodin, and it sits squarely inside the hydroxyanthracene-derivative class that European regulators have restricted over genotoxicity concerns. The cautions below are class cautions applied to the Frangula-bark context in which this molecule is consumed.
- Gentler than the free aglycone as an intact diglycoside. Glycosylation reduces anthranoid cytotoxicity, and the sugars keep it unabsorbed until the colon 6Reference 6Cytotoxicity of structurally diverse anthranoids and correlation with mechanism of action and side effectsView study →.
- It delivers emodin, which carries a genotoxicity signal. EFSA judged hydroxyanthracene derivatives (emodin, aloe-emodin, danthron) genotoxic/carcinogenic unless shown otherwise; the EU restricts them in food 5Reference 5Safety of hydroxyanthracene derivatives for use in foodView study →.
- Short-term laxative use only. Frangula bark is for occasional constipation, not more than ~1 week without medical supervision; chronic anthranoid use risks dependence, electrolyte (potassium) loss and melanosis coli 8Reference 8ReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →.
- Class contraindications. Intestinal obstruction, abdominal pain of unknown cause, and inflammatory bowel conditions; use is not recommended in pregnancy, lactation, or young children 8Reference 8ReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →.
Full Safety & Interactions Detail
Class genotoxicity / carcinogenicity. Glucofrangulin A is metabolised in the colon to emodin, which EFSA’s 2018 review found genotoxic in vitro; the Panel concluded hydroxyanthracene derivatives (emodin, aloe-emodin, the structurally related danthron) “should be considered as genotoxic and carcinogenic unless there are specific data to the contrary,” and could not set a safe intake 5Reference 5Safety of hydroxyanthracene derivatives for use in foodView study →. This underpins the EU restriction of these substances in food. The intact diglycoside is itself the less-cytotoxic form 6Reference 6Cytotoxicity of structurally diverse anthranoids and correlation with mechanism of action and side effectsView study →, but it is the delivery vehicle for the compound that carries the signal.
Chronic-use harms. As with all anthranoid laxatives, prolonged use risks hypokalaemia and fluid/electrolyte disturbance, laxative dependence (an atonic, non-functioning colon), and melanosis coli (reversible dark pigmentation of the colonic mucosa). Potassium loss can compound the risk of cardiac glycosides (digoxin), diuretics and antiarrhythmics 4,
Provenance caution. Freshly harvested Frangula bark contains reduced anthrones/anthranols that cause severe cramping, nausea and vomiting; bark must be aged ~1 year or heat-treated before use 8Reference 8ReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →.
Reproductive note (prose only). Anthranoid laxatives, including Frangula bark, are not recommended in pregnancy or lactation, and are avoided in young children 8Reference 8ReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →. No dedicated reproductive-toxicity dataset exists for isolated glucofrangulin A; the developmental-toxicity and genotoxicity concerns documented for the released aglycone emodin apply to the exposure this prodrug creates 5Reference 5Safety of hydroxyanthracene derivatives for use in foodView study →. Pregnancy/lactation decisions belong to the herb or product page where intake is decided, not to this molecule page.
Dosage
There is no established or safe human dose for isolated glucofrangulin A, and nothing here is a recommendation. Human exposure is via standardised Frangula bark, dosed to its hydroxyanthracene content (the European Pharmacopoeia requires a minimum 7.0% glucofrangulins, expressed as glucofrangulin A) and taken as the smallest amount needed to produce a soft-formed stool, for occasional constipation over no more than about one week without medical advice 8Reference 8ReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →. Any purified glucofrangulin A in circulation is an analytical reference standard, not a dosing form. These are pharmacopoeial and research figures, not a personal recommendation.
References
- Wagner H, Hörhammer HP (1966). [Synthesis and definitive structural analysis of frangulin and glucofrangulin from Rhamnus frangula L.]. Naturwissenschaften. https://pubmed.ncbi.nlm.nih.gov/5992817/
- Rosenthal I, Wolfram E, Peter S, Meier B (2014). Validated method for the analysis of frangulins A and B and glucofrangulins A and B using HPLC and UHPLC. Journal of Natural Products. https://pubmed.ncbi.nlm.nih.gov/24555690/
- Zwerger M, Deisl A, Hammerle F, Ganzera M (2024). Determination of anthraquinones in Frangula alnus by supercritical fluid chromatography. Journal of Chromatography A. https://pubmed.ncbi.nlm.nih.gov/39423601/
- de Witte P, Lemli L (1990). The metabolism of anthranoid laxatives. Hepatogastroenterology. https://pubmed.ncbi.nlm.nih.gov/2289777/
- EFSA ANS Panel (2018). Safety of hydroxyanthracene derivatives for use in food. EFSA Journal. https://pubmed.ncbi.nlm.nih.gov/32625659/
- Demarque DP, et al. (2018). Cytotoxicity of structurally diverse anthranoids and correlation with mechanism of action and side effects. Journal of Pharmacy & Pharmaceutical Sciences. https://pubmed.ncbi.nlm.nih.gov/30321134/
- Dong X, et al. (2016). Emodin: a review of its pharmacology, toxicity and pharmacokinetics. Phytotherapy Research. https://pubmed.ncbi.nlm.nih.gov/27188216/
- Committee on Herbal Medicinal Products (HMPC), European Medicines Agency. European Union herbal monograph on Rhamnus frangula L., cortex. https://www.ema.europa.eu/en/documents/herbal-monograph/european-union-herbal-monograph-rhamnus-frangula-l-cortex-revision-1_en.pdf
- Kremer D, et al. (2012). Anthraquinone profiles, antioxidant and antimicrobial properties of Frangula rupestris (Scop.) Schur and Frangula alnus Mill. bark. Food Chemistry. https://www.sciencedirect.com/science/article/abs/pii/S0308814611013719
