Glucofrangulin B

Glucofrangulin B at a Glance

Glucofrangulin B is an anthraquinone diglycoside — emodin carrying a β-D-apiose at the 6-position and a β-D-glucose at the 8-position (emodin-6-O-apiosyl-8-O-glucoside). It occurs in the bark of alder buckthorn (Frangula alnus, syn. Rhamnus frangula), where it sits beside its more abundant relative glucofrangulin A — the same molecule with a rhamnose instead of the apiose — and the two monoglycoside frangulins.

Its whole significance is collective and analytical, not isolate-specific. Chemically it is a laxative prodrug: like the other Frangula glycosides it is too polar to be absorbed in the upper gut, so it travels to the colon where bacteria strip the sugars to release emodin, which is reduced to the active emodin anthrone that stimulates colonic motility and secretion. And practically it is a quality-control marker: the European Pharmacopoeia standardises Frangula bark to its glucofrangulins (A and B together, expressed as glucofrangulin A), so glucofrangulin B is quantified in routine assays even though it has essentially no pharmacology of its own ^{1,5Reference 1Rosenthal I et al. · 2014Validated method for the analysis of frangulins A and B and glucofrangulins A and B using HPLC and UHPLCView study →Reference 5EFSA ANS Panel (Younes M et al. · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}.

The honest framing for the whole page: glucofrangulin B is a real, defined molecule with almost no isolate data. What is known about “its” effects and risks is inherited from the Frangula-bark glycoside pool and from the aglycone emodin — a stimulant-laxative role and a hydroxyanthracene-class safety signal — not from studies of the purified apioside.

Glucofrangulin B vs. Glucofrangulin A

This is the one distinction the page exists to make, and it is a small one — deliberately so.

They differ by a single sugar. Both are emodin 8-O-glucosides bearing a second sugar at the 6-position:

Glucofrangulin A = emodin-6-O-α-L-rhamnosyl-8-O-β-D-glucoside (the rhamnoside).
Glucofrangulin B = emodin-6-O-β-D-apiosyl-8-O-β-D-glucoside (the apioside).

Remove the 8-O-glucose from each and you get the corresponding monoglycoside frangulins — frangulin A (emodin 6-O-rhamnoside) and frangulin B (emodin 6-O-apioside); remove both sugars and both collapse to the same aglycone, emodin. So the A/B pair, the frangulins, and emodin are one biosynthetic family separated only by how many sugars are attached and which one sits at C-6.

A predominates; B is the minor companion. In alder buckthorn bark glucofrangulin A is the dominant diglycoside and glucofrangulin B the lesser one; supercritical-fluid and HPLC/UHPLC surveys of Frangula bark consistently find A the larger peak, with B a smaller, variable share of the glycoside pool ^{1,3Reference 1Rosenthal I et al. · 2014Validated method for the analysis of frangulins A and B and glucofrangulins A and B using HPLC and UHPLCView study →Reference 3Zwerger M et al. · 2024Determination of anthraquinones in Frangula alnus by supercritical fluid chromatographyView study →}. This is exactly why the pharmacopoeial assay expresses the combined “glucofrangulins” as glucofrangulin A — A is the reference substance, and B is measured against it ^{1,5Reference 1Rosenthal I et al. · 2014Validated method for the analysis of frangulins A and B and glucofrangulins A and B using HPLC and UHPLCView study →Reference 5EFSA ANS Panel (Younes M et al. · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}.

The relationship is analytical, not pharmacological. No study has separated the effect (or the risk) of glucofrangulin B from glucofrangulin A, from the frangulins, or from emodin; they are treated as one value-determining glycoside fraction in quality control and as a shared prodrug pool for the laxative effect ^{2,4Reference 2Çiçek SS et al. · 2019Two-dimensional qNMR of anthraquinones in Frangula alnus (Rhamnus frangula) using surrogate standards and delay time adaptionView study →Reference 4Radić Brkanac S et al. · 2015Toxicity and antioxidant capacity of Frangula alnus Mill. bark and its active component emodinView study →}. Everything below therefore describes the Frangula-glycoside class and its aglycone, with glucofrangulin B as one apioside member — because that is the only honest level at which evidence exists.

What It's Used For

There is no pharmacology specific to isolated glucofrangulin B. The material below is the Frangula-glycoside class effect and the emodin aglycone story, within which the apioside is one contributor. Read every row as collective, not isolate.

A laxative prodrug, as a class:the anthraquinone glycosides of Frangula bark — glucofrangulins A/B and the frangulins — pass intact to the colon, where flora liberate emodin and thence the active emodin anthrone; the purgative effect belongs to this shared pool, not to glucofrangulin B on its own ^{4,6Reference 4Radić Brkanac S et al. · 2015Toxicity and antioxidant capacity of Frangula alnus Mill. bark and its active component emodinView study →Reference 6European Medicines Agency · 2017Assessment report on Rhamnus frangula L., cortex (Frangula bark)View study →}.

An analytical/quality-control marker:glucofrangulin B is one of the glycosides the European Pharmacopoeia quantifies (as part of “glucofrangulins, expressed as glucofrangulin A”) to standardise Frangula bark, and validated HPLC/UHPLC, qNMR and SFC methods measure it as such ^{1,2,3Reference 1Rosenthal I et al. · 2014Validated method for the analysis of frangulins A and B and glucofrangulins A and B using HPLC and UHPLCView study →Reference 2Çiçek SS et al. · 2019Two-dimensional qNMR of anthraquinones in Frangula alnus (Rhamnus frangula) using surrogate standards and delay time adaptionView study →Reference 3Zwerger M et al. · 2024Determination of anthraquinones in Frangula alnus by supercritical fluid chromatographyView study →}.

The honest headline:no purified glucofrangulin B has been tested for efficacy or safety; its risk profile is the hydroxyanthracene-class concern carried by its aglycone emodin — genotoxic to human cells in vitro, and flagged by EFSA — not an isolate finding ^{4,5Reference 4Radić Brkanac S et al. · 2015Toxicity and antioxidant capacity of Frangula alnus Mill. bark and its active component emodinView study →Reference 5EFSA ANS Panel (Younes M et al. · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. Glucofrangulin B has no isolate evidence, so both rows describe the Frangula-glycoside class / the aglycone; scores are low by design.

Mechanisms

Target / pathway	Effect	Relevant to
Colonic bacterial glycosidases	cleave 6-O-apiose + 8-O-glucose → release emodin (prodrug activation)	laxative (class)
Emodin anthrone in the colon	stimulates motility; inhibits Na⁺/water absorption, promotes secretion	laxative (class)
Emodin aglycone (post-hydrolysis)	ROS generation, DNA damage in human cells in vitro	genotoxicity / safety

The load-bearing point: glucofrangulin B has no mechanism of its own — it is an inert delivery form. Its activity, and its hazard, are those of the emodin it releases after colonic hydrolysis ^{4,5Reference 4Radić Brkanac S et al. · 2015Toxicity and antioxidant capacity of Frangula alnus Mill. bark and its active component emodinView study →Reference 5EFSA ANS Panel (Younes M et al. · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}.

Pharmacokinetics

Inferred from the anthranoid class, not measured for the isolate. As a polar diglycoside glucofrangulin B is poorly absorbed from the upper gastrointestinal tract — that is the design of an anthranoid laxative prodrug: the intact glycoside must survive to the colon, where microbial hydrolysis liberates the aglycone ^{4,6Reference 4Radić Brkanac S et al. · 2015Toxicity and antioxidant capacity of Frangula alnus Mill. bark and its active component emodinView study →Reference 6European Medicines Agency · 2017Assessment report on Rhamnus frangula L., cortex (Frangula bark)View study →}. Once freed, emodin is heavily conjugated (glucuronidation/sulfation) with low systemic free-drug exposure, so meaningful concentrations of the active anthrone are largely luminal/colonic rather than systemic. No isolate-specific absorption, half-life or bioavailability figure exists for glucofrangulin B; the apioside vs. rhamnoside difference is not known to change this class behaviour.

Clinical Trials

There are no clinical trials of isolated glucofrangulin B, and none are planned or terminated. The only human-grade evidence in this space is for whole Frangula bark as a short-term stimulant laxative, dosed and standardised to its hydroxyanthracene-derivative content, and even that rests substantially on class experience with other anthranoid laxatives (senna, cascara) ^{6Reference 6European Medicines Agency · 2017Assessment report on Rhamnus frangula L., cortex (Frangula bark)View study →}. Treat all human data as herb-level.

Completed	Planned	Terminated	Preclinical
—(isolate); Frangula-bark laxative use only	—	—	Analytical / class-level only

Last checked: July 2026.

Isolate vs. Plant Studies

For this molecule the isolate-vs-plant question has a blunt answer: there are essentially no isolate studies at all. Glucofrangulin B has not been tested as a purified substance for efficacy, pharmacokinetics or toxicity; the difficulty of obtaining a pure apioside reference standard is itself a recurring theme in the analytical literature, which is part of why a surrogate-standard qNMR method was developed to quantify it without one ^{2Reference 2Çiçek SS et al. · 2019Two-dimensional qNMR of anthraquinones in Frangula alnus (Rhamnus frangula) using surrogate standards and delay time adaptionView study →}. What evidence exists is either (a) plant/extract-level — the laxative use and the genotoxicity signal of whole Frangula alnus bark ^{4,6Reference 4Radić Brkanac S et al. · 2015Toxicity and antioxidant capacity of Frangula alnus Mill. bark and its active component emodinView study →Reference 6European Medicines Agency · 2017Assessment report on Rhamnus frangula L., cortex (Frangula bark)View study →} — or (b) aglycone-level — the well-characterised chemistry and hazard of emodin, the molecule glucofrangulin B releases ^{4,5Reference 4Radić Brkanac S et al. · 2015Toxicity and antioxidant capacity of Frangula alnus Mill. bark and its active component emodinView study →Reference 5EFSA ANS Panel (Younes M et al. · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}. The apioside is quantified as one line in a bark assay and inferred to behave like its glycoside siblings; it is not independently studied.

Prevalence in Nature

Glucofrangulin B is a constituent of the bark of alder buckthorn (Frangula alnus Mill., syn. Rhamnus frangula L.), a Rhamnaceae shrub whose dried, aged bark (Frangulae cortex) is the pharmacopoeial laxative drug — fresh bark contains reactive anthrones that provoke vomiting and cramping, so the bark must be stored ~1 year or heat-treated to oxidise them before use ^{6Reference 6European Medicines Agency · 2017Assessment report on Rhamnus frangula L., cortex (Frangula bark)View study →}. Within that bark the anthraquinones occur overwhelmingly bound as glycosides rather than as free aglycones: the two glucofrangulins (A the rhamnoside, B the apioside) and the two frangulins, together with minor emodin-8-O-glucoside and free emodin ^{1,3Reference 1Rosenthal I et al. · 2014Validated method for the analysis of frangulins A and B and glucofrangulins A and B using HPLC and UHPLCView study →Reference 3Zwerger M et al. · 2024Determination of anthraquinones in Frangula alnus by supercritical fluid chromatographyView study →}.

Across sampled barks glucofrangulin A predominates and glucofrangulin B is the minor diglycoside, with the exact ratio varying by provenance, plant part and processing ^{3Reference 3Zwerger M et al. · 2024Determination of anthraquinones in Frangula alnus by supercritical fluid chromatographyView study →}. The pharmacopoeial floor is expressed for the sum — not less than 7.0% glucofrangulins (as glucofrangulin A) in the dried bark ^{1,5Reference 1Rosenthal I et al. · 2014Validated method for the analysis of frangulins A and B and glucofrangulins A and B using HPLC and UHPLCView study →Reference 5EFSA ANS Panel (Younes M et al. · 2018Safety of hydroxyanthracene derivatives for use in foodView study →} — so a defensible, isolated % dry-weight figure for glucofrangulin B alone is not established here and is tracked in the compound’s gaps note. Related Frangula/Rhamnus barks carry the same glycoside family in differing proportions.

Major Natural Sources

Source	Plant part	Form / notes
Alder buckthorn / frangula (Frangula alnus, syn. Rhamnus frangula)	aged bark (Frangulae cortex)	the pharmacopoeial source; glucofrangulin B is the minor apioside diglycoside beside the dominant glucofrangulin A ^{1,3Reference 1Rosenthal I et al. · 2014Validated method for the analysis of frangulins A and B and glucofrangulins A and B using HPLC and UHPLCView study →Reference 3Zwerger M et al. · 2024Determination of anthraquinones in Frangula alnus by supercritical fluid chromatographyView study →}
Other Frangula / Rhamnus barks	bark	same glycoside family (glucofrangulins + frangulins) in varying proportions

Per-source concentrations of glucofrangulin B specifically are not quantified on a common basis (the pharmacopoeial figure is for the A+B sum, expressed as glucofrangulin A); the holes are listed in the gaps note.

Discovery & Synthesis

Glucofrangulin B was characterised during twentieth-century phytochemical work on Frangula (alder buckthorn) bark, in the course of resolving the bark’s anthraquinone glycosides into the two glucofrangulins and two frangulins; an exact first-isolation date and author for the apioside specifically are not well documented, and it has generally been described together with glucofrangulin A rather than as a standalone discovery. Structurally it is emodin-6-O-β-D-apiosyl-8-O-β-D-glucoside — the apiose analog of glucofrangulin A’s rhamnoside.

Manufacture today is not a factor: glucofrangulin B is not produced or sold as an isolated substance for therapeutic use. It exists in commerce only as a trace analytical reference standard (scarce and costly, which is why surrogate-standard qNMR methods were devised ^{2Reference 2Çiçek SS et al. · 2019Two-dimensional qNMR of anthraquinones in Frangula alnus (Rhamnus frangula) using surrogate standards and delay time adaptionView study →}) and, in bulk, only as a natural constituent of standardised Frangula-bark extracts. There is no total- or semi-synthetic route in routine use; the molecule is obtained, when needed, by isolation from bark.

Patents: not yet researched.

Toxicity & Safety

Glucofrangulin B carries a moderate flag — matching its aglycone emodin and the other Frangula anthraquinones — because it is a hydroxyanthracene derivative that delivers genotoxic emodin to the colon, and because it belongs to the stimulant-laxative class whose chronic-use cautions are well established. The flag is a class/aglycone inheritance, not an isolate finding.

Safety at a Glance

Moderate toxicity

Poorly absorbed as the intact glycoside. As a polar diglycoside, glucofrangulin B itself is largely unabsorbed in the upper gut; systemic exposure to free emodin from ordinary short-term laxative use is limited ^{4,6Reference 4Radić Brkanac S et al. · 2015Toxicity and antioxidant capacity of Frangula alnus Mill. bark and its active component emodinView study →Reference 6European Medicines Agency · 2017Assessment report on Rhamnus frangula L., cortex (Frangula bark)View study →}.
Delivers a genotoxic aglycone. After colonic hydrolysis it releases emodin, which is genotoxic to human peripheral-blood lymphocytes in vitro (DNA damage, ROS); Frangula alnus bark extract is cyto/genotoxic in the same system ^{4Reference 4Radić Brkanac S et al. · 2015Toxicity and antioxidant capacity of Frangula alnus Mill. bark and its active component emodinView study →}.
Hydroxyanthracene-class concern. EFSA judged emodin, aloe-emodin and danthron genotoxic and concluded hydroxyanthracene derivatives should be treated as genotoxic/carcinogenic absent data to the contrary — the class to which glucofrangulin B’s aglycone belongs ^{5Reference 5EFSA ANS Panel (Younes M et al. · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}.
Stimulant-laxative cautions. Short-term use only (about one week); prolonged use of Frangula bark risks electrolyte (potassium) loss, laxative dependence and melanosis coli, and can compound digoxin/diuretic/antiarrhythmic risk ^{6Reference 6European Medicines Agency · 2017Assessment report on Rhamnus frangula L., cortex (Frangula bark)View study →}.
Aged bark required. Fresh Frangula bark provokes vomiting and severe cramping; only aged or heat-treated bark should be used ^{6Reference 6European Medicines Agency · 2017Assessment report on Rhamnus frangula L., cortex (Frangula bark)View study →}.

Full Safety & Interactions Detail

Genotoxicity (aglycone-level). The relevant human-cell data are for the pieces glucofrangulin B is made of, not the intact glycoside: Frangula alnus bark extract caused cell death and DNA damage in human peripheral-blood lymphocytes at 500 µg/mL, and emodin did so at 150–200 µg/mL with a rise in reactive oxygen species from 25 µg/mL — the authors concluded both are cyto/genotoxic and advised caution with F. alnus bark and emodin-containing preparations ^{4Reference 4Radić Brkanac S et al. · 2015Toxicity and antioxidant capacity of Frangula alnus Mill. bark and its active component emodinView study →}. This sits inside the broader EFSA 2018 conclusion that hydroxyanthracene derivatives (emodin, aloe-emodin, danthron) are genotoxic and should be regarded as genotoxic/carcinogenic unless shown otherwise ^{5Reference 5EFSA ANS Panel (Younes M et al. · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}. No genotoxicity study exists for purified glucofrangulin B; its risk is read from its aglycone.

Stimulant-laxative-class and reproductive cautions (prose). As a Frangula-bark hydroxyanthracene, glucofrangulin B shares the anthranoid class concerns: short-term use only (the EMA/HMPC traditional-use limit is about one week), with electrolyte loss (hypokalaemia), laxative dependence and melanosis coli on prolonged use, and potential compounding of digoxin, diuretic and antiarrhythmic effects through potassium loss ^{6Reference 6European Medicines Agency · 2017Assessment report on Rhamnus frangula L., cortex (Frangula bark)View study →}. Stimulant anthraquinone laxatives are generally advised against in pregnancy and lactation, and Frangula bark is not recommended during pregnancy, breastfeeding, or in children under 12 — but because pregnancy/lactation is a per-herb / per-product decision, no isolate-level verdict is issued here; the caution belongs to the Frangula-bark preparation where intake is decided ^{6Reference 6European Medicines Agency · 2017Assessment report on Rhamnus frangula L., cortex (Frangula bark)View study →}. No comprehensive human interaction dataset exists for the isolated molecule.

Dosage

There is no dose for isolated glucofrangulin B — it is not used as a stand-alone substance, and nothing here is a recommendation. Human exposure is entirely as a minor constituent of standardised Frangula bark, which is dosed to its total hydroxyanthracene-derivative content (calculated as glucofrangulin A), not to any single glycoside. The EMA/HMPC traditional-use range for the stimulant-laxative indication is roughly 10–30 mg hydroxyanthracene derivatives once daily at night, taken at the lowest amount that produces a soft stool and for no longer than about one week without medical advice ^{6Reference 6European Medicines Agency · 2017Assessment report on Rhamnus frangula L., cortex (Frangula bark)View study →}. The European Pharmacopoeia’s ≥7.0% glucofrangulins (as glucofrangulin A) floor governs the material’s strength, not a dose of glucofrangulin B ^{1,5Reference 1Rosenthal I et al. · 2014Validated method for the analysis of frangulins A and B and glucofrangulins A and B using HPLC and UHPLCView study →Reference 5EFSA ANS Panel (Younes M et al. · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}. These are herb-level regulatory figures, not a personal recommendation.

References

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/
Çiçek SS, Ugolini T, Girreser U (2019). Two-dimensional qNMR of anthraquinones in Frangula alnus (Rhamnus frangula) using surrogate standards and delay time adaption. Analytica Chimica Acta. https://pubmed.ncbi.nlm.nih.gov/31446950/
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/
Radić Brkanac S, Gerić M, Gajski G, Vujčić V, Garaj-Vrhovac V, Kremer D, Domijan AM (2015). Toxicity and antioxidant capacity of Frangula alnus Mill. bark and its active component emodin. Regulatory Toxicology and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/26399165/
EFSA ANS Panel (Younes M, et al.) (2018). Safety of hydroxyanthracene derivatives for use in food. EFSA Journal. https://pubmed.ncbi.nlm.nih.gov/32625659/
European Medicines Agency, Committee on Herbal Medicinal Products (HMPC) (2017). Assessment report on Rhamnus frangula L., cortex (Frangula bark). EMA/HMPC. https://www.ema.europa.eu/en/documents/herbal-report/assessment-report-rhamnus-frangula-l-cortex-revision-1_en.pdf