Frangulin A

Frangulin A at a Glance

Frangulin A is an anthraquinone glycoside — specifically emodin-6-O-α-L-rhamnoside, the anthraquinone emodin carrying a single rhamnose sugar. It is one of the defining laxative constituents of alder buckthorn (Frangula alnus, syn. Rhamnus frangula) bark, alongside its sister glycoside frangulin B and the diglycosides glucofrangulin A and glucofrangulin B ^{6Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →}.

Its role is best understood as a prodrug. Frangulin A is too polar to be absorbed intact in the small intestine, so it travels to the colon, where bacteria hydrolyse off the rhamnose and reduce the liberated emodin to emodin-anthrone, the species that actually stimulates the bowel ^{6,5Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →Reference 5EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}. In other words, frangulin A does little itself — it is a delivery form for colonic emodin.

Two honest framings run through all of it. First, the human evidence is for standardised buckthorn bark, not for isolated frangulin A — the isolate has essentially no clinical trials of its own. Second, because it releases emodin, frangulin A inherits emodin’s safety questions: it is a hydroxyanthracene derivative inside the EU/EMA restriction on this laxative class, and emodin itself carries a genotoxicity signal and an equivocal animal carcinogenicity finding ^{5,9Reference 5EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →Reference 9National Toxicology Program · 2001AnimalToxicology and carcinogenesis studies of emodin (CAS 518-82-1) in F344/N rats and B6C3F1 mice (feed studies)View study →}.

A Buckthorn Laxative Glycoside

Alder buckthorn belongs to the same stimulant-laxative family as senna and cascara sagrada — all of them “anthranoid” laxatives that work through hydroxyanthracene glycosides. In Frangula, the characteristic actives are the emodin glycosides: the monoglycosides frangulin A and B and the diglycosides glucofrangulin A and B ^{6,2Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →Reference 2Kremer D et al. · 2012Anthraquinone profiles, antioxidant and antimicrobial properties of Frangula rupestris (Scop.) Schur and Frangula alnus Mill. barkView study →}.

The mechanism is the anthranoid class mechanism, and frangulin A follows it exactly:

1. Survival to the colon. As a sugar-bearing glycoside, frangulin A resists absorption and small-intestinal enzymes, reaching the large bowel largely intact ^{6Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →}.
2. Bacterial hydrolysis. Colonic flora cleave the rhamnose, freeing the aglycone emodin ^{6,5Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →Reference 5EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}.
3. Reduction to the anthrone. The bacteria reduce emodin to emodin-anthrone, the active laxative species ^{6Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →}.
4. Bowel stimulation. The anthrone increases colonic motility (stimulating propulsive contractions) and shifts the mucosa toward net fluid secretion, together producing a laxative effect typically 6–12 hours after an oral dose ^{6Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →}.

This delayed, colon-targeted action is why anthranoid laxatives are taken at night for a morning effect — the lag is the time needed for the glycoside to reach the flora that activate it.

The aged-bark requirement is not folklore — it is chemistry. Fresh buckthorn bark is rich in free anthrones (and reduced glycoside forms), which are harsh gastrointestinal irritants that cause violent vomiting and severe cramping. Traditional and pharmacopoeial practice therefore requires the bark to be dried and aged for about a year, or artificially aged by heat and aeration, before use. During storage the free anthrones oxidise to the gentler anthraquinone glycosides (frangulins, glucofrangulins), converting an emetic crude drug into a usable laxative ^{6Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →}. Frangulin A is thus both a product of that ageing and part of what makes aged bark tolerable.

Frangulin A vs. Frangulin B

The “frangulins” are a small family of emodin monoglycosides that differ only in the sugar attached at emodin’s 6-position — and the “glucofrangulins” are the corresponding diglycosides:

Compound	Structure	Type
Frangulin A	emodin 6-O-α-L-rhamnoside	monoglycoside
Frangulin B	emodin 6-O-β-D-apioside	monoglycoside
Glucofrangulin A	emodin 6-O-rhamnoside-8-O-glucoside	diglycoside
Glucofrangulin B	emodin 6-O-apioside-8-O-glucoside	diglycoside

The practical points:

• A vs. B is just the sugar. Frangulin A carries rhamnose; frangulin B carries apiose. Both hydrolyse to the same aglycone — emodin — so they are essentially two sugar-forms of the same laxative prodrug ^{6Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →}.
• Frangulins vs. glucofrangulins is the number of sugars. Glucofrangulins add a second (glucose) sugar at the 8-position; on standing and during extraction they can lose that glucose to give the corresponding frangulin, so the two pools are chemically linked ^{6Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →}. The European Pharmacopoeia standardises Frangula bark on its glucofrangulin content, with the frangulins as accompanying markers ^{6Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →}.
• All roads lead to emodin. Whichever glycoside is dosed, the colon delivers emodin → emodin-anthrone. This is why the whole bark, not any single glycoside, is the meaningful unit of laxative activity — and why frangulin A cannot be given a laxative potency separate from its parent bark.

This distinguishes the Frangula glycosides from the C-glycosyl anthrones of the neighbouring herbs — the cascarosides of cascara and the sennosides of senna — which are built on barbaloin/aloe-emodin- and rhein-type scaffolds rather than an emodin O-glycoside.

What It's Used For

Frangulin A’s pharmacology is almost entirely the pharmacology of the bark it comes from and of the emodin it releases. Very little has been measured on the purified molecule, and the split by what was actually tested — isolate, whole bark, or the freed aglycone — is the load-bearing caveat.

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. Frangulin A’s data are plant/extract- and class-level rather than isolate trials, so scores stay low by design; read each row’s basis.

01Laxative (buckthorn anthranoid)Shaky38%Established use of standardised Frangula bark; emodin-prodrug class mechanism ^{5,6Reference 5EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →}

02Antibacterial / antibiofilm (extract)Shaky22%In-vitro whole-Frangula-extract activity; frangulin a principal component ^{1,2Reference 1Kledecka A et al. · 2022Extracts from Frangula alnus Mill. and Their Effects on Environmental and Probiotic BacteriaView study →Reference 2Kremer D et al. · 2012Anthraquinone profiles, antioxidant and antimicrobial properties of Frangula rupestris (Scop.) Schur and Frangula alnus Mill. barkView study →}

03Antioxidant (anthraquinone fraction)Shaky18%In-vitro bark-extract antioxidant capacity; the aglycone itself is weak ^{2,3Reference 2Kremer D et al. · 2012Anthraquinone profiles, antioxidant and antimicrobial properties of Frangula rupestris (Scop.) Schur and Frangula alnus Mill. barkView study →Reference 3Rusak Brkanac S et al. · 2015Toxicity and antioxidant capacity of Frangula alnus Mill. bark and its active component emodinView study →}

Mechanisms

The load-bearing point: frangulin A has essentially no direct receptor pharmacology of its own — its activity is the sum of a bacterial activation step (to emodin-anthrone) plus whatever the freed emodin does downstream.

Pharmacokinetics

Frangulin A’s kinetics are those of a colon-targeted prodrug. As a polar glycoside it is poorly absorbed in the upper gut and passes largely intact to the colon, where bacteria remove the rhamnose and reduce the aglycone — so the pharmacologically relevant exposure is local (luminal), in the large bowel, not systemic ^{6Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →}. Any emodin that is absorbed faces the aglycone’s own poor systemic bioavailability: emodin is extensively glucuronidated in the intestine and liver and pumped back out by efflux transporters (an MRP/UGT coupling), so free emodin in plasma is low and short-lived, with enterohepatic recycling ^{7,8Reference 7Dong X et al. · 2016ReviewEmodin: A Review of its Pharmacology, Toxicity and PharmacokineticsView study →Reference 8Liu W et al. · 2012Coupling of UDP-glucuronosyltransferases and multidrug resistance-associated proteins is responsible for the intestinal disposition and poor bioavailability of emodinView study →}. Two consequences: (1) the laxative effect depends on an intact, activating colonic flora and is delayed by hours; and (2) systemic emodin exposure from a laxative dose is limited — which constrains, but does not erase, the genotoxicity concern (see Toxicity). No human Cmax / half-life / oral-bioavailability figures are established for isolated frangulin A.

Clinical Trials

There are no controlled clinical trials of isolated frangulin A. The human evidence is for standardised alder buckthorn bark as a laxative — the basis of its regulatory monograph — within which frangulin A is one of several emodin glycosides ^{5,6Reference 5EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →}. Treat all human data as bark-level, not molecule-level.

Last checked: July 2026.

Isolate vs. Plant Studies

This molecule sits firmly on the plant/extract side of the isolate-vs-plant line. The meaningful human evidence — the laxative use — is for whole standardised buckthorn bark, dosed to its hydroxyanthracene content, not for purified frangulin A ^{5,6Reference 5EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →}. The in-vitro antibacterial and antioxidant findings are whole-extract results in which frangulin is one component among many phenolics ^{1,2,3Reference 1Kledecka A et al. · 2022Extracts from Frangula alnus Mill. and Their Effects on Environmental and Probiotic BacteriaView study →Reference 2Kremer D et al. · 2012Anthraquinone profiles, antioxidant and antimicrobial properties of Frangula rupestris (Scop.) Schur and Frangula alnus Mill. barkView study →Reference 3Rusak Brkanac S et al. · 2015Toxicity and antioxidant capacity of Frangula alnus Mill. bark and its active component emodinView study →}. And the mechanistic story that gives frangulin A any activity at all — bacterial conversion to emodin-anthrone — is really the pharmacology of the freed aglycone emodin, which has its own large (but almost entirely preclinical) literature. There is no body of isolated-frangulin-A efficacy work to transfer. The correct framing is: established plant/class use + extract-level in-vitro activity + no isolate trials.

Prevalence in Nature

Frangulin A is a bark anthraquinone of the buckthorns (genus Frangula, formerly folded into Rhamnus). Its classic source is alder buckthorn, Frangula alnus (Rhamnus frangula), where the emodin glycosides — frangulins A and B and glucofrangulins A and B — are the principal laxative constituents; it also occurs in related species such as rock buckthorn (Frangula rupestris) and other Frangula/Rhamnus barks ^{2,6Reference 2Kremer D et al. · 2012Anthraquinone profiles, antioxidant and antimicrobial properties of Frangula rupestris (Scop.) Schur and Frangula alnus Mill. barkView study →Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →}. In the intact plant much of the emodin is stored bound as these glycosides rather than as free aglycone, and the balance among free anthrones, monoglycosides (frangulins) and diglycosides (glucofrangulins) shifts with bark age and drying — fresh bark is anthrone-rich, aged bark glycoside-rich (see A Buckthorn Laxative Glycoside) ^{6Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →}.

Reported anthraquinone content is highly provenance- and method-dependent, and comparative profiling tends to report the total anthraquinone/emodin figures rather than a clean frangulin-A percentage; for example, emodin was measured at ~2 mg/g in F. alnus bark in one comparative study ^{2Reference 2Kremer D et al. · 2012Anthraquinone profiles, antioxidant and antimicrobial properties of Frangula rupestris (Scop.) Schur and Frangula alnus Mill. barkView study →}. A reliable whole-bark frangulin-A concentration for a named provenance is not well pinned down — that hole is logged in this molecule’s gaps tracker.

Discovery & Synthesis

Frangulin A comes out of nineteenth-century buckthorn pharmacognosy: the yellow anthraquinone glycosides of Frangula (Rhamnus frangula) bark were isolated and named as the plant’s active laxative principles, and frangulin A carries the historical synonyms franguloside and rhamnoxanthin from that era. Structurally it was later resolved as emodin 6-O-α-L-rhamnoside — the same emodin aglycone found across the anthraquinone-laxative herbs, distinguished only by its rhamnose sugar.

There is no prominent total synthesis on record; frangulin A is obtained by extraction from buckthorn bark (and is available as a purified reference standard for pharmacopoeial and analytical use), not manufactured synthetically. Its supply chain is the medicinal-bark trade — the same aged Frangula bark used as a laxative crude drug.

Patents: not yet researched.

Toxicity & Safety

Frangulin A carries a moderate flag — heavier than a typical plant glycoside — for two linked reasons: it is a stimulant-laxative anthranoid, and it releases emodin, whose genotoxicity signal drives the regulatory restriction on this whole class.

Safety at a Glance

⚠️ Moderate toxicity

• Short-term laxative use of standardised, aged bark is established. Alder buckthorn is an accepted stimulant laxative for occasional constipation when the bark is properly aged and dosed to its hydroxyanthracene content ^{5,6Reference 5EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →}.
• Fresh bark is emetic. Un-aged Frangula bark is rich in free anthrones that cause violent vomiting and severe cramping — the bark must be dried/aged (~1 year) or heat-treated before use ^{6Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →}.
• Hydroxyanthracene-class safety restriction. Frangulin A liberates emodin, which is genotoxic in vitro and carries an equivocal animal carcinogenicity finding; EFSA/EMA restrict hydroxyanthracene laxatives, and use should be short-term only ^{5,9,4Reference 5EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →Reference 9National Toxicology Program · 2001AnimalToxicology and carcinogenesis studies of emodin (CAS 518-82-1) in F344/N rats and B6C3F1 mice (feed studies)View study →Reference 4Brusick D · 1997Assessment of the genotoxic risk from laxative senna productsView study →}.
• No long-term or high-dose use. Chronic stimulant-laxative use risks dependence, fluid/electrolyte (potassium) loss and pseudomelanosis coli; potassium loss can compound digoxin, diuretic and antiarrhythmic effects ^{6Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →}.
• Populations. Not for bowel obstruction, acute inflammatory bowel conditions, undiagnosed abdominal pain, or children; pregnancy and breastfeeding are cautioned at the herb/product level ^{6Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →}.

Full Safety & Interactions Detail

Class genotoxicity / carcinogenicity signal. Frangulin A’s hazard is inherited from the emodin it releases. Emodin is genotoxic across several in-vitro assays, and the US National Toxicology Program’s 2-year feed bioassay found equivocal evidence of carcinogenicity (marginal Zymbal’s-gland and renal-tubule findings) rather than a clean negative ^{9Reference 9National Toxicology Program · 2001AnimalToxicology and carcinogenesis studies of emodin (CAS 518-82-1) in F344/N rats and B6C3F1 mice (feed studies)View study →}. On that basis EFSA (2018) concluded hydroxyanthracene derivatives — emodin, aloe-emodin, danthron and the parent extracts — raise a genotoxicity/safety concern in food, underpinning the EU/EMA restriction on this laxative class ^{5Reference 5EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}. Comparative work on structurally diverse anthranoids finds cytotoxicity that tracks the anthraquinone scaffold and correlates with the class’s side effects — with emodin among the more cytotoxic aglycones ^{10Reference 10Demarque DP et al. · 2018Cytotoxicity of Structurally Diverse Anthranoids and Correlation with Mechanism of Action and Side EffectsView study →}. The genotoxic risk from correctly-used senna-type laxatives has been argued to be low in an integrated assessment ^{4Reference 4Brusick D · 1997Assessment of the genotoxic risk from laxative senna productsView study →}, but the regulatory posture for the class is now conservative.

Fresh vs. aged bark. The single most important traditional safety rule for Frangula: fresh bark provokes violent emesis and griping because of its free-anthrone content; ageing/drying (about a year, or artificial heat-aeration) oxidises those to the gentler glycosides that make the bark usable ^{6Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →}. This is why only aged bark is a laxative and fresh bark is not.

Direct toxicity of the isolate. A study of F. alnus bark and its component emodin found both to be cyto- and genotoxic to human lymphocytes in vitro, with emodin acting at lower concentrations than the whole extract and oxidative stress implicated — the authors advised caution with bark and emodin-containing preparations ^{3Reference 3Rusak Brkanac S et al. · 2015Toxicity and antioxidant capacity of Frangula alnus Mill. bark and its active component emodinView study →}.

Chronic-use harms and interactions. As with all stimulant (anthranoid) laxatives, prolonged use risks laxative dependence, water/electrolyte loss (notably potassium), and pseudomelanosis coli (a benign, reversible pigmentation of the colonic lining). Potassium depletion can potentiate cardiac glycosides (digoxin) and interact with diuretics, corticosteroids and antiarrhythmics ^{6Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →}. Use is therefore short-term (roughly up to 1–2 weeks) and second-line to bulk/osmotic laxatives.

Reproductive note (prose only). Anthranoid laxatives are generally cautioned in pregnancy and breastfeeding at the herb/product level; no dedicated reproductive-toxicity dataset exists for isolated frangulin A. That decision belongs to the buckthorn herb or laxative-product page where intake is decided, not to this molecule page.

Dosage

There is no established dose for isolated frangulin A, and nothing here is a recommendation. Human use is of standardised alder buckthorn (Frangula) bark, and the operative rules are class rules for stimulant (anthranoid) laxatives ^{5,6Reference 5EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →}:

• Dose to the bark’s standardised hydroxyanthracene / glucofrangulin content, not to any single glycoside, and take the smallest amount that produces a soft-formed stool.
• Short-term use only — occasional constipation, roughly up to 1–2 weeks; it is not for regular or long-term use, and is second-line to bulk-forming and osmotic laxatives.
• Only aged/dried bark (about a year, or heat-treated) — never fresh bark, which is emetic ^{6Reference 6EMA Committee on Herbal Medicinal ProducReviewEuropean Union herbal monograph on Rhamnus frangula L., cortexView study →}.
• Expect the effect 6–12 hours after an oral dose (typically taken at night).

These reflect regulatory/pharmacopoeial guidance for buckthorn bark and are not a personal recommendation; laxative choice and use belong with a clinician or pharmacist.

References

1. Kledecka A, Siejak P, Pratap-Singh A, Kowalczewski PŁ, Fathordoobady F, Jarzębski M, Smułek W (2022). Extracts from Frangula alnus Mill. and Their Effects on Environmental and Probiotic Bacteria. Plants (Basel). https://pubmed.ncbi.nlm.nih.gov/36297744/
2. Kremer D, Kosalec I, Locatelli M, Epifano F, Genovese S, Carlucci G, Zovko Končić M (2012). Anthraquinone profiles, antioxidant and antimicrobial properties of Frangula rupestris (Scop.) Schur and Frangula alnus Mill. bark. Food Chemistry. https://doi.org/10.1016/j.foodchem.2011.09.094
3. Rusak 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/
4. Brusick D, Mengs U (1997). Assessment of the genotoxic risk from laxative senna products. Environmental and Molecular Mutagenesis. https://pubmed.ncbi.nlm.nih.gov/9020301/
5. EFSA ANS Panel (2018). Safety of hydroxyanthracene derivatives for use in food. EFSA Journal. https://pubmed.ncbi.nlm.nih.gov/32625659/
6. EMA Committee on Herbal Medicinal Products (HMPC). European Union herbal monograph on Rhamnus frangula L., cortex. European Medicines Agency. https://www.ema.europa.eu/en/documents/herbal-monograph/european-union-herbal-monograph-rhamnus-frangula-l-cortex-revision-1_en.pdf
7. Dong X, Fu J, Yin X, Cao S, Li X, Lin L, Huyiligeqi, Ni J (2016). Emodin: A Review of its Pharmacology, Toxicity and Pharmacokinetics. Phytotherapy Research. https://pubmed.ncbi.nlm.nih.gov/27188216/
8. Liu W, Feng Q, Li Y, Ye L, Hu M, Liu Z (2012). Coupling of UDP-glucuronosyltransferases and multidrug resistance-associated proteins is responsible for the intestinal disposition and poor bioavailability of emodin. Toxicology and Applied Pharmacology. https://pubmed.ncbi.nlm.nih.gov/22982073/
9. National Toxicology Program (2001). Toxicology and carcinogenesis studies of emodin (CAS 518-82-1) in F344/N rats and B6C3F1 mice (feed studies). NTP Technical Report Series (TR-493). https://pubmed.ncbi.nlm.nih.gov/12563347/
10. Demarque DP, Silva RMP, Santos LF, Leopoldino AM, Espreafico EM, Lopes NP (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/

View all 10 references▾