Cascaroside C

Cascaroside C at a Glance

Cascaroside C is one of the four principal cascarosides — the characteristic laxative glycosides of cascara sagrada bark (Rhamnus purshiana). Structurally it is the chrysophanol-based member of the family: the 8-O-glucoside of chrysaloin, the anthrone C-glucoside of chrysophanol. That single fact is what separates it from the better-known cascarosides A and B, which are built on aloe-emodin instead. Cascaroside C forms a diastereomeric pair with cascaroside D, the two differing only in configuration at the anthrone’s C-10 carbon.

Like every cascaroside, it is a prodrug. It is not itself a laxative — its sugars keep it in the gut lumen until colonic bacteria strip them to release an active anthrone, which stimulates colonic motility and secretion ^{1,4Reference 1Rho T et al. · 2020Isolation of six anthraquinone diglucosides (including cascarosides C and D) from cascara sagrada bark by high-performance countercurrent chromatographyView study →Reference 4Akao T et al. · 1996A purgative action of barbaloin is induced by Eubacterium sp. strain BAR, a human intestinal anaerobe, capable of transforming barbaloin to aloe-emodin anthroneView study →}. It has essentially no isolated-molecule pharmacology of its own: it is measured and studied only as one signal within the standardised cascara-bark glycoside pool, never dosed alone.

Its defining modern context is regulatory. Cascarosides are hydroxyanthracene derivatives, the class flagged for genotoxicity, and they carry cascara’s history: the FDA removed OTC cascara laxatives in 2002, and the EU restricts hydroxyanthracene derivatives in food ^{2,3,5Reference 2Food et al. · 2002Status of certain additional over-the-counter drug category II and III active ingredients (aloe & cascara sagrada stimulant laxatives)View study →Reference 3EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →Reference 5Commission Regulation (EU) 2021/468 · 2021Amending Annex III to Regulation (EC) No 1925/2006 as regards botanical species containing hydroxyanthracene derivativesView study →}. This page keeps that honesty at the centre and does not attribute pharmacology the molecule has not been shown to have.

The Chrysophanol-Based Cascaroside (C vs D)

The four cascarosides are best understood as two aglycone families, each a diastereomeric pair. All of them share the same unusual C,O-diglycoside architecture — one glucose bolted onto the central anthrone through a carbon–carbon (C-glycosidic) bond at C-10, and a second glucose hung off an oxygen at C-8 — but they differ in which anthraquinone parent sits underneath ^{1,4Reference 1Rho T et al. · 2020Isolation of six anthraquinone diglucosides (including cascarosides C and D) from cascara sagrada bark by high-performance countercurrent chromatographyView study →Reference 4Akao T et al. · 1996A purgative action of barbaloin is induced by Eubacterium sp. strain BAR, a human intestinal anaerobe, capable of transforming barbaloin to aloe-emodin anthroneView study →}.

Cascarosides A and B are built on aloe-emodin — they are the 8-O-glucosides of barbaloin (aloin), the aloe-emodin anthrone C-glucoside. This is the pair the European Pharmacopoeia standardises against (bark is assayed and the fraction reported as cascaroside A) ^{3Reference 3EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}.
Cascarosides C and D are built on chrysophanol — they are the 8-O-glucosides of chrysaloin, the chrysophanol anthrone C-glucoside. Chrysophanol lacks the hydroxymethyl group aloe-emodin carries, so C and D are the “plainer-scaffold” cascarosides.

C versus D is pure stereochemistry. Cascaroside C and cascaroside D are diastereomers that differ only in the configuration at the C-10 anthrone centre (the carbon bearing the C-linked glucose) — reported as the 10-S / 10-R (10β / 10α) pair — much as cascarosides A and B are the corresponding stereoisomers on the aloe-emodin scaffold ^{1,4Reference 1Rho T et al. · 2020Isolation of six anthraquinone diglucosides (including cascarosides C and D) from cascara sagrada bark by high-performance countercurrent chromatographyView study →Reference 4Akao T et al. · 1996A purgative action of barbaloin is induced by Eubacterium sp. strain BAR, a human intestinal anaerobe, capable of transforming barbaloin to aloe-emodin anthroneView study →}. They co-occur and are usually reported together.

The practical upshot: the chrysophanol scaffold matters for toxicology, not for a different laxative use. Across the anthranoid series, chrysophanol is a less cytotoxic aglycone than aloe-emodin or emodin, and adding glucose moieties reduces cytotoxicity further ^{6Reference 6Demarque DP et al. · 2018Cytotoxicity of structurally diverse anthranoids and correlation with mechanism of action and side effects (glucose moieties reduce toxicity; cascarosides from cascara sagrada)View study →} — so the chrysophanol-based cascarosides are, if anything, the gentler pair chemically. But they still deliver an anthrone to the colon and sit inside the same restricted hydroxyanthracene class, so the safety framing does not change (see Toxicity).

What It's Used For

Cascaroside C has almost no standalone literature. It is one of the compounds that make up cascara’s laxative activity, quantified for standardisation and authentication of the bark, and studied — when studied at all — collectively as part of the cascaroside/hydroxyanthracene fraction rather than as an isolate ^{1,3Reference 1Rho T et al. · 2020Isolation of six anthraquinone diglucosides (including cascarosides C and D) from cascara sagrada bark by high-performance countercurrent chromatographyView study →Reference 3EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}.

The one genuine effect attributable to the family is stimulant laxation, and even that is the action of a downstream metabolite, not the parent glycoside.

Stimulant laxative — real, but a class/prodrug effect, not cascaroside C’s own:the cascarosides are inactive as given; colonic bacteria cleave their sugars to release an active anthrone that stimulates colonic motility and net fluid secretion. The mechanism is established for anthrone glycosides of this type (e.g. barbaloin → aloe-emodin anthrone) and the cascarosides act through the same colonic-activation route ^{1,4Reference 1Rho T et al. · 2020Isolation of six anthraquinone diglucosides (including cascarosides C and D) from cascara sagrada bark by high-performance countercurrent chromatographyView study →Reference 4Akao T et al. · 1996A purgative action of barbaloin is induced by Eubacterium sp. strain BAR, a human intestinal anaerobe, capable of transforming barbaloin to aloe-emodin anthroneView study →}.

No isolated cascaroside C pharmacology:there are no human or animal efficacy studies of cascaroside C alone; it appears in the literature as an analyte and as one member of the standardised glycoside pool ^{1,3Reference 1Rho T et al. · 2020Isolation of six anthraquinone diglucosides (including cascarosides C and D) from cascara sagrada bark by high-performance countercurrent chromatographyView study →Reference 3EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}.

The honest headline is regulatory:as a hydroxyanthracene derivative, cascaroside C sits inside the class the FDA removed from the US OTC laxative market (cascara, 2002) and the EU restricts in food on genotoxicity grounds ^{2,3,5Reference 2Food et al. · 2002Status of certain additional over-the-counter drug category II and III active ingredients (aloe & cascara sagrada stimulant laxatives)View study →Reference 3EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →Reference 5Commission Regulation (EU) 2021/468 · 2021Amending Annex III to Regulation (EC) No 1925/2006 as regards botanical species containing hydroxyanthracene derivativesView 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. Cascaroside C has only one real (and now-restricted) application, and even that is a whole-bark / class effect rather than an isolate result — so the single row is scored low and honestly.

Mechanisms

Target / pathway	Effect	Relevant to
Colonic bacterial glycosidases	strip the C,O-glucose units → release the active anthrone (the purgative)	laxative activation (prodrug step)
Colonic enterocytes & myenteric neurons (via the anthrone)	stimulate propulsive motility; net water/electrolyte secretion	stimulant-laxative effect
Hydroxyanthracene-derivative class chemistry	colon-delivered reactive anthrone underlies the class genotoxicity concern	toxicity / regulatory

The load-bearing point is the top row: cascaroside C does nothing until colonic flora convert it to an anthrone. The chrysophanol scaffold makes the released anthrone a comparatively less cytotoxic one ^{6Reference 6Demarque DP et al. · 2018Cytotoxicity of structurally diverse anthranoids and correlation with mechanism of action and side effects (glucose moieties reduce toxicity; cascarosides from cascara sagrada)View study →}, but the delivery route — and therefore the class concern — is unchanged.

Pharmacokinetics

Cascaroside C’s kinetics are inferred from the cascaroside/anthrone-glycoside class rather than measured for the isolate. The C,O-diglycoside structure — with a hydrolysis-resistant C-glucosyl bond — means it is poorly absorbed from the upper gastrointestinal tract and reaches the colon largely intact, where bacterial glycosidases release the active anthrone locally ^{1,4Reference 1Rho T et al. · 2020Isolation of six anthraquinone diglucosides (including cascarosides C and D) from cascara sagrada bark by high-performance countercurrent chromatographyView study →Reference 4Akao T et al. · 1996A purgative action of barbaloin is induced by Eubacterium sp. strain BAR, a human intestinal anaerobe, capable of transforming barbaloin to aloe-emodin anthroneView study →}. It is therefore a colon-targeted prodrug by accident of chemistry: little intact parent is expected to circulate, and the pharmacology (and the toxicological concern) happen in the large bowel. No isolate-specific human pharmacokinetic parameters — oral bioavailability, half-life, or quantitative colonic-conversion yield — have been characterised for cascaroside C; activity is expected to be flora-dependent, as for barbaloin ^{4Reference 4Akao T et al. · 1996A purgative action of barbaloin is induced by Eubacterium sp. strain BAR, a human intestinal anaerobe, capable of transforming barbaloin to aloe-emodin anthroneView study →}.

Clinical Trials

There are no clinical trials of isolated cascaroside C. Its only human relevance is as a constituent of cascara-bark laxative preparations — multi-constituent, glycoside-driven products whose effect cannot be attributed to this molecule — and that use was judged by the FDA to lack the requested safety substantiation and removed from the US OTC market ^{2Reference 2Food et al. · 2002Status of certain additional over-the-counter drug category II and III active ingredients (aloe & cascara sagrada stimulant laxatives)View study →}. The contemporary literature touching cascaroside C is analytical (isolation, quantification, authentication) and toxicological/regulatory ^{1,3,5Reference 1Rho T et al. · 2020Isolation of six anthraquinone diglucosides (including cascarosides C and D) from cascara sagrada bark by high-performance countercurrent chromatographyView study →Reference 3EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →Reference 5Commission Regulation (EU) 2021/468 · 2021Amending Annex III to Regulation (EC) No 1925/2006 as regards botanical species containing hydroxyanthracene derivativesView study →}, not therapeutic.

Completed	Planned	Terminated	Preclinical
—(whole-bark laxative use only; no isolate trials)	—	—	Analytical/quantification + class toxicology

Last checked: July 2026.

Isolate vs. Plant Studies

For cascaroside C the isolate-vs-plant question barely arises, because there is effectively no isolate pharmacology to weigh — the molecule is purified for reference-standard and analytical purposes (identity, HPLC/countercurrent isolation, bark authentication), not run through efficacy or safety studies on its own ^{1Reference 1Rho T et al. · 2020Isolation of six anthraquinone diglucosides (including cascarosides C and D) from cascara sagrada bark by high-performance countercurrent chromatographyView study →}. Everything about its function is inherited from the whole cascara bark and from the hydroxyanthracene class: the laxative effect is the bark’s, the prodrug→anthrone mechanism is the class’s (demonstrated for barbaloin) ^{4Reference 4Akao T et al. · 1996A purgative action of barbaloin is induced by Eubacterium sp. strain BAR, a human intestinal anaerobe, capable of transforming barbaloin to aloe-emodin anthroneView study →}, and the genotoxicity/regulatory story is the class’s ^{3,5Reference 3EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →Reference 5Commission Regulation (EU) 2021/468 · 2021Amending Annex III to Regulation (EC) No 1925/2006 as regards botanical species containing hydroxyanthracene derivativesView study →}. So it is worth being explicit that cascaroside C is a plant/class actor quantified as an isolate, not an isolate with its own evidence base.

Prevalence in Nature

Cascaroside C is a constituent of aged cascara sagrada bark (Rhamnus purshiana), where it occurs alongside cascarosides A, B and D as part of the bark’s anthracene-glycoside fraction ^{1,3Reference 1Rho T et al. · 2020Isolation of six anthraquinone diglucosides (including cascarosides C and D) from cascara sagrada bark by high-performance countercurrent chromatographyView study →Reference 3EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}. Within that fraction the cascarosides collectively make up roughly 60–70% of the total O-glycosides, standardised in the pharmacopoeia as cascaroside A; the aloe-emodin-based A/B pair dominates, and the chrysophanol-based C/D pair is a smaller share ^{3Reference 3EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}. High-performance countercurrent chromatography of cascara bark has isolated cascaroside C and D directly (tens of milligrams from a bark extract), confirming their co-occurrence as a minor diastereomeric pair ^{1Reference 1Rho T et al. · 2020Isolation of six anthraquinone diglucosides (including cascarosides C and D) from cascara sagrada bark by high-performance countercurrent chromatographyView study →}.

Its abundance tracks cascara’s provenance rules: the bark must be aged (commonly 1–3 years) before use, during which harsher free anthrones oxidise to the gentler glycosides, and constituent proportions shift with bark age and species. Comparable quantitative figures for cascaroside C specifically, on a dry-weight basis, are not well tabulated (see the compound’s gaps tracker), so no source-levels chart is shown.

Major Natural Sources

Source (botanical)	Part	Notes
Cascara sagrada (Rhamnus purshiana)	Aged bark	The characteristic source; one of cascarosides A–D, standardised collectively ^{1,3Reference 1Rho T et al. · 2020Isolation of six anthraquinone diglucosides (including cascarosides C and D) from cascara sagrada bark by high-performance countercurrent chromatographyView study →Reference 3EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}
Other Rhamnus / Frangula (buckthorn) barks	Bark	Related anthraquinone-laxative barks may carry cascaroside-type C,O-glycosides; not the pharmacopoeial cascara marker

The Regulatory History (FDA & EMA)

Cascaroside C’s defining modern story, like the rest of the cascaroside family, is regulatory — because in the anthranoid laxatives the efficacy and the hazard share the same chemistry. The hydroxyanthracene structure that delivers an active anthrone to the colon is the structure that carries the genotoxicity signal, so regulators acted on the whole class rather than picking winners.

United States — FDA, 2002. After reclassifying cascara sagrada from Category I to Category III and requesting mutagenicity, genotoxicity and carcinogenicity data that were not supplied, the FDA ruled in a final rule effective November 5, 2002 that the stimulant-laxative ingredients aloe and cascara sagrada (including the cascara extracts and casanthranol) in OTC products are “not generally recognized as safe and effective” — removing them from the US OTC market ^{2Reference 2Food et al. · 2002Status of certain additional over-the-counter drug category II and III active ingredients (aloe & cascara sagrada stimulant laxatives)View study →}.

European Union — EFSA/EMA. In a 2018 scientific opinion, EFSA concluded that hydroxyanthracene derivatives should be regarded as genotoxic and carcinogenic unless specific data show otherwise, that aloe-emodin and emodin are genotoxic, and that no safe daily intake could be established ^{3Reference 3EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}. On that basis Commission Regulation (EU) 2021/468 restricted hydroxyanthracene derivatives and preparations containing them in food to trace levels ^{5Reference 5Commission Regulation (EU) 2021/468 · 2021Amending Annex III to Regulation (EC) No 1925/2006 as regards botanical species containing hydroxyanthracene derivativesView study →}. The cascarosides are members of this restricted class.

The honest caveat for cascaroside C specifically. The direct genotoxicity/carcinogenicity data anchoring these actions are for the aloe-emodin/emodin-type anthranoids and for whole extracts — not for cascaroside C or its chrysophanol-derived anthrone, which is the less cytotoxic scaffold in the series ^{6Reference 6Demarque DP et al. · 2018Cytotoxicity of structurally diverse anthranoids and correlation with mechanism of action and side effects (glucose moieties reduce toxicity; cascarosides from cascara sagrada)View study →}. Cascaroside C is regulated as a class member delivering a hydroxyanthracene anthrone to the colon, not on molecule-specific cancer data.

Discovery & Synthesis

The cascarosides A–D were structurally characterised in the 1970s (work associated with Wagner and colleagues), which established the family as the unusual C,O-diglycosides of the aloin/chrysaloin anthrones and separated the aloe-emodin pair (A/B) from the chrysophanol pair (C/D). Cascaroside C and D were subsequently isolated as a discrete diastereomeric pair from Rhamnus purshiana bark — for example by high-performance countercurrent chromatography, which resolved cascarosides C, D, E and F from the bark’s n-butanol fraction ^{1Reference 1Rho T et al. · 2020Isolation of six anthraquinone diglucosides (including cascarosides C and D) from cascara sagrada bark by high-performance countercurrent chromatographyView study →}. Cascaroside C is obtained by extraction from cascara bark (and supplied as an analytical reference standard); there is no practical total synthesis — the complex C,O-diglycosyl anthrone is isolated from the natural source rather than built.

Patents: not yet researched.

Toxicity & Safety

Cascaroside C carries a moderate flag — matching its anthranoid siblings chrysophanol, emodin and barbaloin — because it is a hydroxyanthracene-derivative prodrug that delivers an active anthrone to the colon and sits inside a restricted, genotoxicity-flagged class, even though its own molecule-specific toxicology is thin and its chrysophanol scaffold is the less cytotoxic one.

Safety at a Glance

Moderate toxicity

Comparatively gentle scaffold, chemically. Chrysophanol is less cytotoxic than aloe-emodin/emodin in the anthranoid series, and its glucose moieties reduce cytotoxicity further, so cascaroside C is toward the milder end of the family ^{6Reference 6Demarque DP et al. · 2018Cytotoxicity of structurally diverse anthranoids and correlation with mechanism of action and side effects (glucose moieties reduce toxicity; cascarosides from cascara sagrada)View study →}.
Hydroxyanthracene-derivative class concern. EFSA treats the class as genotoxic/carcinogenic-until-proven-otherwise and could establish no safe intake; cascaroside C is a class member ^{3Reference 3EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}.
Removed / restricted by regulators. FDA took cascara stimulant laxatives off the US OTC market (2002); the EU restricts hydroxyanthracene derivatives in food to trace levels ^{2,5Reference 2Food et al. · 2002Status of certain additional over-the-counter drug category II and III active ingredients (aloe & cascara sagrada stimulant laxatives)View study →Reference 5Commission Regulation (EU) 2021/468 · 2021Amending Annex III to Regulation (EC) No 1925/2006 as regards botanical species containing hydroxyanthracene derivativesView study →}.
Stimulant-laxative harms. As part of the cascaroside/anthrone fraction it contributes to cramping, fluid and electrolyte (notably potassium) loss, and dependence/atony with chronic use — the class cautions.
Flora-dependent and uncharacterised as an isolate. The active anthrone forms only if suitable colonic anaerobes are present, and no isolate-specific safety dataset exists for cascaroside C itself.

Pregnancy (prose only). Stimulant anthranoid laxatives are conventionally cautioned in pregnancy (theoretical uterine-stimulant and fluid/electrolyte concerns), and the class genotoxicity signal is an added reason for avoidance. Any decision about cascara intake in pregnancy or lactation belongs to the cascara sagrada herb page, where intake is actually decided — not to this molecule page. No isolate-specific verdict is issued here.

Dosage

There is no recommended dose for isolated cascaroside C, and it is never dosed alone — it is quantified only as one of cascarosides A–D within standardised cascara bark, which is itself dosed to total hydroxyanthracene / cascaroside content rather than to any single glycoside ^{3Reference 3EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}. That use has been withdrawn or restricted: the FDA removed cascara stimulant-laxative ingredients from the US OTC market in 2002 ^{2Reference 2Food et al. · 2002Status of certain additional over-the-counter drug category II and III active ingredients (aloe & cascara sagrada stimulant laxatives)View study →}, and the EU limits hydroxyanthracene derivatives in food to trace amounts ^{5Reference 5Commission Regulation (EU) 2021/468 · 2021Amending Annex III to Regulation (EC) No 1925/2006 as regards botanical species containing hydroxyanthracene derivativesView study →}. Any historical purgative “doses” are context, not a personal recommendation, and given the class genotoxicity concern, self-dosing isolated cascaroside C is not advisable.

References

Rho T, Kil HW, Seo YJ, Shin KJ, Wang D, Yoon KD (2020). Isolation of six anthraquinone diglucosides (including cascarosides C and D) from cascara sagrada bark by high-performance countercurrent chromatography. Journal of Separation Science. https://pubmed.ncbi.nlm.nih.gov/32876395/
Food and Drug Administration (2002). Status of certain additional over-the-counter drug category II and III active ingredients (aloe & cascara sagrada stimulant laxatives). Final rule. Federal Register 67(90):31125-7. https://pubmed.ncbi.nlm.nih.gov/12001972/
EFSA ANS Panel (2018). Safety of hydroxyanthracene derivatives for use in food. EFSA Journal. https://pubmed.ncbi.nlm.nih.gov/32625659/
Akao T, Che QM, Kobashi K, Hattori M, Namba T (1996). A purgative action of barbaloin is induced by Eubacterium sp. strain BAR, a human intestinal anaerobe, capable of transforming barbaloin to aloe-emodin anthrone. Biological & Pharmaceutical Bulletin. https://pubmed.ncbi.nlm.nih.gov/8820926/
Commission Regulation (EU) 2021/468 (2021). Amending Annex III to Regulation (EC) No 1925/2006 as regards botanical species containing hydroxyanthracene derivatives. Official Journal of the European Union. https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:32021R0468
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 (glucose moieties reduce toxicity; cascarosides from cascara sagrada). Journal of Pharmacy & Pharmaceutical Sciences. https://pubmed.ncbi.nlm.nih.gov/30321134/