Cascara Sagrada (Frangula purshiana / Rhamnus purshiana)
1. Identity
1.1 Botanical and Taxonomic Names
Frangula purshiana (cascara, cascara buckthorn, cascara sagrada, bearberry; synonyms: Rhamnus purshiana) is a species of plant in the family Rhamnaceae.
Official cascara sagrada — sometimes labelled "Sacred Bark" or "Chittern Bark" — is the dried bark of Rhamnus purshianus DC (Frangula purshiana (DC) A. Gray ex J. C. Cooper) (Rhamnaceae).
The name in common commerce remains cascara sagrada, though modern botanical classification places the species in Frangula rather than Rhamnus. Other vernacular names recorded in the literature include bitter bark, sacred bark, purshiana bark, chittem bark (or chitticum bark, from the Chinook Jargon trade language), and buckthorn.
1.2 Plant Description and Geographic Source
The species is native to western North America, from southern British Columbia south to central California, and eastward to northwestern Montana.
Cascara is a large shrub or small tree 4.5–12 m (15–39 ft) tall, with a trunk 20–50 cm (7.9–19.7 in) in diameter.
The bark is collected from wild trees growing on the Pacific coast of North America (British Columbia, Washington, and Oregon). Depleted wild U.S. sources encouraged cultivation of the tree in western Canada, the USA, and Kenya, though these efforts do not appear to have been completely successful.
1.3 Part Used and Preparation Requirements
Only the bark is used medicinally. A critical preparatory requirement distinguishes cascara sagrada from nearly all other botanical medicines: the bark must not be used fresh.
Only the dried bark of the trunk or branches is used, since fresh bark contains free anthrone, which can cause severe vomiting and is therefore destroyed by treatment of the bark with heat and aeration, or by aging it for at least one year.
The bark is collected in the spring or early summer, when it easily peels from the tree.
1.4 Common Dosage Forms and Preparations
Cascara sagrada is commonly found in teas, tinctures, capsules, and herbal laxative blends.
Historical pharmaceutical preparations included fluid extracts, aromatic cascara fluid extract, and powdered bark tablets.
Following the FDA's 2002 ruling, cascara is now available only as an herbal supplement rather than as a drug; it is also employed in the processing of some sunscreens, and it is used in a non-bitter extract form for flavoring in food and beverages.
2. Traditional and Historical Use
2.1 Indigenous Pacific Northwest Peoples
Cascara is typically an extract from the dried, aged bark of Rhamnus purshiana, a species of buckthorn tree or shrub native to North America. Cascara sagrada is Spanish for "sacred bark" and was used for centuries by Native Americans as a laxative.
The name "Sacred Bark" was bestowed by Spanish colonists in the 17th century who learned of its use from local Indigenous tribes, including the Nlaka'pamux, Salish, and Kwakwaka'wakw peoples. For these cultures, the bark was a cornerstone of their traditional medicine, primarily used to support bowel function and relieve occasional constipation.
Tribes such as the Quinault, Shaker, and Stl'atl'imx adopted cascara sagrada's bark to assist with various digestive complaints, and it found use even in ceremonial practices.
2.2 Adoption into Western Medicine
Cascara is a drug of comparatively recent introduction into modern medicine. According to tradition, a cascara, probably R. californica, was known to early Mexican and Spanish priests of California; however, Rhamnus purshianus was not described until 1805 and its bark was not introduced into medicine until 1877.
Following its introduction to formal U.S. medicine in 1877, it replaced the berries of R. catharticus as the favored laxative.
By 1890, cascara sagrada had officially entered the Pharmacopeia of the United States.
Cascara became accepted in western medical practice in the 19th century and is still used in over-the-counter laxative preparations, often in combination with other herbals such as aloe vera.
2.3 Traditional Therapeutic Indications
Traditional use of cascara sagrada included: intestinal tonic, dyspepsia, constipation, digestion-related headaches, loosening stool for conditions such as haemorrhoids, rheumatism, biliary catarrh with jaundice, and chronic liver diseases.
Native Americans also used cascara sagrada as a cathartic.
Commercially, it is called "cascara sagrada" ('sacred bark' in Spanish), while in the local trade language Chinook Jargon it was known as "chittem bark" or "chitticum bark."
3. Key Constituents and Active Compounds
3.1 Primary Active Constituents
The active laxative constituents of cascara include at least 6% to 9% anthracene derivatives, which exist as normal O-glycosides and C-glycosides.
Of these, 70–90% are C-10 glycosides, with the 8-O-glycosides, aloins A and B, and 11-desoxyaloins A and B (chrysaloins A and B) accounting for 10–30%. The diastereoisomeric pairs cascarosides A and B, and cascarosides C and D, and cascarosides E and F constitute 60–70% of the total O-glycosides. Other major hydroxyanthracene glycosides (10–20%) include the hydroxyanthraquinones, chrysophanol-8-O-glucoside and aloe-emodin-8-O-glucoside.
The four primary glycosides (cascarosides A, B, C, and D) contain both O- and C-glycosidin linkages that are chemically designated as the C-10 isomers of the 8-O-beta-D-glucopyranosides of aloin and chrysophanol.
A number of dianthrones are also present, including emodin, chrysophanol, and the heterodianthrones, as well as palmidin A, B, and C. The free anthraquinones are likely formed in the leaves and stored in the bark, mainly as C-glycosides, with older bark containing the highest concentration.
3.2 Full Phytochemical Profile
The bark extract of cascara consists of a mixture of constituents, including anthracenes (10%–20% of glycosides and 80%–90% C-glycosides), emodins, oxanthrone, barbaolin, chrysophanol, linoleic acid, rhamnol, and myristic and syringic acids.
Cascara bark also contains resins, tannins, and lipids.
The hydroxyanthracene heterosides (6–8%) include as major components the cascarosides (60–70%) A, B, C, and D — which are O-heterosides of emodin-anthrone — alongside free anthraquinones such as aloe-emodin, chrysophanol, frangulaemodin, and fyscin, and small amounts of homodianthrones and heterodianthrones.
4. Mechanisms of Action
4.1 Metabolic Activation by Intestinal Microbiota
After oral administration, the hydroxyanthracene glycosides are not absorbed in the upper intestine, but are hydrolysed in the colon by intestinal bacteria to form the pharmacologically active metabolites. These metabolites are partially absorbed in the colon and act as a stimulant and irritant to the gastrointestinal tract, similarly to senna.
Anthraquinones are absorbed into the blood and re-secreted into the colon as active anthraquinones, where they stimulate smooth muscle contraction. Healthy bacterial flora may be required for full therapeutic potential.
4.2 Dual Colonic Mechanism
The mechanism of action, similar to that of senna, is twofold. Firstly, there is stimulation of colonic motility, resulting in increased propulsion and accelerated transit of faeces through the colon (which reduces fluid absorption from the faecal mass).
More specifically, anthraglycosides produce an active secretion of water and electrolytes within the lumen of the small intestine and inhibit their absorption from the large intestine, causing an increase in bowel content volume and strengthening of intestinal dilatation pressure to stimulate peristalsis.
Anthraquinones also inhibit reabsorption of electrolytes and water from the colon.
4.3 Role of Emodin Glycoside
The emodin glycoside is also responsible for laxative action, first requiring metabolism to the active aglycone by intestinal flora and possibly increasing the excitability of the smooth muscles of the intestinal wall.
The laxative action is mild and occurs after about 8–12 hours.
4.4 Myenteric Plexus and Chloride Secretion
Anthraquinone glycosides are primarily responsible for providing laxative effects and promote peristalsis by effects at the myenteric plexus.
The action is manifested by an increase in intestinal peristalsis by direct stimulation of nerve endings (by irritation of the mucosa or by action on the neural plexus) and by an increase in the secretion of water and electrolytes into the intestinal lumen, which causes an increase in intestinal pressure.
5. Scientific Evidence by Area of Use
5.1 Constipation — Primary Therapeutic Application
Traditional and regulatory basis:
Medicinal uses supported by clinical data include short-term treatment of occasional constipation.
The dried bark of cascara was used as a laxative in folk medicine by the indigenous peoples of the Pacific Northwest, and later worldwide in conventional medicines until 2002.
Clinical evidence and its limitations:
There are no dose-finding studies available for cascara preparations.
Clinical studies of cascara have focused on its laxative effects, although cascara is no longer considered safe or effective for this use by the FDA. Attention has shifted to cascara's constituent emodin and its possible therapeutic applications in the treatment of various conditions, based on animal and in vitro data.
Most published human evidence predates modern clinical trial standards and consists of observational case series and small open-label studies rather than randomized controlled trials. The WHO has recognized short-term laxative use based on traditional evidence, and the EMA has similarly acknowledged use for occasional constipation where dietary or bulk-laxative measures have been insufficient.
FDA regulatory action:
The U.S. Food and Drug Administration issued a final rule stating that the stimulant laxative ingredients aloe and cascara sagrada (including casanthranol, cascara fluidextract aromatic, cascara sagrada bark, cascara sagrada extract, and cascara sagrada fluidextract) in over-the-counter drug products are not generally recognized as safe and effective or are misbranded. This final rule was part of FDA's ongoing OTC drug product review.
The agency reclassified these ingredients to category II (nonmonograph) and added them to the list of stimulant laxative ingredients for which the data are inadequate to establish general recognition of safety and effectiveness.
FDA's Drug Listing System had identified approximately 160 laxative products containing cascara sagrada ingredients at the time of the ruling.
Evidence strength for constipation: Limited. The laxative mechanism is pharmacologically well-characterized and supported by preclinical and historical observational data, but robust modern randomized controlled trials in humans are absent. Regulatory bodies have found the totality of evidence insufficient to maintain drug-product approval.
5.2 Anticancer Potential — Preclinical Evidence Only
The cascara constituents aloe-emodin and emodin have anticancer properties in vitro and in animal models, and may therefore warrant additional studies in humans.
In vitro studies suggest anticancer properties, as aloe-emodin induces p53 and p21 expression resulting in G1-phase cell cycle arrest. However, more studies are needed to confirm such effects.
Emodin inhibited the growth of orthotopic breast cancer tumors and attenuated metastasis and angiogenesis. Emodin also inhibited tumor growth in several studies of hepatocellular carcinoma, and oral and lung cancer.
Lab studies show that aloe-emodin from cascara has anticancer activity; however, lab results often do not translate to effectiveness in humans, and clinical trials have not yet been conducted.
A 2002 study published in Life Sciences researched the effects of aloe-emodin, a component of cascara, on two human liver cancer cell lines, Hep G2 and Hep 3B. The researchers found that aloe-emodin inhibited cancer cell proliferation and induced apoptosis in both cell lines.
Evidence strength for anticancer use: Preclinical only (in vitro and animal model data). No human clinical trials have been conducted using cascara sagrada or its isolated constituents for cancer treatment or prevention. These findings cannot be extrapolated to clinical benefit.
5.3 Antiviral Activity — In Vitro and Preclinical Data
Evidence suggests that aloe-emodin exhibits a range of pharmacological effects including antiviral properties. In terms of antiviral effects, aloe-emodin inhibits the replication of enveloped viruses, including herpes simplex virus, influenza virus, and human cytomegalovirus.
Emodin has also demonstrated antiviral activity against coxsackievirus B3, enterovirus 71, herpes simplex virus, human coronavirus OC43, SARS-CoV, SARS-CoV-2, and PRRSV, achieved by blocking the virus–receptor interaction, restraining the main protease activity, and inhibiting the translation of viral proteins.
Evidence strength for antiviral use: Preclinical only. All antiviral studies involving cascara-related constituents have been conducted in cell culture or animal models. No clinical trials in humans have evaluated cascara sagrada or its constituents for antiviral purposes.
5.4 Carcinogenicity Question — Conflicting Evidence
Whether cascara may be a cancer-causing substance is uncertain, as studies have produced conflicting results.
Several anthranoid derivatives (notably the aglycones aloe-emodin, chrysophanol, emodin, and physicon) are genotoxic in bacterial and/or mammalian test systems, and two anthranoid compounds (the synthetic laxative dantron and the naturally occurring 1-hydroxyanthraquinone) have carcinogenic activity in rodents.
In an epidemiological study, chronic abusers of anthranoid laxatives (identified by the presence of pseudomelanosis coli) had an increased relative risk of 3.04 (95% CI = 1.18, 4.90) for colorectal cancer.
However, other evidence points in the opposite direction:
human studies of cascara are limited to prospective observational or case-control studies. Two studies found no association between anthranoid laxative use and the development of aberrant crypt foci, colorectal adenomas, or colorectal cancer.
A study that treated rats with cascara for 13 weeks found no aberrant colonic crypt foci.
Pseudomelanosis coli (pigment spots in the lining of the large intestine) is believed to be harmless, usually reverses with discontinuation, and is not directly associated with an increased risk of developing colorectal adenoma or carcinoma.
German health authorities therefore restricted the indication of herbal anthranoid laxatives to constipation which has not responded to bulk-forming therapy.
5.5 Other Investigated Areas (In Vitro / Preliminary)
In vitro studies suggest that emodin, one of the constituents, has hepatoprotective, neuroprotective, anti-osteoporotic, and chemopreventive effects.
Emodin also enhances the cytotoxic effects of some chemotherapeutic agents in vitro.
Emodin may play a protective role against osteoporosis. It was shown to suppress the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast differentiation of bone marrow macrophages, and bone resorption of mature osteoclasts, via inhibiting expression of RANKL-induced NF-κB, c-Fos, and NFATc1.
All of the above findings are limited to in vitro or animal models and have not been confirmed in human clinical trials.
6. Body Systems and Health Areas Associated with Cascara Sagrada
- Gastrointestinal system — Primary use. Cascara sagrada is defined as an anthraquinone derivative that acts as a gastrointestinal stimulant, promoting fluid and ion accumulation in the colon, thus increasing peristalsis and producing a laxative effect. Cascara is also used for the relief of constipation and haemorrhoids and as a rectoanal postoperative treatment.
- Hepatobiliary system — Historical use as a hepatic tonic and for biliary conditions; paradoxically also a site of rare adverse effects (hepatotoxicity, described in the Safety section below).
- Oncology (preclinical interest) — Emodin and aloe-emodin have been studied in vitro for anticancer properties in multiple cancer cell lines, including hepatocellular, breast, oral, and lung cancer models.
- Musculoskeletal / bone metabolism — Emodin has been studied in preclinical models for osteoclast inhibition.
- Infectious disease (preclinical interest) — Antiviral properties of emodin and aloe-emodin demonstrated in cell culture models against multiple viral species.
7. Dosage Forms and Reported Dosages
Typical doses of cascara are 1 g of the bark, 2 to 6 mL as a fluid extract, or 100 to 300 mg of dried bark extract.
Research indicates that the optimal dose for adults is around 4 cc of aromatic fluidextract, as lower doses such as 2 cc are generally ineffective for treating constipation. For powdered cascara sagrada, the most sensitive dosage for effect is below 0.5 grams daily in constipated patients.
In a documented hepatotoxicity case report, the patient had taken one capsule (425 mg of aged cascara sagrada bark) three times daily for 3 days and subsequently developed serious adverse hepatic effects.
A laxative effect should be allowed at least 6 to 12 hours to occur.
Stimulant laxatives should only be used if occasional constipation cannot be improved by a change of diet or the administration of bulk-forming laxatives. The optimal dosage is the smallest dose required to produce a soft-formed stool.
Use in children younger than 10 years is contraindicated according to the WHO (2002).
There are no formal dose-finding studies available for cascara preparations.
8. Safety Considerations and Drug Interactions
8.1 General Safety Profile
Liver injury from long-term cascara use is rare, and most cases have been self-limited and rapidly reversible upon stopping the laxative.
The anthranoids produce harmless discoloration of the urine. Depending on intrinsic activity and dose, they can also produce abdominal discomfort and cramps, nausea, violent purgation, and dehydration.
Cascara sagrada may cause urine to turn reddish-brown or bright yellow. This change in colour is harmless and should resolve after stopping cascara sagrada.
8.2 Hepatotoxicity
The liver injury due to cascara has been attributed to the direct toxicity of anthraquinone derivatives in the herbal extract; however, the clinical characteristics of the published cases suggest an idiosyncratic rather than direct hepatotoxic etiology. Other anthraquinones used to treat constipation have been implicated in causing liver injury with long-term use, including sennosides and hydroxyanthraquinone. As with other herbal toxicities, the hepatic injury attributed to cascara may actually have been due to an undisclosed contaminant.
The pathogenesis of cascara hepatotoxicity is unknown, but it is assumed that anthracene glycosides are involved. Temporal association of ingestion of cascara with symptoms, and liver biopsy evidence of moderate inflammation with lymphocytes, plasma cells, and eosinophils, suggest an immune-mediated process.
A specific case detailed in the NIH LiverTox database:
A 48-year-old man developed jaundice 3 days after starting cascara sagrada (bilirubin 11.8 mg/dL, ALT 999 U/L, Alk P 309 U/L).
The consumption of cascara sagrada in higher doses is not recommended for more than 6 days because it has been associated with the development of hepatitis.
Liver damage can range from mild enzyme elevation to severe hepatitis, but it is generally reversible upon discontinuation of the herb.
8.3 Electrolyte Disturbances
Long-term use can result in electrolyte disturbances and in atony and dilatation of the colon.
Prolonged use may produce hypokalemia (decreased potassium levels) characterized by weakness and fatigue, albuminuria, and hematuria.
Long-term use or overdose of cascara can cause electrolyte imbalances such as very low blood levels of potassium, sodium, and chloride.
8.4 Laxative Dependence and Colonic Effects
Prolonged use may cause dependence due to altered intestinal motility and decreased laxative effect, so that constipation worsens and the dose must be increased.
Prolonged use may ulcerate the colon mucosa and produce a dark pigmentation of the colon (pseudomelanosis coli) that reverts several months after stopping consumption of the plant.
Use for more than 10 consecutive days can lead to dependence on laxatives for a bowel movement to occur.
8.5 Use of Fresh Bark
The use of improperly processed (e.g., fresh) cascara sagrada bark will cause severe vomiting and possibly spasms.
Adequate aging (minimum one year) or heat treatment is essential before any therapeutic use.
8.6 Contraindications
Cascara is contraindicated in children younger than 10 years; for ileus due to any origin; and for inflammatory diseases of the colon, including ulcerative colitis, irritable bowel syndrome (IBS), and Crohn's disease.
Use is to be avoided in pregnancy, lactation, intestinal obstruction, spastic constipation, acute intestinal inflammation, abdominal pain of unknown origin, and children under 12 years old.
Stimulating laxatives including cascara sagrada are to be avoided during pregnancy. Laxatives containing anthraquinone glycosides are considered overly stimulating during pregnancy, as their effects of increasing intestinal peristalsis can lead to sympathetic uterine stimulation.
Anthranoids can be distributed into breast milk, though not always in sufficient amounts to affect the suckling infant.
8.7 Drug Interactions
Long-term cascara use may lead to potassium deficiency, which can potentiate the effects of cardiac glycosides, antiarrhythmics, and corticosteroids. Interference with the absorption of other drugs is possible with anthranoid-containing plants, including senna and cascara.
Cascara sagrada increases the risk of potassium loss caused by different medications including corticosteroids and some diuretics (e.g., hydrochlorothiazide, furosemide, chlorthalidone). Cascara sagrada also interacts with medications for heart failure (e.g., digoxin), laxatives, and warfarin. Cascara sagrada interacts with natural health products including cardiac glycoside-containing herbs, licorice, and herbs with laxative properties (e.g., aloe, rhubarb, senna).
Emodin, a compound present in cascara, inhibits P-glycoprotein (P-Gp), and may affect how drugs that are substrates of P-Gp are absorbed or metabolized. Clinical relevance of this interaction has yet to be determined.
Due to decrease in transit time, cascara may potentially interfere with the absorption of practically any medication.
8.8 Aflatoxin Contamination Risk
Studies have shown that cascara sagrada can be a substrate for aflatoxin production, a potent toxin, with some samples containing detectable levels of aflatoxins B1, B2, and G1, highlighting the need for stringent quality control measures to ensure safety.
8.9 Rare and Serious Adverse Effects
Rare side effects from long-term usage can include nephrotoxicity, cardiotoxicity, hepatotoxicity, hypokalemia, muscle weakness, cachexia, and melanosis coli.
References
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