Cascara

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Cascara

Common Names

  • Cascara sagrada
  • Sacred bark

For Patients & Caregivers

How It Works

Cascara is a strong laxative. It has not been shown to treat or prevent cancer.

Cascara is made out of the bark of the Cascara sagrada plant. It is known to stimulate the large intestine and produces a well-documented laxative effect. Cascara also causes water and electrolytes such as sodium and potassium to be expelled with the feces. This eases bowel passage but can also lead to dangerously low potassium and sodium levels if cascara is used for prolonged periods of time.

Scientists have isolated a compound called aloe-emodin from cascara. In laboratory studies, this compound inhibited the growth of tumor cells, but it is unknown if this effect would take place in the human body. Scientists have also studied whether cascara might be a carcinogen, with inconsistent results.

Cascara is one of the ingredients in the Hoxsey herbal therapy, which is promoted to treat cancer. However, there is no evidence that Hoxsey herbal therapy is effective in treating cancer.

Purported Uses
  • To relieve constipation
    Scientific evidence supports this use, but prolonged use is not recommended because it can lead to dangerous blood electrolyte imbalances and potential liver toxicity.
  • To treat 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.
Patient Warnings
  • Long-term use or overdose of cascara can cause electrolyte imbalances like very low blood levels of potassium, sodium, and chloride. It may also lead to liver injury.
  • Whether cascara may be a cancer-causing substance is uncertain, as studies have produced conflicting results.
Do Not Take If
  • You are taking drugs that are substrates of P-Glycoprotein (P-Gp): Emodin, a compound present in cascara inhibits P-Gp, and may affect how these drugs are absorbed or metabolized. Clinical relevance has yet to be determined.
Side Effects

Abdominal cramps, electrolyte imbalance, diarrhea and weight loss with excess use.

Case Reports
Liver disease such as severe or acute hepatitis have been reported.

 

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For Healthcare Professionals

Scientific Name
Rhamnus purshiana
Clinical Summary

Cascara sagrada is a species of buckthorn plant native to North America. The bark of the plant has been used to relieve constipation and is marketed as a dietary supplement. It is also used as an ingredient in the Hoxsey herbal formula, an ineffective alternative cancer treatment.

The major constituents are cascarosides that stimulate the large intestine and produce a laxative effect. In vitro studies suggest that emodin, one of the constituents of cascara, has hepatoprotective (17), neuroprotective (18), anti-osteoporotic (21), and chemopreventive effects (10) (12) (13). Emodin also enhances the cytotoxic effects of some chemotherapeutic agents (14) (15) (19) (20). However, human studies have not been conducted to confirm these effects.

Prolonged use or overdose of cascara can cause diarrhea, electrolyte imbalance, and hepatitis (7) (11).

Food Sources

Food flavoring agent

Purported Uses
  • Cancer treatment
  • Constipation
Mechanism of Action

Cascarosides stimulate the large intestine, increasing intestinal motility and contractions to produce a well-documented laxative effect. Increased water and electrolyte content in the lumen also results, which further facilitates bowel passage. The constituent emodin has direct excitatory effect on circular smooth muscle cells in the large intestine (9).

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 (BMMs), and the bone resorption of mature osteoclasts via inhibiting expression of RANKL-induced NF-κB, c-Fos, and NFATc1 (21).

In vitro studies suggest anticancer properties, as aloe-emodin induces p53 and p21 expression that results in G1-phase cell cycle arrest (8). However, more studies are needed to confirm such effects. Studies on the carcinogenic effects of cascara have produced conflicting results (4) (5) (6) (10).

Warnings

Chronic use may cause electrolyte imbalance (11), especially hypokalemia.

Adverse Reactions

Abdominal cramps, electrolyte imbalance, diarrhea, weight loss, and darkened pigmentation of the colonic mucosa with excessive use (11).

Case reports
Cholestatic hepatitis (7), toxic hepatitis (16).

Herb-Drug Interactions

P-Glycoprotein (P-Gp): Emodin inhibits the activity of P-Glycoprotein in vitro and in vivo, and may affect the transport of drugs mediated by this protein (22). Clinical relevance has yet to be determined.

Dosage (OneMSK Only)
References
  1. Barnes J, et al. Herbal Medicines. Second Ed. London: Pharmaceutical Press; 2002.
  2. DerMarderosian A, editor. The Review of Natural Products. St. Louis: Facts and Comparisons; 1999.
  3. Gruenwald J, et al. PDR for Herbal medicines, Montvale (NJ): Medical Economics Company; 1998.
  4. Borrelli F, et al. Effect of bisacodyl and cascara on growth of aberrant crypt foci and malignant tumors in the rat colon. Life Sci 2001;69:1871-7.
  5. Wang H, et al. Induction of cytochromes P450 1A1 and 1B1 by emodin in human lung adenocarcinoma cell line CL5. Drug Metab Dispos 2001;29:1229-35.
  6. Mereto E, et al. Evaluation of the potential carcinogenic activity of Senna and Cascara glycosides for the rat colon. Cancer Lett 1996;101:79-83.
  7. Nadir A, et al. Cascara sagrada-induced intrahepatic cholestasis causing portal hypertension: case report and review of herbal hepatotoxicity. Am J Gastroenterol 2000;95:3634-7.
  8. Kuo P, et al. The antiproliferative activity of aloe-emodin is through p53-dependent and p21-dependent apoptotic pathway in human hepatoma cell lines. Life Sci 2002;71:1879-92.
  9. DeWitte P, et al. Bicascarosides in fluid extracts of cascara. Planta Med 1991;57:440-3.
  10. Koyama J, et al. Chemopreventive effects of emodin and cassiamin B in mouse skin carcinogenesis. Cancer Lett 2002;182:135-9.
  11. National Institutes of Health. Cascara. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-2017 Jan 23.
  12. Wang XD, Gu LQ, Wu JY. Apoptosis-inducing activity of new pyrazole emodin derivatives in human hepatocellular carcinoma HepG2 cells. Biol Pharm Bull. 2007 Jun;30(6):1113-6.
  13. Huang Z, Chen G, Shi P. Emodin-induced apoptosis in human breast cancer BCap-37 cells through the mitochondrial signaling pathway. Arch Pharm Res. 2008 Jun;31(6):742-8.
  14. Huang XZ, Wang J, Huang C, et al. Emodin enhances cytotoxicity of chemotherapeutic drugs in prostate cancer cells: the mechanisms involve ROS-mediated suppression of multidrug resistance and hypoxia inducible factor-1. Cancer Biol Ther. 2008 Mar;7(3):468-75.
  15. Li J, Liu P, Mao H, et al. Emodin sensitizes paclitaxel-resistant human ovarian cancer cells to paclitaxel-induced apoptosis in vitro. Oncol Rep. 2009 Jun;21(6):1605-10.
  16. Jacobsen C, Semb S, Kromann-Andersen H. [Toxic hepatitis following consumption of the herbal medicinal product Cascara Sagrada]. Ugeskr Laeger. 2009 Nov 9;171(46):3367-9.
  17. Bhadauria M. Dose-dependent hepatoprotective effect of emodin against acetaminophen-induced acute damage in rats. Exp Toxicol Pathol. 2010 Nov;62(6):627-35.
  18. Liu T, Jin H, Sun QR, Xu JH, Hu HT. Neuroprotective effects of emodin in rat cortical neurons against beta-amyloid-induced neurotoxicity. Brain Res. 2010 Aug 6;1347:149-60.
  19. Chen RS, Jhan JY, Su YJ, et al. Emodin enhances gefitinib-induced cytotoxicity via Rad51 downregulation and ERK1/2 inactivation. Exp Cell Res. 2009 Sep 10;315(15):2658-72.
  20. Ko JC, Su YJ, Lin ST, et al. Emodin enhances cisplatin-induced cytotoxicity via down-regulation of ERCC1 and inactivation of ERK1/2. Lung Cancer. 2010 Aug;69(2):155-64.
  21. Kim JY, Cheon YH, Kwak SC, et al. Emodin regulates bone remodeling by inhibiting osteoclastogenesis and stimulating osteoblast formation.J Bone Miner Res. 2014 Jul;29(7):1541-53.
  22. Li X, Hu J, Wang B, et al. Inhibitory effects of herbal constituents on P-glycoprotein in vitro and in vivo: herb-drug interactions mediated via P-gp. Toxicol Appl Pharmacol.2014 Mar 1;275(2):163-75.
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