Plant Profiler

Cascara sagrada (Rhamnus purshiana)


Cascara sagrada (Rhamnus purshiana) Image
Synonyms / Common Names / Related Terms
1,8-dihydroxyanthraquinone, aloe, aloe-emodin, amerikanische faulbaumrinde, amerikanische faulbaum, anthracene glycosides, anthranoid (active constituents and metabolites are 1,8-dihydroxyanthraquinone glycosides), anthraquinone, anthroid, anthrone C-glycosides, Artemisia scoparia, ayapin, bearberry bark, bearwood, bitter bark, California buckthorn, carminic acid, casanthranol, cascara buckthorn, cascara fluid extract aromatic, cascara liquid extract, cascararinde, cascara sagrada, cascara sagrada (dried bark), cascara sagrada extract, cascara sagrada fluid extract (bitter cascara), cascarosides, cassia, cassia senna, chittem bark, coffee tree, dihydroxy-anthraquinones, dihydroxy-anthrones, dihydroxy-dianthrones, dogwood bark, emodin, fimbriatone, Frangula purshiana, nepodin, parietin, Persian bark, phytoestrogens, Polygonaceae, purshiana bark, pursh's buckthorn, Rhamnaceae (family), Rhamni purshianae cortex, Rhamnus purshiana, rhein, rheum, sacred bark, sagrada bark, Sagradafaulbaum (German), vegetable laxatives, wahoo plant, xanthoria elegans, yellow bark.

Selected combination products: Bassoran® with cascara (sweet cascara and magnesium oxide), Bicholax® cascara elixir (cascara, licorice, light magnesium oxide, coriander oil, anise oil, ethanol, saccharin sodium, glycerol, water), Cascara Sagrada Whole Herb Active (cascara sagrada bark, cascaroside A), Cascara-SalaxFM, Cas-Evac®, Casylium, Concentrated Milk of Magnesia (Cascara equivalent to 1mL of aromatic fluid extract per teaspoon of milk of magnesia), Elixir Purgans® (cascara, wahoo, senna, blue flag, hyoscyamus leaves aromatics), Kondremul® with Cascara (220mg per teaspoon of mineral oil), Nature's Remedy® Natural Vegetable Laxative Tablets (150mg cascara sagrada and 100mg aloe in tablet), Parke-Davis® Zand® cleansing laxative with cascara sagrada.

Mechanism of Action

Pharmacology:

  • Constituents: The active constituents of cascara are the anthraquinones. They are inactive in the gastrointestinal tract until they reach the colon; there they produce a soft or formed stool within about six to eight hours and cause vigorous peristalsis.
  • Active compounds include anthraquinone glycosides, (emodin, frangulin, iso-emodin, aloe-emodin, and chrysophanol), rhein, aloin, malic acid, tannic acid, cascarosides A, B, C, and D, and hydroxy anthracene derivatives (HAD).1,2
  • Aged/dried bark contains 7-10% of total hydroxyanthracene derivatives of which 60-70% are cascarosides, both calculated (on a dried basis) as cascaroside A (C27H32O14; Mr580.5).
  • Antitumor activity: Cascara's anticancer activities may arise from its emodin and aloe-emodin content.3,4,1,5,6,7,8
  • Emodin, an anthraquinone similar in chemical structure to cascara, is a tyrosine kinase inhibitor.6 Emodin is an active constituent of Rheum palmatum1 and appears to exert antitumor properties possibly by inhibiting tumor cell proliferation3, inducing cell cycle arrest3, apoptosis3,4,9,5 and tumor cell death10. In vitro studies show that aloe-emodin induces p53 and p21 expression resulting in cell cycle arrest in the G1 phase.8 However, more studies are needed to confirm this effect. Studies on the carcinogenic effects of cascara have produced conflicting results.11,12,13,14
  • Emodin has been shown to have highly selective activities against src-Her-2/neu and ras-oncogenes.7 In addition, emodin has been shown to increase the repair of DNA damaged human cells15 and has demonstrated in vitro to reduce the invasiveness of human cancer cells16. Emodin may also have immunosuppressive17, vasorelaxant18, antioxidant19 and hepatoprotective activities19. Since emodin may have genotoxic activity, further research on the human cancer risk is warranted.20
  • Antiviral activity: Aloe-emodin, a constituent in cascara and aloe, has been reported to have antiviral activity in vitro.21 Aloe-emodin was also reported to have a specific in vitro and in vivo anti-neuroectodermal tumor activity in laboratory mice.22 Another constituent, emodin, has been reported in studies to possess anti-inflammatory, antibiotic, and antineoplastic properties.23,24
  • Laxative effects: It is the free anthraquinone and hydroxy anthracene derivative (HAD), which give cascara sagrada its laxative action. These compounds promote more peristalsis in the large intestine and at the same time, trigger a nerve center, which facilitates bowel movement. The active constituents of cascara are absorbed through the small intestine, enter the circulation and stimulate the autonomic nervous system to create peristalsis. Cascara also contains small amounts of bitter anthracene and aloin compounds which account for the cathartic action.
  • The chemical components of cascara also stimulate the organs of the digestive tract including the gallbladder, pancreas and stomach, which results in increased digestive fluids.2
  • The laxative effect of cascara appears to be via induction of the synthesis of nitric oxide.25

Pharmacodynamics/Kinetics:

  • Onset of action: Based on unsubstantiated reports, orally administered cascara laxatives usually produce a bowel movement within 6-8 hours, although the effect may not occur for 24 hours.
  • Absorption: Following oral administration, the anthraquinone glycosides are purported to be poorly absorbed until they are hydrolyzed by colonic bacteria; then moderate absorption of cascara occurs.
  • Metabolism: Occurs at intestinal wall, to an unknown extent.2 Readily transformed to corresponding glucuronide and sulfate derivatives. The colon and jejunum also exert an anthraquinone-conjugating activity. At least a part of these compounds undergo extra-hepatic metabolism.2
  • Elimination: Following oral administration and hydrolysis by colonic bacteria, the anthraquinones are partially eliminated renally.

References

  1. Lee, H. Z., Hsu, S. L., Liu, M. C., and Wu, C. H. Effects and mechanisms of aloe-emodin on cell death in human lung squamous cell carcinoma. Eur J Pharmacol 11-23-2001;431(3):287-295. 11730720
  2. de Witte, P. and Lemli, L. The metabolism of anthranoid laxatives. Hepatogastroenterology 1990;37(6):601-605. 2289777
  3. Chen, H. C., Hsieh, W. T., Chang, W. C., and Chung, J. G. Aloe-emodin induced in vitro G2/M arrest of cell cycle in human promyelocytic leukemia HL-60 cells. Food Chem Toxicol 2004;42(8):1251-1257.
  4. Chen, Y. C., Shen, S. C., Lee, W. R., Hsu, F. L., Lin, H. Y., Ko, C. H., and Tseng, S. W. Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase 3 cascade but independent of reactive oxygen species production. Biochem Pharmacol 12-15-2002;64(12):1713-1724. 12445860
  5. Liu, J. B., Gao, X. G., Lian, T., Zhao, A. Z., and Li, K. Z. [Apoptosis of human hepatoma HepG2 cells induced by emodin in vitro]. Ai Zheng 2003;22(12):1280-1283. 14693052
  6. Lai, G. H., Zhang, Z., and Sirica, A. E. Celecoxib acts in a cyclooxygenase-2-independent manner and in synergy with emodin to suppress rat cholangiocarcinoma growth in vitro through a mechanism involving enhanced Akt inactivation and increased activation of caspases-9 and -3. Mol Cancer Ther 2003;2(3):265-271. 12657721
  7. Chang, C. J., Ashendel, C. L., Geahlen, R. L., McLaughlin, J. L., and Waters, D. J. Oncogene signal transduction inhibitors from medicinal plants. In Vivo 1996;10(2):185-190.
  8. Kuo, P. L., Lin, T. C., and Lin, C. C. The antiproliferative activity of aloe-emodin is through p53-dependent and p21-dependent apoptotic pathway in human hepatoma cell lines. Life Sci 9-6-2002;71(16):1879-1892. 12175703
  9. Lee, H. Z. Protein kinase C involvement in aloe-emodin- and emodin-induced apoptosis in lung carcinoma cell. Br J Pharmacol 2001;134(5):1093-1103. 11682458
  10. Lee, H. Z. Effects and mechanisms of emodin on cell death in human lung squamous cell carcinoma. Br J Pharmacol 2001;134(1):11-20. 11522592
  11. Borrelli, F., Mereto, E., Capasso, F., Orsi, P., Sini, D., Izzo, A. A., Massa, B., Boggio, M., and Mascolo, N. Effect of bisacodyl and cascara on growth of aberrant crypt foci and malignant tumors in the rat colon. Life Sci 9-7-2001;69(16):1871-1877. 11693267
  12. Wang, H. W., Chen, T. L., Yang, P. C., and Ueng, T. H. Induction of cytochromes P450 1A1 and 1B1 by emodin in human lung adenocarcinoma cell line CL5. Drug Metab Dispos  2001;29(9):1229-1235. 11502733
  13. Mereto, E., Ghia, M., and Brambilla, G. Evaluation of the potential carcinogenic activity of Senna and Cascara glycosides for the rat colon. Cancer Lett 3-19-1996;101(1):79-83. 8625286
  14. Koyama, J., Morita, I., Tagahara, K., Nobukuni, Y., Mukainaka, T., Kuchide, M., Tokuda, H., and Nishino, H. Chemopreventive effects of emodin and cassiamin B in mouse skin carcinogenesis. Cancer Lett 8-28-2002;182(2):135-139. 12048158
  15. Chang, L. C., Sheu, H. M., Huang, Y. S., Tsai, T. R., and Kuo, K. W. A novel function of emodin: enhancement of the nucleotide excision repair of UV- and cisplatin-induced DNA damage in human cells. Biochem Pharmacol 1999;58(1):49-57.
  16. Huang, Q., Shen, H. M., and Ong, C. N. Inhibitory effect of emodin on tumor invasion through suppression of activator protein-1 and nuclear factor-kappaB. Biochem Pharmacol 7-15-2004;68(2):361-371. 15194008
  17. Huang, H. C., Chang, J. H., Tung, S. F., Wu, R. T., Foegh, M. L., and Chu, S. H. Immunosuppressive effect of emodin, a free radical generator. Eur J Pharmacol 2-18-1992;211(3):359-364. 1535596
  18. Huang, H. C., Lee, C. R., Chao, P. D., Chen, C. C., and Chu, S. H. Vasorelaxant effect of emodin, an anthraquinone from a Chinese herb. Eur J Pharmacol 12-3-1991;205(3):289-294. 1667913
  19. Jung, H. A., Chung, H. Y., Yokozawa, T., Kim, Y. C., Hyun, S. K., and Choi, J. S. Alaternin and emodin with hydroxyl radical inhibitory and/or scavenging activities and hepatoprotective activity on tacrine-induced cytotoxicity in HepG2 cells. Arch Pharm Res 2004;27(9):947-953. 15473666
  20. Muller, S. O., Eckert, I., Lutz, W. K., and Stopper, H. Genotoxicity of the laxative drug components emodin, aloe-emodin and danthron in mammalian cells: topoisomerase II mediated? Mutat Res 12-20-1996;371(3-4):165-173. 9008718
  21. Sydiskis, R. J., Owen, D. G., Lohr, J. L., Rosler, K. H., and Blomster, R. N. Inactivation of enveloped viruses by anthraquinones extracted from plants. Antimicrob Agents Chemother  1991;35(12):2463-2466. 1810179
  22. Pecere, T., Gazzola, M. V., Mucignat, C., Parolin, C., Vecchia, F. D., Cavaggioni, A., Basso, G., Diaspro, A., Salvato, B., Carli, M., and Palu, G. Aloe-emodin is a new type of anticancer agent with selective activity against neuroectodermal tumors. Cancer Res 6-1-2000;60(11):2800-2804. 10850417
  23. Goel, R. K., Das, Gupta G., Ram, S. N., and Pandey, V. B. Antiulcerogenic and anti-inflammatory effects of emodin, isolated from Rhamnus triquerta wall. Indian J Exp Biol 1991;29(3):230-232. 1874536
  24. Jin, Z. H., Ma, D. L., and Lin, X. Z. [Study on effect of emodin on the isolated intestinal smooth muscle of guinea-pigs]. Zhongguo Zhong Xi Yi Jie He Za Zhi  1994;14(7):429-431. 7950233
  25. Izzo, A. A., Mascolo, N., and Capasso, F. Nitric oxide as a modulator of intestinal water and electrolyte transport. Dig Dis Sci 1998;43(8):1605-1620. 9724140




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