Cascara Sagrada Summary:

Cascara sagrada, otherwise known as buckthorn, comes from the genus Rhamnus. This genus actually has a few species that are used in the same way. The main ones being Rhamnus purshiana, and Rhamnus frangula. The bark of this tree is mainly used as a laxative, and bowel tonic. The fresh bark is rarely used, as it tends to be very powerful and may cause side effects like griping (spasmodic intestinal pain), and vomitting.

Once the bark has been aged around 3 years it's significantly milder, and much more useful medicinally. The taste of the bark is incredibly bitter and hard to palate, which is why this herb is mainly found as an extract in capsule form these days. Cascara sagrada can also be found in a liquid extract form. People who wish to maximize the benefits of the bitter components of this herb often choose to go with the liquid extract version. 

Cascara sagrada stimulates digestion through its bitter components, and through an activation of the bitter receptors on the tongue and throughout the digestive tracts. It also exerts a mild laxative action on the upper instestines. Due to its mild nature, it can be used in the elderly, and in chronic constipation conditions (unlike many of the other laxative botanicals). 


Botanical Name

Rhamnus purshiana
Frangula purshiana

Family

Rhamnaceae

Part Used

Bark

Herbal Actions:

  • Stimulating laxative
  • Cholagogue
  • Bitter digestive stimulant
  • Antiparasitic
  • Mild Laxative
  • Stomachic
  • Appetite stimulant

Dosage

Liquid Extract (1:2)

3-8 mL/day

Find It Here

Indications:

[5, 6]

+ Gastrointestinal System

  • Constipation (Acute and chronic)
  • Flatulence/Bloating/Abdominal fullness
  • Postprandial bloating
  • Dyspepsia
  • Weak gastric secretion
  • Anorexia
  • Coated tongue
  • Itching skin
  • Headache (Due to constipation or intestinal weakness)
  • Haemorrhoids or anal fissures where soft stools are desired

+ Other

  • Anorexia
  • Itching skin
  • Haemorrhoids
  • Headache

Common Names:

  • Cascara sagrada
  • Sacred bark
  • Buckthorn
  • Californian buckthorne
  • Rhamnus purshiana
  • Frangula purshiana

Traditional Uses:

Traditional use of cascara sagrada included: intestinal tonic, dyspepsia, constipation, digestion related headaches, to loosen stool for conditions such as haemorrhoids, rheumatism, biliary catarrh with jaundice, and chronic liver diseases [6]. 

Native Americans used cascara sagrada as a cathartic [6]. 


    Botanical Description

    Cascara sagrada is a small tree, with 8-13 cm long leaves. 


    Habitat Ecology, and Distribution

    Cascara sagrada can be found growing around the rocky mountains of western Canada and the United States. 


    Harvesting Collection, and Preparation

    The bark of cascara sagrada is harvested in spring and early summer. During this time it is easily peeled from the tree. It is then dried in the shade. Aged bark (3 years) is generally the preferred product, as the emetic effects lessen over this time and is much less likely to cause issues with griping and emesis [5].

     

    Constituents

    Chemical class Chemical Name % Dried Weight Solubility
    Anthrone glycosides Cascarosides Unknown N/A
    Anthraquinones Aloe-emodin, Emodin, Chrysophanol Unknown N/A
    Aloins --- Unknown N/A
    Deoxyaloins --- Unknown N/A
    Tannins --- Unknown N/A
    Volatile Oils --- Unknown N/A
     

    Pharmacology and Medical Research:

     

    Anticancer

    The anthraquinone emodin, contained within cascara sagrada and other herbs in its family (Rhamnaceae) as well as the families Lilliaceae, and Leguminoseae, is an important medicinal constituent. It is similar in structure to anthracycline, which is a class of chemicals used in cancer chemotherapy. They work to intercalate the DNA of cancer cells. Similar antitumor antibiotics includes daunorubicin and mitoxantrone. [7]. Emodin possesses many of these effects as well, with documented anti-proliferative [1-3], anti-angiogenic [8, 9], and radio-sensitizing/chemotherapy sensitizing actions on cancer cells [10-12]. It has even been found to reverse multidrug-resistant cancer cells [13]. 

    Emodin has been shown to have a broad spectrum inhibitory action on such cancer cell lines as leukemia [14, 15],  lung cancer [16-18], hepatic cancer [27-29], gallbladder cancer [21-23], pancreatic cancer [24-26], breast cancer [30-32], colon cancer [19, 20], and cervical cancer [33].  Most of this research has been conducted in China, and it should be noted that this chemical is contained within some of the most important and widely used traditional Chinese herbal medicines including Chinese rhubarb (Rheum palmatum) [34]. 

    The anticancer actions of emodin, has been suggested to be due to a variety of mechanisms such as the casein kinase Ⅱ and ERK1/2 pathways [7]. 

    The bioavailability of this chemical is quite low however, and has some toxicity in vivo as well [7]. It may however prove useful in combination, as in the case of many Chinese formulas containing emodin containing botanicals, or may prove useful administered via intravenous, or through modification of one of it's side chains [7]. It was shown in fact, that with the addition of polymethyleneamine, sugar or heterocycle as side chains may actually improve the antitumor activity [35-37]. Rhamnus frangula has been found to have emodin-glycoside derrivatives [38], some of which fit the earlier hypothesis, showing that these emodin glycoside derivatives (emodin with the addition of sugar chains) have a significantly higher antitumor activity than emodin, and have an improved bioavailability as well [39-41].

    The emodin glycoside derivative EM-d-Rha for example has shown a 10 fold improvement in anti-proliferative activity and growth inhibition of cancer cells (HepG2 cells and OVCAR-3 cells). The mechanism of action for this chemical was suggested to be through induction of apoptosis via the intrinsic apoptotic signal pathway (release of apoptosis-inducing factors and Cytochrome C from mitochondria, followed by the activation of caspase-3) [7]. 

     

    Antiviral

    In an older study (1991) anthraquinones extracted from cascara sagrada were found to inhibit enveloped viruses from adsorption into a cell through an interaction with the viral envelope. Thus it was able to prevent its subsequent replication. [4]. 

     

    Laxative

    The laxative actions of cascara sagrada are reported to be from the hydroxyanthracene derivatives. They travel through the digestive tract unabsorbed to the large intestine where they are metabolized to form active aglycones. Here they exert laxative effects by a localized modification of intestinal motility via stimulation of intestinal muscle, and an accumulation of fluid. This occurs due to mediators such as prostaglandin release, and nitric oxide synthase production. [6]. 

     

    Toxicity

  • Pregnancy and lactation (only very small doses acceptable) [6]
  • Intestinal obstruction [6]
  • Intestinal inflammations such as: [6]
    • Chrons disease
    • Ulcerative colitis
    • Appendicitis
  • Not for use in children under 12 [6] 
  •  

    Cautions:

    • May cause bowel pigmentation
    • Do not use over 2 weeks without medical supervision [6]
    • Do not use fresh cascara sagrada. Severe vomiting, and intestinal spasm may ocurr [6]. 

    Synergy:

    • 1 pt cascara, 2 pts chamomile, 4 pts psyllium combination to tone the bowels and improve function. Safe to use in this ratio over many weeks. Take 1 time/day before meals
    • Suggested synergy with boldo for digestive complaints such as constipation, flatulence, and abdominal fullness [6]. 
    • Combine with rhubarb, boldo, and gentian for dyspepsia [6]. 

    Other Uses:

    Cascara sagrada can be used effectively as a mild purgative for dogs with chronic constipation. This is especially useful if the tone of the bowels is weak and needs improvement as is common with chronically constipated dogs [5]. 


    Author:

    Justin Cooke

    The Sunlight Experiment

    Updated: June 2017


    Recent Blog Posts:

    References:

    1. Han YM, Lee SK, Jeong DG, Ryu SE, Han DC, Kim DK. (2012). Emodin inhibits migration and invasion of DLD-1(PRL-3) cells via inhibition of PRL-3 phosphatase activity. Bioorg Med Chem Lett. 22: 323–326, doi: 10.1016/j.bmcl.2011.11.008 PMID: 22137788 2.
    2. Manu KA, Shanmugam MK, Ong TH, Subramaniam A, Siveen KS, Perumal E. (2013). Emodin suppresses migration and invasion through the modulation of CXCR4 expression in an orthotopic model of human hepatocellular carcinoma. PLoS One. 8(3):e57015. doi: 10.1371/journal.pone.0057015 PMID: 23472074 3.
    3. Ok S, Kim SM, Kim C, Nam D, Shim BS, Kim SH. (2012). Emodin inhibits invasion and migration of prostate and lung cancer cells by down regulating the expression of chemokine receptor CXCR4. Immunopharmacol Immunotoxicol. 34(5):768–78. doi: 10.3109/08923973.2012.654494 PMID: 22299827
    4. Sydiskis, R. J., Owen, D. G., Lohr, J. L., Rosler, K. H., & Blomster, R. N. (1991). Inactivation of enveloped viruses by anthraquinones extracted from plants. Antimicrobial Agents and Chemotherapy, 35(12), 2463-2466. doi:10.1128/aac.35.12.2463
    5. A Modern Herbal. (1931). Buckthorn (Californian). Retrieved from http://www.botanical.com/botanical/mgmh/b/buckth80.html#cal
    6. Bone, K. (2003). A clinical guide to blending liquid herbs: Herbal formulations for the individual patient. Edinburgh [u.a.: Churchill Livingstone. (Pg. 127-129).
    7. Xing, J., Song, G., Deng, J., Jiang, L., Xiong, P., Yang, B., & Liu, S. (2015). Antitumor Effects and Mechanism of Novel Emodin Rhamnoside Derivatives against Human Cancer Cells In Vitro. PLOS ONE, 10(12), e0144781. doi:10.1371/journal.pone.0144781
    8. Xin-hua Wang, Shu-ying Wu, Yong-su Zhen. (2004). Inhibitory effects of emodin on angiogenesis. Yao Xue Xue Bao. 39(4):254–258. PMID: 15303652 8.
    9. Kaneshiro T, Morioka T, Inamine M, Kinjo T, Arakaki J, Chiba I. (2006). Anthraquinone derivative emodin inhibits tumor-associated angiogenesis through inhibition of extra-cellular signal-regulated kinase 1/2 phosphorylation.Eur J Pharmacol. Eur J Pharmacol. 553 (1–3):46–53. PMID: 17056031
    10. Subramaniam A, Loo SY, Rajendran P, Manu KA, Perumal E, Li F. (2013). An anthraquinone derivative, emodin sensitives hepatocellular carcinoma cells to TRAIL induced apoptosis through the induction of death receptors and downregulation of cell survival protein. Apoptosis. 18(10):1175–87. doi: 10.1007/s10495-013-0851-5 PMID: 23700228
    11. Zhang W, Chen H, Liu DL, Li H, Luo J, Zhang JH. (2013). Emodin sensitizes the gemcitabine-resistant cell line Bxpc- 3/Gem to gemcitabine via downregulation of NF-κB and its regulated targets. Int J Oncol. 42(4):1189–96. doi: 10.3892/ijo.2013.1839 PMID: 23440366
    12. Ko JC, Su YJ, Lin ST, Jhan JY, Ciou SC, Cheng CM. (2010). Emodin enhances cisplatin- induced cytotoxicity via down- regulation of ERCC1 and inactivation of ERK1/2. Lung Cancer. 69(2):155– 64. doi: 10.1016/j.lungcan.2009.10.013 PMID: 19962780
    13. Chen H, Wei W, Guo Y, Liu A, Tong H, Wang Z, (2011). Enhanced effect of gemcitabine by emodin against pancreatic cancer in vivo via cytochrome C-regulated apoptosis. Oncol Rep. 25 (5):1253–61. doi: 10.3892/or.2011.1174
    14. Muto A, Hori M, Sasaki Y, Saitoh A, Yasuda I, Maekawa T, (2007). Emodin has a cytotoxic activity against human multiple myeloma as a Janus-activated kinase 2 inhibitor. Mol Cancer Ther. 6 (3):987–94. PMID: 17363492
    15. Chun-Guang W, Jun-Qing Y, Bei-Zhong L, Dan-Ting J, Chong W, Liang Z, (2010). Anti- tumor activity of emodin against human chronic myelocytic leukemia K562 cell lines in vitro and vivo. Eur J Pharmacol. Eur J Pharmacol. 627(1–3):33–41. doi: 10.1016/j.ejphar.2009.10.035 PMID: 19857484
    16. Lai JM, Chang JT, Wen CL, Hsu SL. (2009). Emodin induces a reactive oxygen species- dependent and ATMp53-Bax mediated cytotoxicity in lung cancer cells. Eur J Pharmacol. 623(1–3):1–9. doi: 10.1016/j.ejphar.2009.08.031 PMID: 19744477
    17. Ko JC, Su YJ, Lin ST, Jhan JY, Ciou SC, Cheng CM, (2010). Suppression of ERCC1 and Rad51 Expression through ERK1/2 Inactivation is Essential in Emodin-Mediated Cytotoxicity in Human Non-Small Cell Lung Cancer Cells. Biochem Pharmacol. 79(4):655–64. doi: 10.1016/j.bcp.2009.09. 024 PMID: 19799875
    18. Lin He, Juanjuan Bi, Qian Guo, Yin Yu, Xiufeng Ye, Wei Li. (2011). Emodin down-regulatesERCC1 and Rad51 and inhibits proliferation in non-small cell lung cancer cells. J Third Mil Univ. 33(22):2370–2375.
    19. Ma YS, Weng SW, Lin MW, Lu CC, Chiang JH, Yang JS, (2012). Antitumor effects of emodin on LS1034 human colon cancer cells in vitro and in vivo: roles of apoptotic cell death and LS1034 tumor xeno grafts model. Food Chem Toxicol. 50(5):1271–8. doi: 10.1016/j.fct.2012.01.033 PMID: 22321733
    20. Damodharan U, Ganesan R, Radhakrishnan UC. (2011). Expression of MMP2 and MMP9 (gelatinases A and B) in human colon cancer cells. Appl Biochem Biotechnol. 165(5–6):1245–52. doi: 10.1007/ s12010-011-9342-8 PMID: 21866366
    21. Wang W, Sun YP, Huang XZ, He M, Chen YY, Shi GY, (2010). Emodin enhances sensitivity of gallbladder cancer cells to platinum drugs via glutathion depletion and MRP1 downregulation. Biochem Pharmacol. 2010 Apr 15; 79(8):1134–40. doi: 10.1016/j.bcp.2009.12.006 PMID: 20005210
    22. Li XX, Dong Y, Wang W, Wang HL, Chen YY, Shi GY, (2013). Emodin as an effective agent in targeting cancer stem- like side population cells of gallbladder carcinoma. Stem Cells Dev. 22 (4):554–66. doi: 10.1089/scd.2011.0709 PMID: 22974371
    23. Li XX, Wang J, Wang HL, Wang W, Yin XB, Li QW, (2012). Characterization of cancer stem-like cells derived from a side population of a human gallbladder carcinoma cell line, SGC-996. Biochem Biophys Res Commun. 419(4):728–34. doi: 10.1016/j.bbrc.2012.02.090 PMID: 22387537
    24. Liu JX, Zhang JH, Li HH, Lai FJ, Chen KJ, Chen H, (2012). Emodin induces Panc-1 cell apoptosis via declining the mitochondrial membrane potential. Oncol Rep. 28(6): 1991–6. doi: 10.3892/or. 2012.2042 PMID: 22992976
    25. Liu A, Chen H, Wei W, Ye S, Liao W, Gong J, (2011). Antiproliferative and antimetastatic effects of emodin on human pancreatic cancer. Oncol Rep. 26(1):81–9. doi: 10.3892/or.2011.1257 PMID: 21491088
    26. Liu DL, Bu H, Li H, Chen H, Guo HC, Wang ZH, (2012). Emodin reverses gemcitabine resistance in pancreatic cancer cells via the mitochondrial apoptosis pathway in vitro. Int J Oncol. 40(4):1049– 57. doi: 10.3892/ijo.2011.1285 PMID: 22159556
    27. Hsu CM, Hsu YA, Tsai Y, Shieh FK, Huang SH, Wan L, (2010). Emodin inhibits the growth of hepatoma cells: finding the common anti-cancer pathway using Huh7, Hep3B, and HepG2 cells. Biochem Biophys Res Commun. 392(4):473–8. doi: 10.1016/j.bbrc.2009.10.153 PMID: 19895793
    28. Cai J, Niu X, Chen Y, Hu Q, Shi G, Wu H, (2008). Emodin-induced generation of reactive oxygen species inhibits RhoA activation to sensitize gastric carcinoma cells to anoikis. Neoplasia. 10(1):41– 51. PMID: 18231637
    29. Cha TL, Qiu L, Chen CT, Wen Y, Hung MC. (2005). Emodin down-regulates androgen receptor and inhibits prostate cancer cell growth. Cancer Res. 65(6):2287–95. PMID: 15781642
    30. Huang Z, Chen G, Shi P. (2008). Emodin-induced apoptosis in human breast cancer BCap-37 cells through the mitochondrial signaling pathway. Arch Pharm Res. 31(6): 742–8. doi: 10.1007/s12272-001- 1221-6 PMID: 18563356
    31. Huang Z, Chen G, Shi P. (2009). Effects of emodin on the gene expression profiling of human breast carcinoma cells. Cancer Detect Prev 32: 286–291, doi: 10.1016/j.cdp.2008.12.003 PMID: 19185431
    32. Wang S, Chen T, Chen R, Hu Y, Chen M, Wang Y. (2012). Emodin loaded solid lipid nanoparticles: preparation, characterization and antitumor activity studies. Int J Pharm. 430(1–2):238–46. doi: 10. 1016/j.ijpharm.2012.03.027 PMID: 22465546
    33. Yaoxian W, Hui Y, Yunyan Z, Yanqin L, Xin G, Xiaoke W. (2013). Emodin induces apoptosis of human cervical cancer hela cells via intrinsic mitochondrial and extrinsic death receptor pathway. Cancer Cell Int. 13(1):71. doi: 10.1186/1475-2867-13-71 PMID: 23866157
    34. The Sunlight Experiment. (2016, August). The Sunlight Experiment. Retrieved August 2, 2016, from http://thesunlightexperiment.com/rhubarb
    35. Yan YY, Fu LW, Zhang W, Ma HS, Ma CG, Liang YJ, (2014). Emodin azide methyl anthraquinone derivative induced G0/ G1 arrest in HER2/neu-overexpressing MDA- MB-453 breast cancer cells. J BUON. 19(3):650–5.
    36. Yan Y, Su X, Liang Y, Zhang J, Shi C, Lu Y, (2008). Emodin azide methyl anthraquinone derivative triggers mitochondrial-dependent cell apoptosis involving in caspase-8- mediated Bid cleavage. Mol Cancer Ther. 7(6):1688–97. doi: 10.1158/1535-7163.MCT-07-2362 PMID: 18566240
    37. Li J, Chen Y, Chen B, Chen C, Qiu B, Zheng Z, (2015). Inhibition of 32Dp210 cells harboring T315I mutation by a novel derivative of emodin correlates with down-regulation of BCR-ABL and its downstream signaling pathways. J Cancer Res Clin Oncol. 141(2):283–93. doi: 10.1007/s00432-014- 1820-2
    38. Wagner H, Demuth G. (1974). Investigations of the anthrachinone-glycosides from Rhamnus frangula L. 3. 6-O (D-apiofuranosyl)-1,6,8-trihydroxy-3-methyl-anthrachinone, a new glycoside (frangulin B) from the bark of Rhamnus frangula L. (author's transl). Z Naturforsch C. 29(5):204–8.
    39. Lin C, Chung M, Lu C. (1990). Anthraquinones From Rhamnus Formosana[J]. Phytochemistry. 29 (12):3903–3905.
    40. Lin CN, Chung MI, Gan KH, Lu CM. (1991). Flavonol and anthraquinone glycosides from Rhamnus formosana. Phytochemistry. 30(9):3103–6. PMID: 1367798
    41. Mai LP, Guéritte F, Dumontet V, Tri MV, Hill B, Thoison O, (2001). Cytotoxicity of Rhamnosylanthraquinones and Rhamnosylanthrones From Rhamnus Nepalensis[J]. J Nat Prod. 64(9):1162–8. PMID: 11575949