Rhamnaceae Tumorigenicity

Several anthranoid derivatives (notably the aglycones aloe-

GENERAL INFORMATION
The genera in the family of Rhamnaceae (Table 1) include
buckthorn and jujube.
Rhamnus purshiana
The bark of Rhamnus purshiana (cascara sagrada)
contains laxative anthranoid derivatives, which occur pri-
marily in various laxative herbs (such as aloe, cascara
sagrada, medicinal rhubarb, and senna) in the form of
free anthraquinones, anthrones, dianthrones, and/or
O- and C-glycosides derived from these substances.
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. They can be distrib-
uted into breast milk, but not always in sufficient amounts
to affect the suckling infant. Long-term use can result in
electrolyte disturbances and in atony and dilatation of the
colon.
Respiratory
Cascara sagrada can cause IgE-mediated occupational
asthma and rhinitis [1].
emodin, chrysophanol, emodin, and physicon) are geno-
toxic in bacterial and/or mammalian test systems [3], and
two anthranoid compounds (the synthetic laxative dantron
and the naturally occurring l-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 [4]. The German health authorities therefore
restricted the indication of herbal anthranoid laxatives to
constipation which has not responded to bulk-forming ther-
apy (which rules out their inclusion in slimming aids). In
addition, they imposed restrictions on the laxative use of
anthranoid-containing herbs (for example not to be used
for more than 12 weeks without medical advice, not to be
used in children under 12 years of age, and not to be used
during pregnancy and lactation) [4,5].
Zizyphus jujuba
The fruit of Zizyphus jujuba (dazao) is often consumed in
Eastern Asia as food or as a tonic and sedative and in the
management of chronic constipation [6]. Angioedema has
been described after the oral ingestion of dazao [7]. Mild
diarrhea has been described when Zizyphus jujuba was
used to treat neonatal jaundice [8].

Liver
Cascara sagrada has been reported to cause liver damage
[2].

A 48-year-old man developed cholestatic hepatitis and hyper-
tension shortly after he started to use the herbal laxative cas-
cara sagrada. He took one capsule (425 mg of aged cascara
sagrada bark) tds for 3 days and subsequently developed right
upper quadrant pain, nausea, abdominal bloating, anorexia,
and jaundice. The cascara was withdrawn, but his symptoms
persisted and his liver function tests were abnormal. One week
later, he developed ascites and jaundice and underwent liver
biopsy, which showed moderately severe portal inflammation,
intracanalicular bile stasis, portal bridging fibrosis, and mild
steatosis. He gradually improved without specific treatment
and 3 months later his ascites and jaundice had resolved.
REFERENCES
[1] Giavina-Bianchi PF Jr, Castro FF, Machado ML, Duarte AJ.
Occupational respiratory allergic disease induced by Passi-
flora alata and Rhamnus purshiana. Ann Allergy Asthma
Immunol 1997; 79(5): 44954.
[2] Nadir A, Reddy D, Van Thiel DH. Cascara sagrada-induced
intrahepatic cholestasis causing portal hypertension: case
report and review of herbal hepatotoxicity. Am J Gastro-
enterol 2000; 95(12): 36347.
[3] Brown JP, Dietrich PS, Brown RJ. Frame-shift mutagenicity
of certain naturally occurring phenolic compounds in the
Salmonella/microsome test: activation of anthraquinone
and flavonol glycosides by gut bacterial enzymes. Biochem
Soc Trans 1977; 5(5): 148992.

Table 1 Genera of Rhamnaceae

Adolphia (prickbush) Frangula (buckthorn) Paliurus (Jeruselem thorn)

Alphitonia (alphitonia) Gouania (chewstick) Reynosia (darlingplum)
Auerodendron (auerodendron) Hovenia (hovenia) Rhamnus (buckthorn)
Berchemia (supplejack) Karwinskia (karwinskia) Sageretia (mock buckthorn)
Ceanothus (ceanothus) Krugiodendron (krugiodendron) Smythea
Colubrina (nakedwood) Maesopsis (umbrella-tree) Ziziphus (jujube)
Condalia (snakewood)

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