報告者：fellow 1 陳筱惠
指導醫師：方基存教授
Kidney Injury, Electrolyte and Acid-Base Abnormalities Associated With Use of
Alternative Medicine Products
April 2009 Dialysis & Transplantation
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Anthraquinones: laxatives
Parsley (Petroselinum
crispum) and juniper (duniperus communis):
diuretics
Licorice: sodium/water retention, potassium
loss, hypertension
Alfalfa (Medicago sativa), dandelion
(Taraxaturn o~cinale), horsetail (Equisetum
arvense), and nettle (Urtica dioica): contain
potassium Medicinal Herb Use and the Renal Patient
Jourual of Renal Nutritwn, Vol 8, No 1 (January), 1998: pp 40-42
Genus: Glycyrrhiza (Leguminosae)
About 30 species: G. glabra, G. uralensis, G. inflata,
G. aspera, G. Korshinskyi and G. eurycarpa, G. glabra
 Other common names: sweet root
 Description:
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 Perennial herb with sweet tasting roots
 Native to the Mediterranean, the Mideast, Russia, and
Asia
 Used as flavoring, sweetener, and medicinal herb
Medicinal uses of licorice through the millennia: the good and plenty of it
Molecular and Cellular Endocrinology, 78 (1991) 1-6
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Used part: roots, rhizomes
Known active constituents:
 Triterpenoid saponins: mostly glycyrrhizin, which is
50 times sweeter than sugar
 Flavonoids
 Isoflavones
 Coumarin derivatives
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Glycyrrhizin is hydrolyzed to glycyrrhetinic
acid in the intestine by intestional bacteria.
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Glycyrrhizin:
 Peak serum concentration: less 4 hours
 Not detectable at 96 hours
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Glycyrrhetinic acid:
 Peak serum concentration: 24hour
 Still detectable in 72 hour
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Excretion: mostly by GI tract, 2% metabolite
in urine
Phytother. Res. 22, 709–724 (2008)
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Anti-inflammatory activities:
 Inhibit glucocorticoid metabolism and potentiates
their effects
 Inhibit classical complement pathway activation
 Inhibit reactive oxygen species (ROS) generation
by neutrophils
 COX-2 inhibition??
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Antimicrobial and antiviral activities:
 Restore the effects of oxacillin and β- lactam
antibiotic against MRSA
 E. coli, E. aerogenes, K. pneumoniae
 B. subtilis
 Helicobacter pylori
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Antioxidative activities:
 Preventing microsomal lipid peroxidation induced
by Fe (III)-ADP/NADPH and licochalcone B, D
 Inhibited lipid peroxidation in rat liver
 Antioxidant toward LDL oxidation
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Hepatoprotective activities :
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Gastrointestinal activities:
 Antiulcer properties, as effectively as an H2
blocker
 Raising the local concentration of prostaglandins
that promote mucous secretion and cell
proliferation in the stomach
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Antitumor activities:
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Central nervous system activities:
 Inhibit serotonin reuptake, antidepressant activity in both
the forced swim test (FST) and tail suspension test (TST) in
mice
 Anticonvulsant effect in PTZ and lithiumpilocarpineinduced convulsion models
 Protective effects in cerebral ischemia-reperfusion injury
in rats
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Cardiovascular activities:
 Antiplatelet aggregation effect
 Vasorelaxant effect
 Anti-angiogenic effect
 Estrogen-like activities, modulate vascular injury
and atherogenesis
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Immunological activities:
 Inducer of type 2 antagonistic CD41 T cells in in vivo and in
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vitro studies
Stimulate macrophage-derived NO production
Up-regulate iNOS expression through nuclear factor kB
(NF- kB) transactivation in murine macrophages
Induce interferon activity and augment natural killer cell
activity
Inhibitory effects on TNF-alpha-induced IL-8 production in
intestinal epithelial cells
Anticomplementary activity and mitogenic activity
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Licorice toxicity: unknown prevalence, but
not common
 In Denmark, average licorice consumption 2kg per
person per year, no epidemics of licorice toxicity
have been reported
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Almost all reported cases of licorice-induced
problems from licorice containing liqueurs,
candies, gum, laxatives, or chewing tobacco
rather than from the use of licorice as
medicine. In chinese medicine licorice is
always used as part of mixture, and the
synergistic effects of mixtures, as well as
perhaps dose differences, may prevent
problems.
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Licorice induced hypermineralocorticoidism
NEJM Vol. 325 No.17 1223-1227
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How to Diagnose and Treat a Licorice-induced
Syndrome with Findings Similar to that of Primary
Hyperaldosteronism
Internal Medicine Vol. 43, No. 1 (January 2004)
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Pseudoaldosteronism due to the concurrent use of
two herbal medicines containing glycyrrhizin:
interaction of glycyrrhizin with angiotensionconverting enzyme inhibitor
Clin Exp Nephrol (2006) 10:131–135
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Pseudohyperaldosteronism, Liquorice, and
Hypertension
THE Journal of Clinical Hypertension
VOL. 10 NO. 2 February 2008
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The previous theory: the binding of its active
components, glycyrrhizic acid, to
mineralocorticoid receptos
Argument:
 The affinity of glycyrrhetinic acid for
mineralocorticoid receptor is 0.01% of that of
aldosterone.
 Licorice or glycyrrhetinic acid dose not have
mineralcorticoid effects in patients with Addison’s
disease or adrenalectomized rats unless cortisone
or hydrocortisone is administered concomitantly.
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Accepted mechanism now: inhibit 11Bhydroxysteroid dehydrogenase
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The clinical profile of liquorice-induced
pseudohyperaldosteronism is similar to the
syndrome of apparent mineralocorticoid
excess.
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Subjects with history of
chronic licorice ingestion
were found that reninaldosterone axis was
suppressed. Normal
function resumed within
2~4 months after licorice
was discontinued.
The daily dose of glycyrrhizin
that induces
pseudoaldosteronism ranges
from 20mg to 586mg.
 The reported durations of use
have ranged from 6 days to 15
years.
 Artificial liquorice flavoring
agents not containing
glycyrrhizin would not
influence mineralocorticoid
metabolism.
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Disease development has sometimes been
triggered by the concomitant use of
glycyrrhizin with insulin, diuretics, or oral
contraceptives.
The mineralocorticoid effects of glycyrrhizin
had been hidden by the concurrent use of an
ACE inhibitor.
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Treatment of this syndrome:
 Cessation of licorice
 Potassium-sparing diuretic, such as
spironolactone
 Low salt diet
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On encountering clinical manifestations
suggesting mineralocorticoid excess 
 Liddle syndrome
 Cushing syndrome
 Conn syndrome
 Apparent mineralocorticoid excess (AME),
Deoxycorticosterone (DOC)-producing tumor
 Licorice-induced pseudoaldosteronism