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 ProductsApril 2009 Dialysis & Transplantation

Anthraquinones: laxativesParsley (Petroselinumcrispum) and juniper (duniperus

communis): diureticsLicorice: sodium/water retention,

potassium loss, hypertensionAlfalfa (Medicago sativa), dandelion

(Taraxaturn o~cinale), horsetail (Equisetum arvense), and nettle (Urtica dioica): contain potassium

Medicinal Herb Use and the Renal PatientJourual 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:

Perennial herb with sweet tasting roots Native to the Mediterranean, the Mideast,

Russia, and Asia Used as flavoring, sweetener, and medicinal

herbMedicinal uses of licorice through the millennia: the good and plenty of itMolecular and Cellular Endocrinology, 78 (1991) 1-6

Used part: roots, rhizomesKnown active constituents:

Triterpenoid saponins: mostly glycyrrhizin, which is 50 times sweeter than sugar

Flavonoids Isoflavones Coumarin derivatives

Glycyrrhizin is hydrolyzed to glycyrrhetinic acid in the intestine by intestional bacteria.

Glycyrrhizin: Peak serum concentration: less 4 hours Not detectable at 96 hours

Glycyrrhetinic acid: Peak serum concentration: 24hour Still detectable in 72 hour

Excretion: mostly by GI tract, 2% metabolite in urine

Phytother. Res. 22, 709–724 (2008)

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??

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

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

Hepatoprotective activities :

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

Antitumor activities:

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 lithiumpilocarpine- induced convulsion models

Protective effects in cerebral ischemia-reperfusion injury in rats

Cardiovascular activities: Antiplatelet aggregation effect Vasorelaxant effect Anti-angiogenic effect Estrogen-like activities, modulate

vascular injury and atherogenesis

Immunological activities: Inducer of type 2 antagonistic CD41 T cells in in

vivo and in 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

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

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.

Licorice induced hypermineralocorticoidismNEJM Vol. 325 No.17 1223-1227

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) Pseudoaldosteronism due to the concurrent use of

two herbal medicines containing glycyrrhizin: interaction of glycyrrhizin with angiotension-converting enzyme inhibitor

Clin Exp Nephrol (2006) 10:131–135 Pseudohyperaldosteronism, Liquorice, and

Hypertension THE Journal of Clinical HypertensionVOL. 10 NO. 2 February 2008

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.

Accepted mechanism now: inhibit 11B-hydroxysteroid dehydrogenase

The clinical profile of liquorice-induced pseudohyperaldosteronism is similar to the syndrome of apparent mineralocorticoid excess.

Subjects with history of chronic licorice ingestion were found that renin-aldosterone 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.

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.

Treatment of this syndrome: Cessation of licorice Potassium-sparing diuretic, such as

spironolactone Low salt diet

On encountering clinical manifestations suggesting mineralocorticoid excess Liddle syndrome Cushing syndrome Conn syndrome Apparent mineralocorticoid excess (AME),

Deoxycorticosterone (DOC)-producing tumor

Licorice-induced pseudoaldosteronism