LICORICE AND SYNDROME OF APPARENT MINERAL CORTICOID EXCESS
Licorice originates from the root of Glycyrrhiza glabra, which has a herbal ingredient, glycyrrhizic acid, and has a mineralocorticoid-like effect. Chronic intake of licorice induces a syndrome similar to that found in primary hyperaldosteronism(1). Excessive intake of licorice may cause a hypermineralocorticoidism-like syndrome characterized by sodium and water retention, hypertension, edema, hypokalemia, metabolic alkalosis, low-renin activity, and hypoaldosteronism. Licorice induces hypokalemia resulted in rhabdomyolysis(2). The rhabdomyolysis along with the effect of licorice led to secondary hypocalcaemia, which in turn triggered secondary hyperparathyroidism. This might have had a phosphaturic effect that caused hypophosphatemia, further worsening rhabdomyolysis.
Licorice ingestion, as well as mutations in the HSD11B2 gene, inhibits 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) enzyme activity, causing the syndrome of apparent mineral corticoid excess (AME). It can produce overt hypertension in an individual without medical history of hypertension who is heterozygous for wild-type and mutant HSD11B2 genes(3). Licorice ingestion is an environmental risk factor for hypertension or AME state in patients with a mutation in HSD11B2. Carrying a mutation in HSD11B2 is, conversely, a genetic risk factor for licorice-induced hypertension or AME state. Herbal medicine containing licorice may, therefore, be contraindicated in patients with an HSD11B2 mutation(3).
(1) Licorice induced hypokalemia, edema, and thrombocytopenia 2012
(2) Licorice-related rhabdomyolysis: a big price for a sweet tooth 2012
(3) Herbal Medicine Containing Licorice May Be Contraindicated for a Patient with an HSD11B2 Mutation 2011
LICORICE AND OBESITY
Diacylglycerol acyltransferase (DGAT) catalyzes triglyceride synthesis in the glycerol phosphate pathway(1). It has relations with the excess supply and accumulation of triglycerides. Therefore, DGAT inhibitors may act as a potential therapy for obesity and type 2 diabetes. Five flavonoids were isolated from the ethanol extracts of licorice roots, using an in vitro DGAT inhibitory assay. One isoprenyl flavonoid showed most potential inhibition of DGAT on five flavonoids.
Licorice flavonoid oil (LFO) has been reported to minimize body weight and visceral adipose tissue gain in obese mice and to result in a decrease in body weight and body fat in humans(2). Specifically, LFO has been shown to posses nutrigenomic properties that effect cellular pathways with regards to decreasing the mRNA levels of rate-limiting enzymes involved in the epatic fatty acid synthetic pathway, while increasing the mRNA levels of a rate-limiting enzyme in the hepatic fatty acid oxidative pathway.
(1) Inhibitory Activity of Diacylglycerol Acyltransferase by Glabrol Isolated from the Roots of Licorice 2010
(2) A dual investigation of the effect of dietary supplementation with licorice flavinoid oil on anthropometric and biochemical markers of health and adiposity 2011
LICORICE AND ESTROGENS
The roots of licorice are a rich source of flavonoids, in particular, prenylated flavonoids, such as the isoflavan glabridin and the isoflavene glabrene. Fractionation of an ethyl acetate extract from licorice root by centrifugal partitioning chromatography yielded 51 fractions.
One third of the fractions displayed estrogenic activity towards either one or both estrogen receptors (ERs; ERα and ERβ). Glabrene-rich fractions displayed an estrogenic response, predominantly to the ERα. Surprisingly, glabridin did not exert agonistic activity to both ER subtypes. Several fractions displayed higher responses than the maximum response obtained with the reference compound, the natural hormone 17β-estradiol (E2). The estrogenic activities of all fractions, including this so-called superinduction, were clearly ER-mediated, as the estrogenic response was inhibited by 20–60% by known ER antagonists. Most fractions displaying superinduction were rich in flavonoids with single prenylation. Glabridin displayed ERα-selective antagonism, similar to the ERα-selective antagonist RU 58668. Whereas glabridin was able to reduce the estrogenic response of E2 by approximately 80% at 6 × 10−6 M, glabrene-rich fractions only exhibited agonistic responses, preferentially on ERα.
Agonistic and Antagonistic estrogens in licorice root 2011
LICORICE AND ALZHEIMER'S DISEASE
Alzheimer’s disease is characterized by neuronal loss and the presence of extracellular senile plaques whose major constituent is amyloid-β peptide (Aβ). Some studies investigated the effects of a water extract of licorice (Glycyrrhiza uralensis) (GWE) on Aβ25-35-induced apoptosis in PC12 cells. Exposure to Aβ25-35-induced apoptosis, such as decreased mitochondrial transmembrane potential, increased lipid peroxide formation, decreased antiapoptotic bcl-2 and poly(ADP-ribose) polymerase, and elevated proapoptotic bax, and caspase-3. However, treatment of GWE effectively decreased cell deaths evoked by Aβ25-35.This result suggests that GWE exerts protective effect against apoptotic neuronal cell death induced by Aβ fragments. The extract of licorice binds alpha and beta estrogen receptors. They are very close in structure, but beta estrogen receptors are more localized in the brain and have different effects on brain cells. Studies are testing the ability of plant-derived phytoestrogens, such as licorice, to help nerve cells survive in neurodegenerative diseases and keep neurons connected and functional.
Effect of Licorice (glycyrrhiza uralensis fisch) on amyloid-β-induced neurotoxicity in PC12 cells 2010
Liquorice root may protect brain cells 2010
LICORICE AND ANTIBACTERIAL EFFECT
Aqueous extracts from the roots of Glycyrrhiza glabra are widely used for treatment of stomach ulcer. The clinical proven effects are related to the presence of anti-inflammatory 12-keto-triterpensaponins in the extracts. Apart from that the influence of Glycyrrhiza glabra extract on the bacterial adhesion of Helicobacter pylori to stomach tissue was to be investigated. Raw polysaccharides from Glycyrrhiza glabra were shown to have strong antiadhesive effects against Porphyromonas gingivalis.
Aqueous extracts and polysaccharides from liquorice roots (Glycyrrhiza glabra L.) inhibit adhesion of Helicobacter pylori to human gastric mucosa 2009
LICORICE AND CONSUMPION
Compared to other countries, licorice consumption in the Netherlands is very high; on average it is 2 kg per person annually. Also licorice tea is growing in popularity. Both products contain glycyrrhizin. a daily consumption of glycyrrhetinic acid of 95 mg or more caused an increase in blood pressure. A practical guideline for an acceptable daily intake of glycyrrhetinic acid seems to be 9.5 mg a day. This means no more than 10-30 g licorice and no more than half a cup of liquorice tea a day. On diagnosing hypertension, the effects of licorice and licorice tea consumption on blood pressure should be kept in mind.
Hypertension due to liquorice and liquorice tea consumption 2007