A Licorice Ethanolic Extract with Peroxisome Proliferator-Activated Receptor-γ Ligand-Binding Activity Affects Diabetes in KK-Ay Mice, Abdominal Obesity in Diet-Induced Obese C57BL Mice and Hypertension in Spontaneously Hypertensive Rats

Abstract

The metabolic syndrome, including type 2 diabetes, insulin resistance, obesity/abdominal obesity, hypertension and dyslipidemia, is a major public health problem. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands such as thiazolidinediones are effective against this syndrome. In this study, we showed that nonaqueous fractions of licorice (Glycyrrhiza uralensis Fisher) extracted with ethanol, ethyl acetate and acetone, but not an aqueous extract, had PPAR-gamma ligand-binding activity with a GAL4-PPAR-gamma chimera assay. Some prenylflavonoids including glycycoumarin, glycyrin, dehydroglyasperin C and dehydroglyasperin D, a newly found compound, were identified as active compounds with PPAR-gamma ligand-binding activity in the nonaqueous fraction of licorice. A licorice ethanolic extract contained these four active compounds at a total concentration of 16.7 g/100 g extract. Feeding the licorice ethanolic extract at 0.1-0.3 g/100 g diet [approximately 100 to 300 mg/(kg body x d)] for 4 wk decreased (P < 0.05) blood glucose level in younger (6 wk old) and older (13 wk old) diabetic KK-Ay mice and reduced (P < 0.05) weights of intra-abdominal adipose tissues in high fat diet-induced obese C57BL mice. An increase in blood pressure in spontaneously hypertensive rats was suppressed (P < 0.01) by 3 wk of oral administration of the licorice ethanolic extract at 300 mg/(kg body x d). These findings indicate that licorice ethanolic extract is effective in preventing and ameliorating diabetes, ameliorating abdominal obesity and preventing hypertension, and suggest that licorice ethanolic extract would be effective in preventing and/or ameliorating the metabolic syndrome.

Investigation of the Anti-Obesity Action of Licorice Flavonoid Oil in Diet-Induced Obese Rats

“…9,10) Licorice flavonoid oil (LFO), which contains hydrophobic flavonoids from G. glabra LINNE, is a new ingredient for functional foods. [9][10][11][12] We recently found that LFO decreases the size of hepatic lipid droplets, which are mainly composed of triglyceride (TG), and abdominal adipose tissue weight in diet-induced obese mice. 10) It is well-known that TG is synthesized in the liver, secreted into the blood-stream, and transported to the peripheral organs, including the adipose tissues.…”

Bile acid activated receptors are targets for regulation of integrity of gastrointestinal mucosa

“…Glycyrrhizic acid, the main active ingredient of licorice root extracts [57][58][59], is a triterpenoid glycosidic saponin used as a sweetener. Glycyrrhizic acid is converted in glycyrrhetinic acid in the small intestine by the activity of the intestinal microbiota and undergoes an extensive metabolic biotransformation in the liver [57][58][59]. Thus, glycyrrhizic acid is not detectable in the blood.…”

“…Despite their beneficial effects on ulcer healing, extracts of licorice roots are known to produce severe hypertension and hypokalemia [57][58][59]. This mineralcorticoid-like syndrome is primarily caused by the inhibition of 11b-hydroxysteroid dehydrogenase, an enzyme that inactivates intracellular glucocorticoids in mineralocorticoid-responsive organs, such as the kidney, increasing relative levels of cortisol, which stimulates aldosterone receptors, leading to a functional mineralocorticoid excess [57][58][59].…”

“…This mineralcorticoid-like syndrome is primarily caused by the inhibition of 11b-hydroxysteroid dehydrogenase, an enzyme that inactivates intracellular glucocorticoids in mineralocorticoid-responsive organs, such as the kidney, increasing relative levels of cortisol, which stimulates aldosterone receptors, leading to a functional mineralocorticoid excess [57][58][59]. Our data indicate that in addition to inhibition of 11b-hydroxysteroid dehydrogenase or activation of estrogen receptors or peroxisome-proliferator-activated receptors [60], glycyrrhizic acid might also function as an FXR ligand/ modulator.…”

Formulation and Evaluation of Herbal Fairness Cream Comprising Hydroalcoholic Extracts of Pleurotus ostreatus, Glycyrrhiza glabra and Camellia sinensis

“…[13][14][15] . Glycyrrhiza glabra are reported to be used as sweetners, flavorings and as herbal medicine and also used for improving health, detoxification, antioxidant property and cures for injury [16][17][18][19][20] . Camellia sinensis commonly known as green tea reported to have anticarcinogenic, antiviral, antioxidant property, antibacterial, antigentoxic activity etc [21][22][23][24] .…”