Licorice Flavonoids Suppress Abdominal Fat Accumulation and Increase in Blood Glucose Level in Obese Diabetic KK-Ay Mice

Abstract

Licorice, the root of the leguminous Glycyrrhiza plant species, has been used for over 4000 years since ancient Egyptian times, and is one of the most frequently employed botanicals in traditional medicines.1) There are several species of licorice, including Glycyrrhiza uralensis FISCHER, G. glabra LINNE and G. inflata BATALIN, and they include species-specific flavonoids.1,2) Our previous study showed that nonaqueous fractions of G. uralensis have peroxisome proliferator-activated receptor-g (PPAR-g) ligand-binding activity, and that the active compounds in the nonaqueous fractions are prenylflavonoids such as glycycoumarin, glycyrin, dehydroglyasperin C and dehydroglyasperin D.3,4) A licorice ethanolic extract from G. uralensis has been found to be effective in preventing and/or ameliorating diabetes, abdominal obesity and hypertension in three animal models. 3)Glabridin in G. glabra, one of the most frequently studied flavonoids of licorice, has antinephritic and radical scavenging activities, 5) exhibits inhibition of serotonin re-uptake, 6) has anti-Helicobacter pylori activity, 7) estrogen-like activity, 8) and antioxidative activity, [9][10][11][12][13][14] and inhibits melanogenesis and inflammation. 15)The metabolic syndrome is a cluster of several metabolic and cardiovascular disease risk factors including central obesity, dyslipidemia, glucose intolerance, insulin resistance and hypertension, 16) and is becoming recognized as a major public health problem. Central obesity, so-called abdominal obesity or visceral fat obesity, is believed to elicit insulin resistance, which is a major cause of the metabolic syndrome. Thiazolidinedione drugs such as troglitazone, pioglitazone and rosiglitazone, which have been approved for type 2 diabetes, 17,18) have potent PPAR-g agonistic activity and stimulate adipocyte differentiation through PPAR-g activation. 19,20) Many studies of these drugs indicate that PPAR-g agonists have significant effects on the metabolic syndrome. [21][22][23] In this study, we demonstrated the effects of licorice hydrophobic flavonoids from G. glabra on abdominal fat accumulation and blood glucose level in obese diabetic KK-A y mice, and elucidated their mechanisms of action by showing that they induce differentiation of human adipocytes. MATERIALS AND METHODS Preparation of Licorice Flavonoid Oil (LFO)The roots of licorice, Glycyrrhiza glabra LINNE, harvested in Afganistan were extracted with 5 volumes of 95% ethanol twice, and licorice ethanolic extract was obtained by filtration and concentration. The licorice ethanolic extract was dissolved in medium-chain triglycerides (MCT; C8 : C10ϭ 99 : 1; Riken Vitamin Co., Ltd., Tokyo, Japan), mixed, evaporated to remove ethanol, and filtered. The obtained oil including licorice flavonoids was used as LFO, after adjusting glabridin concentration to 1.2% (w/w) in oil. A standard for glabridin, a major compound of licorice flavonoid, was purchased from Wako Pure Chemical Inductries, Ltd. (Osaka, Japan).Animal Experiment Female genetically type 2...

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

“…7,8) There are several species of licorice, including Glycyrrhiza uralensis FISCHER, G. glabra LINNE, and G. inflate BATALIN, and each of which contains speciesspecific flavonoids. 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.…”

Dietary Antioxidants: From Micronutrients and Phytochemicals to Enzymes - Preventive Effects on Early Atherosclerosis and Obesity

“…More recently, Wolfram et al (2005) showed that supplementation with Teavigo ® , a green tea extract containing about 94% EGCG, abolishes diet-induced obesity and claimed that this was a valuable natural treatment option for obesity. Nakagawa et al (2004) demonstrated the abdominal fat lowering and hypoglycemic effects of licorice hydrophobic flavonoids in obese diabetic mice and elucidated their mechanisms of action by showing that they induce differentiation of human adipocytes. Sugiyama et al (2007) suggested that oligomeric procyanidin was the main contributor to the effect of apple polyphenol extract on inhibiting triglyceride absorption in mice and humans.…”

Enhancement of Fat Oxidation by Licorice Flavonoid Oil in Healthy Humans during Light Exercise

“…Our previous study suggested that LFO is effective in reducing visceral fat accumulation and suppressing elevated blood glucose levels in obese diabetic KK-Ay mice (2). Subsequently, a double-blind placebo-controlled clinical trial showed that LFO was effective in suppressing body weight gain by reducing body fat mass in overweight volunteers (3).…”

“…Licorice flavonoid oil (LFO) is a new functional food ingredient containing hydrophobic flavonoids derived from G. glabra (2). Our previous study suggested that LFO is effective in reducing visceral fat accumulation and suppressing elevated blood glucose levels in obese diabetic KK-Ay mice (2).…”