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Biochemical and Molecular Actions of Nutrients

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

Tatsumasa Mae¹, Hideyuki Kishida^*, Tozo Nishiyama, Misuzu Tsukagawa, Eisaku Konishi, Minpei Kuroda, Yoshihiro Mimaki, Yutaka Sashida, Kazuma Takahashi^**, Teruo Kawada, Kaku Nakagawa and Mikio Kitahara

Functional Foods Development Division and ^* Life Science Research Laboratories, Life Science RD Center, Kaneka Corporation, Takasago, Hyogo 676-8688, Japan; Laboratory of Medicinal Plant Science, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji 192-0392, Japan; ^** Department of Molecular Metabolism and Diabetes, Department of Internal Medicine, Tohoku University School of Medicine, Sendai 980-8574, Japan; and Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan

¹To whom correspondence should be addressed. E-mail: Tatsumasa.Mae{at}kn.kaneka.co.jp.

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- (PPAR-) 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- ligand-binding activity with a GAL4-PPAR- chimera assay. Some prenylflavonoids including glycycoumarin, glycyrin, dehydroglyasperin C and dehydroglyasperin D, a newly found compound, were identified as active compounds with PPAR- 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 [100 to 300 mg/(kg body · d)] for 4 wk decreased (P < 0.05) blood glucose level in younger (6 wk old) and older (13 wk old) diabetic KK-A^y 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 · 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.

KEY WORDS: • licorice extract • prenylflavonoids • PPAR- ligand • metabolic syndrome

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