Turmeric, the rhizome of Curcuma longa L., has a wide range of effects on human health. The chemistry includes curcuminoids and sesquiterpenoids as components, which are known to have antioxidative, anticarcinogenic, and antiinflammatory activities. In this study, we investigated the effects of three turmeric extracts on blood glucose levels in type 2 diabetic KK-A(y) mice (6 weeks old, n = 5/group). These turmeric extracts were obtained by ethanol extraction (E-ext) to yield both curcuminoids and sesquiterpenoids, hexane extraction (H-ext) to yield sesquiterpenoids, and ethanol extraction from hexane-extraction residue (HE-ext) to yield curcuminoids. The control group was fed a basal diet, while the other groups were fed a diet containing 0.1 or 0.5 g of H-ext or HE-ext/100 g of diet or 0.2 or 1.0 g of E-ext/100 g of diet for 4 weeks. Although blood glucose levels in the control group significantly increased (P < 0.01) after 4 weeks, feeding of 0.2 or 1.0 g of E-ext, 0.5 g of H-ext, and 0.5 g of HE-ext/100 g of diet suppressed the significant increase in blood glucose levels. Furthermore, E-ext stimulated human adipocyte differentiation, and these turmeric extracts had human peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand-binding activity in a GAL4-PPAR-gamma chimera assay. Also, curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone had PPAR-gamma ligand-binding activity. These results indicate that both curcuminoids and sesquiterpenoids in turmeric exhibit hypoglycemic effects via PPAR-gamma activation as one of the mechanisms, and suggest that E-ext including curcuminoids and sesquiterpenoids has the additive or synergistic effects of both components.
The turmeric (Curcuma longa L. rhizomes) EtOH extract significantly suppressed an increase in blood glucose level in type 2 diabetic KK-A y mice. In an in vitro evaluation, the extract stimulated human adipocyte differentiation in a dose-dependent manner and showed human peroxisome proliferator-activated receptor (PPAR)-g g ligand-binding activity in a GAL4-PPAR-g g chimera assay. The main constituents of the extract were identified as curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone, which had also PPAR-g g ligand-binding activity. These results indicate that turmeric is a promising ingredient of functional food for the prevention and/or amelioration of type 2 diabetes and that curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone mainly contribute to the effects via PPAR-g g activation.
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...
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.
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