**8. Conclusion**

HRESIMS as 3-(2,4-dihydroxyphenyl)-5,7-dimethoxy-6-(3-methyl-2-butenyl)-2H-chromene

Of the isolated compounds, the new compound **40** and known compounds **41**–**45** exhibited significant PPAR-γ ligand-binding activity (**Figure 6**). The activity of **40** at 5.0 μg/mL (=13.6 μM) was stronger than that of 2.0 μM TRG (relative luminescence intensity of 3.7). The coumestan derivative **46**, which was less active than **40**, was structurally similar to the active compound **43**, and the only detected difference between **43** and **46** was the formation of a five-membered ether ring between C-4 and C-2′ in **46**. This suggested that the presence of a hydroxy group at C-2′ in the isoflavan, isoflavene, or arylcoumarin skeleton is necessary for PPAR-γ ligand-binding activity. Furthermore, the isoflavones, **48** and **49**, which have a hydroxy group at C-2′ and no isoprenyl group at C-6, did not exhibit activity, suggesting that the isoprenyl group at C-6 was also involved in PPAR-γ ligand-binding activity. In conclusion, the isoprenyl group at C-6 and the C-2′ hydroxy group in the aromatic C ring of the isoflavan, isoflavene, or arylcoumarin skeleton were structural requirements for PPAR-γ

 **mice**

diabetes, were studied using pioglitazone as a positive control. There was no difference in the food intake or body weight of mice between the treated groups and the control group. Test compound intake, calculated from the food intake and body weight of the mice, was approximately 100 mg/(kg day) in the glycyrin and glycyrol (**46**) groups and 23 mg/(kg day) in the pioglitazone group. Blood glucose levels significantly decreased after 4 days of feeding in both the glycyrin- and pioglitazone-treated groups compared to that in the control group, whereas the blood glucose levels of the glycyrol-treated group were comparable to those of

mice, an animal model of genetic type 2

**6. PPAR-γ ligand-binding activity of compounds 40–52 isolated** 

and was named dehydroglyasperin D.

86 Biological Activities and Action Mechanisms of Licorice Ingredients

ligand-binding activity (**Figure 9**).

**7. Ameliorative effects on diabetic KK-A<sup>y</sup>**

**Figure 9.** Structural requirements for the isoflavan skeleton for PPAR-γ ligand binding [2].

The ameliorative effects of glycyrin (**44**) in KK-Ay

the control group (**Table 1**).

**from** *G. uralensis*

Fractionation of the EtOH extract of *G. glabra* roots and the EtOAc extract of *G. uralensis* roots, guided by a GAL-4-PPAR-γ chimera assay method, resulted in the isolation of 52 phenolics, including 11 new compounds. The structures of the new compounds were determined by spectroscopic analysis. Of the isolated compounds, more than 10 phenolics exhibited significant PPAR-γ ligand-binding activity and the prenylflavone derivative, licoflavanone A (**31**), exhibited the most potent ligand-binding activity. The activity of these compounds at a sample concentration of 10 μg/mL was approximately three times greater than that of 0.5 μM TRG. Six phenolics were isolated from the EtOAc extract of *G. uralensis* roots as PPAR-γ ligands and one, glycyrin (**44**), reduced the blood glucose levels of genetically diabetic KK-Ay mice through its PPAR-γ ligand-binding activity. We have therefore discovered a possible new application of *G. glabra* and *G. uralensis* roots and their constituents for the amelioration of type 2 diabetes, a representative insulin resistance syndrome that is becoming a serious worldwide public health problem.
