Aldose reductase inhibitory compounds from Glycyrrhiza uralensis.
We evaluated the inhibitory effects of components from the root of Glycyrrhiza uralensis (G. uralensis) on aldose reductase (AR) and sorbitol formation in rat lenses with high levels of glucose as part of our ongoing search of natural sources for therapeutic and preventive agents for diabetic complications. In order to identify the bioactive components of G. uralensis, 5 prenylated flavonoids (semilicoisoflavone B, 7-O-methylluteone, dehydroglyasperin C, dehydroglyasperin D, and isoangustone A), three flavonoids (liquiritigenin, isoliquiritigenin, and licochalcone A), and two triterpenoids (glycyrrhizin and glycyrrhetinic acid) were isolated; their chemical structures were then elucidated on the basis of spectroscopic evidence and comparison with published data. The anti-diabetic complication activities of 10 G. uralensis-derived components were investigated via inhibitory assays using rat lens AR (rAR) and human recombinant AR (rhAR). From the 10 isolated compounds, semilicoisoflavone B showed the most potent inhibition, with the IC(50) values of rAR and rhAR at 1.8 and 10.6microM, respectively. In the kinetic analyses using Lineweaver.Burk plots of 1/velocity and 1/concentration of substrate, semilicoisoflavone B showed noncompetitive inhibition against rhAR. The results clearly indicated that the presence of a gamma,gamma-dimethylchromene ring is partly responsible for the AR inhibitory activity of isoprenoid-type flavonoids. Further, semilicoisoflavone B inhibited sorbitol formation of rat lens incubated with a high concentration of glucose, indicating that this compound may be effective for preventing osmotic stress in hyperglycemia.
Lee
Yeon Sil
YS
Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University, Chuncheon 200-702, Republic of Korea.
Kim
Seon Ha
SH
Jung
Sang Hoon
SH
Kim
Jin Kyu
JK
Pan
Cheol-Ho
CH
Lim
Soon Sung
SS
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D048909:Diabetes Complications / Q000188:drug therapy* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D029882:Glycyrrhiza uralensis / Q000737:chemistry*; D006801:Humans; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D009997:Osmotic Pressure / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D027343:Rhizome; D013012:Sorbitol / Q000378:metabolism*; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
D004791:Enzyme Inhibitors; D005419:Flavonoids; D010936:Plant Extracts; D011994:Recombinant Proteins; D014315:Triterpenes; D013012:Sorbitol; D000449:Aldehyde Reductase; D005947:Glucose; C554447:semilicoisoflavone B