Inhibitory effect of isoliquiritin, a compound in licorice root, on angiogenesis in vivo and tube formation in vitro.
A water extract of licorice root inhibits granuloma angiogenesis in adjuvant-induced chronic inflammation (Phytother. Res., 5, 195. 1991). The present study has investigated the effects of licorice-derived compounds on granuloma angiogenesis. Isoliquiritin (0.31-3.1 mg/kg), a licorice-derived flavonoid, inhibited the carmine content of granuloma tissue 50-fold greater than licorice extract. Glyeyrrhizin (20-80 mg/kg), a licorice-derived saponin, inhibited carmine content with a weak potency. The licorice extract (0.01-1 mg/ml) also inhibited tube formation from vascular endothelial cells in a concentration-dependent manner. From the chemical structure-activities of used licorice-derived flavonoids (0.1-100 microM), their potencies for anti-tube formation were in the order isoliquiritigenin > isoliquiritin > liquiritigenin >> isoliquiritin-apioside. Glycyrrhizin (0.1-100 microM) and glycyrrhetinic acid (0.1-10 microM) increased tube formation. A glycyrrhizin (82 micrograms/ml)-induced increase in tube formation was inhibited by isoliquiritin. The combined effect of a mixture of 82 micrograms/ml glycyrrhizin and 4.2 micrograms/ml isoliquiritin, a similar concentration ratio to their yield ratio in the licorice extract, corresponded to the effect of 100 micrograms/ml extract. In conclusion, the anti-angiogenic effect of licorice extract depended on the anti-tube formation effect of isoliquiritin.
Kobayashi
S
S
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Miyamoto
T
T
Kimura
I
I
Kimura
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D005960:Glucosides / Q000494:pharmacology*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006035:Glycyrrhiza / Q000737:chemistry*; D019695:Glycyrrhizic Acid; D006099:Granuloma / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008870:Microtubules / Q000187:drug effects*; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control*; D010936:Plant Extracts / Q000494:pharmacology; D010946:Plants, Medicinal; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005960:Glucosides; D010936:Plant Extracts; C098467:neoisoliquiritin; D002599:Chalcone; D019695:Glycyrrhizic Acid; D006034:Glycyrrhetinic Acid