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As part of our search for anti-arteriosclerosis agents from traditional Chinese medicines, the 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase (HCR)-inhibitory constituent, kakkalide, was isolated from the flower of Pueraria thunbergiana (PT, family Leguminosae). The antihyperlipidemic effects of kakkalide and its metabolite, irisolidone, which may be a bioactive form in vivo and potently inhibit the HCR activity, were investigated in vivo. Both the oral and interperitoneal administrations of kakkalide and irisolidone, with the exception of intraperitoneally treated kakkalide, potently lowered the serum levels of total cholesterol (TC) and triglyceride (TG) in Trition WR1339-induced hyperlipidemic mice. The oral administrations of kakkalide and irisolidone in hyperlipidemic mice induced, by the long-term feeding of a high fat diet, also potently reduced the serum levels of TC and TG and epididymal fat pad weight. These findings suggest that PT can improve hyperlipidemia, and the hypolipidemic effect may be due to HMG-CoA reductase.

Kakkalide and Irisolidone: HMG-CoA Reductase Inhibitors Isolated from the Flower of Pueraria thunbergiana