Protective Effects of Kakkalide From Flos Puerariae on Ethanol-Induced Lethality and Hepatic Injury Are Depaendent on Its Biotransformation by Human Intestinal Microflora

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When kakkalide, which was isolated from Flos Puerariae, was incubated with human fecal bacteria, kakkalide was metabolized to irisolidone via kakkalidone. When kakkalide (250 mg/kg) was orally administered to rats, irisolidone, but not kakkalide, was detected in the blood. The mortality associated with ethanol treatment was slightly reduced when the mice were intraperitoneally treated with kakkalide. Intraperitoneally administered kakkalide and kakkalidone did not reduce alcohol toxicity. However, orally administered kakkalide and intraperitoneally administered irisolidone significantly reduced the mortality. Orally administered kakkalide and intraperitoneally injected irisolidone greatly reduced serum alanine aminotransferase and aspartate aminotransferase activities in ethanol-intoxified mice. Orally administered kakkalide and intraperitoneally administered irisolidone significantly lowered the level of blood ethanol. The results indicate that kakkalide is a prodrug of irisolidone in protecting against ethanol-induced lethality and hepatic injury.
社団法人日本薬理学会の論文
2003-11-01