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Applied and Environmental Microbiology, July 2005, p. 3653-3658, Vol. 71, No. 7
0099-2240/05/$08.00+0     doi:10.1128/AEM.71.7.3653-3658.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Effect of 26-Oxygenosterols from Ganoderma lucidum and Their Activity as Cholesterol Synthesis Inhibitors

Hassan Hajjaj,{dagger} Catherine Macé, Matthew Roberts,{ddagger} Peter Niederberger,* and Laurent B. Fay

Nestlé Research Centre, Nestec Ltd., Vers-chez-les-Blanc, P.O. Box 44, 1000 Lausanne 26, Switzerland

Received 16 August 2004/ Accepted 3 February 2005

Ganoderma lucidum is a medicinal fungus belonging to the Polyporaceae family which has long been known in Japan as Reishi and has been used extensively in traditional Chinese medicine. We report the isolation and identification of the 26-oxygenosterols ganoderol A, ganoderol B, ganoderal A, and ganoderic acid Y and their biological effects on cholesterol synthesis in a human hepatic cell line in vitro. We also investigated the site of inhibition in the cholesterol synthesis pathway. We found that these oxygenated sterols from G. lucidum inhibited cholesterol biosynthesis via conversion of acetate or mevalonate as a precursor of cholesterol. By incorporation of 24,25-dihydro-[24,25-3H2]lanosterol and [3-3H]lathosterol in the presence of ganoderol A, we determined that the point of inhibition of cholesterol synthesis is between lanosterol and lathosterol. These results demonstrate that the lanosterol 14{alpha}-demethylase, which converts 24,25-dihydrolanosterol to cholesterol, can be inhibited by the 26-oxygenosterols from G. lucidum. These 26-oxygenosterols could lead to novel therapeutic agents that lower blood cholesterol.


* Corresponding author. Mailing address: Nestlé Research Centre, Nestec Ltd., Vers-chez-les-Blanc, P.O. Box 44, 1000 Lausanne 26, Switzerland. Phone: 41 217858915. Fax: 41 217858549. E-mail: Peter.niederberger{at}rdls.nestle.com.

{dagger} Present address: Université des Sciences et Technologies de Lille, Cité Scientifique, 59655 Villeneuve d'Ascq Cédex, France.

{ddagger} Present address: Nestle Purina Pet Care, Mail Zone 11T, Number One Checkerboard Square, St. Louis, MO 63164.


Applied and Environmental Microbiology, July 2005, p. 3653-3658, Vol. 71, No. 7
0099-2240/05/$08.00+0     doi:10.1128/AEM.71.7.3653-3658.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.