Effect of 26-oxygenosterols from Ganoderma lucidum and their activity as cholesterol synthesis inhibitors
Effect of 26-oxygenosterols from Ganoderma lucidum and their activity as cholesterol synthesis inhibitors
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DOI：
10.1128/aem.71.7.3653-3658.2005
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发表时间：
2005-07-01
影响因子：
4.4
通讯作者：
Fay, LB
中科院分区：
文献类型：
--
作者：
Hajjaj, H;Macé, C;Fay, LB
灵芝（Ganoderma lucidum）是一种属于多孔菌科（Polyporaceae）的药用真菌，在日本长期被称为灵芝（Reishi），并已被广泛用于传统中药中。我们报告了26-氧甾体化合物灵芝醇A、灵芝醇B、灵芝醛A和灵芝酸Y的分离和鉴定，以及它们在体外对人肝细胞系胆固醇合成的生物学效应。我们还研究了胆固醇合成途径中的抑制位点。我们发现，这些含氧甾醇从G。灵芝通过转化作为胆固醇前体的乙酸或甲羟戊酸来抑制胆固醇的生物合成。通过在灵芝醇A存在下掺入24，25-二氢-[24，25-H-3（2）]羊毛甾醇和[3-H-3]赤藓甾醇，我们确定胆固醇合成的抑制点在羊毛甾醇和赤藓甾醇之间。这些结果表明，将24，25-二氢羊毛甾醇转化为胆固醇的羊毛甾醇14 α-脱甲基酶可被来自G.灵芝。这些26-氧骨素可能导致新的治疗剂，降低血液胆固醇。
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-H-3(2)]lanosterol and [3-H-3]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.