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

Abstract

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-[24,25-3 H 2 ]lanosterol and [3-3 H]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␣-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.

Ganoderic acids suppress growth and invasive behavior of breast cancer cells by modulating AP-1 and NF-κB signaling

“…The active GA-H is hydroxylated at position 3 and GA-A at position 7 and 15; whereas inactive GA-F is not hydroxylated. In addition, other triterpenes with hydroxyl or acetoxy groups at the positions 3, 7 and/or 15 such as ganoderic acid C1, ganoderic acid C2 (30), ganoderic acid D (31), ganoderic acid T (20), ganoderic acid X (19), ganoderic acid Y (32), ganoderiol A (31), ganoderol B (32,33), lucidumol B and ganodermadiol (30,31) were shown to have inhibitory biological activity. Shiao (34) demonstrated that several Ganoderma triterpenes with hydroxyl or acetoxy groups in these positions were cytotoxic to hepatoma cells and inhibited histamine release, cholesterol synthesis, and farnesylation of Ras protein.…”

Development of two novel specific SCAR markers by cloning improved RAPD fragments from the medicinal mushroom Ganoderma lucidium (Leysser: Fr) Karst

“…Due to their significant medicinal importance, mushrooms of the Ganoderma species have gained noticeable interest from biomedical researchers. A number of studies have revealed the medicinal values of Ganoderma mushrooms against various life-threatening diseases and health complications like cancer, immunodeficiency, cardiovascular complications, diabetes, hepatic disease, neurodegeneration, and infectious disease (Hajjaj et al, 2005;Paterson, 2006;Ma et al, 2011;Chu et al, 2012;Tie et al, 2012;Xiao et al, 2012;Boh, 2013;Wang et al, 2013;Wu et al, 2013;Yue et al, 2013). There are numerous variations in the size, shape, and color of Ganoderma mushrooms, and they differ in biological properties as well.…”

Antitumor effects and mechanisms of Ganoderma extracts and spores oil

“…Ganoderma extracts and spores oil 4 /well) were seeded into 96-well plates and treated with a series of concentrations of Ganoderma spores oil (0.31, 0.63, 1.25, 2.5, 5 and 10 mg/ml) for 24 h. Control cells were exposed to double distilled water containing the same concentration of Tween 80. Subsequently, 20 µl of 5 mg/ml MTT (Sigma-Aldrich, St. Louis, MO, USA) was added to each well and incubated for 4 h. The dark blue formazan crystals were solubilized in lysis buffer containing 10% sodium dodecyl sulfate (SDS), 5% isobutyl alcohol and 12 mmol/l HCl, and the optical density (OD) was detected at 492 nm with a spectrophotometer.…”

“…Modern pharmacological and clinical studies have confirmed that Ganoderma contains abundant biologically active substances in its fruiting body, mycelia and spores, and possesses variable functions, including immunomodulation, anti-aging, reducing blood lipids, anti-viral and anti-tumor activities (1)(2)(3)(4)(5)(6). The present study examined the antitumor activity of a mixture of aqueous and ethanol extracts of the Ganoderma fruiting body and Ganoderma spores oil, which was extracted from broken spores by supercritical CO 2 extraction technology and explored the possible underlying mechanisms.…”