Methyl Ganoderic Acid DM: A Selective Potent Osteoclastogenesis Inhibitor

Abstract

Increased osteoclastic bone resorption plays a central role in the pathogenesis of many bone diseases, and osteoclast inhibitors are the most widely used treatments for these diseases. Ganoderic acid DM, the main component of Ganoderma lucidum, has been known for its medicinal effects such as anti-androgen and anti-proliferative activities. In this study, we investigated the inhibitory effects of ganoderic acid DM and its analog (methyl ganoderic acid DM and 7- oxo-methyl ganoderic acid Z) on osteoclastogenesis using RAW264 cell in vitro. Methyl ganoderic acid DM blocked osteoclastogenesis completely at 12.5 μM with low cytotoxicity less than 30%. On the other hands, ganoderic acid DM blocked osteoclastogenesis completely at the higher concentration of 50 μM, but 7-oxo-methyl ganoderic acid Z did not up to 100 μM. These results implicated the carbonyl group at C-3 is essentially for selective osteoclastogenesis inhibitory activity, and methyl esters at C-26 should play an important role in enhancing its osteoclastogenesis inhibitory activity. Keyword: Ganoderma lucidum, methyl ganoderic acid DM, osteoporosis, rheumatoid arthritis.