Anti-osteoclastogenic cycloartane saponins from Mussaenda pubescens.

ABSTRACT

The methanolic extract of Mussaenda pubescens Dryand leaves exhibited significant anti-osteoclastogenic activity. Chemical investigation of M. pubescens led to the isolation of one new cycloartane saponin, mussaendoside X (1) along with eight known compounds heinsiagenin A 3-O-[α-L-rhamnopyranosyl-(1→2)-O-ß-D-glucopyranosyl-(1→2)]-O-ß-D-glucopyranoside (2), mussaendoside O (3), heinsiagenin A 3-O-[α-L-rhamnopyranosyl-(1→2)-O-ß-D-glucopyranosyl-(1→2)]-O-ß-D-glucopyranosyl-(1→4)-O-ß-D-glucopyranoside (4), mussaendoside G (5), mussaendoside U (6), shanzhiside methyl ester (7), barlerin (8) and musaenoside (9). Their structures were elucidated by extensive spectroscopic methods including 1D- and 2D-NMR as well as MS analysis and comparison with the literature. Cycloartane saponins 1-6 positively suppressed osteoclast formation in an anti-osteoclastogenic screening assay. Consequently, treatment of RANKL-stimulated RAW 264.7 cells with compounds 1-4 significantly decreased the number of osteoclasts in a concentration-dependent manner. Six compounds from M. pubescens, with the new cycloartane, mussaendoside X, were shown for the first time as potential effective inhibitors of osteoclastogenesis.