RGDS-modified ursolic acid: insights into self-assembly, nano-properties, osteoporosis inhibition and molecular mechanisms

Herein, a novel anti-osteoporosis agent is presented, namely, RGDS (Arg-Gly-Asp-Ser)-conjugated UA (ursolic acid) (abbreviated as UA-RGDS). In ultrapure water, UA-RGDS existed as a tetramer. In the serum of ovariectomized (OVX) mice and at 10^-4 M concentration, the self-assembled UA-RGDS formed nano-particles of 16-156 nm in height, suitable for transportation in blood circulation. <i>In vivo</i> bio-distribution data showed that UA-RGDS was only distributed in the femur of OVX mice, while null distribution was found in the blood and other organs. These observations suggested that UA-RGDS can target the femur, thereby preventing bone loss. ELISA results showed that as an anti-osteoporosis agent, UA-RGDS downregulated the expressions of IL-1β in the serum of OVX mice. Thus, serum IL-1β levels could be a biomarker to clinically detect menopause, and UA-RGDS could help prevent bone loss.