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RGDS modifying ursolic acid: Getting insight into self-assembly, nano-property, osteoporosis inhibition and molecular mechanism

XIAOXIAO YUAN,Xiaoyi Zhang,YIFAN YANG,YAONAN WANG,SHURUI ZHAO,QIQI FENG,Jianhui Wu,MING ZHAO,Shiqi Peng

Here a novel anti-osteoporosis agent UA-RGDS, namely RGDS (Arg-Gly-Asp-Ser) conjugated UA (ursolic acid), was presented. In ultrapure water UA-RGDS existed as the tetramer. In the serum of OVX mice (ovariectomized mice), and at 10-4 M of concentration the self-assemble led UA-RGDS to the formation of nano-particles of 16 nm-156 nm in height, the size of suitably transporting in the blood circulation. In vivo bio-distribution supported that UA-RGDS only distributed in the femur of OVX mice, while null distribution been found in the blood and the other organs. These observations suggested that UA-RGDS was capable of targeting the femur, thereby blocked bone loss. ELISA experiment explored that as anti-osteoporosis agent UA-RGDS down regulated the expressions of IL-1β in the serum OVX mice. Thus UA-RGDS provided a linker for bone loss and down regulation of the expressions of IL-1β, thereby made serum IL-1β to be a biomarker for menopause women clinically.