RRC ID 58036
Author Tan H, Zhao C, Zhu Q, Katakura Y, Tanaka H, Ohnuki K, Shimizu K.
Title Ursolic Acid Isolated from the Leaves of Loquat ( Eriobotrya japonica) Inhibited Osteoclast Differentiation through Targeting Exportin 5.
Journal J Agric Food Chem
Abstract One of the conventional strategies for treating osteoporosis is to eliminate the multinucleated osteoclasts that are responsible for bone resorption. Our previous study revealed that ursolic acid, isolated from leaves of loquat that is used as tasty tea in Japan, suppressed osteoclastogenesis. We confirmed that ursolic acid exhibited osteoclast differentiation inhibitory activity with an 50% inhibitory concentration (IC50) value of 5.4 ± 0.96 μM. To disclose its mechanism of action, this study first uses polymer-coated magnetic nanobeads to identify potential target proteins. As a result, we identified a nuclear exporter protein named exportin 5 (XPO5). Further studies demonstrated that knockdown of XPO5 significantly blocks osteoclast differentiation ( P < 0.01). Expression profiling of mature microRNAs in the cells revealed that downregulation of XPO5 by small interfering RNA or by ursolic acid could downregulate the expression of mature microRNA let-7g-5p during osteoclast differentiation ( P < 0.01). Collectively, our findings suggest that ursolic acid inhibits osteoclast differentiation through targeting XPO5, which provides further evidence for the healthy function of the tea. This study also provides new insights into the role of XPO5 and its mediated microRNAs in treatment for bone resorption diseases.
Volume 67(12)
Pages 3333-3340
Published 2019-3-27
DOI 10.1021/acs.jafc.8b06954
PMID 30827108
MeSH Animals Cell Line Down-Regulation / drug effects Eriobotrya / chemistry* Karyopherins / genetics Karyopherins / metabolism* Mice Osteoclasts / cytology* Osteoclasts / drug effects Osteoclasts / metabolism Osteogenesis / drug effects* Plant Extracts / chemistry Plant Extracts / pharmacology* Plant Leaves / chemistry Triterpenes / analysis Triterpenes / pharmacology*
IF 3.571
Times Cited 2
Human and Animal Cells RAW 264(RCB0535)