Ursolic Acid Isolated from the Leaves of Loquat (Eriobotrya japonica) Inhibited Osteoclast Differentiation through Targeting Exportin 5

Hui Tan, Chong Zhao, Qinchang Zhu, Yoshinori Katakura, Hiroyuki Tanaka, Koichiro Ohnuki, Kuniyoshi Shimizu

Research output: Contribution to journalArticle

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 (IC 50 ) 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.

Original languageEnglish
Pages (from-to)3333-3340
Number of pages8
JournalJournal of Agricultural and Food Chemistry
Volume67
Issue number12
DOIs
Publication statusPublished - Mar 27 2019

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Eriobotrya
Karyopherins
Eriobotrya japonica
ursolic acid
osteoclasts
Osteoclasts
MicroRNAs
microRNA
bone resorption
leaves
Tea
Bone Resorption
tea
inhibitory concentration 50
Bone
Down-Regulation
Bone Diseases
nuclear proteins
osteoporosis
Nuclear Proteins

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

Cite this

Ursolic Acid Isolated from the Leaves of Loquat (Eriobotrya japonica) Inhibited Osteoclast Differentiation through Targeting Exportin 5. / Tan, Hui; Zhao, Chong; Zhu, Qinchang; Katakura, Yoshinori; Tanaka, Hiroyuki; Ohnuki, Koichiro; Shimizu, Kuniyoshi.

In: Journal of Agricultural and Food Chemistry, Vol. 67, No. 12, 27.03.2019, p. 3333-3340.

Research output: Contribution to journalArticle

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