RRC ID 36939
著者 Tan H, Ashour A, Katakura Y, Shimizu K.
タイトル A structure-activity relationship study on antiosteoclastogenesis effect of triterpenoids from the leaves of loquat (Eriobotrya japonica).
ジャーナル Phytomedicine
Abstract Our previous results elucidated that the leaves of Eriobotrya japonica possessed the potential to suppress ovariectomy-induced bone mineral density deterioration, and ursolic acid, the major bioactive component in these leaves, suppressed the osteoclast differentiation. The aim of this study was to discover more candidates for development of novel antiosteoclastogenesis agents from the leaves of E. japonica. Phytochemical analysis following a cell-based osteoclastic tartrate-resistant acid phosphatase (TRAP) activity assay revealed 11 more compounds with a potent antiosteoclastogenesis effect. The potency of ursane-type triterpenoids from the leaves of E. japonica prompted us to investigate the structure-activity relationships underlying their antiosteoclastogenesis. The results revealed that both the hydroxyl group at C-3 and the carboxylic group at C-17 played indispensable roles in the antiosteoclastogenesis activity of ursane-type triterpenoids. The configuration at C-3 (a beta-form of the hydroxyl group) was found to be important for this activity. While introducing a hydroxyl group at C-19 increased the inhibitory activity of ursane-type triterpenoids carrying an alpha-form hydroxyl group at C-3. The bioactivity analyses of ursolic acid and oleanolic acid demonstrated that the antiosteoclastogenesis effect of ursolic acid may be related to different positions of the C-29 and C-30 methyl groups on the E-ring, since oleanolic acid showed limited activity. The addition of a hydroxyl group at C-2 would dramatically improve the inhibition of oleanane-type triterpenoids. Collectively, these findings could provide important clues for the improvement of multi-targeted antiosteoclastogenesis agents from the leaves of E. japonica.
巻・号 22(4)
ページ 498-503
公開日 2015-4-15
DOI 10.1016/j.phymed.2015.03.002
PII S0944-7113(15)00068-9
PMID 25925972
MeSH Acid Phosphatase / metabolism Animals Bone Resorption Cell Line Eriobotrya / chemistry* Isoenzymes / metabolism Mice Molecular Structure Oleanolic Acid / analogs & derivatives* Oleanolic Acid / chemistry Osteoclasts / drug effects* Plant Leaves / chemistry Structure-Activity Relationship Tartrate-Resistant Acid Phosphatase Triterpenes / chemistry*
IF 4.268
引用数 13
WOS 分野 INTEGRATIVE & COMPLEMENTARY MEDICINE PLANT SCIENCES PHARMACOLOGY & PHARMACY CHEMISTRY, MEDICINAL
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)