A structure-activity relationship study on antiosteoclastogenesis effect of triterpenoids from the leaves of loquat (Eriobotrya japonica).
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.
Department of Agro-environmental Sciences, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
Hui
H
Tan
Department of Agro-environmental Sciences, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan; Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt.
Ahmed
A
Ashour
Department of Genetic Resources Technology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
Yoshinori
Y
Katakura
Department of Agro-environmental Sciences, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan. Electronic address: shimizukuni@gmail.com.
Kuniyoshi
K
Shimizu
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001862:Bone Resorption; D002460:Cell Line; D031983:Eriobotrya / Q000737:chemistry*; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D010010:Osteoclasts / Q000187:drug effects*; D018515:Plant Leaves / Q000737:chemistry; D013329:Structure-Activity Relationship; D000071681:Tartrate-Resistant Acid Phosphatase; D014315:Triterpenes / Q000737:chemistry*; D000097245:Ursolic Acid
D000135:Acid Phosphatase; D007527:Isoenzymes; D009828:Oleanolic Acid; D000071681:Tartrate-Resistant Acid Phosphatase; D014315:Triterpenes; D000097245:Ursolic Acid; C413246:oleanane; C000605511:Acp5 protein, mouse
Eriobotrya japonica; Loquat leave; Osteoclast; Structure–activity relationship; Tartrate-resistant acid phosphatase; Triterpenoids