Inhibition of osteoclastogenesis by 6-[10'(Z)-heptadecenyl] salicylic acid from Syzygium tetragonum Wall via preventing nuclear translocation of NFATc1.
Syzygium tetragonum Wall is a Chinese folk medicine for the treatment of rheumatism, joint swelling and pain. By High Content Screening (HCS), 8 compounds (1-8) from Syzygium tetragonum Wall were evaluated for their inhibitory activity on the nuclear translocation of NFATc1 in EGFP-NFATc1 U2OS cells. Among them, 6-[10'(Z)-heptadecenyl] salicylic acid (8) exhibited a significant inhibitory activity. In RAW 264.7 cells, it could dose-dependently prevent nuclear NFATc1 translocation induced by receptor activator of nuclear factor κB ligand (RANKL). The differentiation of osteoclasts from bone marrow derived macrophages (BMMs) was significantly inhibited by 8 in a dose-dependent manner. The mRNA expression of TRAP, CtsK, and MMP9, key enzymes for the bone resorption secreted by osteoclasts, were also significantly down-regulated; and MMP9 activity was also obviously decreased. More importantly, the bone resorption activity of osteoclasts was dose-dependently suppressed by compound 8. Our results suggest that compound 8 can effectively inhibit osteoclastogenesis and bone erosion via preventing NFATc1 nuclear translocation and might be a promising drug candidate for relevant diseases.
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, China.
Xin-Wen
XW
Zhang
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, China.
Chun
C
Zhou
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, China.
Han-Dong
HD
Zhu
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, China.
Weiwei
W
Shao
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, China.
Yan
Y
You
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, China.
Jin
J
Peng
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, China. Electronic address: yinsh2@mail.sysu.edu.cn.
Sheng
S
Yin
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, China; Department of Pharmacology, School of Pharmacy, Fudan University, China. Electronic address: shxiaoy@fudan.edu.cn.
Xiaoyan
X
Shen
D000135:Acid Phosphatase / Q000235:genetics; D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D001862:Bone Resorption / Q000235:genetics; D056657:Cathepsin K / Q000235:genetics; D002460:Cell Line / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008264:Macrophages / Q000187:drug effects; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008516:Medicine, Chinese Traditional; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D050778:NFATC Transcription Factors / Q000378:metabolism*; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000032:analysis / Q000737:chemistry; D053245:RANK Ligand / Q000378:metabolism / Q000494:pharmacology; D012459:Salicylates / Q000302:isolation & purification / Q000494:pharmacology*; D027842:Syzygium / Q000737:chemistry*; D000071681:Tartrate-Resistant Acid Phosphatase
C000597834:6-(10'-heptadecenyl)salicylic acid; D007527:Isoenzymes; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; D010936:Plant Extracts; D053245:RANK Ligand; D012459:Salicylates; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K; C534132:Ctsk protein, mouse; D020780:Matrix Metalloproteinase 9
6-[10′(Z)-Heptadecenyl] salicylic acid; Bone resorption; NFATc1; Osteoclastogenesis