Gambogic acid inhibits osteoclast formation and ovariectomy-induced osteoporosis by suppressing the JNK, p38 and Akt signalling pathways
Gambogic acid inhibits osteoclast formation and ovariectomy-induced osteoporosis by suppressing the JNK, p38 and Akt signalling pathways
复制标题
藤黄酸通过抑制 JNK、p38 和 Akt 信号通路抑制破骨细胞形成和卵巢切除引起的骨质疏松
DOI：
10.1042/bj20150151
复制
发表时间：
2015-08-01
影响因子：
4.1
通讯作者：
Fan, Shunwu
中科院分区：
文献类型：
--
作者：
Ma, Jianjun;Ma, Yan;Fan, Shunwu
骨细胞的形成和骨吸收过多是骨质疏松症的关键原因。天然化合物可以用作预防和治疗骨质疏松症的替代治疗剂，并且某些天然化合物可能比传统药物具有优势。在本文中，我们报告说，天然化合物GBA（Gambogic Acid）是生物利用，有效且毒性较小的，抑制了破骨细胞的形成，从而减弱了体外破骨骨骨吸收。进一步的体内研究表明，GBA以剂量依赖性方式阻止了卵巢切除术诱导的骨质损失。此外，我们证明了GBA抑制了RANKL（核因子Kappa B配体的受体激活剂）诱导的2JNK（C-JUN N末端激酶），p38和Akt磷酸化。综上所述，我们的结果表明，GBA在体外和体内抑制破骨细胞的形成，这表明它在治疗与破骨细胞相关疾病的治疗中具有潜在的价值。
Excessive osteoclast formation and bone resorption are key causes of osteoporosis. Natural compounds can serve as alternative therapeutic agents for the prevention and treatment of osteoporosis, and some natural compounds may have advantages over traditional drugs. In the present paper, we report that the natural compound GBA (gambogic acid), which is bioavailable, effective and less toxic, inhibits osteoclast formation, thereby attenuating osteoclastic bone resorption in vitro. Further in vivo studies demonstrated that GBA prevented ovariectomy-induced bone loss in a dose-dependent manner. Moreover, we demonstrated that GBA suppressed RANKL (receptor activator of nuclear factor kappa B ligand)-induced 2JNK (c-Jun N-terminal kinase), p38 and Akt phosphorylation. Taken together, our results demonstrate that GBA inhibits osteoclast formation in vitro and in vivo, suggesting that it is of potential value in the treatment of osteoclast-related diseases.