Zhou Chen-He, Meng Jia-Hong, Yang Yu-Te, Hu Bin, Hong Jian-Qiao, Lv Zheng-Tao, Chen Kun, Heng Boon Chin, Jiang Guang-Yao, Zhu Jian, Cheng Zhao-Hui, Zhang Wei, Cao Le, Wang Wei, Shen Wei-Liang, Yan Shi-Gui, Wu Hao-Bo
Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Orthopedic Research Institute of Zhejiang University, Hangzhou, China.
Front Pharmacol. 2018 Mar 27;9:210. doi: 10.3389/fphar.2018.00210. eCollection 2018.
Osteoporosis is a common health problem worldwide caused by an imbalance of bone formation vs. bone resorption. However, current therapeutic approaches aimed at enhancing bone formation or suppressing bone resorption still have some limitations. In this study, we demonstrated for the first time that cepharanthine (CEP, derived from Hayata) exerted a protective effect on estrogen deficiency-induced bone loss. This protective effect was confirmed to be achieved through inhibition of bone resorption , rather than through enhancement of bone formation . Furthermore, the study revealed that CEP attenuated receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast formation, and suppressed bone resorption by impairing the c-Jun N-terminal kinase (JNK) and phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathways. The inhibitory effect of CEP could be partly reversed by treatment with anisomycin (a JNK and p38 agonist) and/or SC79 (an AKT agonist) . Our results thus indicated that CEP could prevent estrogen deficiency-induced bone loss by inhibiting osteoclastogenesis. Hence, CEP might be a novel therapeutic agent for anti-osteoporosis therapy.
骨质疏松症是一种全球范围内常见的健康问题，由骨形成与骨吸收失衡引起。然而，目前旨在增强骨形成或抑制骨吸收的治疗方法仍存在一些局限性。在本研究中，我们首次证明了千金藤素（CEP，源自台湾金线莲）对雌激素缺乏诱导的骨质流失具有保护作用。这种保护作用被证实是通过抑制骨吸收而非增强骨形成来实现的。此外，研究表明CEP可减弱核因子κB受体激活剂配体（RANKL）诱导的破骨细胞形成，并通过损害c-Jun氨基末端激酶（JNK）和磷脂酰肌醇3激酶（PI3K）-AKT信号通路来抑制骨吸收。用茴香霉素（一种JNK和p38激动剂）和/或SC79（一种AKT激动剂）处理可部分逆转CEP的抑制作用。因此，我们的结果表明CEP可通过抑制破骨细胞生成来预防雌激素缺乏诱导的骨质流失。因此，CEP可能是一种用于抗骨质疏松治疗的新型治疗药物。
