Cepharanthine Prevents Estrogen Deficiency-Induced Bone Loss by Inhibiting Bone Resorption.
Cepharanthine Prevents Estrogen Deficiency-Induced Bone Loss by Inhibiting Bone Resorption.
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Cepharanthine 通过抑制骨吸收来防止雌激素缺乏引起的骨质流失
DOI：
10.3389/fphar.2018.00210
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发表时间：
2018
影响因子：
5.6
通讯作者：
Wu HB
中科院分区：
文献类型：
--
作者：
Zhou CH;Meng JH;Yang YT;Hu B;Hong JQ;Lv ZT;Chen K;Heng BC;Jiang GY;Zhu J;Cheng ZH;Zhang W;Cao L;Wang W;Shen WL;Yan SG;Wu HB
骨质疏松症是一种由骨形成与骨吸收失衡引起的全球性常见健康问题。然而，目前旨在促进骨形成或抑制骨吸收的治疗方法仍有一些局限性。在这项研究中，我们首次证明千金藤素（CEP，来自千金藤）对雌激素缺乏引起的骨丢失具有保护作用。这种保护作用被证实是通过抑制体内骨吸收而不是通过增强体内骨形成来实现的。此外，体外研究表明，CEP减弱核因子κB配体受体激活剂（RANKL）诱导的破骨细胞形成，并通过损害c-Jun N-末端激酶（JNK）和磷脂酰肌醇3-激酶（PI 3 K）-AKT信号通路抑制骨吸收。CEP的抑制作用可被JNK和p38激动剂茴香霉素和/或AKT激动剂SC 79部分逆转。因此，我们的研究结果表明，CEP可以防止雌激素缺乏引起的骨丢失，抑制破骨细胞生成。因此，CEP可能成为一种新的抗骨质疏松治疗药物。
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 Stephania cepharantha Hayata) exerted a protective effect on estrogen deficiency-induced bone loss. This protective effect was confirmed to be achieved through inhibition of bone resorption in vivo, rather than through enhancement of bone formation in vivo. Furthermore, the in vitro 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) in vitro. 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.
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