Boldine Ameliorates Estrogen Deficiency-Induced Bone Loss via Inhibiting Bone Resorption.

Boldine Ameliorates Estrogen Deficiency-Induced Bone Loss via Inhibiting Bone Resorption.
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Boldine 通过抑制骨吸收改善雌激素缺乏引起的骨质流失

DOI:
10.3389/fphar.2018.01046
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发表时间:
2018
影响因子:
5.6
通讯作者:
Chen AM
Chen AM
中科院分区:
医学2区
文献类型:
--
作者:
Chen K;Lv ZT;Cheng P;Zhu WT;Liang S;Yang Q;Parkman VA;Zhou CH;Jing XZ;Liu H;Wang YT;Lin H;Liao H;Chen AM

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骨质疏松症是一个巨大的健康问题所造成的骨吸收和骨形成之间的不平衡。目前骨质疏松症的治疗策略仍有一定的局限性。Boldine是一种从Peumus boldus中分离的生物碱,已被证明在体内具有抗氧化和抗炎作用。我们首次发现boldine对雌激素缺乏引起的小鼠骨丢失具有保护作用。根据Micro-CT和组织形态计量学分析,boldine通过抑制骨吸收而不影响体内骨形成来进行这种保护作用。此外,我们发现boldine可以通过破坏AKT信号通路抑制核因子-κB配体受体激活剂(RANKL)诱导的破骨细胞形成,而SC 79(AKT激动剂)部分挽救了这种作用。总之,我们的研究结果表明,boldine可以通过抑制破骨细胞生成来预防雌激素缺乏引起的骨质疏松症。因此,boldine可能作为一种新的治疗药物,用于抗肿瘤治疗。
Osteoporosis is an enormous health problem caused by the imbalance between bone resorption and bone formation. The current therapeutic strategies for osteoporosis still have some limitations. Boldine, an alkaloid isolated from Peumus boldus, has been shown to have antioxidant and anti-inflammatory effects in vivo. For the first time, we discover that boldine has a protective effect for the estrogen deficiency-induced bone loss in mice. According to the Micro-CT and histomorphometry assays, boldine conducts this protective effect through inhibiting bone resorption without affecting bone formation in vivo. Moreover, we showed that boldine can inhibit receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation via impairing the AKT signaling pathways, while SC79 (an AKT agonist) partially rescue this effect. In conclusion, our results suggest that boldine can prevent estrogen deficiency-induced osteoporosis by inhibiting osteoclastogenesis. Thus, boldine may be served as a novel therapeutic agent for anti-osteoporotic therapy.
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