Effects of Polymethoxyflavonoids on Bone Loss Induced by Estrogen Deficiency and by LPS-Dependent Inflammation in Mice.
Effects of Polymethoxyflavonoids on Bone Loss Induced by Estrogen Deficiency and by LPS-Dependent Inflammation in Mice.
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DOI：
10.3390/ph11010007
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发表时间：
2018-01-20
期刊：
影响因子：
--
通讯作者：
Inada M
中科院分区：
文献类型：
--
作者：
Matsumoto S;Tominari T;Matsumoto C;Yoshinouchi S;Ichimaru R;Watanabe K;Hirata M;Grundler FMW;Miyaura C;Inada M
多甲氧基黄酮（Polymethoxyflavonoids，PMFs）是柑橘类水果中的一类天然化合物，主要由陈皮素、柑桔素、七甲氧基黄酮（HMF）和四甲氧基黄酮（Tetramethoxyflavonoids，HMF）组成。PMF具有多种生物学功能，包括抗氧化作用。我们以前的研究表明，川陈皮素、橘子素和HMF都通过抑制前列腺素E2的合成来抑制白细胞介素（IL）-1介导的破骨细胞分化。在这项研究中，我们创建了一个原始的混合物PMFs（nobilastatin，tangeretin，HMF，和PGEX），并检查是否PMFs表现出合作的抑制作用，破骨细胞生成和骨吸收。在骨髓细胞和成骨细胞的共培养中，PMFs剂量依赖性地抑制IL-1诱导的破骨细胞分化和骨吸收。PMFs抑制破骨细胞分化的最适浓度低于单独使用的浓度，表明PMFs的体外抑制破骨细胞分化的能力强于单独使用的浓度。口服PMFs可恢复去卵巢小鼠雌激素缺乏引起的股骨骨丢失。我们进一步测试了PMFs对脂多糖诱导的小鼠牙槽骨骨吸收的影响。在牙周炎的离体实验模型中，PMFs显著抑制了小鼠牙槽骨器官培养物中的骨吸收活性。这些结果表明，纯化的川陈皮素、柑橘素、HMF和甘草素的混合物在骨疾病的小鼠模型中表现出针对骨丢失的保护的协同抑制作用，这表明PMFs可能是用于预防骨吸收疾病如骨质疏松症和牙周炎的潜在候选物。
Polymethoxyflavonoids (PMFs) are a family of the natural compounds that mainly compise nobiletin, tangeretin, heptamethoxyflavone (HMF), and tetramethoxyflavone (TMF) in citrus fruits. PMFs have shown various biological functions, including anti-oxidative effects. We previously showed that nobiletin, tangeretin, and HMF all inhibited interleukin (IL)-1-mediated osteoclast differentiation via the inhibition of prostaglandin E2 synthesis. In this study, we created an original mixture of PMFs (nobiletin, tangeretin, HMF, and TMF) and examined whether or not PMFs exhibit co-operative inhibitory effects on osteoclastogenesis and bone resorption. In a coculture of bone marrow cells and osteoblasts, PMFs dose-dependently inhibited IL-1-induced osteoclast differentiation and bone resorption. The optimum concentration of PMFs was lower than that of nobiletin alone in the suppression of osteoclast differentiation, suggesting that the potency of PMFs was stronger than that of nobiletin in vitro. The oral administration of PMFs recovered the femoral bone loss induced by estrogen deficiency in ovariectomized mice. We further tested the effects of PMFs on lipopolysaccharide-induced bone resorption in mouse alveolar bone. In an ex vivo experimental model for periodontitis, PMFs significantly suppressed the bone-resorbing activity in organ cultures of mouse alveolar bone. These results indicate that a mixture of purified nobiletin, tangeretin, HMF, and TMF exhibits a co-operative inhibitory effect for the protection against bone loss in a mouse model of bone disease, suggesting that PMFs may be potential candidates for the prevention of bone resorption diseases, such as osteoporosis and periodontitis.
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影响因子：
4.8
作者：
Miyaura, C;Inada, M;Suda, T
通讯作者：
Suda, T
影响因子：
6.1
作者：
Tanabe, N;Maeno, M;Ito, K
通讯作者：
Ito, K
影响因子：
64.5
作者：
Lacey, DL;Timms, E;Boyle, WJ
通讯作者：
Boyle, WJ
DOI：
10.1016/j.bbrc.2009.01.146
发表时间：
2009-04-03
影响因子：
3.1
作者：
Hirata, Michiko;Kobayashi, Megumi;Inada, Masaki
通讯作者：
Inada, Masaki
影响因子：
4.4
作者：
Suda, K;Udagawa, N;Nagai, K
通讯作者：
Nagai, K