A diarylheptanoid phytoestrogen from Curcuma comosa, 1,7-diphenyl-4,6-heptadien-3-ol, accelerates human osteoblast proliferation and differentiation.
A diarylheptanoid phytoestrogen from Curcuma comosa, 1,7-diphenyl-4,6-heptadien-3-ol, accelerates human osteoblast proliferation and differentiation.
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DOI：
10.1016/j.phymed.2013.02.008
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发表时间：
2013-06-15
期刊：
影响因子：
7.9
通讯作者：
Blair, Harry C.
中科院分区：
文献类型：
--
作者：
Tantikanlayaporn, Duangrat;Robinson, Lisa J.;Suksamrarn, Apichart;Piyachaturawat, Pawinee;Blair, Harry C.
关键词：
姜黄 (Cucuma comosa Roxb.)是姜科植物，用于缓解更年期症状。先前的研究表明，C. comosa 提取物可以保护小鼠免受卵巢切除引起的骨质减少，同时对生殖器官的影响最小，并确定二芳基庚烷 (3R)-1,7-二苯基-(4E,6E)-4,6-heptadien-3-ol (DPHD) 是 C. comosa 根茎的主要活性成分。在 1-10 μM 时，DPHD 增加了转化小鼠成骨细胞的分化，但 DPHD 对正常骨细胞的影响尚不清楚。我们在未转化的人成骨细胞（h-OB）中检查了 DPHD 相对于 17β-雌二醇的浓度依赖性和作用机制。 h-OB 对 DPHD 的敏感性比转化的成骨细胞高 10-100 倍：DPHD 在 10 nM 时增加 h-OB 增殖，在 100 nM 时在 30 分钟内激活 MAP 激酶信号传导。在长期分化测定中，h-OB 对 DPHD 的反应在 10 nM 时显着，大多数情况下最佳反应是在 100 nM 时。 7-21 天时，碱性磷酸酶活性和成骨细胞特异性 mRNA 的产生表明，DPHD 加速了成骨细胞分化。雌激素受体拮抗剂 ICI182780 消除了 DPHD 的影响。在分化过程中，DPHD 促进成骨细胞转录因子 RUNX2 和 osterix 的早期表达。随后，DPHD 加速了骨结构基因的产生，包括与 17β-雌二醇相当的 COL1A1 和骨钙素。在 h-OB 中，DPHD 增加了骨保护素与 RANKL 的比率，并且比 10 nM 17β-雌二醇更有效地支持矿化。我们得出的结论是，DPHD 在纳摩尔浓度下可在体外有效促进人成骨细胞功能，使其成为保护更年期妇女骨骼的有前途的化合物。
Curcuma comosa Roxb. is ginger-family plant used to relieve menopausal symptoms. Previous work showed that C. comosa extracts protect mice from ovariectomy-induced osteopenia with minimal effects on reproductive organs, and identified the diarylheptanoid (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (DPHD) as the major active component of C. comosa rhizomes. At 1–10 μM, DPHD increased differentiation in transformed mouse osteoblasts, but the effect of DPHD on normal bone cells was unknown. We examined the concentration dependency and mechanism of action of DPHD relative to 17β-estradiol in nontransformed human osteoblasts (h-OB). The h-OB were 10–100 fold more sensitive to DPHD than transformed osteoblasts: DPHD increased h-OB proliferation at 10 nM and, at 100 nM, activated MAP kinase signaling within 30 minutes. In long-term differentiation assays, responses of h-OB to DPHD were significant at 10 nM, and optimal response in most cases was at 100 nM. At 7–21 days, DPHD accelerated osteoblast differentiation, indicated by alkaline phosphatase activity and osteoblast-specific mRNA production. Effects of DPHD were eliminated by the estrogen receptor antagonist ICI182780. During differentiation, DPHD promoted early expression of osteoblast transcription factors, RUNX2 and osterix. Subsequently, DPHD accelerated production of bone structural genes, including COL1A1 and osteocalcin comparably to 17β-estradiol. In h-OB, DPHD increased the osteoprotegerin to RANKL ratio and supported mineralization more efficiently than 10 nM 17β-estradiol. We conclude that DPHD promotes human osteoblast function in vitro effectively at nanomolar concentrations, making it a promising compound to protect bone in menopausal women.
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影响因子：
10.4
作者：
Winuthayanon W;Piyachaturawat P;Suksamrarn A;Ponglikitmongkol M;Arao Y;Hewitt SC;Korach KS
通讯作者：
Korach KS
影响因子：
20.3
作者：
Riggs, BL;Khosla, S;Melton, LJ
通讯作者：
Melton, LJ
DOI：
10.1111/j.1742-7843.2006.pto_277.x
发表时间：
2006-03-01
影响因子：
3.1
作者：
Bernstein, L
通讯作者：
Bernstein, L
影响因子：
3.6
作者：
Kuhnle, Gunter G. C.;Ward, Heather A.;Khaw, Kay-Tee
通讯作者：
Khaw, Kay-Tee
影响因子：
2.5
作者：
Shedd-Wise, Kristine M.;Alekel, D. Lee;Hofmann, Heike;Hanson, Kathy B.;Schiferl, Dan J.;Hanson, Laura N.;Van Loan, Marta D.
通讯作者：
Van Loan, Marta D.