Department of Physiology, Mahidol University, Bangkok 10400, Thailand.
Phytomedicine. 2013 Jun 15;20(8-9):676-82. doi: 10.1016/j.phymed.2013.02.008. Epub 2013 Apr 1.
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 1-10μM, 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 10nM and, at 100nM, activated MAP kinase signaling within 30 min. In long-term differentiation assays, responses of h-OB to DPHD were significant at 10nM, 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 10nM 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.
莪术是姜科植物，用于缓解更年期症状。先前的工作表明，莪术提取物可保护去卵巢小鼠免受骨质疏松症的影响，对生殖器官的影响很小，并鉴定出二芳基庚烷（3R）-1,7-二苯基-（4E,6E）-4,6-庚二烯-3-醇（DPHD）是莪术根茎的主要活性成分。在 1-10μM 时，DPHD 可增加转化的鼠成骨细胞的分化，但 DPHD 对正常骨细胞的影响尚不清楚。我们研究了 DPHD 相对于 17β-雌二醇在非转化人成骨细胞（h-OB）中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 10nM 时增加 h-OB 的增殖，在 100nM 时，在 30 分钟内激活 MAP 激酶信号通路。在长期分化实验中，h-OB 对 DPHD 的反应在 10nM 时就很显著，在大多数情况下，最佳反应在 100nM 时。在 7-21 天内，DPHD 加速成骨细胞分化，碱性磷酸酶活性和成骨细胞特异性 mRNA 产物表明。DPHD 的作用被雌激素受体拮抗剂 ICI182780 消除。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 COL1A1 和骨钙素，与 17β-雌二醇相当。在 h-OB 中，DPHD 增加了骨保护素与核因子κB 受体激活剂配体（RANKL）的比值，并比 10nM 17β-雌二醇更有效地支持矿化。我们得出结论，DPHD 以纳摩尔浓度有效地促进人成骨细胞的体外功能，使其成为保护绝经后妇女骨骼的有前途的化合物。
