Department of Nutriproteomics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Bioorg Med Chem Lett. 2011 Jun 1;21(11):3248-51. doi: 10.1016/j.bmcl.2011.04.041. Epub 2011 Apr 17.
Osteogenic activity of six diarylheptanoids, acerogenin A (1), (R)-acerogenin B (2), aceroside I (3), aceroside B(1) (4), aceroside III (5) and (-)-centrolobol (6) and two phenolic compounds; (+)-rhododendrol (7) and (+)-cathechin (8), isolated from the stem bark of Acer nikoense (Nikko maple) was evaluated using alkaline phosphatase (ALP) activity as a marker for early osteoblast differentiation. We found that the diphenyl ether-type cyclic diarylheptanoids 1-5 promoted ALP activity in mouse preosteoblastic MC3T3-E1 cells without affecting cell proliferation, but linear-type diarylheptanoid 6 and phenolic compounds 7 and 8 did not. Diphenyl ether-type cyclic diarylheptanoids 1-4 also increased protein production of osteocalcin, a late stage maker for osteoblast differentiation, and induced osteoblastic mineralization. Structure-activity relationships of these compounds demonstrated that the stimulative efficacy of aglycones was higher than that of its glycosides. Taken together, diphenyl ether-type cyclic diarylheptanoids promote early- and late-stage osteoblastogenesis, which may open the possibility for the development of novel osteogenic agents.
从日本槭（Nikko maple）的茎皮中分离得到的六种二芳基庚烷类化合物，包括 acerogenin A（1）、(R)-acerogenin B（2）、aceroside I（3）、aceroside B1（4）、aceroside III（5）和(-)-centrolobol（6），以及两种酚类化合物；（+）-杜鹃醇（7）和（+）-儿茶素（8），以碱性磷酸酶（ALP）活性作为早期成骨细胞分化的标志物，评估其成骨活性。我们发现，二苯醚型环状二芳基庚烷类化合物 1-5 促进了小鼠前成骨细胞 MC3T3-E1 细胞中的 ALP 活性，而不影响细胞增殖，但线性型二芳基庚烷类化合物 6 和酚类化合物 7 和 8 则没有。二苯醚型环状二芳基庚烷类化合物 1-4 还增加了骨钙素的蛋白质产生，骨钙素是成骨细胞分化的晚期标志物，并诱导成骨细胞矿化。这些化合物的结构-活性关系表明，苷元的刺激效果高于其糖苷。总之，二苯醚型环状二芳基庚烷类化合物促进了早期和晚期成骨细胞的形成，这可能为新型成骨剂的开发开辟了可能性。
