Department of Physiology, Faculty of Science, Mahidol University , Bangkok 10400, Thailand.
Department of Chemistry, Faculty of Science, Mahidol University , Bangkok 10400, Thailand.
J Agric Food Chem. 2017 May 3;65(17):3490-3496. doi: 10.1021/acs.jafc.7b00769. Epub 2017 Apr 24.
Diarylheptanoids from Curcuma comosa, of the Zingiberaceae family, exhibit diverse estrogenic activities. In this study we investigated the estrogenic activity of a major hydroxyl diarylheptanoid, 7-(3,4 -dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene (compound 092) isolated from C. comosa. The compound elicited different transcriptional activities of estrogen agonist at low concentrations (0.1-1 μM) and antagonist at high concentrations (10-50 μM) using luciferase reporter gene assay in HEK-293T cells. In human breast cancer (MCF-7) cells, compound 092 showed an anti-estrogenic activity by down-regulating ERα-signaling and suppressing estrogen-responsive genes, whereas it attenuated the uterotrophic effect of estrogen in immature ovariectomized rats. Of note, compound 092 promoted mouse pre-osteoblastic (MC3T3-E1) cell differentiation and the related bone markers, indicating its positive osteogenic effect. Our findings highlight a new, nonsteroidal, estrogen agonist/antagonist of catechol diarylheptanoid from C. comosa, which is scientific evidence supporting its potential as a dietary supplement to prevent bone loss with low risk of breast and uterine cancers in postmenopausal women.
姜科姜黄属植物莪术中的二芳基庚烷类化合物具有多种雌激素活性。本研究采用萤光素酶报告基因检测法，在 HEK-293T 细胞中研究了从莪术中分离得到的主要羟基二芳基庚烷类化合物 7-(3,4-二羟基苯基)-5-羟基-1-苯基-(1E)-1-庚烯（化合物 092）的雌激素活性。该化合物在低浓度（0.1-1 μM）时表现出雌激素激动剂的不同转录活性，而在高浓度（10-50 μM）时表现出雌激素拮抗剂的活性。在人乳腺癌（MCF-7）细胞中，化合物 092 通过下调 ERα 信号通路和抑制雌激素反应基因表现出抗雌激素活性，而在去卵巢未成熟大鼠中则减弱了雌激素的子宫增殖作用。值得注意的是，化合物 092 促进了小鼠前成骨细胞（MC3T3-E1）的分化和相关的骨标志物，表明其具有正向的成骨作用。我们的研究结果突出了一种新的非甾体类儿茶酚二芳基庚烷类化合物，作为雌激素激动剂/拮抗剂，具有预防绝经后妇女乳腺癌和子宫癌风险低的骨质疏松症的潜力，为其作为膳食补充剂提供了科学依据。
