Department of Environmental Toxicology, University of California, One Shields Avenue, Davis, CA 95616, USA.
BMC Complement Altern Med. 2013 Jun 14;13:133. doi: 10.1186/1472-6882-13-133.
The plant genus Fallopia is well-known in Chinese traditional medicine and includes many species that contain bioactive compounds, namely phytoestrogens. Consumption of phytoestrogens may be linked to decreased incidence of breast and prostate cancers therefore discovery of novel phytoestrogens and novel sources of phytoestrogens is of interest. Although phytoestrogen content has been analyzed in the rhizomes of various Fallopia sp., seeds of a Fallopia sp. have never been examined for phytoestrogen presence.
Analytical chemistry techniques were used with guidance from an in vitro estrogen receptor bioassay (a stably transfected human ovarian carcinoma cell line) to isolate and identify estrogenic components from seeds of Fallopia convolvulus. A transiently transfected human breast carcinoma cell line was used to characterize the biological activity of the isolated compounds on estrogen receptors (ER) α and β.
Two compounds, emodin and the novel flavan-3-ol, (-)-epiafzelechin-3-O-p-coumarate (rhodoeosein), were identified to be responsible for estrogenic activity of F. convolvulus seed extract. Absolute stereochemistry of rhodoeosein was determined by 1 and 2D NMR, optical rotation and circular dichroism. Emodin was identified by HPLC/DAD, LC/MS/MS, and FT/ICR-MS. When characterizing the ER specificity in biological activity of rhodoeosein and emodin, rhodoeosein was able to exhibit a four-fold greater relative estrogenic potency (REP) in breast cells transiently-transfected with ERβ as compared to those transfected with ERα, and emodin exhibited a six-fold greater REP in ERβ-transfected breast cells. Cell type-specific differences were observed with rhodoeosein but not emodin; rhodoeosein produced superinduction of reporter gene activity in the human ovarian cell line (> 400% of maximum estradiol [E2] induction) but not in the breast cell line.
This study is the first to characterize the novel flavan-3-ol compound, rhodoeosein, and its ability to induce estrogenic activity in human cell lines. Rhodoeosein and emodin may have potential therapeutic applications as natural products activating ERβ, and further characterization of rhodoeosein is necessary to evaluate its selectivity as a cell type-specific ER agonist.
藤属植物在中药中广为人知，其中包含许多含有生物活性化合物的物种，即植物雌激素。植物雌激素的摄入可能与乳腺癌和前列腺癌发病率的降低有关，因此发现新的植物雌激素和植物雌激素的新来源是很有意义的。尽管已经分析了各种藤属植物的根茎中的植物雌激素含量，但从未对藤属植物的种子进行过植物雌激素存在的检测。
在体外雌激素受体生物测定（稳定转染的人卵巢癌细胞系）的指导下，使用分析化学技术从鸡矢藤种子中分离和鉴定具有雌激素活性的成分。使用瞬时转染的人乳腺癌细胞系来表征分离化合物对雌激素受体 (ER) α 和 β 的生物学活性。
两种化合物，大黄素和新型黄烷-3-醇，（-）表儿茶素-3-O-对香豆酸酯（鸡矢藤素），被鉴定为鸡矢藤种子提取物具有雌激素活性的原因。通过 1 和 2D NMR、旋光和圆二色性确定了鸡矢藤素的绝对立体化学。通过 HPLC/DAD、LC/MS/MS 和 FT/ICR-MS 鉴定了大黄素。在表征鸡矢藤素和大黄素在生物活性中的 ER 特异性时，鸡矢藤素在瞬时转染 ERβ的乳腺癌细胞中表现出比转染 ERα的细胞高出四倍的相对雌激素效价（REP），而大黄素在转染 ERβ的乳腺癌细胞中表现出六倍的更高 REP。观察到鸡矢藤素的细胞类型特异性差异，但大黄素没有；鸡矢藤素在人卵巢细胞系中产生报告基因活性的超诱导（超过最大雌二醇 [E2] 诱导的 400%），但在乳腺癌细胞系中没有。
这项研究首次对新型黄烷-3-醇化合物鸡矢藤素及其在人细胞系中诱导雌激素活性的能力进行了表征。鸡矢藤素和大黄素可能具有作为激活 ERβ 的天然产物的潜在治疗应用，需要进一步对鸡矢藤素进行表征，以评估其作为细胞类型特异性 ER 激动剂的选择性。
