植物雌激素与前列腺癌及良性前列腺增生

植物雌激素是一类广泛分布于各类植物中的结构与雌激素相似并具有弱雌激素及抗雄激素活性的天然活性物质。PCa与BPH是雄激素依赖性及与年龄相关的疾病,近年来流行病学调查和实验研究均表明植物雌激素对PCa与BPH有防治作用。其机制可能与植物雌激素对性激素的调节、对细胞增生的抑制、诱导细胞凋亡及抗氧化作用等有关。     

Synthesis of [2H8]‐enterolactone and [2H10]‐enterodiol

Enterolactone and enterodiol are the main mammalian metabolites of dietary butyrolactone type lignans. The study of biological properties and potential health effects of these compounds requires isotopically labelled compounds as standards for quantitative measurements. An expedient deutero‐labelling method for enterolactone is to use the D₃PO₄·BF₃/D₂O complex at room temperature which will exchange all eight aromatic hydrogens, even from inactivated meta positions, to form [2,4,5,6,2′,4′,5′,6′‐²H₈]‐enterolactone in 74% yield and 99% isotopic purity. [2,4,5,6,9,9,2′,4′,5′,6′‐²H₁₀]‐Enterodiol was prepared from [2,4,5,6,2′,4′,5′,6′‐²H₈]‐enterolactone by reduction with LiAlD₄ which introduces two more deuterium atoms into the molecule. Copyright © 2003 John Wiley & Sons, Ltd.     

The influence of phytoestrogens on different physiological and pathological processes: An overview

Functional foods have nutritional properties and organic functions, which are beneficial to health. Certain types of functional food components are so‐called phytoestrogens, non‐steroidal compounds derived from the metabolism of precursors contained in plants, which originate secondary metabotypes known to induce biological responses and by mimicry or modulating the action of endogenous estrogen. These molecules are involved in several physiological and pathological processes related to reproduction, bone remodeling, skin, cardiovascular, nervous, immune systems, and metabolism. This review aimed to present an overview of phytoestrogens regarding their chemical structure, actions, and effects in the organism given several pathologies. Several studies have demonstrated beneficial phytoestrogen actions, such as lipid profile improvement, cognitive function, menopause, oxidative stress, among others. Phytoestrogens effects are not completely elucidated, being necessary future research to understand the exact action mechanisms, whether they are via estrogen receptor or whether other hidden mechanisms produce these effects. Thus, this review makes a general approach to the phytoestrogen actions, beneficial effects, risk and limitations. However, the complexities of biological effects after ingestion of phytoestrogens and the differences in their metabolism and bioavailability indicate that interpretation of either risk or benefits needs to be made with caution.     

Dietary intake of phytoestrogens, estrogen receptor-beta polymorphisms and the risk of prostate cancer

BACKGROUND: The causes of prostate cancer are poorly understood, but genetic factors may be more important than for many other malignancies, and dietary phytoestrogens may be protective. Because phytoestrogens bind tightly to the estrogen receptor-beta, we conducted an epidemiologic investigation of synergistic effects between phytoestrogen intake and estrogen receptor-beta gene polymorphisms. METHODS: We performed a population-based case-control study in Sweden. All participants reported their phytoestrogen intake and donated a blood sample. We identified four haplotype-tagging single nucleotide polymorphisms (htSNPs) and genotyped these htSNPs in 1314 prostate cancer patients and 782 controls. Odds ratios were estimated by multivariate logistic regression. Interactions between phytoestrogen intake and estrogen receptor-beta SNPs on prostate cancer risk were evaluated considering both multiplicative and additive effect scales. RESULTS: We found a significant multiplicative interaction (P = 0.04) between dietary intake of phytoestrogens and a promoter SNP in the estrogen receptor-beta gene (rs 2987983-13950), but not with any of the three other htSNPs (P = 0.11, 0.69, 0.85). Among carriers of the variant promoter alleles, we found strong inverse associations with increasing intake of total phytoestrogens (odds ratio for highest vs. lowest quartile = 0.43; P for trend <0.001), isoflavonoids (odds ratio = 0.63; P for trend = 0.05), and coumestrol (odds ratio = 0.57; P for trend = 0.003). We found no association between phytoestrogens and prostate cancer among carriers homozygous for the wild-type allele (TT). CONCLUSIONS: Our study provides strong evidence that high intake of phytoestrogens substantially reduce prostate cancer risk among men with specific polymorphic variation in the promoter region of the estrogen receptor-beta gene.     

补骨脂素的植物雌激素作用及其机制探讨

目的:利用雌激素受体(ER)α,β阳性T47D细胞和子宫内膜癌Ishikawa细胞观察补骨脂素的雌激素样作用,并探讨其可能的作用机制。方法:以1×10^-8mol.L^-1雌二醇(E₂)为阳性对照药,利用MTT细胞增殖试验观察1×10^-5~1×10^-9mol.L^-1补骨脂素对T47D增殖的影响,同时观察1×10^-6mol.L^-1和1×10^-7mol.L^-1补骨脂素对Ishikawa细胞增殖的影响;以半定量RT-PCR法检测1×10^-6mol.L^-1和1×10^-7mol.L^-1补骨脂素对T47D细胞雌激素效应基因PR mRNA表达情况的影响;并以雌激素受体拮抗剂ICI 182,780为工具药进行干预。同时,通过流式细胞术检测1×10^-6mol.L^-1和1×10^-7mol.L^-1补骨脂素引起T47D细胞ER-α,ER-β含量的变化。结果:1×10^-5~1×10^-7mol.L^-1补骨脂素能够显著促进T47D细胞增殖;1×10^-6mol.L^-1和1×10^-7mol.L^-1补骨脂素对Ishikawa细胞增殖也有显著的促进作用;RT-PCR结果显示:1×10^-6mol.L^-1和1×10^-7mol.L^-1补骨脂素可使T47D细胞PR mRNA表达显著增加,表现出雌激素样作用,而且以上效应可被ICI 182,780拮抗。1×10^-6mol.L^-1和1×10^-7mol.L^-1补骨脂素还可诱导T47D细胞ER-α,ER-β表达明显增加。结论:补骨脂素具有植物雌激素作用,并且其作用是通过ER途径介导的。     

植物雌激素与性激素失调导致的干眼症

植物雌激素是一类天然的结构及生物活性均类似于雌激素的非甾体类化合物，可与雌激素受体结合，对内源性雌激素起双向调节作用。多种原因引起的性激素失调可以导致干眼症。作者认为植物雌激素因其特有的优势可以治疗此类干眼症，值得进一步研究。     

红花等10种中药的植物雌激素活性研究

目的：评价红花、川牛膝、丹参、女贞子、枸杞、甘草、肉苁蓉、淫羊藿、补骨脂、菟丝子等10味中药的植物雌激素活性。方法：选用昆明种雌性乳鼠,随机分为A,B二组：A组又分为12组（溶剂对照组、己烯雌酚组和10个中药组）；B组也分为12组（溶剂对照组、己烯雌酚组和10个中药拮抗组）,其中中药拮抗组每天同时灌胃中药和己烯雌酚；各组给药4 d后分离血清。利用雌激素受体（ER）阳性MCF-7细胞,以MTT法检测中药含药血清对细胞增殖的影响。结果：A组中,红花、川牛膝、丹参、枸杞、肉苁蓉、淫羊藿、补骨脂和菟丝子等中药含药血清可显著促进MCF-7细胞增殖；而女贞子组可见细胞增殖受到明显抑制。B组中,红花、川牛膝、丹参、甘草、淫羊藿、补骨脂和菟丝子组可见己烯雌酚促细胞增殖的作用受到了显著抑制；而肉苁蓉可协同并显著增强己烯雌酚促细胞增殖的作用。结论：红花、川牛膝、丹参、淫羊藿、补骨脂、菟丝子等6种中药在单独用药时具有拟雌激素作用,在与雌激素同时用药时具有抗雌激素作用,其双向调节效应依赖于体内雌激素水平的高低。     

红三叶草异黄酮及其代谢研究进展

红三叶草异黄酮具有多种生理活性,从其结构特点上阐述了红三叶草异黄酮的植物雌激素功能。近年来国内外学者对其生理功能的研究发现,红三叶草异黄酮的植物雌激素作用与其代谢产物密切相关。红三叶草异黄酮属于4’-甲氧基类异黄酮,需要在生物体内通过微生物酶系作用下转化成具有双羟基结构以及活性更高的4’-羟基类异黄酮,从而能够更好地与雌激素受体结合,发挥植物雌激素作用。