Phytoestrogen-derived multifunctional ligands for targeted therapy of breast cancer

Nano-targeted delivery systems have been widely used for breast tumor drug delivery.Estrogen receptors are considered to be significant drug delivery target receptors due to their overexpression in a variety of tumor cells.However,targeted ligands have a significant impact on the safety and effectiveness of active delivery systems,limiting the clinical transformation of nanoparticles.Phytoestrogens have shown good biosafety characteristics and some affinity with the estrogen receptor.In the present study,molecular docking was used to select tanshinone IIA(Tan IIA)among phytoestrogens as a target ligand to be used in nanodelivery systems with somemodifications.Modified Tan IIA(Tan-NH2)showed a good biosafety profile and demonstrated tumor-targeting,anti-tumor and anti-tumor metastasis effects.Moreover,the ligand was utilized with the anti-tumor drug Dox-loaded mesoporous silica nanoparticles via chemical modification to generate a nanocomposite Tan-Dox-MSN.Tan-Dox-MSN had a uniform particle size,good dispersibility and high drug loading capacity.Validation experiments in vivo and in vitro showed that it also had a better targeting ability,anti-tumor effect and lower toxicity in normal organs.These results supported the idea that phytoestrogens with high affinity for the estrogen receptor could improve the therapeutic efficacy of nano-targeted delivery systems in breast tumors.

Effect of Epimedium-derived Phytoestrogen on Bone Turnover and Bone Microarchitecture in OVX-induced Osteoporotic Rats

To investigate the preventive effect of epimedium-derived phytoestrogen （PE） on osteoporosis induced by ovariectomy （OVX） in rats, 11-month-old female Wistar rats were randomly divided into Sham, OVX and PE groups. One week after OVX, daily oral administration of PE （0.4 g·kg^-1·day^-1） started in PE group, and rats in Sham and OVX groups were given vehicle accordingly. The administrations lasted for 12 weeks. The biological markers including serum osteocalcin （OC） and urinary deoxypyridinoline （DPD） for bone tumover were evaluated at the end of the 12th week. On the 13th week, all the rats were sacrificed. The right proximal tibiae were removed, subjected to micro CT for determination of trabecular bone structure and then bone histomorphometry was performed to assess bone remodeling. The OVX rats were in a high bone tumover status as evidenced by increased bone formation markers and bone resorption markers. Treatment with PE could suppress the high bone turnover rate in OVX rats. Micro CT data revealed that PE treatment could ameliorate the deterioration of the micro-architecture of proximal tibiae induced by OVX, as demonstrated by greater bone volume, increased trabecular thickness and less trabecular separation in PE group in comparison with OVX group. The static and dynamic parameters of bone histomorphometry indicated that there were significant increases in bone formation variables and significant decreases in bone resorption variables between PE and OVX groups. The findings suggest that PE has a beneficial effect on trabecular bone in OVX rat model and this effect is possibly associated with stimulation of bone formation as well as inhibition of bone resorption.

Phytoestrogens and prevention of breast cancer: The contentious debate

Phytoestrogens have multiple actions within target cells, including the epigenome, which could be beneficial to the development and progression of breast cancer. In this brief review the action of phytoestrogens on oestrogen receptors, cell signalling pathways, regulation of the cell cycle, apoptosis, steroid synthesis and epigenetic events in relation to breast cancer are discussed. Phytoestrogens can bind weakly to oestrogen receptors(ERs) and some have a preferential affinity for ERβ which can inhibit the transcriptional growthpromoting activity of ERα. However only saturating doses of phytoestrogens, stimulating both ERα and β, exert growth inhibitory effects. Such effects on growth may be through phytoestrogens inhibiting cell signalling pathways. Phytoestrogens have also been shown to inhibit cyclin D1 expression but increase the expression of cyclin-dependent kinase inhibitors(p21 and p27) and the tumour suppressor gene p53. Again these effects are only observed at high(> 10) μmol/L doses of phytoestrogens. Finally the effects of phytoestrogens on breast cancer may be mediated by their ability toinhibit local oestrogen synthesis and induce epigenetic changes. There are, though, difficulties in reconciling epidemiological and experimental data due to the fact experimental doses, both in vivo and in vitro, far exceed the circulating concentrations of "free" unbound phytoestrogens measured in women on a high phytoestrogen diet or those taking phytoestrogen supplements.

phytoestrogens/insoluble fibers and colonic estrogen receptor β: randomized, double-blind, placebo-controlled study

AIM:To assess the safety and effect of the supplementation of a patented blend of dietary phytoestrogens and insoluble fibers on estrogen receptor (ER)-β and biological parameters in sporadic colonic adenomas. METHODS:A randomized, double-blind placebo-controlled trial was performed. Patients scheduled to undergo surveillance colonoscopy for previous sporadic colonic adenomas were identified, and 60 eligible patients were randomized to placebo or active dietary intervention (ADI) twice a day, for 60 d before surveillance colonoscopy. ADI was a mixture of 175 mg milk thistle extract, 20 mg secoisolariciresinol and 750 mg oat fiber extract. ER-β and ER-α expression, apoptosis and proliferation (Ki-67 LI) were assessed in colon samples. RESULTS:No adverse event related to ADI was recorded. ADI administration showed a significant increases in ER-β protein (0.822 ± 0.08 vs 0.768 ± 0.10, P = 0.04) and a general trend to an increase in ER-β LI (39.222 ± 2.69vs 37.708 ± 5.31,P = 0.06), ER-β/ER-α LI ratio (6.564 ± 10.04 vs 2.437 ± 1.53, P = 0.06), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (35.592 ± 14.97 vs 31.541 ± 11.54, P = 0.07) and Ki-67 (53.923 ± 20.91 vs 44.833 ± 10.38, P = 0.07) approximating statistical significance. A significant increase of ER-β protein (0.805 ± 0.13 vs 0.773 ± 0.13,P = 0.04), mRNA (2.278 ± 1.19vs 1.105 ± 1.07, P < 0.02) and LI (47.533 ± 15.47 vs 34.875 ± 16.67,P < 0.05) and a decrease of ER-α protein (0.423 ± 0.06vs 0.532 ± 0.11,P < 0.02) as well as a trend to increase of ER-β/ER-α protein in ADI vs placebo group were observed in patients without polyps (1.734 ± 0.20 vs 1.571 ± 0.42, P = 0.07). CONCLUSION:The role of ER-β on the control of apoptosis, and its amenability to dietary intervention, are supported in our study.

Role of phytoestrogens in prevention and management of type 2 diabetes

Type 2 diabetes(T2D)has become a major public health threat across the globe.It has been widely acknowledged that diet plays an important role in the development and management of T2D.Phytoestrogens are polyphenols that are structurally similar to endogenous estrogen and have weak estrogenic properties.Emerging evidence from pre-clinical models has suggested that phytoestrogens may have anti-diabetic function via both estrogendependent and estrogen-independent pathways.In the current review,we have summarized the evidence linking two major types of phytoestrogens,isoflavones and lignans,and T2D from epidemiological studies and clinical trials.The cross-sectional and prospective cohort studies have reported inconsistent results,which may due to the large variations in different populations and measurement errors in dietary intakes.Long-term intervention studies using isoflavone supplements have reported potential beneficial effects on glycemic parameters in postmenopausal women,while results from short-term smallsize clinical trials are conflicting.Taken together,the current evidence from different study designs is complex and inconsistent.Although the widespread use of phytoestrogens could not be recommended yet,habitual consumption of phytoestrogens,particularly their intact food sources like soy and whole flaxseed,could be considered as a component of overall healthy dietary pattern for prevention and management of T2D.

Combination of low-concentration of novel phytoestrogen(8,9)-furanyl-pterocarpan-3-ol from Pachyrhizus erosus attenuated tamoxifen-associated growth inhibition on breast cancer T47D cells

Objective:To investigate the estrogenic effect of(8,9)-furanyl-pterocarpan-3-ol(FPC)on growth of human breast cancer T47D cells and the interactions between the FPC and tamoxifen(TAM),on the growth of estrogen receptor-dependent breast cancer T47D cells.Methods:The proliferation effect of FPC were conducted on T47D cells in vitro by MTT test.T47D cells were treated with FPC alone(0.01-200μmol/L)or in combination with TAM 20 nmol/L.Furthermore,the expression of ERαor c-Myc were also determined by immunohistochemistry.Results:The results indicated that administration of an anti-estrogen TAM showed growth inhibitory effect on T47D cells,wheraes co-administered with low concentration(less than 1μmol/L)of FPC attenuated to promote cell proliferation.In contrast,the combination of TAM with higher doses(more than 20μmol/L)of FPC showed growth inhibitory.This result was supported by immunocytochemistry studies that the administration of 20 nmol/L TAM down-regulated ER-αand c-Myc,but the combination of 20 nmol/L TAM and 1μmol/L FPC robustly up-regulated expression of ER-α.Thus,the reduced growth inhibition of TAM 20 nmol/L by FPC 1μmol/L on T47D cells may act via the modulation of ER-α.Conclusions:The findings indicate and suggest that FPC had estrogenic activity at low concentrations and anti-estrogenic effect that are likely to be regulated by c-Myc and estrogen receptors.We also confirm that low concentration of FPC attenuated the growth-inhibitory effects of TAM on mammary tumor prevention.Therefore,the present study suggests that caution is warranted regarding the consumption of dietary FPC by breast cancer patients while on TMA therapy.

Effect of Phytoestrogen Activity on hFOB 1.19 Osteoblast Cells of Vanilla Siamensis

The unsaponifiable compounds derived from the fresh green beans of Vanilla siamens＆ Rol. ex. Dow were assayed for the first time to detect their estrogenic activity. We used a simple screening method using the yeast two hybrid system based on the binding of a ligand to estrogen receptors. Yeast cells carrying the hER （human estrogen receptor） gene, ERE （estrogen response elements） and lacZ （β-galactosidase gene） are very suitable for screening and sensitive analysis of estrogenic compound. Our results showed that V. siamensis plant extracts bind with relatively affinity to YES- hERa was 2.27-fold the relative potency ofestradiol （E2） in YES-hERa. The effects of phytoestrogen activity on the osteoblast cells were examined on the proliferation of hFOB 1.19 cells and the bone mineralization process. V. siamens＆ was a positive screening result and induced mineralization ofosteoblasts. This study indicated that V. siamensis plant extract exhibited the characteristic effects of a nature bone promoter compound as phytoestrogen.

Involvement of Estrogen Receptors in the Anxiolytic-Like Effect of Phytoestrogen Genistein in Rats with 12-Weeks Postovariectomy

Phytoestrogens are natural compounds found in some vegetables, and they replicate many of the physiochemical and physiological properties of estrogens, including the regulation of mood. The phytoestrogen genistein exerts anxiolytic-like effects in rats with a chronic absence of ovarian hormones, but the mechanism involved in this effect remains to be explored. The present study explored the participation of estrogen receptor-β in the anxiolytic-like effect of genistein (1.0 mg/kg, i.p., for 4 days) in Wistar rats with 12-weeks postovariectomy, considered as experimental model of post-surgical menopause. In the light/dark test, a useful tool for anxiety study and for the screening of anxiolytic drugs, genistein reduced the latency to enter and increased the time spent in the light compartment and significantly increased the frequency and time spent exploring the light compartment compared with the control group, which is considered as an anxiolytic-like effect at experimental level. All behavioral effects produced by genistein in the light/dark test were blocked by previous tamoxifen administration (5.0 mg/kg, s.c., for 6 days), a non selective antagonist for estrogen receptor-β. The effects produced by genistein or tamoxifen in this test were not related to significant changes in general motor activity evaluated in the open field test. In conclusion, the specific contribution of present investigation was identify that estrogen receptor-β is involved in the anxiolytic-like effect produced by phytoestrogen genistein in rats with a long-term absence of ovarian hormones;supporting the hypothesis that estrogen receptor-β participates in the regulation of anxiety associated with low concentration of ovarian hormones and in the anxiolytic-like effects produced by natural estrogenic compounds such as phytoestrogens.

植物雌激素大豆黄酮对断奶期小鼠乳腺退化的减缓作用研究

旨在研究植物雌激素大豆黄酮(DZ)对断奶期小鼠乳腺退化的影响。选取48只孕鼠,随机分为对照组(CON组),腹腔注射无菌PBS;大豆黄酮组(DZ组),每天每kg体重腹腔注射DZ 100 mg,连续处理1周。孕鼠正常分娩后,在哺乳期第10天强制断奶。各组分别在断奶第1、3、7天选取8只小鼠取血后处死,取所有乳腺组织,称重计算乳腺指数;ELISA法测定血液中雌二醇(E2)、催乳素(PRL)、胰岛素样生长因子(IGF-Ⅰ)的浓度;常规法制作乳腺组织切片,进行HE染色;Western blot及荧光定量PCR(RT-qPCR)分析乳腺组织内促凋亡因子Bax和抗凋亡因子Bcl-2的蛋白与基因表达水平。结果:与CON组相比,DZ组增加了断奶1 d母鼠的乳腺指数,但降低断奶3 d、7 d的乳腺指数;与CON组相比,断奶1 d时,DZ组极显著提高母鼠血清中PRL和IGF-Ⅰ浓度(P<0.01),断奶3 d时DZ组极显著提高了PRL和E2浓度(P<0.01),显著提高断奶7 d母鼠血清中E2浓度(P<0.05);HE染色结果显示,与CON组相比,DZ组显著降低断奶母鼠乳腺组织中脂肪细胞面积比(P<0.05),提高腺泡的面积比(P>0.05);与CON组相比,DZ组极显著上调断奶期乳腺组织Bcl-2蛋白的表达水平(P<0.01),极显著下调断奶1 d Bax基因的表达水平(P<0.01),断奶3 d时极显著下调Bax蛋白与基因的表达水平(P<0.01),断奶7 d时极显著上调乳腺中Bax和Bcl-2蛋白的表达水平(P<0.01),在断奶1 d和3 d,Bcl-2/Bax比值均极显著升高(P<0.01)。本研究表明,DZ处理可升高断奶母鼠血清中IGF-Ⅰ、PRL及E2浓度,上调乳腺中Bcl-2/Bax比值,抑制细胞凋亡,降低脂肪细胞所占面积比,提示DZ可能通过抑制母鼠乳腺细胞凋亡,延缓乳腺早期退化。

植物雌激素鹰嘴豆芽素A(BCA)对肝纤维化去势小鼠模型的改善作用及机制

目的探究植物雌激素鹰嘴豆芽素A(BCA)对CCl4诱导的雌性双侧卵巢切除(去势)小鼠肝纤维化的影响及其机制。方法取50只去势雌性昆明小鼠,腹腔注射CCl4建立肝纤维化模型,将建模小鼠按体质量随机分成模型组、阳性对照组、BCA低、中、高剂量组各10只,同时选取10只同批雌性小鼠切除双侧卵巢旁少量脂肪组织作为假手术组。假手术组和模型组灌胃等体积的0.5%羧甲基纤维素钠溶液,阳性对照组用雌二醇2 mg/kg灌胃,BCA低、中、高剂量组分别按25、50、100 mg/kg BCA灌胃,1次/d,连续7周。给药结束后麻醉处死小鼠取材,测定肝指数和子宫指数,HE及Masson染色观察肝组织病理改变,生化法检测AST、ALT活性,ELISA法检测肝组织中IL-6、TNF-α水平,Western Blot法测定肝组织中Ⅰ型胶原蛋白(CollagenⅠ)、转化生长因子-β1(TGF-β1)、α-平滑肌肌动蛋白(α-SMA)、雌激素受体β(ERβ)、p-NF-κBp65/NF-κBp65蛋白的相对表达量。计量资料两组间比较采用成组t检验,多组间比较采用单因素方差分析;进一步两两比较采用LSD-t检验。非正态分布的计量资料多组间比较及进一步两两比较均采用Kruskal-Wallis H检验。结果与假手术组相比,模型组肝指数升高,子宫指数降低,血清AST和ALT活性、肝组织中IL-6、TNF-α水平及CollagenⅠ、TGF-β1、α-SMA、p-NF-κBp65/NF-κBp65蛋白表达均升高(P值均<0.05),肝组织ERβ表达变化不明显(P>0.05),模型组肝组织明显纤维化病变,出现肝细胞水肿、脂肪样变、坏死并伴有炎细胞浸润,胶原纤维增生沉积、交错分布。与模型组比较,BCA各剂量组肝指数降低,血清ALT和AST活性、肝组织IL-6、TNF-α水平及CollagenⅠ、TGF-β1、α-SMA、p-NF-κBp65/NF-κBp65的蛋白表达均降低(P值均<0.05),子宫指数无明显变化(P>0.05),肝组织ERβ蛋白表达升高(P<0.05),肝组织的纤维化病变有不同程度改善。结论BCA可有效改善CCl4诱导的雌性去势小鼠肝纤维化,其作用机制可能是通过上调ERβ抑制NF-κB信号通路,减轻炎症反应而实现的。

Bidirectional regulation of angiogenesis by phytoestrogens through estrogen receptor-mediated signaling networks

Sex hormone estrogen is one of the most active intrinsic angiogenesis regulators; its therapeutic use has been limited due to its carcinogenic potential. Plant-derived phytoestrogens are attractive alternatives, but reports on their angiogenic activities often lack in-depth analysis and sometimes are controversial. Herein, we report a data-mining study with the existing literature, using IPA system to classify and characterize phytoestrogens based on their angiogenic properties and pharmacological consequences. We found that pro-angiogenic phytoestrogens functioned predominantly as cardiovascular protectors whereas anti-angiogenic phytoestrogens played a role in cancer prevention and therapy. This bidirectional regulation were shown to be target-selective and, for the most part, estrogen-receptor-dependent. The transactivation properties of ERa and ERβ by phytoestrogens were examined in the context of angiogenesis-related gene transcription. ERa and ERβ were shown to signal in opposite ways when complexed with the phytoestrogen for bidirectional regulation of angiogenesis. With ERa, phytoestrogen activated or inhibited transcription of some angiogenesis-related genes, resulting in the promotion of angiogenesis, whereas, with ERβ, phytoestrogen regulated transcription of angiogenesis-related genes, resulting in inhibition of angiogenesis. Therefore, the selectivity of phytoestrogen to ERa and ERβ may be critical in the balance of pro- or anti-angiogenesis process.

植物雌激素防治阿尔茨海默病的研究进展

植物雌激素是指植物中能与哺乳动物体内雌激素受体结合并将其激活的一类化合物,对机体有着不同程度的保护和改善的作用。近代药理学研究发现,植物雌激素在心血管系统,神经系统,内分泌系统,免疫系统等方面均有治疗作用。值得注意是植物雌激素与脑内雌激素受体结合可产生中枢神经保护作用,并通过多个环节靶点改善阿尔茨海默病患者的学习与认知障碍。该文将对植物雌激素样作用的单体、中草药及复方防治阿尔茨海默病研究进展及相关机制进行阐述,以期为中医药有效治疗老年痴呆提供新的设计思路和解决途径。

芒柄花素药理作用及机制的研究进展

芒柄花素是一种天然异黄酮类化合物,广泛存在于黄芪、葛根、鸡血藤、红三叶草等中药中,是典型的植物雌激素,能双向调节雌激素活性。现代药理研究表明,芒柄花素可通过雌激素依赖或独立机制发挥多种潜在的药理作用,包括雌激素样作用、抗炎、抗氧化、抗增殖活性等。这种活性成分在多种慢性疾病,如心脑血管疾病、代谢性疾病、骨质疏松、恶性肿瘤、肝肾功能损伤等疾病中也显示出预防和治疗的潜力,主要涉及沉默调节蛋白1(SIRT1)、过氧化物酶体增殖物激活受体α(PPARα)、PPARγ、核转录因子-κB(NF-κB)、核转录因子红细胞相关因子2/血红素加氧酶-1(Nrf2/HO-1)、内皮型一氧化氮合酶/一氧化氮(eNOS/NO)、B淋巴细胞瘤-2相关X蛋白(Bax)、B淋巴细胞瘤-2(BCL-2)等信号通路的调节。对芒柄花素的多种生物学作用和其所涉及的信号通路进行综述,以期为芒柄花素的基础研究和临床应用提供参考。

Phytoestrogens Inhibiting Androgen Receptor Signal and Prostate Cancer Cell Proliferation

The androgen receptor（AR） signaling activated by dihydrotestosterone（DHT） plays critical roles in pros- tate cancer development and progression. Phytoestrogens, which are diphenolic compounds with estrogen and an- ti-estrogen effects, can bind to estrogen receptors. However, their function on AR signaling has not been fully eluci- dated. In this study, dual-luciferase reporter assay, immunobloting, docking system test, MTT assay, immunofluores- cence and chromatin immunoprecipitation（ChlP） assays were employed to examine the potential effects of three phytoestrogens（genistein, daidzein, flavone） on DHT-activated prostate specific antigen（PSA） activation, cell proli- feration and AR transactivation in lymph node carcinoma of prostate（LNCaP） cells. Phytoestrogens were detected to down-regulate DHT-activated AR-mediated PSA promoter transactivation by dual-luciferase reporter system. Fur- thermore, three phytoestrogens, especially genistein, were demonstrated to significantly decrease AR-activated PSA protein expression by Western blotting analysis. MTT experiment proves that phytoestrogens, especially genistein, remarkably inhibits the DHT-indueed cell proliferation in LNCaP cells. To provide reasonable explanations for expe- rimental phenomena mentioned above, we did docking system test and detected phytoestrogens to share the same AR-binding site with DHT. To further prove the competition between phytoestrogen and DHT on AR binding, we examined the effects of phytoestrogens on DHT-activated AR nuclear translocation and immunofluorescence analysis which confirms that phytoestrogens, especially genistein, inhibit DHT-activated androgen receptor nuclear transloca- tion. Results from ChIP show that phytoestrogens down-regulate DHT-induces AR binding to the androgen response elements（AREs, including AREI, AREII, and AREIII） in PSA promoter. Genistein remarkably down-regulates AR, binding to the AREI located in -250---39 bp and AREIII in --4170---3978 bp in the presence of DHT. In general, three phytoestrogens were identified to inhibit DHT-AR binding by competitively binding to AR and inhibit AR-mediated transactivation. And genistein shows the strongest effects among three phytoestrogens. Our findings confirm that phytoestrogens are AR antagonist in the regulation of AR-related PSA activation and cell proliferation, which provides valuable insights into the treatment of prostate cancer.

Expression of Phytoestrogens in pGL2/AQPI Promoter Reporter System

In this study, we amplified aqnaporin I（AQP1） promoter sequence with polymerase chain reaction（PCR）, then AQP1 promoter fragment and pGL2 basic vector were linked to create an artificial pGL2/AQP1 promoter re- porter system. A certain concentration of 17β-estradiol（E2） activated pGL2/AQPlp, which demonstrated the pGL2/AQPlp transcriptional system effective. The pGL2/AQP1 promoter reporter system was applied to evaluate the activate effect on AQP1 of different kinds of phytoestrogens. Dual hiciferase reporter gene activity assay showed that a certain concentration phytoestrogens including daidzein and genistein can increase AQP1 promoter transcription activity. In addition, E2, daidzein and genistein can make AQP1 protein endogenous expression level increase and promote the function of water scretion. The result can guide the clinical application to treat the Sjogren＇s syndrome and provide a necessary molecular tool for the subsequent drug screening.

基于网络药理学及分子对接方法探讨大豆异黄酮治疗骨质疏松的机制

目的 基于网络药理学及分子对接方法探讨大豆异黄酮(SI)治疗骨质疏松(OP)的可能作用机制。方法 通过文献检索收集SI所含成分,并利用SwissADME数据库根据Lipinski类药五原则评估各成分的药代动力学参数,筛选SI有效活性成分。通过STITCH及SwissTargetPrediction数据库预测SI有效活性成分的作用靶点;通过TTD、DrugBank及DisGeNET疾病数据库获取OP疾病相关靶点。将SI活性成分靶点与OP疾病相关靶点导入Draw Venn Diagram在线平台,得到两者交集靶点(共同靶点),即SI治疗OP的潜在作用靶点。利用Cytoscape 3.7.1软件构建SI治疗OP的“活性成分-潜在作用靶点”网络。通过STRING数据库和Cytoscape软件对交集靶点进行蛋白相互作用(PPI)分析,并用cytoHubba插件筛选出核心靶点。利用Metascape平台对交集靶点进行GO功能及KEGG通路富集分析。利用AutoDock Vina软件对SI有效活性成分与核心靶点进行分子对接。结果 共收集大豆异黄酮成分12种,通过SwissADME数据库筛选出3种有效活性成分:大豆苷元(Daidzein)、染料木素(Genistein)和黄豆黄素(Glycitein),均为游离型苷元。共获得活性成分作用靶点243个,OP疾病相关靶点471个,得到二者的共同靶点(交集靶点)62个,即SI治疗OP的潜在作用靶点。通过PPI网络分析筛选出了10个核心(Hub)基因,包括IGF1、MAPK1、IL6、MAPK3等。GO功能富集结果显示,交集靶点主要参与类固醇代谢、骨化等生物学过程。KEGG通路富集发现,交集靶点主要与类固醇激素的合成和TGF-β、雌激素、IL-17、Jak-STAT等信号通路有关。分子对接显示,3种活性成分和9种靶蛋白之间具有较好的结合能力。结论 大豆异黄酮可能主要通过游离苷元促进内源性雌激素生成及参与成骨分化、骨吸收相关信号通路及生物学途径防治骨质疏松。

植物雌激素在心血管领域研究的可视化分析

目的探究植物雌激素(PE)在心血管领域的研究热点、前沿及未来研究趋势。方法在Web of Science Core Collection(Wo SCC)数据库中检索相关文献,以纯文本的格式导出检索文献的全记录与引用的参考文献,运用Cite Space V对这些文献的国家、机构、作者、学科领域、共被引文献、关键词、聚类、突发词进行可视化分析。结果1048篇文献由个74国家(地区)、1329个机构、5207例作者完成。发文量最多的国家和机构分别是美国和中国医学科学院,中国的陈裕明与意大利的Alessandra Bitto为最具生产力的作者。饮食与营养学、药理学、内分泌代谢学与心脏病学为该领域的主要学科。大豆异黄酮、金雀异黄素、绝经后女性、心血管疾病、冠心病、动脉粥样硬化、血压等为高频关键词,NFκB、炎症、凋亡、多酚、胰岛素抵抗等为突现词。结论PE在心血管领域的研究涉及多国家、多机构、多学科的多位学者,本研究分析得到了目前该领域的研究热点和未来的研究趋势。未来仍需要更多的随机双盲对照试验及系统评价来探索PE对心血管系统的影响。

雌激素的3D-QSAR模型构建及其在饲料与鸡肉中含量的测定以及对人体的影响

雌激素对人体有显著的内分泌干扰效应.本文以雌激素受体相对亲和力(relative binding affinity,RBA)作为生物活性,对雌激素进行了三维定量构效关系(3D-QSAR)计算,得到具有较好预测能力的CoMFA(交叉验证相关系数q^(2)=0.721,非交叉验证相关系数r^(2)=0.925)和CoMSIA(q^(2)=0.824,r^(2)=0.961)模型.并对国内各地区鸡肉进行了雌激素含量检测与雌激素效应评估.植物雌激素在鸡饲料和鸡肉中检出率为69%和84%;天然雌激素在鸡饲料和鸡肉中检出率为53%和50%.检测及评估结果显示绝大部分鸡肉可以安全食用,但鸡肉中含有的己烯雌酚、17α-乙炔雌二醇以及香芹酚所具有的雌激素效应值得引起重视.

植物雌激素类中药诱导白色脂肪组织棕色化的研究进展

当前全球范围内肥胖率急剧上升,并可诱发多种急慢性疾病,然而尚缺少安全有效的控制肥胖手段。通过减少机体的能量摄入或者促进能量消耗是控制体重增长的主要治疗方法与策略。作为调节能量平衡的主要器官,白色脂肪组织(WAT)负责储存机体摄入的多余能量,而棕色脂肪组织(BAT)则负责以适应性产热的方式消耗能量。当机体受到某些外部信号的影响时,如交感神经受到刺激、β_(3)肾上腺素能受体(β_(3)-ARs)被激活后,WAT中会出现功能与棕色脂肪细胞类似的脂肪细胞群,称为米色脂肪细胞,这一过程则称为WAT棕色化。通过激活BAT产热或促进WAT棕色化成为了目前预防和改善肥胖状态的重要途径之一。目前,有多项研究报道了具有雌激素样活性的中药单体及含有植物雌激素的中药提取物可以改善代谢综合征的各种症状。因此,本文就植物雌激素类中药通过激活BAT及促进WAT棕色化在预防或治疗肥胖及相关病理状态的研究展开综述,以期为今后探究植物雌激素类中药预防和治疗肥胖及相关代谢疾病的机制提供新的研究思路。

女性绝经与非酒精性脂肪性肝病的关系及相关治疗的研究进展

非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)是慢性非传染性疾病,是代谢综合征(metabolic syndrome,MS)在肝脏的表现。绝经是女性因卵巢功能衰退所呈现的生理现象,表现为下丘脑-垂体功能退化。临床和流行病学研究表明,NAFLD的发病趋势具有两性差异,且与血糖、血脂、血尿酸等代谢参数有关。女性绝经前NAFLD发病率低于男性,而绝经后NAFLD的发病率逐渐升高至与男性相当,其机制可能主要与女性绝经后体内性激素的变化(以雌激素的下降为主)有关。性激素的变化,如雌激素和性激素结合球蛋白(sex hormone binding globulin,SHBG)水平降低而雄激素水平相对升高,会增加腹型肥胖、血脂代谢异常及胰岛素抵抗(insulin resistance,IR)等异常指标的发生率,使绝经成为女性NAFLD的重要的独立危险因素;而雄激素受体拮抗剂、雌激素及植物雌激素等可通过多种途径改善肝脏脂肪变性及IR,减轻NAFLD的严重程度,延缓肝纤维化进展,对绝经女性NAFLD有一定治疗意义,但也具有部分局限性。该文就近年来女性绝经与NAFLD相关关系的研究进展予以综述,为绝经女性NAFLD的预防和治疗提供思路和参考。