Genistein

摘要： Objective:To compare the cardioprotective efficacy of equimolar doses(50 mM/kg,p.o.)of phloretin and genistein against doxorubicin-induced cardiotoxicity in rats.Methods:Cardiotoxicity was induced in rats by intraperitoneal injection of 6 mg/kg doxorubicin on alternative days till the cumulative dose reached 30 mg/kg.This study included four treatment groups of rats(n=6):the control group(0.5%carboxymethyl cellulose solution-treated),the doxorubicin-treated group(0.5%carboxymethyl cellulose solution along with doxorubicin),the genistein-treated group(50 mM/kg/day;p.o.along with doxorubicin)and phloretin-treated group(50 mM/kg/day;p.o.along with doxorubicin).On the 10th day of dosing,rats were anesthetized for recording ECG,mean arterial pressure,and left ventricular function.Oxidative stress,nitric oxide levels,and inflammatory cytokines were estimated in the cardiac tissue.Cardiac function parameters(creatine kinase MB,lactate dehydrogenase,aspartate aminotransferase,and alanine transaminase)were estimated in the serum samples.Results:Phloretin treatment inhibited doxorubicin-induced oxidative stress and also reduced nitric oxide levels in cardiac tissues of rats.Phloretin administration attenuated doxorubicin-induced alterations in hemodynamic parameters(heart rate,mean arterial blood pressure,and left ventricular function)and suppressed the expression of pro-inflammatory cytokines.The cardiac injury markers like creatine kinase MB,lactate dehydrogenase,aspartate aminotransferase,and alanine transaminase were reduced by both genistein and phloretin.All these effects of phloretin were more prominent than genistein.Conclusions:Phloretin offers cardioprotection that is comparable to genistein,a clinically validated cardioprotectant against doxorubicin-induced cardiotoxicity.Further studies are needed to confirm and establish the therapeutic utility of phloretin as a chemopreventive adjuvant to doxorubicin chemotherapy.

摘要： Exposure to Bisphenol A (BPA) worldwide is on the increase. Its toxicities in various tissues expressing estrogen receptors have been reported. However, limited information exists on its effects on the gastric tissue. This study therefore investigated the gastric effects of BPA exposure and the likely ameliorative potential of genistein, a phytoestrogen antioxidant, known to interact with estrogen receptors. Eighty-four male Wistar rats were randomly divided into 6 groups (n = 14) and orally treated for 28 days. Group I-IV received distilled water (0.2 ml), corn oil (3 ml/kg), BPA (50 mg/kg) and genistein (50 mg/kg) respectively. Group V was pre-treated daily with BPA one hour prior to genistein administration while Group VI was pre-treated daily with genistein one hour prior to BPA treatment. Thereafter, blood was collected into heparinized bottles for hematological analysis. Gastric juice was collected for pH and electrolytes determination. Gastric tissue was excised and analyzed for superoxide dismutase (SOD), reduced glutathione (GSH), malondialdehyde, nitric oxide (NO), mucin, parietal and mucous cell counts, and histology. The BPA only treatment group exhibited significant increases (p < 0.05) in white blood cell count, neutrophil-lymphocyte ratio, mucin concentration, NO, and malondialdehyde while gastric juice pH, bicarbonate, SOD, and GSH levels were reduced compared to control. The gastric mucosa also showed pathologies consistent with inflammation. Genistein pre-and post-treatment in BPA exposed rats significantly (p < 0.05) ameliorated these effects of BPA. However, some signs of gastric inflammation were still evident in the mucosal samples. Bisphenol A induces gastro-toxicity by increasing gastric acidity, reducing gastric juice bicarbonate level and disrupting prooxidant/antioxidant balance. Genistein pre- and post-treatment ameliorated these gastro-toxic effects of Bisphenol A via gastroprotective, antioxidant and anti-inflammatory mechanisms.

摘要： [Objectives]The paper was to establish the quality standard of Yi herb medicine Millettia dielsiana.[Methods]Yi herb medicine M.dielsiana was qualitatively identified by microscopic identification and thin layer identification.The content of total isoflavones was determined by UV-Vis spectrophotometry,and the contents of moisture,total ash,acid-insoluble ash and extract were checked according to the method introduced in Chinese Pharmacopoeia(2020 edition).[Results]The microscopic identification features,including stone cells,fiber bundles,calcium oxalate square crystals,starch granules,pigment blocks,ducts,etc.,were distinct.A TLC method for identification of M.dielsiana was established.The contents of water,total ash,acid-insoluble ash and extract should be no more than 13%,no more than 7%,no more than 0.5%and no less than 6%in 10 batches of samples,respectively.The total isoflavones of M.dielsiana based on genistein(C_(15)H_(10)O_(5))should be no less than 0.25%.The linear relationship of genistein was good in the range of 0.002-0.007 mg/mL(R^(2)=0.9996);the average recovery was 97.01%and the RSD was 2.62%.[Conclusions]The method is simple,accurate and well-reproducible,and can be used for the quality control of Yi herb medicine M.dielsiana.

摘要： 目的 探讨Genistein对卵巢癌细胞增殖和细胞周期调控的效应.方法 Genistein处理卵巢癌OVCAR-5细胞后,通过细胞计数和MTS检测明确细胞增殖和活性的变化,Real-time PCR及Western blotting检测重要细胞周期调节因子表达的变化.结果 Genistein显著促进了OVCAR-5细胞的增殖和活性,引起PCNA、Cyclin D1、CDK4等细胞周期活化因子mRNA和蛋白表达升高,p21和p27等细胞周期抑制因子等表达下降.结论 Genistein能够促进卵巢癌OVCAR-5细胞的增殖以及G1-S期的转变.这种差异可能是由不同的实验条件和/或细胞株不同的雌激素表达模式引起的.本研究结果可为深入分析Genistein在卵巢癌细胞中的作用和机制提供基础信息.

摘要： 目的 探讨大豆异黄酮(Genistein)对原代大鼠肠系膜动脉平滑肌细胞(MASMC)泡沫化影响.方法 木瓜蛋白酶-胶原酶F消化法获取MASMC,与氧化型低密度脂蛋白(ox-LDL)共培养建立泡沫细胞模型,分为对照组、模型组、Genistein组、大豆苷元(Daidzein)组、酪氨酸激酶抑制剂(Tyrphostin)组.台盼蓝染色鉴定其活力,油红O染色、油红萃取、免疫荧光评估泡沫化程度.结果 显微镜下观察MASMC呈长梭形,培养呈典型"峰-谷"样生长;MASMC特异肌动蛋白(α-SMA)阳性表达占95％;细胞活性达99％以上.与未刺激对照相比,使用ox-LDL刺激后,模型组油红O染色染色显示ox-LDL促使MASMC内脂滴的蓄积(P＜ 0.01),α-SMA表达减少(P＜ 0.01);实验组Genistein、Tyrphostin抑制脂质蓄积及诱导α-SMA表达增多,与模型组相比有显著差异(P＜ 0.05),而Daidzein不影响脂质蓄积和o-SMA表达,与模型组相比差异无统计学意义(P＞ 0.05).结论 Genistein能够抑制ox-LDL诱导的MASMC源性泡沫细胞的形成,与抑制酪氨酸激酶活性有关.

摘要： Objective:To investigate the effects and mechanisms of genistein on the gene expression in the Wnt pathway in acute leukemia(AL)cells.Methods:The expression of Wnt pathway genes and cell cycle-related genes were analyzed in two AL cell lines.Pyrophosphate sequencing was performed to determine the methylation degree.Then,the enrichment of H4K20mel and H3K9ac was determined using ChIP-qPCR.Flow cytometry was used to analyze the cell cycle.Results:The IC_(50) of genistein in the two AL cell lines was lower than that for the bone marrow mesenchymal stem cell line.Genistein upregulated H4K20mel,KMT5A and Wnt suppressor genes,including Wnt5a,and downregulated the downstream target genes of Wnt,such as c-myc and β-catenin.The methylation degree and H3K9ac enrichment in the Wnt5a promoter region remained unchanged.However,the enrichment of H4K20mel in the Wnt5a promoter and coding regions increased.In addition,genistein upregulated Phospho-cdc2,Mytl,Cyclin A,Cyclin E2,p21 and Phospho-histone H3,but downregulated Phospho-weel.Cell cycle arrest was induced in the G2/M phase.Conclusion:Genistein inhibits the activation of the Wnt pathway by promoting the expression of Wnt5a through the activation of KMT5A and enrichment of H4K20mel in the Wnt5a gene promoter and coding regions,rather than demethylation.Genistein also blocks the cell cycle in the G2/M phase.Therefore,genistein is a potential anti-leukemia drug.

摘要： 目的 观察Genistein对雌性大鼠卵巢颗粒细胞卵泡刺激素受体(FSHR)基因表达的影响,及其与雌激素受体(ER)的关系.方法 选取25～28日龄雌性大鼠,皮下注射孕马血清促性腺激素,建立促卵泡发育模型,分离卵巢颗粒细胞进行培养,分别给予Genistein(0、0.1、1、5、10、100 μmol/L)及雌激素受体阻断剂ICI 182,780(1μmol/L)处理24 h后,采用逆转录-聚合酶链反应(RT-PCR)检测芳香化酶基因上游调控因子FSHR mRNA的表达.结果 与空白对照组比较,10 μmol/L Genistein组FSHR mRNA表达显著增加(P＜0.05).ICI 182,780(1 μmol/L)预处理细胞30 min后加入1和10 μmol/L Genistein,其FSHR mRNA表达分别较1和10 μmol/L Genistein组显著下降(P＜0.05或P＜ 0.01).结论 10 μmol/L的Genistein可上调雌性大鼠卵巢颗粒细胞中FSHR表达,且该作用可能是通过ER介导的.

摘要： OBJECTIVE Vanadium is a necessary trace element in the human body and has a certain role in the treatment and prevention of diabetes.Organic vanadium is more easily absorbed and less toxic than inorganic vanadium.Thus,in this study,vanadium complex was synthesized from genistein which had good hypoglycemic activity and inor⁃ganic vanadium element,and its hypoglycemic activity and acute oral toxicity were studied.METHODS The vanadium genistein complex was synthesized by chelating vanadium with genistein in methanol and its structure was determined by LC-MS,atomic absorption spectroscopy,UV-visible spectroscopy,elemental and thermodynamic analysis.The antidiabetic activity of the complex was assessed in db/db mice and C57 mice by daily oral gavage for 4 weeks.These db/db mice were divided into test groups〔high(30 mg·kg^-1),medium(20 mg·kg^-1)and low(10 mg·kg^-1)dose group〕,model group,genistein group,inorganic vanadium group,each group of 8;8 C57 mice was for normal control group.The acute toxicity test was carried out on KM mice with this complex by a maximum limit dose method.Randomly 20 healthy KM mice were divided into negative control group and test group,each group of 10,male and female half.RESULTS The molecular structure of this complex was inferred as a complex(VL2)formed by two ligands and one vanadium element.It was found that its hypoglycemic activity was better than that of genistein and inorganic vanadium.The hypoglycemic activity of the high dose group was better than that of the medium dose group and low dose group.The complex can signifi⁃cantly improve the body mass of db/db mice,fasting blood glucose,random blood glucose,liver/body,kidney/body,and the performance of oral glucose tolerance test and insulin tolerance test in db/db mice.The morphology of liver,kidney,pancreas and skeletal muscle also had obvious improvement and repair.Effect on serum index of db/db mice showed that,total cholesterol,triglyceride,low-density lipoprotein cholesterol had no significant improvement compared with the model group,but high-density lipoprotein cholesterol of complex group had significant improvement compared with the model group.In addition,this complex did not produce any hazardous symptoms or deaths in acute oral toxicity test.CONCLUSION complex has good hypoglycemic activity in vivo,and did not have the potential toxicity.This would provide an important reference for the development of functional hypoglycemic foods.

摘要： Applephenon®, a purified extract prepared from green apples, was examined for its cytotoxicity and inhibitory effects on the proliferation of cultures of normal human keratinocytes and several epidermoid cancer cell lines. Our HPLC studies demonstrated a high content of phenolic compounds (>65%), including catechin, epicatechin, caffeic acid and phloretin as well as polyphenols such as proanthocyanidins. Applephenon® demonstrated a greater cytotoxic effect against HeLa, A431 cancer cell lines and HaCaT, an immortalized keratinocyte cell line than serum-free cultures of proliferating normal human keratinocytes (NHK). Proliferation of NHK was inhibited at concentrations above 0.0013% while concentrations above 0.005% were cytotoxic. By contrast, Applephenon® solutions above 0.00025% killed each of the cancer cell lines. Treated cells displayed increased intercellular separation and evidence of keratinizing stratification. We also tested the effect of epicatechin, and two isoflavonoids, genistein and daidzein, on cancer cell lines. Hela cells were more sensitive to epicatechin and genistein inhibition of cell growth and cytotoxicity than were NHK. Daidzein at these concentrations had little effect on cancer cells. These results indicate that Applephenon® and some of its phenolic components have selective anticancer activity.

摘要： Objective:to study the effects of genistein on hematopoiesis and surivial of irradiated mice. Methods: adult male mice were administered orally with genisstein(160mg/kg b.w.) 24h before exposure to a sublethal dose of 6.0gy gamma irradiation. The 30-day survival rate, behavior of hematograms, endogenous hematopoietic spleen colony formation (endocfus), numbers of nucleated cell and granulocyte-macrophage colony forming unit (cfu-gm) in bone marrow following irradiation were examined. In the meantime, protective actions of genistein were compared to those of diethylstilbestrol (des), which was given to mice at dose of 5mg/kg b.w. 24h before irradiation. Results:it was demonstrated that genistein was an effective radioprotector. The survival of irradiated mice protected by genistein was significantly increased and statistically higher than that of mice pre-treated with des. After administration of genistein, enhanced endocfus, numbers of nucleated cell and cfu-gm in bone marrow in mice were found and endocfus numbers was 3.47-fold higher than in irradiated control group. Stimulated recovery of leukocytes, erythrocytes, and thrombocytes were observed in micepre-treated with genistein All above-mentioned results were similar to those in mice protected by des,but the protecting actions of genistein on promoting recovery of nucleated cells and leukocytes were significantly higher than those of des. Conclusion: it could be deduced that the uncertain radioprotective action against death is induced by a possible process of enhanced regeneration of the hematopoietic stem cells due to not only strengthened radioresistance and increased numbers of remained hematopoietic cells, but also enhanced post-irradiation repair or promoted proliferation of the hematopoietic stem cells. These effects of genistein may have some therapeutic implications for radiation-induced injuries.

摘要： 目的：探讨Cenistein对乳腺癌细胞致成骨细胞(osteoblast, OB)增殖、分化和矿化功能的影响，观察Genistein在乳腺癌骨转移的病理条件下是否能调节OB生物学功能。rn 方法：源于大鼠颅盖骨的原代OB与50%来自人源性乳腺癌细胞系或MCF-7的条件培养基（conditioned medium, CM)共同培养，并加人5×10-7 mol/L (G7)、5×10-8 mol/L(G8)或5×10-9　mol/L(G9)的Genistein进行干預。MTT法观察其对OB增殖的影响；PNPP偶氮法观察其对OB碱性磷酸酶（alkaline phosphatase,ALP)活性的影响；茜素红S(ARS)进行矿化结节染色并计算面积以观察其对OB矿化能力的影响。rn 结果：MDA-MB-231和MCF-7细胞条件培养基可显著抑制OB的增殖。用Cenistein干预1d、3d和5d 后,OB增值率可有不同程度的提高,差异有统计学意义（P<0.05)。此外,乳腺癌细胞条件培养基可明显下调OB的AIP活性，而用不同浓度的Genirtein干预后，OB的AIP活性分别较MDA-MB-231和 MCF-7细胞条件培养基组增加22.7%、32.4%、63.5%和27.7%、32.0%，58.3%(P<0.05)=Genistein 还可改善乳腺癌细胞条件培养基对OB矿化能力的抑制，增加OB形成的矿化结节面积。rn 结论：在乳腺癌骨转移的病理条件下,Genistein可促进OB的增殖、分化和矿化能力，改善乳腺癌细胞对OB生物学功能的抑制作用。

摘要： 目的：探讨Cenistein对乳腺癌细胞致成骨细胞(osteoblast, OB)增殖、分化和矿化功能的影响，观察Genistein在乳腺癌骨转移的病理条件下是否能调节OB生物学功能。rn 方法：源于大鼠颅盖骨的原代OB与50%来自人源性乳腺癌细胞系或MCF-7的条件培养基（conditioned medium, CM)共同培养，并加人5×10-7 mol/L (G7)、5×10-8 mol/L(G8)或5×10-9　mol/L(G9)的Genistein进行干預。MTT法观察其对OB增殖的影响；PNPP偶氮法观察其对OB碱性磷酸酶（alkaline phosphatase,ALP)活性的影响；茜素红S(ARS)进行矿化结节染色并计算面积以观察其对OB矿化能力的影响。rn 结果：MDA-MB-231和MCF-7细胞条件培养基可显著抑制OB的增殖。用Cenistein干预1d、3d和5d 后,OB增值率可有不同程度的提高,差异有统计学意义（P<0.05)。此外,乳腺癌细胞条件培养基可明显下调OB的AIP活性，而用不同浓度的Genirtein干预后，OB的AIP活性分别较MDA-MB-231和 MCF-7细胞条件培养基组增加22.7%、32.4%、63.5%和27.7%、32.0%，58.3%(P<0.05)=Genistein 还可改善乳腺癌细胞条件培养基对OB矿化能力的抑制，增加OB形成的矿化结节面积。rn 结论：在乳腺癌骨转移的病理条件下,Genistein可促进OB的增殖、分化和矿化能力，改善乳腺癌细胞对OB生物学功能的抑制作用。

摘要： 目的：探讨Cenistein对乳腺癌细胞致成骨细胞(osteoblast, OB)增殖、分化和矿化功能的影响，观察Genistein在乳腺癌骨转移的病理条件下是否能调节OB生物学功能。rn 方法：源于大鼠颅盖骨的原代OB与50%来自人源性乳腺癌细胞系或MCF-7的条件培养基（conditioned medium, CM)共同培养，并加人5×10-7 mol/L (G7)、5×10-8 mol/L(G8)或5×10-9　mol/L(G9)的Genistein进行干預。MTT法观察其对OB增殖的影响；PNPP偶氮法观察其对OB碱性磷酸酶（alkaline phosphatase,ALP)活性的影响；茜素红S(ARS)进行矿化结节染色并计算面积以观察其对OB矿化能力的影响。rn 结果：MDA-MB-231和MCF-7细胞条件培养基可显著抑制OB的增殖。用Cenistein干预1d、3d和5d 后,OB增值率可有不同程度的提高,差异有统计学意义（P<0.05)。此外,乳腺癌细胞条件培养基可明显下调OB的AIP活性，而用不同浓度的Genirtein干预后，OB的AIP活性分别较MDA-MB-231和 MCF-7细胞条件培养基组增加22.7%、32.4%、63.5%和27.7%、32.0%，58.3%(P<0.05)=Genistein 还可改善乳腺癌细胞条件培养基对OB矿化能力的抑制，增加OB形成的矿化结节面积。rn 结论：在乳腺癌骨转移的病理条件下,Genistein可促进OB的增殖、分化和矿化能力，改善乳腺癌细胞对OB生物学功能的抑制作用。

摘要： 目的：探讨Cenistein对乳腺癌细胞致成骨细胞(osteoblast, OB)增殖、分化和矿化功能的影响，观察Genistein在乳腺癌骨转移的病理条件下是否能调节OB生物学功能。rn 方法：源于大鼠颅盖骨的原代OB与50%来自人源性乳腺癌细胞系或MCF-7的条件培养基（conditioned medium, CM)共同培养，并加人5×10-7 mol/L (G7)、5×10-8 mol/L(G8)或5×10-9　mol/L(G9)的Genistein进行干預。MTT法观察其对OB增殖的影响；PNPP偶氮法观察其对OB碱性磷酸酶（alkaline phosphatase,ALP)活性的影响；茜素红S(ARS)进行矿化结节染色并计算面积以观察其对OB矿化能力的影响。rn 结果：MDA-MB-231和MCF-7细胞条件培养基可显著抑制OB的增殖。用Cenistein干预1d、3d和5d 后,OB增值率可有不同程度的提高,差异有统计学意义（P<0.05)。此外,乳腺癌细胞条件培养基可明显下调OB的AIP活性，而用不同浓度的Genirtein干预后，OB的AIP活性分别较MDA-MB-231和 MCF-7细胞条件培养基组增加22.7%、32.4%、63.5%和27.7%、32.0%，58.3%(P<0.05)=Genistein 还可改善乳腺癌细胞条件培养基对OB矿化能力的抑制，增加OB形成的矿化结节面积。rn 结论：在乳腺癌骨转移的病理条件下,Genistein可促进OB的增殖、分化和矿化能力，改善乳腺癌细胞对OB生物学功能的抑制作用。

摘要： 目的：探讨Cenistein对乳腺癌细胞致成骨细胞(osteoblast, OB)增殖、分化和矿化功能的影响，观察Genistein在乳腺癌骨转移的病理条件下是否能调节OB生物学功能。rn 方法：源于大鼠颅盖骨的原代OB与50%来自人源性乳腺癌细胞系或MCF-7的条件培养基（conditioned medium, CM)共同培养，并加人5×10-7 mol/L (G7)、5×10-8 mol/L(G8)或5×10-9　mol/L(G9)的Genistein进行干預。MTT法观察其对OB增殖的影响；PNPP偶氮法观察其对OB碱性磷酸酶（alkaline phosphatase,ALP)活性的影响；茜素红S(ARS)进行矿化结节染色并计算面积以观察其对OB矿化能力的影响。rn 结果：MDA-MB-231和MCF-7细胞条件培养基可显著抑制OB的增殖。用Cenistein干预1d、3d和5d 后,OB增值率可有不同程度的提高,差异有统计学意义（P<0.05)。此外,乳腺癌细胞条件培养基可明显下调OB的AIP活性，而用不同浓度的Genirtein干预后，OB的AIP活性分别较MDA-MB-231和 MCF-7细胞条件培养基组增加22.7%、32.4%、63.5%和27.7%、32.0%，58.3%(P<0.05)=Genistein 还可改善乳腺癌细胞条件培养基对OB矿化能力的抑制，增加OB形成的矿化结节面积。rn 结论：在乳腺癌骨转移的病理条件下,Genistein可促进OB的增殖、分化和矿化能力，改善乳腺癌细胞对OB生物学功能的抑制作用。

摘要： 目的：探讨Cenistein对乳腺癌细胞致成骨细胞(osteoblast, OB)增殖、分化和矿化功能的影响，观察Genistein在乳腺癌骨转移的病理条件下是否能调节OB生物学功能。rn 方法：源于大鼠颅盖骨的原代OB与50%来自人源性乳腺癌细胞系或MCF-7的条件培养基（conditioned medium, CM)共同培养，并加人5×10-7 mol/L (G7)、5×10-8 mol/L(G8)或5×10-9　mol/L(G9)的Genistein进行干預。MTT法观察其对OB增殖的影响；PNPP偶氮法观察其对OB碱性磷酸酶（alkaline phosphatase,ALP)活性的影响；茜素红S(ARS)进行矿化结节染色并计算面积以观察其对OB矿化能力的影响。rn 结果：MDA-MB-231和MCF-7细胞条件培养基可显著抑制OB的增殖。用Cenistein干预1d、3d和5d 后,OB增值率可有不同程度的提高,差异有统计学意义（P<0.05)。此外,乳腺癌细胞条件培养基可明显下调OB的AIP活性，而用不同浓度的Genirtein干预后，OB的AIP活性分别较MDA-MB-231和 MCF-7细胞条件培养基组增加22.7%、32.4%、63.5%和27.7%、32.0%，58.3%(P<0.05)=Genistein 还可改善乳腺癌细胞条件培养基对OB矿化能力的抑制，增加OB形成的矿化结节面积。rn 结论：在乳腺癌骨转移的病理条件下,Genistein可促进OB的增殖、分化和矿化能力，改善乳腺癌细胞对OB生物学功能的抑制作用。

摘要： 用发酵大豆提取的genistein在生物体中有直接的生物活性,食后无胀气,能保持一定的体内浓度,不受个体差异的影响等优点。Genistein有植物激素样的作用,与体内的游离的环境荷尔蒙产生竞争,将细胞的受体部位占据。加用genistein的动物可减少二恶英引起的发癌;与人参、叶绿素、植物纤维、中药等并用、可增强二恶英的排出和机体的免疫系统功能。