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isoflavone Regulates Lipid Metabolism via Expression of Related Genes in OVX Rats Fed on a High-fat Diet

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Biomedical and Environmental Sciences 2008年第5期21卷 357-364页

作者： XIAO-LIN NA JUNKO EZAKI FUMIE SUGIYAMA HONG-BIN CUI AND YOSHIKO ISHIMI Department of Food Nutrition and Hygiene Public Health College Harbin Medical University Harbin 150086 Heilongjiang China Nutritional Epidemiology Program National Institute of Health and Nutrition Tokyo 162-8636 Japan

Objective To investigate the effects of isoflavone on body weight, fat mass, and gene expression in relation to lipid metabolism. Methods Thirty-six female SD rats were ovariectomized or sham-operated and fed on a high-fat diet. Two months later, abdominal incision was made, blood was collected to separate serum, and the liver and adipose tissue were immediately collected and weighed. Some portions of these tissues were frozen in liquid nitrogen and stored at -80℃. Results Ovariectomy （OVX） with a high-fat diet could induce obesity in rats, while treatment with isoflavone significantly inhibited the increase in body weight and fat mass in abdomen. Serum total cholesterol and leptin were significantly decreased in isoflavone group, compared with the OVX group. The mRNA expression of liver fatty acid synthase （FAS） in the OVX group was significantly higher than that in sham-operated group, while this difference was not observed in the isoflavone group. The mRNA expression of liver hormone-sensitive lipase （HSL） in the OVX rats tended to be lower than that in the sham-operated rats. Furthermore, a large amount of isoflavone maintained the mRNA expression at a sham level. Conclusion isoflavone may prevent obesity induced by ovariectomy with a high-fat diet, in part by modulating gene expression related to lipid metabolism.

关键词： isoflavone Lipid metabolism Ovariectomy Obesity Gene expression

An isoflavone derivative potently inhibits the angiogenesis and progression of triple-negative breast cancer by targeting the MTA2/SerRS/VEGFA pathway

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Cancer Biology & Medicine 2020年第3期17卷 693-706页

作者： Xiaotong Zhang Gengyi Zou Xiyang Li Lun Wang Tianyu Xie Jin Zhao Longlong Wang Shunchang Jiao Rong Xiang Haoyu Ye Yi Shi School of Medicine Nankai UniversityTianjin 300071China 2011 Project Collaborative Innovation Center for Biotherapy of Ministry of Education Tianjin 300071China Department of Oncology Chinese PLA General HospitalBeijing 100853China State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan Universityand Collaborative Innovation Center for BiotherapyChengdu 610041China

Objective:Angiogenesis plays a vital role in tumor growth and metastasis.Here,we aimed to find novel efficient antiangiogenic molecules targeting vascular endothelial growth factor A(VEGFA)at the transcriptional level to treat triple-negative breast cancer(TNBC).Methods:We used a cell-based seryl tRNA synthetase(SerRS)promoter-driven dual-luciferase reporter system to screen an in-house library of 384 naturally occurring small molecules and their derivatives to find candidate molecules that could upregulate the expression of SerRS,a potent transcriptional repressor of VEGFA.The levels of SerRS and VEGFA were examined by quantitative RT-PCR(qRT-PCR),western blotting,and/or ELISAs in TNBC cells after candidate molecule administration.Zebrafish,the Matrigel plug angiogenesis assay in mice,the TNBC allograft,and xenograft mouse models were used to evaluate thein vivoanti-angiogenic and anti-cancer activities.Furthermore,the potential direct targets of the candidates were identified by proteomics and biochemical studies.Results:We found the most active compound was 3-(4-methoxyphenyl)quinolin-4(1H)-one(MEQ),an isoflavone derivative.In TNBC cells,MEQ treatment resulted in increased SerRS mRNA(P<0.001)and protein levels and downregulated VEGFA production.Both the vascular development of zebrafish and Matrigel plug angiogenesis in mice were inhibited by MEQ.MEQ also suppressed the angiogenesis in TNBC allografts and xenografts in mice,resulting in inhibited tumor growth and prolonged overall survival(P<0.05).Finally,we found that MEQ regulated SerRS transcription by interacting with MTA2(Metastasis Associated 1 Family Member 2).Conclusions:Our findings suggested that the MTA2/SerRS/VEGFA axis is a drug-treatable anti-angiogenic target,and MEQ is a promising anti-tumor molecule that merits further investigation for clinical applications.

关键词： isoflavone MTA2 SerRS tumor angiogenesis VEGFA

Soy isoflavone and Its Effect to Regulate Hypothalamus and Peripheral Orexigenic Gene Expression in Ovariectomized Rats Fed on A High-Fat Diet

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Biomedical and Environmental Sciences 2010年第1期23卷 68-75页

作者： YUN-BO ZHANG YANG ZHANG LI-NA LI XIN-YU ZHAO XIAO-LIN NA Department of Environmental Hygiene Department of Environmental Hygiene Toxicology Nutrition and Food Hygiene College of Public Health Harbin Medical University Harbin 150086 Heilongjiang China

Objective To explore the effect of soy isoflavone on obesity in the light of hypothalamus and peripheral orexigenic gene regulation. Methods Fifty-four female rats were randomly assigned to 6 groups： one sham-operated group （SHAM）, one ovariectomized （OVX） control group, three OVX groups fed with 400 ppm （L-SI）, 1 200 ppm （M-SI） and 3 600 ppm （H-SI） isoflavone respectively, and one OVX group receiving 0.45 ppm diethylstilbestrol （EC）. All rats were allowed to take high-fat diet for 4 weeks. Some neuropeptides were measured by RT-PCR. These neuropeptides included NPY, pro-opiomelanocortin （POMC）, cocaine and amphetamine regulated transcript （CART）, orexin, melanin-concentrating hormone （MCH）, ting hormone precursor （P-MCH）, ghrelin, and leptin. Results Compared with the OVX control group, the body weight and food intake in the H-S1 group were reduced significantly and there was a significant dose-dependent manner in the 3 isoflavone groups. The results of RT-PCR showed that the NPY level in the 3 isoflavone groups was significantly increased and the POMC/CART gene expression decreased significantly in rats＇ hypothalamus compared with that in the OVX control group. However, the expression of orexin, MCH and P-MCH had no change. The peripheral grelin mRNA expression was higher in the 3 isoflavone groups, while leptin gene expression in the fat was not consistent. Conclusions This research showed that isoflavone could prevent obesity induced by high-fat diet and ovariectomy through regulating hypothalamus and peripheral orexigenic gene expressions associated with food intake.

关键词： isoflavone Hypothalamus Orexigenic gene express Obesity

Influence of dietary isoflavone intake on gastrointestinal symptoms in ulcerative colitis individuals in remission

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World Journal of Gastroenterology 2017年第29期23卷 5356-5363页

作者： Dominika Glabska Dominika Guzek Dominika Grudzińska Gustaw Lech Department of Dietetics Faculty of Human Nutrition and Consumer SciencesWarsaw University of Life Sciences(WULS-SGGW) Department of Organization and Consumption Economics Faculty of Human Nutrition and Consumer SciencesWarsaw University of Life Sciences(WULS-SGGW) Department of General Gastroenterological and Oncological SurgeryMedical University of Warsaw

AIM To analyse the association between isoflavone intake and ulcerative colitis motility symptoms in individuals in remission. METHODS Cross-sectional study was conducted in a group of ulcerative colitis remission individuals, in subgroups characterised by various intestinal motility and functioning characteristics(abdominal pain, flatulence, constipations, tenesmus). Total of 56 individuals with ulcerative colitis in remission(19 males and 37 females) were recruited for the study. Assessment of diet was based on self-reported data from each patient's dietary records taken over a period of three typical, random days(2 weekdays and 1 d of the weekend). The daily isoflavone intake(daidzein, genistein, glycitein and total isoflavones) and daily isoflavone intake per 1000 kcal of diet were assessed.RESULTS No correlations between isoflavone intake levels and number of bowel movements per day were observed both in the case of intake and intake per 1000 kcal of diet. In the group of individuals declaring lack of abdominal pain, the higher intakes of daidzein(P = 0.0075), daidzein per 1000 kcal of diet(P = 0.0358) and total isoflavone(P = 0.0358) were stated, than in the group of individuals declaring abdominal pain. In the group of individuals declaring lack of constipations, the lower intakes of glycitein(P = 0.0213) and glycitein per 1000 kcal of diet(P = 0.0213) were stated, than in the group of individuals declaring presence of constipations. No differences were observed in isoflavone intake between groups of ulcerative colitis individuals declaring lack of flatulence and declaring presence of flatulence, as well as between groups declaring lack of tenesmus and declaring presence of tenesmus.CONCLUSION The moderate dietary isoflavone intake may be beneficial for individuals with ulcerative colitis in remission, however, before including it into recommendations, further prospective studies are needed.

关键词：腹的疼痛便秘 ulcerative 大肠炎 Daidzein Genistein Glycitein isoflavone

Systematic review of soy isoflavone supplements on osteoporosis in women

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Asian Pacific Journal of Tropical Medicine 2012年第3期5卷 243-248页

作者： Pan Wei Ming Liu Yan Chen De-Cai Chen Department of Endocrinology West China HospitalSichuan University

Objective:To clarify the effect of soy isoflavones on prevention of osteoporosis,and the effective dosage of soy isoflavones and its duration.Methods:Random control trials that investigated the association of soy isoflavones and osteoporosis were included in the meta-analysis by researching MEDLINE,EMBASE and the Chinese Biomedical Database up to October 2011.The RevMan software was used for all of the statistical analysis.Results:The present meta-analysis found that soy isoflavones significantly increased the bone mineral density by 54%and decreased the bone resorption marker urinary deoxypyridinoline(DPD) by 23%compared to baseline in women. Using random effects model,the effect of isoflavones on bone mineral density(BMD) regarding menopausal status and isoflavone dose revealed higher weighted mean difference changes were found in postmenopausal women and isoflavone dose above 75 mg/d.Subgroup analysis of trials with menopausal status,supplement type,isoflavone dose and intervention duration that used soy isoflavone extracts resulted in significant diflerent overall effect of DPD using by random effects model.Sensitivity analysis indicated that the effect of soy isoflavones on BMD and DPD was robust.Conclusions:The present meta-analysis reveals that soy isoflavone supplements significandy increase bone mineral density and decrease the bone,resorption marker urinary DPD.It shows no significant effect on bone formation markers serum bone alkaline phosphatase. The significant effect of soy isoflavones on BMD and urinary DPD is relative to menopausal status, supplement type,isoflavone dose and intervention duration.

关键词： Systematic review Soy isoflavone Bone mineral density Urine deoxypyridinoline Serum bone alkaline phosphatase

Effects of Dietary isoflavone Supplementation on Meat Quality and Oxidative Stability During Storage in Lingnan Yellow Broilers

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Journal of Integrative Agriculture 2014年第2期13卷 387-393页

作者： JIANG Shou-qun JIANG Zong-yong ZHOU Gui-lian LIN Ying-cai ZHENG Chun-tian Guangdong Key Laboratory of Animal Breeding and Nutrition/Guangdong Public Laboratory of Animal Breeding and Nutrition/Key Laboratory of Animal Nutrition and Feed Science (South China) Ministry of Agriculture/State Key Laboratory of Livestock and Poultry BreedingInstitute of Animal ScienceGuangdong Academy of Agricultural Sciences

To investigate the effects of a synthetic isoflavone （SI） on meat quality and oxidative stability, 1 500 43-d-old Lingnan yellow male broilers were randomly assigned to five dietary treatments： diets supplemented with 0, 10, 20, 40, or 80 mg SI kg-1, fed ad libitum for a period of 3 wk. After refrigerated storage, a＊ value of the meat increased with dietary SI supplementation using 10 and 40 mg kg-1 level （P〈0.05）, L＊ value decreased （P〈0.05）, and 40 mg kg-j increased the pH （P〈0.05）. Supplementation with SI, at all levels, increased water holding capacity （P〈0.05） and decreased lactic acid content of meat （P〈0.05）. The concentration of malondialdehyde at 72 h decreased linearly （P=0.005） and quadratically （P=0.004） with increasing levels of SI. Dietary SI at 20 and 40 mg kg-1 levels enhanced total superoxide dismutase activity in meat （P〈0.05）. Meat pH quadratically decreased as the storage time increased （P〈0.05）, with the highest value at 24 h （P〈0.05）. Lactic acid and malondialdehyde concentrations of meat increased over time, with value at 96 h being far higher than at earlier times （P〈0.05）. Supplemental SI linearly and quadratically increased the mRNA abundance ofglutathione peroxidase （GPX）（P=0.001 and P=0.002） and catalase （CAT）（P=0.003 and P=0.006） in breast muscle. The results from this study indicate that dietary supplementation with SI can improve meat quality during refrigerated storage by decreasing lipid peroxidation and enhancing oxidative stability and, for male broilers from 43 to 63 d of age, the optimal level of SI was 40 mg kg-1.

关键词： Lingnan yellow broilers isoflavone meat quality oxidative stability glutathione peroxidase mRNA

Effects of Nitrogen Source and Bacterial Elicitor on isoflavone Accumulation in Root Cultures of Albizzia kalkora （Roxb.） Prain

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Journal of Integrative Plant Biology 2006年第9期48卷 1108-1114页

作者： So-Young Park Wi-Young Lee Youngki Park Jin-Kwon Ahn Biotechnology Division Korea Forest Research Institute Suwon 441-350 Korea

Changes in cellular isoflavone （daidzein and genistein） contents were monitored in root cultures of Albizzia kalkora （Roxb.） Prain after feeding different ratios of NH4^＋/NO3^- and treatment with a biotic elicitor （three strains of Rhizobium sp.）. The NH4^＋/NO3^- ratio appears to be positively correlated with daidzein content in the roots and shows a negative correlation with genistein. Among the three different strains of Rhizobium used, the strain ATCC 15834 caused a 35% increase in daidzein production by infection. In the case of genistein, maximum production （94%） was obtained when cultures were treated on Day 6 by the strains ATCC 15834 and KCTC 1541. The biosynthetic pathway of the two isoflavones apparently reacts differently to the same culture conditions and the same strains of Rhizobium. Therefore, the present data suggest that the production of daidzein and genistein could be modulated by changing the NH4^＋/NO3^- ratio and the application of Rhizobium.

关键词： Albizzia kalkora infection isoflavone nitrogen root culture

Nematogenic and smectogenic liquid crystals from new heterocyclic isoflavone derivatives:Synthesis,characterization and X-ray diffraction studies

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Chinese Chemical Letters 2011年第2期22卷 229-232页

作者： Wan Sinn Yam Guan Yeow Yeap Liquid Crystal Research Laboratory School of Chemical SciencesUniversiti Sains MalaysiaMinden 11800Malaysia

A new series of liquid crystals comprising eight heterocyclic isoflavone esters,7-alkanoyloxy-3-[4＇-（3-methylbutyloxyphenyl）]- 4H-1-benzopyran-4-ones exhibiting enantiotropic nematic（N） and smectic C（SmC） phases were synthesized and investigated.The mesomorphic properties of all derivatives were investigated by means of differential calorimetry and polarized optical microscopy. Wide angle X-ray diffraction technique was employed to investigate the molecular packing associated with the intermolecular interaction as well as the correlation between the thermal behaviour of these compounds with their anisotropy properties within a mesophase.

关键词： Heterocyclic isoflavone Enantiotropic Mesophase

Rapid HPLC Method for Determination of 12 isoflavone Components in Soybean Seeds

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Agricultural Sciences in China 2011年第1期10卷 70-77页

作者： SUN Jun-ming SUN Bao-li HAN Fen-xia YAN Shu-rong YANG Hua Akio Kikuchi Institute of Crop Sciences Chinese Academy of Agricultural Sciences/National Key Facility for Crop Gene Resources and Genetic Improvement （NFCR1） Beij ing 100081 P.R. China Institute of Agricultural Environment and Sustainable Development Chinese Academy of Agricultural Sciences Beijing 100081 P.R. China Soybean Breeding Research Subteam National Agricultural Research Center for Tohoku Region Akita 019-2112 Japan

It is important to determine the isoflavone components by high-performance liquid chromatography （HPLC） for the molecular assistant selection of isoflavone in soybean. Based on the standard samples of 12 isoflavone components, the isoflavone components were analyzed using the determination of absorbance peaks method by HPLC. The results showed that there were different maximum ultraviolet （UV） absorbance for the aglycones of daidzein, glycitein, and genistein, which were at 250, 257, and 260 nm, respectively. A linear gradient elution of acetonitrile （13-30%） containing 0. 1% acetic acid as a mobile phase was applied on a YMC-C18 column at 35℃. The 12 isoflavone components were determined using the UV detector by HPLC. We concluded that this is a rapid and precise method which adapted to determine the large numbers of samples with microanalysis.

关键词： soybean （Glycine max L. Merri） isoflavone HPLC