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1.
Article in Chinese | WPRIM | ID: wpr-936141

ABSTRACT

OBJECTIVE@#To investigate the effects and mechanisms of equol and its enantiomers on urethane-induced lung cancer in mice.@*METHODS@#A total of 120 5-week-old male C57BL/6 mice were randomly divided into 8 groups: lung cancer tumor control group (CG), genistein control group (GCG), low dose racemic equol group (LEG), high dose racemic equol group (HEG), low dose R-equol group (LRE), high dose R-equol group (HRE), low dose S-equol group (LSE) and high dose S-equol group (HSE). Urethane was injected subcutaneously twice a week for 4 weeks to induce lung cancer and then the mice were fed for 4 months. The body weight and food intake of each group were measured and recorded weekly. After the mice were sacrificed, the blood, livers and lungs of the mice were collected. The incidence of lung cancer in each group was recorded. The concentration of serum superoxide dismutase (SOD), malondialdehyde (MDA) and 8-hydroxydeoxygunosine (8-OHdG) were detected by the corresponding kits. Western blotting was used to detect the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in the livers. Between-group differences in body weight and food intake of the mice were compared using repeated measures ANOVA, and ANOVA for the differences between non-repeated measurements, with post hoc analysis using Tukey's method if there were between-group differences. Comparisons of categorical data were performed by chi-square test, and if there were differences between the groups, the Bonferroni method was used for pairwise comparison.@*RESULTS@#A total of 49 in the 120 mice developed lung cancer. The overall incidence of lung cancer was 40.8%. Compared with the control group, the incidence of lung cancers in each experimental group was lower, and the difference was statistically significant. The incidence of lung cancer in the high-dose experimental group was significantly lower than that in the low-dose experimental group. However, the incidence of lung cancer was similar in the three equol groups and the genistein group at the same dose. Compared with the control group, the high-dose experimental group had higher serum SOD concentration, lower MDA and 8-OHdG concentrations, and the differences were statistically significant. Western blotting analysis showed that the expression levels of Nrf2 protein in the experimental groups were higher than those in the control group except the low-dose racemic equol group, and the Nrf2 protein expression level in the high-dose equol groups was higher than that in the low-dose equol groups.@*CONCLUSION@#Racemic equol and its enantiomers mayinhibit lung carcinogenesis through antioxidant effects.


Subject(s)
Animals , Body Weight , Equol , Genistein , Lung Neoplasms/prevention & control , Male , Mice , Mice, Inbred C57BL , NF-E2-Related Factor 2 , Superoxide Dismutase , Urethane/toxicity
2.
Article in English | WPRIM | ID: wpr-939803

ABSTRACT

OBJECTIVES@#Neuropathic pain (NP) is a chronic pain caused by somatosensory neuropathy or disease, and genistein (Gen) might be a potential drug for the treatment of NP. Therefore, this study aims to investigate the effect of Gen on lipopolysaccharide (LPS)-induced inflammatory injury of dorsal root ganglion neuron (DRGn) in rats and the possible molecular mechanism.@*METHODS@#The DRGn of 1-day-old juvenile rats were taken for isolation and culture. The DRGn in logarithmic growth phase were divided into a control group, a LPS group, a tubastatin hydrochloride (TSA)+LPS group, a Gen1+LPS group, a Gen2+LPS group, a Gen2+LPS+TSA group, a Gen2+pcDNA-histone deacetylase 6 (HDAC6)+LPS group, and a Gen2+pcDNA3.1+LPS group. The LPS group was treated with 1 μg/mL LPS for 24 h; the TSA+LPS group, the Gen1+LPS group, the Gen2+LPS group were treated with 5 μmol/L TSA, 5 μmol/L Gen, 10 μmol/L Gen respectively for 0.5 h, and then added 1 μg/mL LPS for 24 h; the Gen2+TSA+LPS group was treated with 10 μmol/L Gen and 5 μmol/L TSA for 0.5 h and then added 1 μg/mL LPS for 24 h; the Gen2+pcDNA-HDAC6+LPS group and the Gen2+pcDNA3.1+LPS group received 100 nmol/L pcDNA-HDAC6 and pcDNA3.1 plasmids respectively, and 24 h after transfection, 10 μmol/L Gen was pretreated for 0.5 h, and then added 1 μg/mL LPS for 24 h. Real-time RT-PCR was used to detect the HDAC6 mRNA expression in DRGn; CCK-8 method was used to detect cell viability of DRGn; flow cytometry was used to detect cell apoptosis of DRGn; ELISA was used to detect the levels of IL-1β, IL-6, and TNF-α in DRGn culture supernatant; Western blotting was used to detect the protein expression of HDAC6, Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and NF-κB p65 in DRGn.@*RESULTS@#Compared with the control group, the expression levels of HDAC6 mRNA and protein, the expression levels of TLR4 and MyD88 protein in DRGn of LPS group rats were significantly up-regulated, the ratio of p-NF-κB p65/NF-κB p65 was significantly increased, and the activity of DRGn was significantly decreased, the apoptosis rate was significantly increased, and the levels of IL-1β, IL-6 and TNF-α in the DRGn culture supernatant were significantly increased (all P<0.05). Compared with the LPS group, the expression levels of HDAC6 mRNA and protein, TLR4 and MyD88 protein expression levels in DRGn of the TSA+LPS group, the Gen1+LPS group, the Gen2+LPS group and the Gen2+TSA+LPS group were significantly down-regulated, the ratio of p-NF-κB p65/NF-κB p65 was significantly decreased, the activity of DRGn was significantly increased, the apoptosis rate was significantly decreased, and the levels of IL-1β, IL-6 and TNF-α in the DRGn culture supernatant were significantly decreased (all P<0.05), and the above changes were most obvious in the Gen2+TSA+LPS group. Compared with the Gen2+LPS group, the expression levels of HDAC6 mRNA and protein, TLR4 and MyD88 protein expression levels in DRGn of the Gen2+pcDNA-HDAC6+LPS group were significantly up-regulated, the ratio of p-NF-κB p65/NF-κB p65 was significantly increased, the activity of DRGn was significantly decreased, and the apoptosis rate was significantly increased, and the levels of IL-1β, IL-6 and TNF-α in the DRGn culture supernatant were significantly increased (all P<0.05).@*CONCLUSIONS@#Gen can alleviate LPS-induced DRGn inflammatory injury in rats, which might be related to down-regulating the expression of HDAC6 and further inhibiting the activation of TLR4/MyD88/NF-κB signaling pathway.


Subject(s)
Animals , Ganglia, Spinal , Genistein/pharmacology , Histone Deacetylase 6/metabolism , Interleukin-6/metabolism , Lipopolysaccharides , Myeloid Differentiation Factor 88 , NF-kappa B/metabolism , Neurons/metabolism , RNA, Messenger , Rats , Toll-Like Receptor 4/metabolism , Tumor Necrosis Factor-alpha/metabolism
3.
Chinese Journal of Biotechnology ; (12): 749-759, 2022.
Article in Chinese | WPRIM | ID: wpr-927741

ABSTRACT

Genistein and its monoglucoside derivatives play important roles in food and pharmaceuticals fields, whereas their applications are limited by the low water solubility. Glycosylation is regarded as one of the effective approaches to improve water solubility. In this paper, the glycosylation of sophoricoside (genistein monoglucoside) was investigated using a cyclodextrin glucosyltransferase from Penibacillus macerans (PmCGTase). Saturation mutagenesis of D182 from PmCGTase was carried out. Compared with the wild-type (WT), the variant D182C showed a 13.42% higher conversion ratio. Moreover, the main products sophoricoside monoglucoside, sophoricoside diglucoside, and sophoricoside triglucoside of the variant D182C increased by 39.35%, 56.05% and 64.81% compared with that of the WT, respectively. Enzymatic characterization showed that the enzyme activities (cyclization, hydrolysis, disproportionation) of the variant D182C were higher than that of the WT, and the optimal pH and temperature of the variant D182C were 6 and 40℃, respectively. Kinetics analysis showed the variant D182C has a lower Km value and a higher kcat/Km value than that of the WT, indicating the variant D182C has enhanced affinity to substrate. Structure modeling and docking analysis demonstrated that the improved glycosylation efficiency of the variant D182C may be attributed to the increased interactions between residues and substrate.


Subject(s)
Cyclodextrins , Genistein , Glucosyltransferases/metabolism , Glycosylation , Kinetics
4.
Article in English | WPRIM | ID: wpr-929243

ABSTRACT

Pueraria thomsonii has long been used in traditional Chinese medicine. Isoflavonoids are the principle pharmacologically active components, which are primarily observed as glycosyl-conjugates and accumulate in P. thomsonii roots. However, the molecular mechanisms underlying the glycosylation processes in (iso)flavonoid biosynthesis have not been thoroughly elucidated. In the current study, an O-glucosyltransferase (PtUGT8) was identified in the medicinal plant P. thomsonii from RNA-seq database. Biochemical assays of the recombinant PtUGT8 showed that it was able to glycosylate chalcone (isoliquiritigenin) at the 4-OH position and glycosylate isoflavones (daidzein, formononetin, and genistein) at the 7-OH or 4'-OH position, exhibiting no enzyme activity to flavonones (liquiritigenin and narigenin) in vitro. The identification of PtUGT8 may provide a useful enzyme catalyst for efficient biotransformation of isoflavones and other natural products for food or pharmacological applications.


Subject(s)
Cloning, Molecular , Genistein , Glucosyltransferases/metabolism , Isoflavones/pharmacology , Pueraria/chemistry
5.
Actual. osteol ; 16(2): 140-153, mayo.-ago. 2020. ilus, graf
Article in Spanish | LILACS | ID: biblio-1129814

ABSTRACT

La osteoporosis y las enfermedades cardiovasculares son patologías prevalentes en mujeres posmenopáusicas. La calcificación vascular es un proceso en el que se produce una distorsión de la arquitectura natural del tejido arterial con una transformación símil osteogénica. La fisiología vascular y la osteogénesis (formación y remodelación ósea) comparten una complejidad metabólica y funcional crítica, que ha sido poco explorada en forma conjunta, lo que ha impulsado la concepción del Eje Óseo-Vascular como nueva área de investigación, con una visión de estudio integradora con la finalidad de identificar vínculos entre ambos sistemas. En virtud de la controversia planteada sobre los riesgos/beneficios de la terapia de reemplazo hormonal para prevenir enfermedades asociadas a la menopausia, se ha incentivado la búsqueda de nuevas opciones de tratamiento. Los fitoestrógenos, como compuestos nutracéuticos, surgen como una potencial alternativa terapéutica. En particular, las isoflavonas presentan gran analogía estructural con el estrógeno humano 17ß-estradiol, lo que les permite unirse al receptor de estrógenos e inducir acciones estrogénicas tanto en células animales como humanas. Basado en la experiencia propia como en lo reportado en la bibliografía, este artículo analiza la información disponible sobre las acciones vasculares y óseas de los fitoestrógenos (específicamente la isoflavona genisteína), con una visión de ciencia traslacional. Es de esperar que los avances en el conocimiento derivado de la ciencia básica, en un futuro cercano, pueda contribuir a decisiones clínicas a favor de promover terapias naturales de potencial acción dual, para la prevención de enfermedades de alta prevalencia y significativo costo social y económico para la población. (AU)


Osteoporosis and cardiovascular diseases are prevalent diseases in postmenopausal women. Vascular calcification is a cellmediated process that leads to the loss of the natural architecture of the arterial vessels due to osteogenic transdifferentiation of smooth muscle cells, and matrix mineralization. Vascular physiology and osteogenesis (bone formation and remodeling) share a critical metabolic and functional complexity. Given the emerging integrative nature of the bonevascular axis, links between both systems are a matter of ongoing interest. In view of the controversy stated about the risks/benefits of hormone replacement therapy to prevent diseases associated with menopause, phytoestrogens arise as a potential natural therapeutic alternative. In particular, isoflavones have a strong structural analogy with the human estrogen 17ß-estradiol, that allows them to bind to the estrogen receptor and induce estrogenic actions in animal and human cells. Based in on our own experience and the information available in the literature, in this paper we provide an overview of the role of phytoestrogens on vascular and bone tissues, with focus on Genistein actions. We wish that the basic knowledge acquired may contribute to guide clinical decisions for the promotion of natural therapies for the treatment of diseases that conspire against human health. (AU)


Subject(s)
Humans , Male , Female , Osteogenesis/drug effects , Phytoestrogens/therapeutic use , Atherosclerosis/drug therapy , Vascular Calcification/drug therapy , Osteogenesis/physiology , Menopause , Cardiovascular Diseases/complications , Osteoporosis, Postmenopausal , Bone Remodeling , Genistein/therapeutic use , Phytoestrogens/classification , Phytoestrogens/pharmacology , Atherosclerosis/physiopathology , Estrogens/biosynthesis , Vascular Calcification/physiopathology , Vascular Calcification/metabolism
6.
Acta cir. bras ; 34(11): e201901104, Nov. 2019. graf
Article in English | LILACS | ID: biblio-1054677

ABSTRACT

Abstract Purpose: Myocardial ischemia/reperfusion (Ml/R) injury is a leading cause of damage in cardiac tissues, with high rates of mortality and disability. Biochanin A (BCA) is a main constituent of Trifolium pratense L. This study was intended to explore the effect of BCA on Ml/R injury and explore the potential mechanism. Methods: In vivo MI/R injury was established by transient coronary ligation in Sprague-Dawley rats. Triphenyltetrazolium chloride staining (TTC) was used to measure myocardial infarct size. ELISA assay was employed to evaluate the levels of myocardial enzyme and inflammatory cytokines. Western blot assay was conducted to detect related protein levels in myocardial tissues. Results: BCA significantly ameliorated myocardial infarction area, reduced the release of myocardial enzyme levels including aspartate transaminase (AST), creatine kinase (CK-MB) and lactic dehydrogenase (LDH). It also decreased the production of inflammatory cytokines (IL-1β, IL-18, IL-6 and TNF-α) in serum of Ml/R rats. Further mechanism studies demonstrated that BCA inhibited inflammatory reaction through blocking TLR4/NF-kB/NLRP3 signaling pathway. Conclusion: The present study is the first evidence demonstrating that BCA attenuated Ml/R injury through suppressing TLR4/NF-kB/NLRP3 signaling pathway-mediated anti-inflammation pathway.


Subject(s)
Animals , Male , Cardiotonic Agents/pharmacology , Myocardial Reperfusion Injury/prevention & control , NF-kappa B/drug effects , Genistein/pharmacology , Toll-Like Receptor 4/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/drug effects , Aspartate Aminotransferases/blood , Reference Values , Myocardial Reperfusion Injury/metabolism , Signal Transduction/drug effects , Blotting, Western , Reproducibility of Results , Cytokines/blood , NF-kappa B/metabolism , Rats, Sprague-Dawley , Creatine Kinase/blood , Lactate Dehydrogenases/blood , Toll-Like Receptor 4/metabolism , Anti-Inflammatory Agents/pharmacology
7.
Article in English | WPRIM | ID: wpr-760663

ABSTRACT

OBJECTIVE: To investigate the effect of genistein on the anticancer effects of chemotherapeutic agents, we examined the effect of a genistein and cisplatin combination on CaSki human cervical cancer cells. METHODS: After the cervical cancer cells (HeLa cells, CaSki cells) had been cultured, cisplatin and genistein were added to the culture medium, and the cell activity was measured using MTT assay. The CaSki cells were cultured in a medium containing cisplatin and genistein, and then, the cells were collected in order to measure p53, Bcl2, ERK, and caspase 3 levels by western blotting. RESULTS: Both the HeLa and CaSki cells had decreased cell viabilities when the cisplatin concentration was 10 μM or higher. When combined with genistein, the cell viabilities of the HeLa and CaSki cells decreased at cisplatin concentrations of 8 μM and 6 μM, respectively. The administration of genistein increased the toxicity of cisplatin in the HeLa and CaSki cells. In the CaSki cells, the p-ERK1/2 level decreased by 37%, the p53 expression level increased by 304%, and the cleaved caspase 3 level increased by 115% in the cisplatin+genistein group compared to that in the cisplatin group. Bcl2 expression was reduced by 69% in the cisplatin+genistein group compared to that in the cisplatin group. CONCLUSION: Genistein enhances the anticancer effect of cisplatin in CaSki cells, and can be used as a chemotherapeutic adjuvant to increase the activity of a chemotherapeutic agent.


Subject(s)
Blotting, Western , Caspase 3 , Cell Line , Cell Survival , Cisplatin , Genistein , HeLa Cells , Humans , Uterine Cervical Neoplasms
8.
Article in Chinese | WPRIM | ID: wpr-772043

ABSTRACT

OBJECTIVE@#To investigate the inhibitory effect of genistein on activation of hepatic stellate cells (HSCs) and the role of the autophagy pathway regulated by PPAR-γ in mediating this effect.@*METHODS@#Cultured HSC-T6 cells were exposed to different concentrations of genistein for 48 h, and HSC activation was verified by detecting the expressions of -SMA and 1(I) collagen; autophagy activation in the cells was determined by detecting the expressions of LC3-II and p62 using Western blotting. The autophagy inhibitor 3-MA was used to confirm the role of autophagy in genistein-induced inhibition of HSC activation. A PPAR-γ inhibitor was used to explore the role of PPAR-γ in activating autophagy in the HSCs.@*RESULTS@#Genistein at concentrations of 5 and 50 μmol/L significantly inhibited the expressions of -SMA and 1(I) collagen ( < 0.05), markedly upregulated the expressions of PPAR-γ and the autophagy-related protein LC3-II ( < 0.05) and significantly down-regulated the expression of the ubiqutin-binding protein p62 ( < 0.05) in HSC-T6 cells. The cells pretreated with 3-MA prior to genistein treatment showed significantly increased protein expressions of -SMA and 1(I) collagen compared with the cells treated with genistein only ( < 0.05). Treatment with the PPAR-γ inhibitor obviously lowered the expression of LC3-II and enhanced the expression p62 in genistein-treated HSC-T6 cells, suggesting the activation of the autophagy pathway.@*CONCLUSIONS@#PPAR-γ- regulated autophagy plays an important role in mediating genistein-induced inhibition of HSC activation .


Subject(s)
Anticarcinogenic Agents , Pharmacology , Autophagy , Collagen Type I , Genistein , Pharmacology , Hepatic Stellate Cells , Humans , PPAR gamma , Physiology
9.
Article in English | WPRIM | ID: wpr-785918

ABSTRACT

BACKGROUND: BRCA1 mutated breast cancer cells exhibit the elevated cell proliferation and the higher metastatic potential. G protein-coupled receptor 30 (GPR30) has been shown to regulate growth of hormonally responsive cancers, such as ovarian and breast cancers, and high expression of GPR30 is found in estrogen receptor (ER)-negative breast cancer cells. ER-negative breast cancer patients often have a mutation in the tumor suppressor gene, BRCA1. This study explored antiproliferative effects of genistein, a chemopreventive isoflavone present in legumes, and underlying molecular mechanisms in triple negative breast cancer cells with or without functionally active BRCA1.METHODS: Expression of BRCA1, GPR30 and Nrf2 was measured by Western blot analysis. Reactive oxygen species (ROS) accumulation was monitored by using the fluorescence-generating probe, 2’,7’-dichlorofluorescein diacetate. The effects of genistein on breast cancer cell viability and proliferation were assessed by the MTT, migration and clonogenic assays.RESULTS: The expression of GPR30 was dramatically elevated at both transcriptional and translational levels in BRCA1 mutated breast cancer cells compared to cells with wild-type BRCA1. Notably, there was diminished Akt phosporylation in GPR30 silenced cells. Treatment of BRCA1 silenced breast cancer cells with genistein resulted in the down-regulation of GPR30 expression and the inhibition of Akt phosphorylation as well as the reduced cell viability, migration and colony formation. Genistein caused cell cycle arrest at the G₂/M phase in BRCA1-mutant cells through down-regulation of cyclin B1 expression. Furthermore, BRCA1-mutant breast cancer cells exhibited higher levels of intracellular ROS than those in the wild-type cells. Genistein treatment lowered the ROS levels through up-regulation of Nrf2 expression.CONCLUSIONS: Lack of functional BRCA1 activates GPR30 signaling, thereby stimulating Akt phosphorylation and cell proliferation. Genistein induces G2/M phase arrest by down-regulating cyclin B1 expression, which is attributable to its suppression of GPR30 activation and Akt phosphorylation in BRCA1 impaired breast cancer cells.


Subject(s)
Blotting, Western , Breast Neoplasms , Breast , Cell Cycle Checkpoints , Cell Proliferation , Cell Survival , Cyclin B1 , Down-Regulation , Estrogens , Fabaceae , Genes, Tumor Suppressor , Genistein , Humans , Phosphorylation , Reactive Oxygen Species , Triple Negative Breast Neoplasms , Up-Regulation
10.
Article in Chinese | WPRIM | ID: wpr-813226

ABSTRACT

To investigate the effects of genistein (Gen) on nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in myocardial tissues of diabetic rats.
 Methods: Thirty-two male SD rats were randomly divided into 4 groups: a normal control (NC) group, a diabetic control (DM) group, a low-dose Gen treatment (L-Gen) group, and a high-dose Gen treatment (H-Gen) group (n=8). Intraperitoneal injection of streptozotocin was utilized to induce diabetic rat model. After the establishment of diabetic model, the rats in L-Gen and H-Gen groups were intragastric administration with 10 and 50 mg/kg Gen solution. Following 8 weeks, the left ventricular hemodynamic parameters and fasting blood glucose (FBG) levels were measured. The levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) in myocardial tissue were determined. The ultrastructure of myocardium was observed under transmission electron microscopy. The expression of HO-1 at mRNA level in myocardial tissue was detected by RT-PCR. The protein levels of Nrf2 and HO-1 in myocardial tissue were detected by Western blotting. 
 Results: Compared with the NC group, left ventricular systolic pressure (LVSP), maximal rise/fall rate of left ventricular pressure (±dp/dtmax), and the levels of GSH-Px, SOD and CAT were decreased (all P<0.01), while the left ventricular end-diastolic pressure (LVEDP), FBG and MDA were increased (all P<0.01) in the DM group. The myocardial ultrastructure was obviously damaged, and the expressions of myocardial Nrf2 and HO-1 were significantly decreased (both P<0.01) in the DM group. Compared with the DM group, there was no difference in FBG in the L-Gen group, while ±dp/dtmax and LVSP were significantly increased (all P<0.05), and LVEDP and MDA were decreased (P<0.05 or P<0.01), and the levels of GSH-Px, SOD and CAT were increased (P<0.05 or P<0.01) in the L-Gen group. The myocardial ultrastructure damage was alleviated and the expressions of Nrf2 and HO-1 were increased (both P<0.01) in the L-Gen group. Compared with L-Gen group, the aforementioned indexes were improved in the H-Gen group (P<0.05 or P<0.01).
 Conclusion: Genistein exerted antioxidant effects on myocardial injury in diabetic rats, and the mechanisms might be related to regulating the Nrf2/HO-1 pathway and enhancing the activities of antioxidant enzymes in myocardial tissues.


Subject(s)
Animals , Diabetes Mellitus, Experimental , Genistein , Heme Oxygenase (Decyclizing) , Male , Myocardium , NF-E2-Related Factor 2 , Rats , Rats, Sprague-Dawley
11.
Article in English | WPRIM | ID: wpr-765770

ABSTRACT

The purpose of the present overview of meta-analysis is to summarize and critically assess the effect of isoflavones and genistein on glucose metabolism among the peri- and post-menopausal women. Two independent authors searched the databases of MEDLINE, Scopus and Cochrane Library for meta-analysis. Three databases were searched from inception to January 2018. Methodological quality of each meta-analysis of randomized controlled trials was evaluated using the AMSTAR (a measurement tool used to assess systematic reviews). Four meta-analyses were included to the current overview. Fasting insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values were significantly lower in peri-menopausal and postmenopausal. Two meta-analyses showed that treatment with isoflavones could not alter fasting blood glucose. However, one meta-analysis depicted that isoflavones significantly improved blood glucose levels in non-Asian postmenopausal women. Treatment with genistein could have significant beneficial effects on fasting insulin, blood glucose and HOMA-IR in comparison to the control group. Regardless of the population, the treatment with genistein is effective in improving fasting insulin, HOMA-IR and glucose levels. Nevertheless, the high heterogeneity among studies and poor methodology of reviews made it difficult to draw a definite conclusion on the positive impacts of soy on glucose metabolism.


Subject(s)
Blood Glucose , Fasting , Female , Genistein , Glucose Metabolism Disorders , Glucose , Humans , Insulin , Insulin Resistance , Insulins , Isoflavones , Menopause , Metabolism , Population Characteristics
12.
Chinese Journal of Biotechnology ; (12): 857-870, 2019.
Article in Chinese | WPRIM | ID: wpr-771324

ABSTRACT

To investigate the effects of genistein (Gen) on the biosynthesis of N-glycolylneuraminic acid (Neu5Gc) in rats, 80 4-week-old male SD rats were randomly equally into the control and genistein groups. The rats of control and genistein groups were fed 5% ethanol and 300 mg/(kg·d) genistein respectively by gavage. The contents of Neu5Gc in hind leg muscle, kidney and liver tissues of rats were measured by using high performance liquid chromatography coupled with fluorescence detector (HPLC/FLD), and the mechanism of inhibition of Neu5Gc synthesis was investigated by using the molecular docking of Gen and sialyltransferase. On the 15th day, the content of Neu5Gc in hind leg muscle and liver tissues decreased 13.77% and 15.45%, respectively, and there was no significant change in the content of Neu5Gc in kidney tissues. On the 30th day, the content of Neu5Gc in liver tissues decreased 13.35%, however, there was no significant change in the content of Neu5Gc in kidney tissues and Neu5Gc was not detected in hind leg muscle. The content of Neu5Gc in hind leg muscle, kidney and liver tissues decreased respectively 32.65%, 32.78%, 16.80% and 12.72%, 11.42%, 12.30% while rats fed on the 45th and the 60th days. Genistein has formed the hydrogen bond with sialyltransferase activity site residues His319, Ser151, Gly293, Thr328 and formed a hydrophobic interactions with the residues His302, His301, Trp300, Ser271, Phe292, Thr328, Ser325 and Ile274. The results of molecular docking indicated that the weak intermolecular interaction was the main cause of genistein inhibiting sialyltransferase activity. The research results provided an experimental basis for the subsequent reduction of Neu5Gc in red meat before slaughter.


Subject(s)
Animals , Gene Expression Regulation, Enzymologic , Genistein , Pharmacology , Male , Molecular Docking Simulation , Neuraminic Acids , Metabolism , Random Allocation , Rats , Rats, Sprague-Dawley , Transferases , Metabolism
13.
Anatomy & Cell Biology ; : 183-190, 2019.
Article in English | WPRIM | ID: wpr-762214

ABSTRACT

Nicotine is the most toxic factor of tobacco. Genistein is a phytoestrogen and antioxidant that has numerous health benefits. The aim of this study is to evaluate the effects of genistein against toxic properties of nicotine to the pancreas of mice. For this purpose, 48 male mice were randomly assigned into six groups (n=8): normal control, nicotine control (2.5 mg/kg), genistein (25 and 50 mg/kg), and nicotine+genistein (25 and 50 mg/kg) treated groups. Various doses of genistein and genistein+nicotine were administered intraperitoneally to animals for 4 weeks. The weight of pancreas, total antioxidant capacity and nitrite oxide of serum, insulin levels, and the number and diameter of islets of Langerhans were investigated. Nicotine administration reduced significantly total antioxidant capacity, insulin, pancreas weight, and the number and diameter of islets of Langerhans and increased nitrite oxide in serum compared to the control normal group (P<0.05). Conversely, genistein and genistein+nicotine increased significantly insulin, total antioxidant capacity, and the number and diameter islets of Langerhans and decreased serum nitrite oxide compared to the nicotine control group. It seems that the genistein can improve pancreas damage following the nicotine administration.


Subject(s)
Animals , Genistein , Humans , Insulin , Insurance Benefits , Islets of Langerhans , Male , Mice , Nicotine , Pancreas , Phytoestrogens , Tobacco
14.
Article in Chinese | WPRIM | ID: wpr-771699

ABSTRACT

Genistein is a kind of isoflavone compounds, also called phytoestrogens, with clinical effects on cardiovascular disease, cancer and postmenopausal-related gynecological diseases, and also has the potentiality in the prevention and treatment of Alzheimer's disease(AD). In this study, the protective effect of genistein on Aβ₂₅₋₃₅-induced PC12 cell injury and effect on CaM-CaMKIV signaling pathway were observed to investigate its mechanism for AD. PC12 cells were cultured and then the safe concentration of genistein and the modeling concentration and optimal time point of administration of Aβ₂₅₋₃₅ were screened by MTT assay. After being pretreated with different concentrations of genistein(25, 50, 100 μmol·L⁻¹) on PC12 cells, the AD model of PC12 cells was induced by Aβ₂₅₋₃₅. Then the survival rate of cells was detected by MTT assay; morphological change of cells was observed under the inverted microscope, and apoptosis of cells was assessed by AO/EB fluorescence staining; the neuroprotective effects of genistein on AD cell model were observed and the optimal concentration of genistein was determined. Expressions of mRNA and protein levels of CaM, CaMKK, CaMKIV and tau were detected by qRT-PCR and Western blot assay, respectively. The results showed that as compared with the blank group, the cell survival rate was decreased; the cell damage and apoptosis were increased; and the expressions of mRNA and protein levels of CaM, CaMKK, CaMKIV and tau were increased in AD model group. Genistein could significantly improve the cell survival rate, reduce the cell damage and apoptosis of AD cell model, and significantly down-regulate the expressions of mRNA and protein levels of CaM, CaMKK, CaMKIV and tau of AD cell model. These results indicated that genistein has obviously neuroprotective effect on the AD cell model induced by Aβ₂₅₋₃₅, and the mechanism may be related to the down-regulation of CaM-CaMKIV signaling pathway and Tau protein expression.


Subject(s)
Amyloid beta-Peptides , Animals , Apoptosis , Calcium-Calmodulin-Dependent Protein Kinase Type 4 , Metabolism , Calmodulin , Metabolism , Cell Survival , Genistein , Pharmacology , PC12 Cells , Peptide Fragments , Protective Agents , Pharmacology , Rats , Signal Transduction
15.
Article in Chinese | WPRIM | ID: wpr-771673

ABSTRACT

Magnetic molecularly imprinted polymers(MMIPs) were prepared with ZL006 as template, acrylamide(AA) as the functional monomer, and acetonitrile as pore-forming agent; then Fourier transform infrared spectroscopy(FT-IR) and scanning electron microscopy(SEM) were used to characterize their forms and structures. Simultaneously, the MMIPs prepared previously were used as sorbents for dispersive magnetic solid phase extraction(DSPE) to capture and identify potential nNOS-PSD-95 uncouplers from extracts of Trifolium pratense and the the activities of the screened compounds were evaluated by the neuroprotective effect and co-immunoprecipitation test. The experiment revealed that the successfully synthesized MMIPs showed good dispersiveness, suitable particle size and good adsorption properties. Formononetin, prunetin and biochanin A were separated and enriched from Trifolium pratense by using the MMIPs as artificial antibodies and finally biochanin A was found to have higher cytoprotective action and uncoupling action according to the neuroprotective effect and co-immunoprecipitation test.


Subject(s)
Adsorption , Genistein , Chemistry , Molecular Imprinting , Phytochemicals , Chemistry , Polymers , Chemistry , Solid Phase Extraction , Spectroscopy, Fourier Transform Infrared , Trifolium , Chemistry
16.
Psychiatry Investigation ; : 919-925, 2018.
Article in English | WPRIM | ID: wpr-717535

ABSTRACT

OBJECTIVE: Recent studies have indicated the possibility that genistein may improve depression via regulating the expression of miR-221/222. This study is to explore whether genistein could improve depression by altering miR-221/222 levels and investigate the possible mechanisms involved in the improvement effect of genistein. METHODS: The animal model of depression was established through unpredictable chronic mild stress. Nest building test and splash test were adapted to evaluate the effects of genistein on depressive symptoms in mice. qRT-PCR and western blot analysis were used to detect the expression of miR-221/222 and connexin 43 (Cx43) in the prefrontal cortex of the mice. In vitro, U87-MG astrocytes were treated with genistein and the expression of miR-221/222 and Cx43 was measured. The dual-luciferase reporter assay was used to verify whether Cx43 was a direct target of miR-221/222. RESULTS: The behavioral tests showed that genistein could significantly reduce depression symptoms of mice, and this remission was not affected by gender. Genistein in vivo and in vitro could reduce increased levels of miR-221 and miR-222 in the prefrontal cortex of depressed mice, while upregulate Cx43 expression. Dual-luciferase reporter assay suggested Cx43 was directly regulated by miR-221/222 in astrocytes. CONCLUSION: Genistein can play its antidepressant effect through down-regulating miR-221/222 by targeting Cx43.


Subject(s)
Animals , Astrocytes , Behavior Rating Scale , Blotting, Western , Connexin 43 , Depression , Genistein , In Vitro Techniques , Mice , Models, Animal , Prefrontal Cortex
17.
Article in English | WPRIM | ID: wpr-812046

ABSTRACT

Soy isoflavones exhibit various biological activities, such as antioxidant, anti-tumor, anti-inflammatory, and cardiovascular protective effects. The present study was designed to investigate the effects of sixteen synthesized 3-amino-2-hydroxypropoxy genistein derivatives on cell proliferation and activation of Nrf2 (Nuclear factor erythroid 2-related factor 2)/ARE (antioxidant response elements) pathway in human cancer cell lines. Most of the tested compounds exerted greater cytotoxic activity than genistein, as measured by MTT assay. Moreover, compound 8c showed the highest ARE-luciferase reporter activity among the test compounds. It strongly promoted Nrf2 nuclear translocation and up-regulated the expression of total Nrf2 and downstream targets NQO-1 and HO-1 at protein level. The present study may provide a basis for the application of isoflavone derivatives as Nrf2/ARE pathway inducers for cancer therapy and cancer prevention.


Subject(s)
Antioxidant Response Elements , Cell Line, Tumor , Cell Proliferation , Genistein , Pharmacology , Therapeutic Uses , Heme Oxygenase-1 , Metabolism , Humans , Isoflavones , NF-E2-Related Factor 2 , Metabolism , Neoplasms , Drug Therapy , Metabolism , Signal Transduction , Soybeans , Chemistry , Up-Regulation
18.
Dominguezia ; 33(2): 5-21, 2017. ilus, graf
Article in Spanish | LILACS, MTYCI | ID: biblio-1005196

ABSTRACT

Una de las estrategias alternativas utilizadas para encontrar nuevas moléculas bioactivas es investigar otros organismos que habitan en los biotopos, y se presta especial atención a las interacciones ambientales entre sí y las plantas que podrían producir aún una mayor cantidad de metabolitos secundarios. Dentro de estos microorganismos, los endófitos son considerados una importante fuente de nuevos metabolitos secundarios de explotación potencial para usos médicos, agrícolas o por otras áreas industriales. En este trabajo la investigación se centró en la búsqueda de compuestos bioactivos de Erythrina crista-galli infectada con un hongo endofítico. Se recolectaron muestras de E. crista-galli de los alrededores de la Provincia de Buenos Aires y de todas estas muestras se aisló e identificó al endófito como perteneciente al género Phomopsis. Se estudiaron las actividades antimicrobiana y antiinflamatoria de los extractos de E. crista-galli relacionadas con algunos de sus usos tradicionales. El extracto acetónico de las ramas jóvenes presentó actividad antibacteriana sobre Bacillus brevis y B. subtilis y antiinflamatoria in vivo (en edema de oreja de ratón) e in vitro (en macrófagos activados por lipopolisacáridos). Del extracto acetónico con actividad antimicrobiana se aislaron e identificaron dos compuestos, daidzeína y coumestrol, y se identificó genisteína por cromatografía contra testigos. La concentración inhibitoria mínima de daidzeína, coumestrol y genisteína frente a B. brevis fue de 137,81, 16,33 y 64,81 µM, respectivamente. En el extracto acetónico con actividad antiinflamatoria se identificaron, por cromatografía contra testigos, daidzeína, genisteína, coumestrol, biochanina A y formononetina. Genisteína, coumestrol y biochanina A presentaron una dosis efectiva 50, de 0,14, 0,54 y 0.75 µg/ml, respectivamente, en el modelo de edema en oreja de ratón. Para evaluar la influencia del endófito en el metabolismo secundario de E. crista-galli se obtuvieron plantines de cultivo. No se pudieron obtener plantines libres de hongo con los tratamientos aplicados. Se sobreinfectó un lote de plantines con Phomopsis sp. y se cuantificó su contenido de coumestrol (0,04 %) y daidzeína (0,05 %) en comparación con el de un grupo control (0,01 % y 0,02 %, respectivamente). Del extracto acetónico de los plantines sobreinfectados se aisló e identificó un glicósido de isorhamnetina. (AU)


Subject(s)
Animals , Erythrina , Endophytes , Anti-Infective Agents , Anti-Inflammatory Agents , Argentina , Plant Extracts , Chromatography , Genistein , Coumestrol , Phytochemicals
19.
Article in English | WPRIM | ID: wpr-728754

ABSTRACT

Anesthetics are used extensively in surgeries and related procedures to prevent pain. However, there is some concern regarding neuronal degeneration and cognitive deficits arising from regular anesthetic exposure. Recent studies have indicated that brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB) are involved in learning and memory processes. Genistein, a plant-derived isoflavone, has been shown to exhibit neuroprotective effects. The present study was performed to examine the protective effect of genistein against isoflurane-induced neurotoxicity in rats. Neonatal rats were exposed to isoflurane (0.75%, 6 hours) on postnatal day 7 (P7). Separate groups of rat pups were orally administered genistein at doses of 20, 40, or 80 mg/kg body weight from P3 to P15 and then exposed to isoflurane anesthesia on P7. Neuronal apoptosis was detected by TUNEL assay and FluoroJade B staining following isoflurane exposure. Genistein significantly reduced apoptosis in the hippocampus, reduced the expression of proapoptotic factors (Bad, Bax, and cleaved caspase-3), and increased the expression of Bcl-2 and Bcl-xL. RT-PCR analysis revealed enhanced BDNF and TrkB mRNA levels. Genistein effectively upregulated cAMP levels and phosphorylation of CREB and TrkB, leading to activation of cAMP/CREB-BDNF-TrkB signaling. PI3K/Akt signaling was also significantly activated. Genistein administration improved general behavior and enhanced learning and memory in the rats. These observations suggest that genistein exerts neuroprotective effects by suppressing isoflurane-induced neuronal apoptosis and by activating cAMP/CREB-BDNF-TrkB-PI3/Akt signaling.


Subject(s)
Anesthesia , Anesthetics , Animals , Apoptosis , Body Weight , Brain-Derived Neurotrophic Factor , Cognition Disorders , Cyclic AMP Response Element-Binding Protein , Genistein , Hippocampus , In Situ Nick-End Labeling , Isoflurane , Learning , Memory , Neurons , Neuroprotective Agents , Phosphatidylinositol 3-Kinase , Phosphorylation , Rats , RNA, Messenger , Spatial Learning
20.
Article in English | WPRIM | ID: wpr-147979

ABSTRACT

In this study, the effect of particle size of genistein-loaded solid lipid particulate systems on drug dissolution behavior and oral bioavailability was investigated. Genistein-loaded solid lipid microparticles and nanoparticles were prepared with glyceryl palmitostearate. Except for the particle size, other properties of genistein-loaded solid lipid microparticles and nanoparticles such as particle composition and drug loading efficiency and amount were similarly controlled to mainly evaluate the effect of different particle sizes of the solid lipid particulate systems on drug dissolution behavior and oral bioavailability. The results showed that genistein-loaded solid lipid microparticles and nanoparticles exhibited a considerably increased drug dissolution rate compared to that of genistein bulk powder and suspension. The microparticles gradually released genistein as a function of time while the nanoparticles exhibited a biphasic drug release pattern, showing an initial burst drug release, followed by a sustained release. The oral bioavailability of genistein loaded in solid lipid microparticles and nanoparticles in rats was also significantly enhanced compared to that in bulk powders and the suspension. However, the bioavailability from the microparticles increased more than that from the nanoparticles mainly because the rapid drug dissolution rate and rapid absorption of genistein because of the large surface area of the genistein-solid lipid nanoparticles cleared the drug to a greater extent than the genistein-solid lipid microparticles did. Therefore, the findings of this study suggest that controlling the particle size of solid-lipid particulate systems at a micro-scale would be a promising strategy to increase the oral bioavailability of genistein.


Subject(s)
Absorption , Animals , Biological Availability , Drug Liberation , Genistein , Nanoparticles , Particle Size , Powders , Rats
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