Combination Of Genistein Research Articles

Genistein Enhances the Beneficial Effects of Exercise on Antioxidant and Anti-Inflammatory Balance and Cardiomyopathy in Ovariectomized Diabetic Rats.

This study aimed to investigate the effects of genistein, swimming exercise, and their co-treatment on heart oxidative stress, inflammation, and cardiomyopathy in ovariectomized diabetic rats. It is well-established that diabetes is a major risk factor for cardiovascular disease in both young and postmenopausal women. Genistein is a natural phytoestrogen that has estrogenic effects. Studies have shown that genistein has a positive impact on menopause, cardiovascular dis-ease, and diabetes in women. However, the impact of genistein treatment alone and in combination with exercise training on the management of cardiac disease in diabetic women after ovarian hor-mone deprivation has not been fully explored. The objective of this study was to evaluate the effect of genistein alone or in combination with exercise training on the cardiac expression of oxidative/inflammation biomarkers (MDA, OSI, TOS, TNF- α, and NF-κB) and miRNA-133, IGF-1, and Bcl-2 in the diabetic ovariectomized rats. A group of Wistar rats were randomly divided into seven groups, with eight rats in each group. The groups were named control, sham, ovariectomized group (OVX), OVX +diabetes (OD), OD+ genistein (1 mg/kg, eight weeks; daily SC), OD+exercise (eight weeks), and OD+ genistein+exercise (eight weeks). The rats were given a high-fat diet and low-dose streptozotocin injection to induce diabetes. After eight weeks, the rats were anesthetized, and their hearts were removed. The study assessed the effects of treatment by measuring the expression of miRNA-133 using Real-time Polymerase Chain Reaction (PCR) and the protein levels of Bcl-2, Bax, and IGF-1 using Western blotting. The study also evaluated the levels of inflammation and oxidative stress markers using ELISA. Pathological changes were also assessed using periodic acid Schiff and he-matoxylin & eosin. After ovariectomy, the levels of cardiac miRNA-133, IGF-1, and Bcl-2 expression were down-regulated, and the levels of MDA, OSI, TOS, TNF-α, and NF-κB were increased, with a reduced total antioxidant capacity. Diabetes had an additive effect on these factors. Genistein was found to have a positive impact on oxidative and inflammation levels, and it also increased the expression of miRNA-133, Bcl-2, and IGF-1 in rats with OD. Furthermore, the combination of genistein and exercise had a positive effect on miRNA-133, Bcl-2, and IGF-1 expression in the heart, leading to a decrease in Bax levels. The combined intervention showed a noticeable improve-ment in oxidative and inflammation conditions. Histological examination revealed some abnormal-ities in cardiac tissue, which were found to be improved with genistein and/or exercise treatments. Genistein or/and exercise as a natural replacement therapy could improve diabetic-induced cardiac complications in ovariectomized rats' hearts.

Anti-inflammatory effect of swimming exercise and genistein in combination in the pancreas of ovariectomized diabetic rats

Background. Menopause is associated with an increase in blood sugar and an increase in inflammatory cytokines. Exercise and genistein have biological activities, including anti-inflammatory and antidiabetic activity. This study examined the combined effects of regular swimming exercise and genistein as a preventive strategy against inflammation and pancreatic cell damage in ovariectomized diabetic rats. Methods. A total of 42 female Wistar rats were divided into six groups: Sham, ovariectomy (OVX), diabetic ovariectomy (OVX.D), diabetic ovariectomy + exercise (OVX.D.E), diabetic ovariectomy + genistein (OVX.D.G), and diabetic ovariectomy + exercise + genistein (OVX.D.E.G). Animals underwent swimming training or received genistein or a combination of both for eight weeks. At the end of this period, the levels of TNF-α, Nf-κB, IL-1β, and SIRT1 proteins were evaluated using western blot in pancreatic tissue. Results. Ovariectomy increased the expression of TNF-α, Nf-κB, and IL-1β and decreased the expression of SIRT1, and these effects were more significant in ovariectomized diabetic rats. Treatment with genistein and swimming exercise individually reversed these changes in the level of proteins and improved the inflammation, but the combined effect of these two interventions exhibited more effect. Conclusion. The combination of genistein and regular swimming exercise provides enhanced protection for pancreatic tissue and effectively prevents damage to it. Therefore, performing appropriate physical activities and consuming compounds containing phytoestrogens can prevent the occurrence of disorders such as diabetes during menopause. Practical Implications. The results of this study can guide health policymakers to prevent disorders and complications caused by menopause.

Genistein Alleviates Dextran Sulfate Sodium-induced Ulcerative Colitis in Mice by Regulating Th17/Treg Cell Balance: Implication for the G Protein-coupled Estrogen Receptor

Objectives This study aimed to evaluate the therapeutic effects and mechanism of genistein on dextran sulfate sodium-induced mouse model of ulcerative colitis (UC). Materials and Methods A DSS-induced mouse model for UC was used in this study. Mice were then treated with genistein or a combination of genistein and the G protein-coupled estrogen receptor (GPER) antagonist G15. Colon length, disease activity index (DAI), spleen index (SI), histopathological alterations, and integrity of the colonic barrier were evaluated. The expression of inflammatory cytokines and antioxidant capacity were detected. Populations of T helper 17 cells (Th17) and Regulatory T cells (Treg) in the mesenteric lymph nodes (MLN) were analyzed. The expression of a transcription factor for Th17 and Treg in the colonic tissues was detected. Results Genistein treatment significantly alleviated DSS-induced colitis, summarized as increased colonic length, decreased DAI, SI, improved histopathological alterations, and colonic barrier integrity. Genistein treatment restrained pro-inflammatory cytokines and oxidative enzyme release while promoting anti-inflammatory and anti-oxidative enzyme release. Flow cytometry indicated that genistein significantly reduced the Th17 population while boosting Treg populations. Furthermore, genistein inhibited the expression of transcription factors associated with Th17 and promoted the expression of transcription factors associated with Treg in the colonic tissue. Intriguingly, these observed effects of genistein were abolished when UC mice were treated with a combination of genistein and GPER antagonist G15. Conclusion This study suggests that genistein is potent in protecting against DSS-induced colonic injuries by rebalancing Th17/Treg and that GPER may be a vital target for genistein-mediated immunomodulatory effects in UC.

Genistein in combination with Chlorogenic acid ameliorates insulin resistance and oxidative stress in skeletal muscle of high-fat diet fed mice

Objectives: Increasing evidence has demonstrated that oxidative stress plays a significant role in the pathogenesis of muscle insulin resistance. The beneficial impacts of genistein (GEN) and chlorogenic acid (CGA) on insulin resistance have already been revealed. However, their combined effects on skeletal muscle oxidative stress and insulin resistance have not been completely understood. The aim of the present study was to determine the effect of GEN in combination with CGA on skeletal muscle insulin resistance in high-fat diet (HFD) fed C57BL/6 mice.
 Methods: C57BL/6 male mice were fed an HFD for 15 weeks. The mice were then divided into five groups: standard chow diet (SCD), HFD, HFD + GEN, HFD + CGA, and HFD + GEN + CGA for 10 weeks.
 Results: The findings indicated that single treatment with GEN or CGA, and with a stronger effect of GEN+CGA combined treatment, decreased body weight gain and improved glucose intolerance. Moreover, following treatment with GEN and CGA alone or in combination with further effect, the level of plasma and muscle triglyceride (TG) were reduced. Furthermore, the combination therapy of GEN and CGA with greater efficacy than the single treatments, could decrease several oxidative stress markers in the skeletal muscle. Treatment with GEN and CGA alone or in combination could increase the expression of NF-E2–related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P): Quinone Oxidoreductase 1 (NQO1).
 Conclusion: The data of this study suggest that the combination of GEN and CGA might ameliorate insulin resistance and reduce oxidative stress in the skeletal muscle of mice fed HFD.

A Comprehensive Review of Genistein's Effects in Preclinical Models of Cervical Cancer.

Cervical cancer is associated with persistent Human Papilloma Virus (HPV) infections and is the fourth most common cancer in women worldwide. Current treatment options; surgery, chemotherapy, and radiation, are often associated with severe side effects including possible infertility. Novel treatment options are required to help combat this disease and reduce side effects. Many plant-derived chemicals, including paclitaxel and docetaxel, are already in use as treatments for various cancers. Genistein is a polyphenolic isoflavone found in foods including soybeans and legumes, and studies have shown that it has various biological effects and anti-cancer properties. This review aims to summarize the existing studies examining the effects of genistein on cervical cancer. All relevant in vitro and in vivo studies are summarized, and the key findings are highlighted in the associated tables. Based on the available in vitro/cell culture studies reported here, genistein inhibits cervical cancer cell proliferation and induces apoptosis. Use of genistein in combination with radiation or chemotherapy agents resulted in enhanced response indicating radio- and chemo-sensitization properties. More animal studies are required to examine the effectiveness of genistein in vivo. Such studies will form the basis for future human studies exploring the potential of genistein to be used in the treatment of cervical cancer.

Combined anticancer effects of neutron radiation and genistein on prostate cancer cells

Prostate cancer is the most frequent cancer in men and the second largest cause of cancer-related mortality after lung cancer. Today, studies on neutron radiation therapy show that this method alone is not able to prevent the progression of the disease in most patients with prostate cancer, so it is better to combine neutron radiation with an auxiliary antitumor such as genistein. We found that genistein has anticancer properties and few antioxidant capabilities and could cause the death of prostate cancer cells, mostly through triggering apoptosis. Here the purpose of this study was to evaluate the effect of very low dose rate neutron irradiation emitted from 241Am-Be neutron source as well as the effect of the combination of neutron irradiation and adding the optimal concentration of genistein (480 μM) on the attenuation of prostate cancer PC3 cells in 3D culture environment. MTT assay, Neutral red assay, NO assay, Catalase activity, Reduced glutathione (GSH), Cytochrome c releasing, and Comet assay were used to assess the effect and type of mortality caused by neutron radiation and also neutron and genistein combination in prostate cancer cells. The results of cytotoxicity test reveal that very low dose rate neutron radiation (0.6 mGy/h) with or without genistein at 5, 10, 15, and 20h reduced the survival of prostate cancer cells. Moreover, the rate of necrosis due to the neutron effect at different irradiation times enhanced with the increasing time. Despite significant anticancer effect of Genistein, it cannot be used simultaneously with neutron radiation for prostate cancer treatment.

Combined Bazedoxifene and Genistein Ameliorate Ovariectomy-Induced Hippocampal Neuro-Alterations via Activating CREB/BDNF/TrkB Signaling Pathway.

The scientific research community devotes stupendous efforts to control the arguable counterbalance between the undesirable effects of hormone replacement therapy (HRT) and post-menopausal syndrome. The recent emergence of 3rd generation selective estrogen receptor modulators and phytoestrogens has provided a promising alternative to HRT. Hence, we assessed the potential effects of combined Bazedoxifene and Genistein on hippocampal neuro-alterations induced by experimental ovariectomy. For this purpose, we utilized forty-eight healthy sexually mature female Wistar rats assorted to control, ovariectomy (OVX), Genistein-treated ovariectomized (OVX+GEN) and Bazedoxifene and Genistein-treated ovariectomized (OVX+BZA+GEN) groups. Hippocampi samples from various groups were examined by H&E, silver stains and immunohistochemical examination for calbindin-D28k, GFAP, and BAX proteins. We also assessed hippocampal mRNA expression of ERK, CREB, BDNF and TrkB. Our histopathological results confirmed that combined BZA+GEN induced restoration of hippocampal neuronal architecture, significant reduction of GFAP and BAX mean area % and significant upregulation of calbindin-D28k immunoexpression. Furthermore, we observed significant upregulation of ERK, CREB, BDNF and TrkB mRNA expression in the BZA+GEN group compared to the OVX group. Taken together, our findings have provided a comprehensive assessment of histological, immunohistochemical and cyto-molecular basis of combined Genistein and Bazedoxifene ameliorative impacts on hippocampal neuro-alterations of OVX rats via upregulation of Calbindin, CERB, BDNF, Trk-B and ERK neuronal expression.

Role of soy lecithin combined with soy isoflavone on cerebral blood flow in rats of cognitive impairment and the primary screening of its optimum combination.

Soy isoflavone (SIF) and soy lecithin (SL) have beneficial effects on many chronic diseases, including neurodegenerative diseases. Regretfully, there is little evidence to show the combined effects of these soy extractives on the impairment of cognition and abnormal cerebral blood flow (CBF). This study examined the optimal combination dose of SIF + SL to provide evidence for improving CBF and protecting cerebrovascular endothelial cells. In vivo study, SIF50 + SL40, SIF50 + SL80 and SIF50 + SL160 groups were obtained. Morris water maze, laser speckle contrast imaging (LSCI), and hematoxylin-eosin staining were used to detect learning and memory impairment, CBF, and damage to the cerebrovascular tissue in rat. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the oxidized glutathione (GSSG) were detected. The anti-oxidative damage index of superoxide dismutase (SOD) and glutathione (GSH) in the serum of an animal model was also tested. In vitro study, an immortalized mouse brain endothelial cell line (bEND.3 cells) was used to confirm the cerebrovascular endothelial cell protection of SIF + SL. In this study, 50 μM of Gen were used, while the 25, 50, or 100 μM of SL for different incubation times were selected first. The intracellular levels of 8-OHdG, SOD, GSH, and GSSG were also detected in the cells. In vivo study, SIF + SL could increase the target crossing times significantly and shorten the total swimming distance of rats. The CBF in the rats of the SIF50 + SL40 group and SIF50 + SL160 group was enhanced. Pathological changes, such as attenuation of the endothelium in cerebral vessels were much less in the SIF50 + SL40 group and SIF50 + SL160 group. The 8-OHdG was reduced in the SIF50 + SL40 group. The GSSG showed a significant decrease in all SIF + SL pretreatment groups, but the GSH showed an opposite result. SOD was upregulated by SIF + SL pretreatment. Different combinations of Genistein (Gen)+SL, the secondary proof of health benefits found in vivo study, showed they have effective anti-oxidation and less side reaction on protecting cerebrovascular endothelial cell. SIF50 + SL40 in rats experiment and Gen50 + SL25 in cell test were the optimum joint doses on alleviating cognitive impairment and regulating CBF through protecting cerebrovascular tissue by its antioxidant activity. SIF+SL could significantly prevent cognitive defect induced by β-Amyloid through regulating CBF. This kind of effect might be attributed to its antioxidant activity on protecting cerebral vessels.

Mitigation of MAFLD in High Fat-High Sucrose-Fructose Fed Mice by a Combination of Genistein Consumption and Exercise Training.

PurposeMetabolic dysfunction-associated fatty liver disease (MAFLD) is fueled by escalations in both sedentary behavior and caloric intake and is noted in obese type 2 diabetic (T2DM) patients. This study aimed to examine the effects of exercise and the phytoestrogen genistein in mice fed a high fat (60% fat) high sugar (55% fructose with 45% sucrose), HFHS diet.MethodsMale C57BL/6J mice were assigned to five groups: HFHS, HFHS with genistein (600 mg/kg diet, HFHS+Gen), HFHS with moderate exercise (HFHS+Ex), and HFHS with combined genistein and moderate exercise (HFHS-Gen+Ex). Control lean mice were fed standard chow and water. Exercise consisted of 30-minute sessions of treadmill running five days/week for the 12-week study duration. Body weight was assessed weekly. Liver, kidney, fecal pellets and serum were extracted at the end of the study and maintained at −80°C.ResultsAfter 12 weeks of treatment, mice in the HFHS group had the highest hepatic lipid content. Plasma levels of glucose, insulin, leptin, cholesterol, amylin, and total fat content were significantly elevated in HFHS mice compared to control mice. HFHS feeding increased protein expression of carnitine palmitoyltransferase 1b (CPT-1b isoform) in gastrocnemius, CPT1a, glucose transporter protein 2 (GLUT2), glucocorticoid receptor (GR), and fructose 1,6-bisphosphate 1 (FBP1) expression in liver. Exercise alone had minor effects on these metabolic abnormalities. Genistein alone resulted in improvements in body weight, fat content, amylin, insulin sensitivity, and liver histopathology, GR, FBP1, and acetyl-CoA carboxylase 1 (ACC1). Combination treatment resulted in additional metabolic improvements, including reductions in hepatic lipid content and lipid area, alanine transferase activity, CPT1b, and CPT1a.ConclusionOur results indicate that a HFHS diet is obesogenic, inducing metabolic perturbations consistent with T2DM and MAFLD. Genistein alone and genistein combined with moderate intensity exercise were effective in reducing MAFLD and the aberrations induced by chronic HFHS feeding.

Therapeutic potentials of genistein: New insights and perspectives.

Genistein, a polyphenolic isoflavone compound found abundantly in soy or soy-based products, is widely consumed in the Asian population. Genistein has poor bioavailability, to overcome this problem many advanced nano-drug delivery carrier systems are designed to enhance its water solubility and stability. However, further research is required to develop more efficient bioavailability improvement strategies. Genistein is a phytoestrogen which has been associated with reducing the risk of cancer, cardiovascular disorders, and diabetes mellitus. This plant-based bioactive compound possesses numerous biological activities such as anti-oxidant, anti-inflammatory, anti-obesity, anti-cancer, cardioprotective, and anti-diabetic activities to treat various disease states. Genistein has been used as an active therapeutic agent in many medications. Moreover, several clinical trials are in the ongoing stage to develop more efficient treatment therapies, especially for cancer treatment. This article highlights the protective and therapeutic benefits of genistein in the treatment of different ailments, and more specifically elaborates on the anti-cancer potential of genistein regarding various types of cancers. PRACTICAL APPLICATIONS: Genistein possesses versatile biological activities, including anti-diabetic, anti-inflammatory, anti-oxidant, anti-obesity, and anti-angiogenic. The most studied activity is anti-cancer. Currently, a number of pre-clinical and clinical trials are being carried out on anti-neoplastic and cytotoxic activities of genistein to develop novel therapeutic agents with excellent anti-cancer potential for the treatment of various kinds of cancer. Moreover, many bioavailability enhancement strategies have been developed to improve the bioavailability of genistein. Genistein shows significant hypoglycemic effects alone or in combination with other anti-diabetic agents. Genistein in combination with other chemotherapeutic agents is used for the treatment of prostate, bone, colorectal, glioma, breast, and bladder cancer.

The Combination of Genistein and Imatinib has an Increased Effect on Cell Proliferation Inhibition in Philadelphia Positive Leukemia Cell Lines

Background: This study investigated the possible role of Genistein as a combination with Imatinib in controlling leukemia cell line proliferation. Methods: Three cell lines, K562, Kcl22, and CCRF, were cultured and analyzed for MTT, LDH, apoptosis, and cycle cell gene expression in the presence of different dosages of Imatinib and Genistein in combination or separately. Results: Data has shown a decrease in proliferation and an increase in apoptosis activity during combination treatment. LDH assay has shown no additional toxicity due to Genistein consumption in combination therapy. Analysis of the expression of responsible genes for cell cycle demonstrated both G1 (p53, p21 upregulation) and G2 (cdc25c downregulation) inhibitory effect in combination treatment. Conclusion: Altogether, this study suggests thatthe combination treatment of Imatinib and Genistein for leukemia cells resistant to Imatinib can increase treatment efficiency.

Cellular and Gene Expression Response to the Combination of Genistein and Kaempferol in the Treatment of Mucopolysaccharidosis Type I.

Flavonoids are investigated as therapeutics for mucopolysaccharidosis, a metabolic disorder with impaired glycosaminoglycan degradation. Here we determined the effects of genistein and kaempferol, used alone or in combination, on cellular response and gene expression in a mucopolysaccharidosis type I model. We assessed the cell cycle, viability, proliferation, subcellular localization of the translocation factor EB (TFEB), number and distribution of lysosomes, and glycosaminoglycan synthesis after exposure to flavonoids. Global gene expression was analysed using DNA microarray and quantitative PCR. The type and degree of flavonoid interaction were determined based on the combination and dose reduction indexes. The combination of both flavonoids synergistically inhibits glycosaminoglycan synthesis, modulates TFEB localization, lysosomal number, and distribution. Genistein and kaempferol in a 1:1 ratio regulate the expression of 52% of glycosaminoglycan metabolism genes. Flavonoids show synergy, additivity, or slight antagonism in all analysed parameters, and the type of interaction depends on the concentration and component ratios. With the simultaneous use of genistein and kaempferol in a ratio of 4:1, even a 10-fold reduction in the concentration of kaempferol is possible. Flavonoid mixtures, used as the treatment of mucopolysaccharidosis, are effective in reducing glycosaminoglycan production and storage and show a slight cytotoxic effect compared to single-flavonoid usage.

Combined Beneficial Effect of Genistein and Atorvastatin on Adipogenesis in 3T3-L1 Adipocytes.

Genistein (4,5,7-trihydroxyisoflavone) is abundant in various dietary vegetables, especially soybeans, and is known to have not only an estrogenic effect but also an antiadipogenic effect. Atorvastatin (dihydroxy monocarboxylic acid) is a statin used to prevent heart disease. Although genistein and atorvastatin have been reported to possess antiadipogenic effects, their combined effects are still unclear. The aim of the current study was to explore whether the combination of genistein and atorvastatin at low concentrations significantly suppresses adipogenesis in a murine preadipocyte cell line (3T3-L1) compared to treatment with genistein or atorvastatin alone. Our results showed that cotreatment with 50 µM genistein and 50 nM atorvastatin significantly suppressed preadipocyte differentiation, whereas when each compound was used alone, there was no inhibitory effect. Additionally, cotreatment with genistein and atorvastatin significantly downregulated adipogenic marker proteins, including mitogen-activated protein kinases (MAPKs), peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), glucocorticoid receptor (GR), and CCAAT/enhancer-binding protein β (C/EBPβ). This is the first evidence of the combined antiadipogenic effects of genistein and atorvastatin. Although additional experiments are required, combinational treatment with genistein and atorvastatin may be an alternative treatment for menopause-associated lipid metabolic disorders and obesity.

The employment of UV-Vis spectroscopy and chemometrics techniques for analyzing the combination of genistein and curcumin

The employment of UV-Vis spectroscopy and chemometrics techniques for analyzing the combination of genistein and curcumin

Genistein-Calcitriol Mitigates Hyperosmotic Stress-Induced TonEBP, CFTR Dysfunction, VDR Degradation and Inflammation in Dry Eye Disease.

Dry eye disease (DED) signs and symptoms are causally associated with increased ocular surface (OS) inflammation. Modulation of key regulators of aberrant OS inflammation is of interest for clinical management. We investigated the status and the potential to harness key endogenous protective factors, such as cystic fibrosis transmembrane conductance regulator (CFTR) and vitamin D receptor (VDR) in hyperosmotic stress‐associated inflammation in patients with DED and in vitro. Conjunctival impression cytology samples from control subjects (n = 11) and patients with DED (n = 15) were used to determine the status of hyperosmotic stress (TonEBP/NFAT5), inflammation (IL‐6, IL‐8, IL‐17A/F, TNFα, MMP9, and MCP1), VDR, and intracellular chloride ion (GLRX5) by quantitative polymerase chain reaction and/or immunofluorescence. Human corneal epithelial cells (HCECs) were used to study the effect of CFTR activator (genistein) and vitamin D (calcitriol) in hyperosmotic stress (HOs)‐induced response in vitro. Western blotting was used to determine the expression of these proteins, along with p‐p38. Significantly, higher expression of inflammatory factors, TonEBP, GLRX5, and reduced VDR were observed in patients with DED and in HOs‐induced HCECs in vitro. Expression of TonEBP positively correlated with expression of inflammatory genes in DED. Increased TonEBP and GLRX5 provides confirmation of osmotic stress and chloride ion imbalance in OS epithelium in DED. These along with reduced VDR suggests dysregulated OS homeostasis in DED. Combination of genistein and calcitriol reduced HOs‐induced TonEBP, inflammatory gene expression, and p‐p38, and abated VDR degradation in HCECs. Henceforth, this combination should be further explored for its relevance in the management of DED.

(±)-Equol does not interact with genistein on estrogen-dependent breast tumor growth

Equol (EQ) is a prominent microbial metabolite of the soy isoflavone, daidzein, with estrogen-like properties. The major soy isoflavone, genistein (GEN), stimulated growth of estrogen-dependent breast cancer (EDBC) cells in vitro and tumor growth in vivo but EQ did not. To understand possible interactions of EQ and GEN on EDBC, EQ was used with GEN in combination in vitro and in vivo. Effects of EQ, GEN and EQ + GEN were evaluated using MCF-7 and T47D EDBC. Ovariectomized athymic mice were used as a model for in vivo tumor growth. Dietary EQ had no effect on MCF-7 tumor growth and the absence of effect was confirmed using a T47D EDBC in vivo model. EQ alone or in combination with GEN increased EDBC cell proliferation in vitro. EQ alone neither stimulated EDBC tumor growth in vivo at various doses nor suppressed tumor growth induced by dietary GEN. In summary, EQ has similar estrogenic effect as GEN in vitro but does not interact with GEN on EDBC tumor growth. Based on the evidence presented here, dietary EQ is unlikely to have estrogenic effects in vivo.

Inhibitory effects of genistein in combination with gefitinib on the hepatocellular carcinoma Hep3B cell line.

Combination therapy is an important method for treating advanced hepatocellular carcinoma (HCC). Gefitinib is an epidermal growth factor receptor (EGFR) inhibitor, which has profound effects on HCC. The purpose of the present study was to investigate the effects of genistein in combination with gefitinib on the proliferation and apoptosis of HCC cells and the associated mechanism. Cell counting kit-8 assay was performed to calculate the IC50 values and cytotoxicity, whilst flow cytometry was used to assess cell apoptosis. Protein expression was detected using western blot analysis. The IC50 of genistein and gefitinib on Hep3B cells were calculated to be 128.078 and 13.657 µM, respectively. Genistein in combination with gefitinib significantly inhibited cell viability, promoted apoptosis and reduced EGFR, vascular endothelial growth factor receptor and platelet-derived growth factor receptor phosphorylation. Genistein in combination with gefitinib promoted the expression of cleaved caspase-3 and cleaved poly ADP-ribose polymerase. In addition, combined treatment of genistein and gefitinib strongly inhibited the activation of the Akt/Erk/mTOR signaling pathway. In conclusion, findings from the present study suggest that genistein in combination with gefitinib inhibit HCC cell proliferation and promote apoptosis by inhibiting the Akt/Erk/mTOR pathway.

Cell Cycle Modulation of CHO-K1 Cells Under Genistein Treatment Correlates with Cells Senescence, Apoptosis and ROS Level but in a Dose-Dependent Manner.

Purpose: Genistein, a soy isoflavone, exhibits a biphasic effect on cells proliferation with some different effects between ER-alpha and ER-beta. The objective of this present study is to determine the modulatory effect based on cell cycle progression under genistein treatment in combination with 17-β estradiol (E2) on CHO-K1 cells. Methods: The effect of genistein 0.1-100 µM on cells proliferation was examined by MTT assay. The modulation of genistein and estradiol (E2) on cell cycle and apoptosis were observed by using flowcytometry with PI and PI/AnnexinV staining, respectively. Moreover, the effect of genistein and E2 on senescence cells, and ROS level were determined by senescence-associated β-galactosidase (SA β-gal) staining and by using flowcytometry with 2’, 7’–dichlorofluorescin diacetate (DCFDA) staining, respectively. The expression level of the cell cycle and senescence protein markers were observed by immunoblotting. Results: Single treatment of genistein at physiologically achievable (low) concentration (<2 µM) induced proliferation of CHO-K1 cells while at a pharmacological (high) concentration (50 and 100 µM) suppressed cells proliferation. Interestingly, treatment of genistein at the physiological concentration in combination with E2 for 24, 48 and 72 h decreased cells viability on CHO-K1 cells compared to untreated cells. Further analysis of the cells showed that 50 µM genistein induced G2/M phase accumulation and induced apoptosis. Moreover, genistein induced cell senescence and increased ROS level. Immunoblotting analysis showed the decreasing of ERalpha, Bcl2, and ppRb protein level upon treatment of 1 µM Gen and 1 nM E2. Conclusion: Our results suggest that the cell proliferation inhibitory mechanism of genistein at pharmacological concentration involved the induction of cell senescence, and the elevation of ROS level. Moreover, the decreased of cells proliferation upon treatment of physiological concentration of genistein in combination with E2 may be correlated with the alteration of ER expression.

Capsaicin And Genistein Override The Action Of Obestatin To Decrease Lipid Accumulation In 3T3-L1 Cells.

Satiety peptides convey information about short-term energy reserves in the gut to the hypothalamus and aid in regulation of appetite and food intake. Obestatin is one such gastro peptide that has been shown to upregulate glycerolipid metabolism and PPARγ signalling. Obestatin brings about moderate reduction in circulating and stored triglyceride levels and reduction in gain in body weight in mice. We wanted to test whether obestatin could be further potentiated by co-administration with nutraceuticals genistein and capsaicin that are well known to reduce triglyceride levels. Hence, we chose to administer the compounds individually and pair-wise with obestatin in 3T3-L1 cells at concentrations of 200 nM obestatin, 10 µM capsaicin and 100 µM genistein. When treated along with induction of differentiation, both capsaicin and genistein in combination with obestatin reduced triglyceride levels in 3T3-L1 cells by 25 and 20%, respectively, when accessed on day 14 after induction. The combined administrations were dominated by the effect of the nutraceuticals and showed the same effect as of capsaicin or genistein. Upregulation of Fatty acid synthase (Fasn) and Adipose triglyceride lipase (Atgl/Pnpla2) by obestatin were reversed by both capsaicin and genistein. However, their ability to upregulate Peroxisome proliferation activating receptor gamma (Pparγ), Hormone sensitive lipase (Hsl), Lipoprotein lipase (Lpl) were retained while upregulation of Uncoupling protein 1 (Ucp1) by capsaicin was unchanged upon co-administration. Over expression of the lipases and UCP1 in case of capsaicin could be resulting in net lowering of lipid accumulation in the cells.

Study of the effect of exposure to Phytoestrogens (Genistein) and estradiol (17β- estradiol) in the level of gene expression (CYP19A1) and quantifica-tion of aromatase in female rats

The current study was carried out to investigate the role of Phytoestrogens (genistein) in different concentrations and estrogens manufactured in tablets coated with or without progesterone at the level of gene expression of CYP19A1 and quantitative estimation of aromatase compared to control group. The results of the present study showed a significant increase in (P &lt;0.05) In the level of quantitative estimation of serum aromatase enzyme and for all treatments compared to the control group (124.12). The highest level of the enzyme (322.00) in the group treated with genistein in combination with estradiol, while, the lowest rise in the level of aromatase enzyme (164.37) in the group treated with genistein combined with progesterone. There was also a significant decrease in the concentration of ribosomal RNA and all the treatments compared to the control group (1068.95), the Lower of RNA concentration was (373.70) in the group treated with genistein at a concentration of 50 mg | kg, While Less low concentration of RNA (1068.95) was observed in the groups treated with concurrent genistein with estradiol. The results of the present study indicate that there was a significant increase (P &lt;0.05) in the level of gene expression of the aromatase enzyme in ovarian tissue and for all the treatments compared to control group (305.51). The highest level of gene expression of the enzyme (7.189) was observed in the groups treated with concurrent genistein with estradiol, While the lowest level of gene expression of aromatase (2.204) was observed in the groups treated with genistein combined with progesterone.