Showing papers on "Isoflavones published in 2020"
TL;DR: In this article, the effect of solid-state fermentation (SSF) with Lactobacillus casei on the changes of nutritional components, isoflavones, phenolic acids and antioxidant activity of whole soybean flour (WSF) was investigated.
Abstract: This work researched the effect of solid-state fermentation (SSF) with Lactobacillus casei on the changes of nutritional components, isoflavones, phenolic acids and antioxidant activity of whole soybean flour (WSF). Results showed that total protein, vitamin B1, vitamin B2, and β-carotene of WSF increased after fermentation. Fermented whole soybean flour (FWSF) showed higher essential amino acids contents and essential amino acid index. There was no significant change in ash, Fe, Ca, Zn, and K content (P > 0.05). SSF treatment caused a significant decrease in lipids, crude fibre, and antinutritional factors (lipoxygenase-1, lipoxygenase-3, trypsin inhibitor, and urease) (P
53 citations
TL;DR: The objective of this article is to review the recent understanding of the biological activities, adverse effects, and use of isoflavones in functional food development.
Abstract: Soybeans and their food products exist in the market in various forms, ranging from crude oils and bean meals to nutritious products (e.g. soy milk powers). With the availability of technologies for mass production of soy products and for enrichment of soy components (e.g. phospholipids, saponins, isoflavones, oligosaccharides and edible fiber), the nutritional values of soy products have been enhanced remarkably, offering the potential for functional food development. Among different bioactive components in soybeans, one important component is isoflavones, which have been widely exploited for health implications. While there are studies supporting the health benefits of isoflavones, concerns on adverse effects have been raised in the literature. The objective of this article is to review the recent understanding of the biological activities, adverse effects, and use of isoflavones in functional food development.
46 citations
TL;DR: This review organizes and collects newly-found reports of aglycones and their metabolites’ bioavailability toward metabolism in human body, and the application in the prevention and treatment of various disorders such as cancers, obesity, diabetes, hypertension, hyperlipidemia, cardiovascular diseases, neurological disorders and osteoporosis from the past decade providing the latest findings and evidence in different pathways.
45 citations
TL;DR: There is scientific evidence showing the beneficial effect of isoflavones on bone health and thus in the prevention and treatment of osteoporosis on postmenopausal women, although the results do not seem entirely conclusive as there are discrepancies among the studies, probably related to their experimental designs.
Abstract: Isoflavones are phenolic compounds with a chemical structure similar to that of estradiol. They are present in several vegetables, mainly in legumes such as soy, white and red clover, alfalfa and beans. The most significant food source of isoflavones in humans is soy-derived products. Isoflavones could be used as an alternative therapy for pathologies dependent on hormonal disorders such as breast and prostate cancer, cardiovascular diseases, as well as to minimize menopausal symptoms. According to the results gathered in the present review, it can be stated that there is scientific evidence showing the beneficial effect of isoflavones on bone health and thus in the prevention and treatment of osteoporosis on postmenopausal women, although the results do not seem entirely conclusive as there are discrepancies among the studies, probably related to their experimental designs. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. Regarding cancer, scientific evidence suggests that isoflavones could be useful in reducing the risk of suffering some types of cancer, such as breast and endometrial cancer, but further studies are needed to confirm these results. Finally, isoflavones could be useful in reducing hot flushes associated with menopause. However, a limitation in this field is that there is still a great heterogeneity among studies. Lastly, with regard to isoflavone consumption safety, it seems that they are safe and that the most common adverse effect is mild and occurs at the gastrointestinal level.
40 citations
TL;DR: In this paper, isoflavones can form complexes with RANKL limiting binding of the cytokine to its receptor, which is a cytokine responsible for bone resorption.
Abstract: Receptor activator of nuclear factor-κB ligand (RANKL) is a cytokine responsible for bone resorption. It binds its receptor RANK, which activates osteoporosis. High levels of osteoprotegerin (OPG) competitively binding RANKL limit formation of ligand-receptor complexes and enable bone mass maintenance. The new approach to prevent osteoporosis is searching for therapeutics that can bind RANKL and support OPG function. The aim of the study was to verify the hypothesis that isoflavones can form complexes with RANKL limiting binding of the cytokine to its receptor. Interactions of five isoflavones with RANKL were investigated by isothermal titration calorimetry (ITC), by in silico docking simulation and on Saos-2 cells. Daidzein and biochanin A showed the highest affinity for RANKL. Among studied isoflavones coumestrol, formononetin and biochanin A showed the highest potential for Saos-2 mineralization and were able to regulate the expression of RANKL and OPG at the mRNA levels, as well as osteogenic differentiation markers: alkaline phosphatase (ALP), collagen type 1, and Runt-related transcription factor 2 (Runx2). Comparison of the osteogenic activities of isoflavones showed that the use of physicochemical techniques such as ITC or in silico docking are good tools for the initial selection of substances showing a specific bioactivity.
38 citations
TL;DR: Genistin is a potent anti-adipogenic and anti-lipogenic agent in 3T3-L1 cells through a similar signaling pathway in a dose-dependent manner.
Abstract: Soy isoflavones are popular ingredients with anti-adipogenic and anti-lipogenic properties. The anti-adipogenic and anti-lipogenic properties of genistein are well-known, but those of genistin and glycitein remain unknown, and those of daidzein are characterized by contrasting data. Therefore, the purpose of our study was to investigate the effects of daidzein, glycitein, genistein, and genistin on adipogenesis and lipogenesis in 3T3-L1 cells. Proliferation of 3T3-L1 preadipocytes was unaffected by genistin and glycitein, but it was affected by 50 and 100 µM genistein and 100 µM daidzein for 48 h. Among the four isoflavones, only 50 and 100 µM genistin and genistein markedly suppressed lipid accumulation during adipogenesis in 3T3-L1 cells through a similar signaling pathway in a dose-dependent manner. Genistin and genistein suppress adipocyte-specific proteins and genes, such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα), and adipocyte binding protein 2 (aP2)/fatty acid-binding protein 4 (FABP4), and lipogenic enzymes such as ATP citrate lyase (ACL), acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FAS). Both isoflavones also activate AMP-activated protein kinase α (AMPKα), an essential factor in adipocyte differentiation, and inhibited sterol regulatory element-binding transcription factor 1c (SREBP-1c). These results indicate that genistin is a potent anti-adipogenic and anti-lipogenic agent.
37 citations
TL;DR: Isolated soy protein significantly reduced serum TG, TC, LDL-C, HDL-C and Apo-B levels in postmenopausal women and strongly depends on the protein and isoflavone content of soy products, duration and dosage of consumption.
Abstract: Background: Many randomized controlled trials (RCTs) have assessed the effects of soy products on serum lipids. However, the responsible soy components and the magnitude of effects in healthy or hy...
29 citations
TL;DR: Overall, among all microorganisms, actinomycetes are the main producers of flavonoids and the functional genes involved in flavonoid biosynthesis are summarized and classified.
Abstract: Flavonoids and isoflavonoids are polyphenolic secondary metabolites usually produced by plants adapting to changing ecological environments over a long period of time. Therefore, their biosynthesis pathways are considered as the most distinctive natural product pathway in plants. Seemingly, the flavonoids and isoflavones from fungi and actinomycetes have been relatively overlooked. In this review, we summarized and classified the isoflavones and flavonoids derived from fungi and actinomycetes and described their biological activities. Increasing attention has been paid to bioactive substances derived from microorganism whole-cell biotransformation. Additionally, we described the utilization of isoflavones and flavonoids as substrates by fungi and actinomycetes for biotransformation through hydroxylation, methylation, halogenation, glycosylation, dehydrogenation, cyclisation, and hydrogenation reactions to obtain rare and highly active biofunctional derivatives. Overall, among all microorganisms, actinomycetes are the main producers of flavonoids. In our review, we also summarized the functional genes involved in flavonoid biosynthesis.
29 citations
TL;DR: This work investigated the potential occurrence and content of isoflavones in soya agricultural waste collected directly from the ground after mechanically harvesting, and assessed the extraction performances of ethanol and acetone for these materials as an alternative to acetonitrile, a problematic solvent from an environmental point of view.
28 citations
TL;DR: Transcriptional analysis of isoflavonoid biosynthetic genes demonstrated that most metabolic genes were highly activated in response toUV-B 24 and UV-B 36 treatments, and it was found that GmCHS6, GMCHS7, and Gm CHS8 genes among the eight known genes encoding chalcone synthase were specifically related to UV- B response.
23 citations
TL;DR: Evidence supporting the efficacy of most dietary factors appears inadequate to recommend their use and several antioxidants, including lycopene, selenium, curcumin, coenzyme Q10, phytoestrogens and flavonoids are examined.
Abstract: The quest for dietary patterns and supplements efficient in down-regulating prostate-specific antigen (PSA) concentrations among men with prostate cancer (PCa) or increased PCa risk has been long. Several antioxidants, including lycopene, selenium, curcumin, coenzyme Q10, phytoestrogens (including isoflavones and flavonoids), green tea catechins, cernitin, vitamins (C, E, D) and multivitamins, medicinal mushrooms (Ganoderma lucidum), fruit extracts (saw palmetto, cranberries, pomegranate), walnuts and fatty acids, as well as combined supplementations of all, have been examined in randomized controlled trials (RCTs) in humans, on the primary, secondary, and tertiary PCa prevention level. Despite the plethora of trials and the variety of examined interventions, the evidence supporting the efficacy of most dietary factors appears inadequate to recommend their use.
TL;DR: The potential of LAB and Bifidobacterium strains to produce functional soy drink enriched with bioactive isoflavones is demonstrated in this work.
TL;DR: In this paper, a fermented soybean milk with Lactobacillus plantarum (HFY01) was used for weight and lipid reduction in mice with obesity induced by a high-fat diet.
Abstract: Soybean milk fermented with Lactobacillus plantarum HFY01 (LP-HFY01) was used for weight and lipid reduction in mice with obesity induced by a high-fat diet. We evaluated the gastrointestinal tolerance in vitro, organ index, body fat rate, pathological changes, serum index, mRNA expression and changes of isoflavones in soybean milk. Results indicated that LP-HFY01 exhibited good tolerance to pH 3.0 artificial gastric juice (69.87 ± 0.04%) and 0.3% bile salt (15.94 ± 0.3%). LP-HFY01-fermented soybean milk reduced the body fat rate and liver index of obese mice (p < 0.05). Organ sections showed that LP-HFY01-fermented soybean milk improved fatty degeneration and liver cell damage caused by a high-fat diet. LP-HFY01-fermented soybean milk inhibited increases in low-density lipoprotein cholesterol (LDL-c), triglyceride (TG), alkaline phosphatase (AKP), and glutamic oxaloacetic transaminase (GOT) and the decrease in high-density lipoprotein cholesterol (HDL-c) in the serum of obese mice, and inhibited CCAAT/enhancer-binding protein-α (C/EBP-α) and peroxisome proliferator-activated receptor-γ (PPAR-γ) mRNA expression, as well as activated cuprozinc-superoxide dismutase (SOD1) and lipoprotein lipase (LPL) mRNA expression in the liver and epididymal fat of obese mice (p < 0.05). Daidzin, glycitin, daidzein, glycitein, genistein, and genistin contents in soybean milk were determined before and after fermentation by high-performance liquid chromatography (HPLC); the daidzin and genistin contents in the fermented soybean milk decreased, whereas the daidzein and genistein contents increased significantly. Therefore, the LP-HFY01-fermented soybean milk strongly inhibits obesity induced by a high-fat diet, and shows good potential for utilization.
TL;DR: The origin of the English name of soybean and its scientific name, Glycine max (L.) Merrill, and the reports of soy isoflavones discovered over a period of about 100 years are reviewed.
Abstract: The production of soybean continues to increase worldwide. People are showing more interest in the beneficial health effects of soybeans than before. However, the origin and history of soybeans are still being discussed among many researchers. Chromatographic methods enable the desirable separation of a variety of isoflavones from soybeans. The structures of isolated soy isoflavones have been successfully identified in tandem with spectroscopic analytical instruments and technologies such as liquid chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy. The theoretical background behind spectroscopy may help improve the understanding for the analysis of isoflavones in soybeans and soy-derived foods. This review covers the origin of the English name of soybean and its scientific name, Glycine max (L.) Merrill, based on the evidence reported to date. Moreover, the reports of soy isoflavones discovered over a period of about 100 years have been briefly reviewed.
TL;DR: EQL was evaluated for its neuroprotective effects against MPP+ induced neurotoxicity using in vivo PD model including Caenorhabditis elegans lifespan assay and data from the in vivo assay supported EQL’s neuroProtective effect as it increases survival of C. elegans exposed to MPP + from 72 to 108 h.
Abstract: Emerging data support that plant food based isoflavones have ameliorating effects on a variety of neurodegenerative diseases including Parkinson’s disease (PD). Our previous investigation revealed that dietary isoflavones including genistein (GEN), daidzein (DAI), and equol (EQL; a gut microbial metabolite of DAI) showed promising blood–brain barrier permeability and anti-neuroinflammatory activity in murine microglial BV2 cells. However, the neuroprotective effects of EQL against neurotoxins induced toxicity in PD related models remains unclear. Herein, EQL, along with GEN and DAI, were evaluated for their cytoprotective effect in a non-contact co-culture model with LPS-BV2-conditioned media and human neuroblastoma SH-SY5Y cells. In addition, their neuroprotective effects against PD related neurotoxins including 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP+) induced cytotoxicity were evaluated in SH-SY5Y cells. Furthermore, EQL was evaluated for its neuroprotective effects against MPP+ induced neurotoxicity using in vivo PD model including Caenorhabditis elegans lifespan assay. DAI (10 μM) and EQL (10 and 20 μM) showed cytoprotective effects by decreasing LPS-BV2-conditioned media induced cytotoxicity in SH-SY5Y cells by 29.2, 32.4 and 27.2%, respectively. EQL (10 and 20 μM) also showed neuroprotective effects by decreasing 6-OHDA and MPP+ induced cytotoxicity in SH-SY5Y cells by 30.6–34.5 and 17.9–18.9%, respectively. Additionally, data from the in vivo assay supported EQL’s neuroprotective effect as it increases survival of C. elegans exposed to MPP+ from 72 to 108 h. Our findings support a growing body of evidence of the neuroprotective effects of dietary isoflavones and further studies are warranted to elucidate their mechanisms of action.
TL;DR: In this article, the authors investigated the potential of beta-glucosidase from two sources: almonds and soy yoghurt cultures (lactic cultures) to react with soy in the biotransformation of soy isoflavones.
Abstract: beta-Glucosidase is an enzyme that hydrolyzes the isoflavone bonds and develops the active form of aglycones providing various health benefits. The potential of beta-glucosidase from two sources: almonds and soy yoghurt cultures (lactic cultures) to react with soy in the biotransformation of soy isoflavones was studied. This study investigated 1) the optimum amount of culture (1, 2, 3, 4%) and incubation temperature (30, 35, 42 degrees C) for fermentation of soymilk (SM); 2) the production of beta-glucosidase and its ability to react with isoflavones with and without the addition of skim milk powder (SMP). The ability of beta-glucosidase to convert isoflavones into aglycones was measured using spectrophotometry and reverse-phase high-pressure liquid chromatography. The results showed that a 1% lactic acid culture at 30 degrees C produced the highest viable count of lactic acid bacteria (similar to 10(8) CFU/ml) in fermented SM. Fermentation at 30 degrees C and 1% inoculation showed the maximum beta-glucosidase activity (4.28 U/ml) while 8 U/ml of beta-glucosidase from almonds had the highest activity (daidzein: 1.48 g/l and genistein: 0.78 g/l). Among the yoghurt cultures, 2% inoculation in soymilk led to the highest aglycones (daidzein: 1.14 g/l and genistein: 0.50 g/l). Supplementing soymilk with skim milk powder led to aglycone levels similar to beta-glucosidase from almond.
TL;DR: The results highlight the important and complex influence of metabolic transformation on isoflavones physiological effects and demonstrate the need to take biotransformation into account when assessing the potential health benefits of consumption of soy is oflavones in cancer.
Abstract: Although soy consumption is associated with breast cancer prevention, the low bioavailability and the extensive metabolism of soy-active components limit their clinical application. Here, the impact of daidzein (D) and its metabolites on estrogen-dependent anti-apoptotic pathway has been evaluated in breast cancer cells. In estrogen receptor α-positive breast cancer cells treated with D and its metabolites, single or in mixture, ERα activation and Neuroglobin (NGB) levels, an anti-apoptotic estrogen/ERα-inducible protein, were evaluated. Moreover, the apoptotic cascade activation, as well as the cell number after stimulation was assessed in the absence/presence of paclitaxel to determine the compound effects on cell susceptibility to a chemotherapeutic agent. Among the metabolites, only D-4'-sulfate maintains the anti-estrogenic effect of D, reducing the NGB levels and rendering breast cancer cells more prone to the paclitaxel treatment, whereas other metabolites showed estrogen mimetic effects, or even estrogen independent effects. Intriguingly, the co-stimulation of D and gut metabolites strongly reduced D effects. The results highlight the important and complex influence of metabolic transformation on isoflavones physiological effects and demonstrate the need to take biotransformation into account when assessing the potential health benefits of consumption of soy isoflavones in cancer.
TL;DR: In this article, the results suggested that the okara could be used as a source of nutraceuticals and isoflavones with potential antioxidant, anti-inflammatory, and enzyme inhibitory activities.
Abstract: Soybean waste (okara) may be used for sustainable processing of bioactive compounds and development of functional foods. Okara was analyzed for isoflavones, antioxidant, cytotoxic and enzyme inhibitory activities. High performance liquid chromatography analysis showed the presence of daidzein (6.20), daidzin (5.85), genistein (3.65), genistin (2.15), glycitin (1.98), and glycitein (1.17 mg/100 g) in okara. Among all the solvent extracts and isolated compounds, the acetonitrile extract, genistein and daidzein showed maximum antioxidant and anti-inflammatory activities. Okara showed high dietary fiber (56) and crude protein (33) compared to crude fat (8.7) and carbohydrate (3.8 g/100 g DM) composition. Okara extracts and isoflavones showed enzyme inhibitory effects; with IC50 values for urease of 41 ± 1 to 65 ± 2 for okara and 10 ± 1 to 21 ± 1 for isoflavones, with the positive control thiourea (7.1 ± 0.1 μg/mL) and for xanthine oxidase 35 ± 1 to 56 ± 2 for okara and 7.3 ± 0.9 to 16 ± 1 for isoflavones, with the positive control allopurinol (5.4 ± 0.1) μg/mL. In cytotoxic studies, the genistein (5.8 and 3.5, μM/mL) and daidzein (7.2 and 4.2 μM/mL) showed higher cytotoxic effects compared to berberine as the control (10.5 and 9.1) IC50 values, respectively. The results suggested that the okara could be used as a source of nutraceuticals and isoflavones with potential antioxidant, anti-inflammatory, and enzyme inhibitory activities. Individual isoflavones from okara might be studied as possible functional ingredients that can act as natural therapeutic agents for conditions involving the xanthine oxidase and urease enzymes.
TL;DR: Fermented soybean has strong antioxidant activity, probably due to its increased total phenolic contents and aglycone isoflavone that resulted from fermentation, which could be used in drug and food industries and can be considered to alleviate oxidative stress.
Abstract: Soybean (Glycine max L.) is a good source of natural antioxidants and commonly consumed as fermented products such as cheonggukjang, miso, tempeh, and sufu in Asian countries. The aim of the current study was to examine the influence of novel endophytic bacterial strain, Bacillus amyloliquefaciens RWL-1 as a starter for soybean fermentation. During fermentation, the cooked soybeans were inoculated with different concentrations (1%, 3%, and 5%) of B. amyloliquefaciens RWL-1. The changes in 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging activities, total phenolic contents, isoflavones (Daidzin, Genistin, Glycitin, Daidzein, Glycitein, and Genistein), amino acids (aspartic acid, threonine, serine, glutamic acid, glycine, alanine, cysteine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, lysine, histidine, arginine, and proline) composition, and minerals (calcium, copper, iron, potassium, magnesium, manganese, sodium, nickel, lead, arsenic, and zinc) were investigated. The level of antioxidants, total phenolic contents, isoflavones, and total amino acids were higher in fermented soybean inoculated with 1% B. amyloliquefaciens RWL-1 after 60 h of fermentation as compared to control, 3% and 5% B. amyloliquefaciens RWL-1. Additionally, fermented soybean inoculated with 5% B. amyloliquefaciens RWL-1 showed the highest values for mineral contents. Changes in antioxidant activities and bioactive compounds depended on the concentration of the strain used for fermentation. From these results, we conclude that fermented soybean has strong antioxidant activity, probably due to its increased total phenolic contents and aglycone isoflavone that resulted from fermentation. Such natural antioxidants could be used in drug and food industries and can be considered to alleviate oxidative stress.
TL;DR: In-silico study indicated that daidzein was found to be safe in acute and repeated oral dose toxicity studies at all selected doses and demonstrated risks ranging from low to a nontoxic level.
Abstract: Daidzein is a naturally occurring compound belonging to the class isoflavones and found in soya beans and other legumes. Acute oral toxicity was performed as per OECD guideline (TG 423) with slight...
TL;DR: In this paper, a review of the therapeutic potential of isoflavones in diabetes prevention and treatment is presented, focusing on the molecular mechanisms of the drug's action that are critical to their anti-diabetic properties.
Abstract: Given the growing number of type 2 diabetic individuals and the substantial social and financial costs associated with diabetes management, every effort should be made to improve its prevention and treatment methods. There is an ongoing search for natural dietary compounds that could be used for this purpose. This narrative review focuses on the therapeutic potential of isoflavones in diabetes prevention and treatment. This review summarizes (i) the molecular mechanisms of isoflavones action that are critical to their anti-diabetic properties; (ii) preclinical (in vitro and in vivo) studies evaluating the influence of isoflavones on the function of key organs involved in the pathogenesis of diabetes; and (iii) epidemiological studies and clinical trials that assessed the effectiveness of isoflavones in the prevention and treatment of type 2 diabetes in humans. Apart from discussing the effects of isoflavones on the function of organs "classically" associated with the pathogenesis of diabetes (pancreas, liver, muscles, and adipose tissue), the impact of these compounds on other organs that contribute to the glucose homeostasis (gastrointestinal tract, kidneys, and brain) is also reviewed.
TL;DR: Protection for HepG2 cells against ABAP damage and inhibited the proliferation of the HT‐29 cells and Caco‐2 cells may be attributed to the enhanced level of total phenolic, aglycone isoflavones, and free amino acids in the L. casei 16‐fermented soymilk.
Abstract: In this study, soymilk was fermented with Lactobacillus casei 16. The contents of aglycone isoflavones, saponins, total phenolic, and free amino acid in the fermented soymilk, and the protection for the HepG2 cells against 2,2'-azobis(2-amidinopropane) dihydrochloride (ABAP) damage and the antiproliferative effects of the fermented soymilk on the HT-29 cells and Caco-2 cells were studied. The results showed that the levels of total phenolic, aglycone isoflavones, and free amino acids in the L. casei 16-fermented soymilk were enhanced. The ethanol extract and the water extract of the L. casei 16-fermented soymilk showed protection for HepG2 cells against ABAP damage and inhibited the proliferation of the HT-29 cells and Caco-2 cells, which may be attributed to the enhanced level of total phenolic, aglycone isoflavones, and free amino acids in the L. casei 16-fermented soymilk.
TL;DR: The data elucidated the detailed mechanism by which isoflavones inhibit renal inflammation and provided a potential practical adjunct therapy to restrict DN progression and suggested the distinct protective roles of soy protein or is oflavones in DN.
Abstract: Scope Dietary soy reportedly protects from diabetic nephropathy (DN), but its active components and mechanism of action remain unknown. Methods and results In this study, KKAy mice are fed three types of diet: Dietary soy isoflavones with soy protein (Soy-IP) diet, reduced isoflavones soy protein (RisoP), and oral administration of isoflavones aglycones (IsoAgc). Albuminuria and glycosuria are decreased only in the soy-IP group. The risoP group show reduced expansion of mesangial matrix and renal fibrosis, the IsoAgc group show renal anti-fibrotic and anti-inflammatory effects; however, these renal pathological changes are repressed in the soy-IP group, suggesting the distinct protective roles of soy protein or isoflavones in DN. The isoflavone genistein has a better inhibitory effect on the inflammatory response and cellular interactions in both mouse tubular cells and macrophages when exposed to high glucose and albumin (HGA). Genistein also represses HGA-induced activator protein 1 activation and reactive oxidases stress generation, accompanied by reduced NADPH oxidase (NOX) gene expression. Finally, diabetic mice show a decrease in lipid peroxidation levels in both plasma and urine, along with lower NOXs gene expression. Conclusion The data elucidate the detailed mechanism by which isoflavones inhibit renal inflammation and provide a potential practical adjunct therapy to restrict DN progression.
TL;DR: A preliminary mechanism accounting for the in vitro activity of Trifolium pratense L. isoflavones is proposed, which can be considered a potent source of biological active phytoestrogens and a dietary supplement with anti-cancer and anti-invasion properties.
Abstract: Uncontrolled growth and migration and invasion abilities are common for cancer cells in malignant tumors with low therapeutic effectiveness and high mortality and morbidity. Estrogen receptor β (ERβ), as a member of the nuclear receptor superfamily, shows potent tumor suppressive activities in many cancers. Phytoestrogens' structural resemblance to 17 β-estradiol allows their binding to ERβ isoform predominantly, and therefore, expression of genes connected with elevated proliferation, motility and invasiveness of cancer cells may be downregulated. Among polyphenolic compounds with phytoestrogenic activity, there are isoflavones from Trifolium pratense L. (red clover) sprouts, containing high amounts of formononetin and biochanin A and their glycosides. To determine the source of the most biologically active isoflavones, we obtained four extracts from sprouts before and after their lactic fermentation and/or β-glucosidase treatment. Our previous results of ITC (isothermal titration calorimetry) modelling and a docking simulation showed clover isoflavones' affinity to ERβ binding, which may downregulate cancer cell proliferation and migration. Thus, the biological activity of T. pratense sprouts' extracts was checked under in vitro conditions against highly invasive human breast cancer cell line MDA-MB-231 and non-invasive human breast cancer cell line MCF-7 cells. To compare extracts' activities acquired for cancer cells with those activities against normal cells, as a third model we choose human umbilical vein endothelial cells (HUVEC), which, due to their migration abilities, are involved in blood vessel formation. Extracts obtained from fermented sprouts at IC0 dosages were able to inhibit migration of breast cancer cells through their influence on intracellular ROS generation; membrane stiffening; adhesion; regulation of MMP-9, N-cadherin and E-cadherin at transcriptional level; or VEGF secretion. Simultaneously, isolated phenolics revealed no toxicity against normal HUVEC cells. In the manuscript, we proposed a preliminary mechanism accounting for the in vitro activity of Trifolium pratense L. isoflavones. In this manner, T. pratense sprouts, especially after their lactic fermentation, can be considered a potent source of biological active phytoestrogens and a dietary supplement with anti-cancer and anti-invasion properties.
TL;DR: The findings of the present study indicate that isoflavones may be an effective supplement to promote astrocyte migration in developing and/or injured adult brains.
Abstract: Soybean isoflavones, such as genistein, daidzein, and its metabolite, S-equol, are widely known as phytoestrogens. Their biological actions are thought to be exerted via the estrogen signal transduction pathway. Estrogens, such as 17β-estradiol (E2), play a crucial role in the development and functional maintenance of the central nervous system. E2 bind to the nuclear estrogen receptor (ER) and regulates morphogenesis, migration, functional maturation, and intracellular metabolism of neurons and glial cells. In addition to binding to nuclear ER, E2 also binds to the G-protein-coupled estrogen receptor (GPER) and activates the nongenomic estrogen signaling pathway. Soybean isoflavones also bind to the ER and GPER. However, the effect of soybean isoflavone on brain development, particularly glial cell function, remains unclear. We examined the effects of soybean isoflavones using an astrocyte-enriched culture and astrocyte-derived C6 clonal cells. Isoflavones increased glial cell migration. This augmentation was suppressed by co-exposure with G15, a selective GPER antagonist, or knockdown of GPER expression using RNA interference. Isoflavones also activated actin cytoskeleton arrangement via increased actin polymerization and cortical actin, resulting in an increased number and length of filopodia. Isoflavones exposure increased the phosphorylation levels of FAK (Tyr397 and Tyr576/577), ERK1/2 (Thr202/Tyr204), Akt (Ser473), and Rac1/cdc42 (Ser71), and the expression levels of cortactin, paxillin and ERα. These effects were suppressed by knockdown of the GPER. Co-exposure of isoflavones to the selective RhoA inhibitor, rhosin, selective Cdc42 inhibitor, casin, or Rac1/Cdc42 inhibitor, ML-141, decreased the effects of isoflavones on cell migration. These findings indicate that soybean isoflavones exert their action via the GPER to activate the PI3K/FAK/Akt/RhoA/Rac1/Cdc42 signaling pathway, resulting in increased glial cell migration. Furthermore, in silico molecular docking studies to examine the binding mode of isoflavones to the GPER revealed the possibility that isoflavones bind directly to the GPER at the same position as E2, further confirming that the effects of the isoflavones are at least in part exerted via the GPER signal transduction pathway. The findings of the present study indicate that isoflavones may be an effective supplement to promote astrocyte migration in developing and/or injured adult brains.
TL;DR: In this article, the content of aglycone isoflavones released from kefir associated with soybean germ (KSG) was evaluated in a gastrointestinal digestion model in vitro, and the anxiolytic and antidepressant activity of KSG and the fermentation solution of kefir (FSK) were evaluated in models of anxiety and depression in zebrafish (Danio rerio).
TL;DR: It is suggested that an isoflavone conjugate profile might be a more appropriate marker than total is oflavone levels for discriminating between the consumption of FS and NFS diets.
TL;DR: Results indicate that some isoflavonoids, in particular biochanin A, are able to have vasodilatory effects in micromolar concentrations, which is of potential clinical interest for the management of cardiovascular pathologies.
Abstract: The dietary intake of flavonoids seems to be inversely related to cardiovascular mortality. The consumption of isoflavonoids is increasing in the general population, especially due to the use of food supplements and a variety of isoflavonoid-rich foods. However, detailed studies on the vascular influence of individual pure isoflavonoids are mostly missing. For this study, 16 isoflavonoids were initially screened for their vasorelaxant properties on rat aortas. The 2 most potent of them, biochanin A and glycitein, were further tested for the mechanism of action on porcine coronary arteries. They both induced an endothelium independent vascular relaxation, with EC50 below 6 and 17 µM, respectively. Biochanin A, but not glycitein, was able to block the vasoconstriction caused by KCl, CaCl2, serotonin, and U46619 in a dose-dependent manner. Another series of experiments suggested that the major mechanism of action of biochanin A was the inhibition of L-type calcium channels. Moreover, biochanin A in relatively small concentrations (2 – 4 µM) interfered with the cGMP, but not cAMP, pathway in isolated coronary arteries. These results indicate that some isoflavonoids, in particular biochanin A, are able to have vasodilatory effects in micromolar concentrations, which is of potential clinical interest for the management of cardiovascular pathologies.
TL;DR: Dietary supplementation with isoflavones proves to be a key means to improve the overall gut function and health and future mechanistic studies with is oflavone interventions will help treat clinically related diseases such as cystic fibrosis and inflammatory-related gut problems such as colitis and diabetes.
Abstract: Soy isoflavones are known to have beneficial effects on several aspects of gastrointestinal physiological functions (contractility or motility, secretion, morphology, and barrier function). In this review, we discuss the effects of soy isoflavones on the overall gut function and inflammation and assess how these effects might be implicated in the treatment of several gut-related diseases. Soy isoflavones influence several key aspects of gastrointestinal health: improve basal intestinal secretion, alleviate inflammation, limit intestinal morphological damage, and improve epithelial barrier function in several clinically relevant murine models of gastrointestinal diseases. Dietary supplementation with isoflavones proves to be a key means to improve the overall gut function and health. Future mechanistic studies with isoflavone interventions will help treat clinically related diseases such as cystic fibrosis and inflammatory-related gut problems such as colitis and diabetes.
TL;DR: In this paper, the ability of Bifidobacterium strains (n = 25) to produce lignan and flavonoids aglycones from flaxseed and soybean extracts was analyzed.
Abstract: Flaxseed and soybean are an important source of phytochemical compounds, mainly lignans and isoflavones, but also of flavones, flavanones and flavonols. These compounds appear mainly glycosylated in plant food and are converted into aglycones by the intestinal microbiota, increasing their bioavailability. In this work, we analyse the ability of Bifidobacterium strains (n = 25) to produce lignan and flavonoids aglycones from flaxseed and soybean extracts. Most of the Bifidobacterium strains increased the concentrations of secoisolariciresinol, daidzein, genistein, naringenin, eriodyctiol, luteolin and apigenin. Moreover, Bifidobacterium pseudocatenulatum and Bifidobacterium breve strains showed high production of herbacetin, increased the kaempferol concentration and produced quercetin and quercetagetin. B. pseudocatenulatum INIA P815 and B. breve INIA P367 produced 32.37 ± 2.81 and 28.64 ± 3.36 mg respectively of herbacetin g⁻¹ of lignan extract. Bifidobacterium strains transformed the glycosides of a wide range of flavonoids into their aglycones, increasing the antioxidant activity and improving their bioavailability.