Search Results (46)

Extending healthy lifespans is an important public health goal in societies with a long life expectancy. Late-onset hypogonadism (LOH), a condition associated with an age-related decrease in testosterone level, contributes to the onset of various diseases. Previously, we demonstrated that the oral ingestion of bean sprouts rich in the HASPIN inhibitor coumestrol increased blood testosterone levels in mice. In the present study, we showed that the oral ingestion of bean sprouts also led to increased blood testosterone levels in humans. These results suggested that bean sprouts, which are rich in coumestrol, have potential as a dietary intervention for the treatment of LOH. Full article

As a traditional medicinal food, Kudzu root (KR) has been proven to be an effective medicine for treating osteoporosis (OP). However, its precise targets and underlying integrated pharmacological mechanisms on OP have not yet been systematically investigated. The aim of the present study was to systemically explore the active ingredients, molecular targets, and ingredient-target network of KR against OP by the methods of network pharmacology followed by biological validation in a glucocorticoid-induced bone loss model of zebrafish. Our results identified a total of 15 active compounds with good pharmacokinetic properties in KR and 119 targets related to OP from correspondent databases, forming an ingredient-target network. Additionally, the protein–protein interaction (PPI) network further identified 39 core targets. Enrichment analyses with functional annotation revealed that the TNF signaling pathway and osteoclast differentiation process were significantly enriched by multi-targets including AKT1, P65, MAPK14, JUN, TNF-α, MMP9, IL6, and IL1B, etc., and served as the critical targets for molecular docking, molecular dynamics simulation, and in vivo experiment validation. These critical targets performed effectively in molecular docking and molecular dynamics, with AKT1, MMP9, and TNF-α exhibiting more prominent binding energy with Coumestrol, Genistein, and Genistein 7-glucoside, respectively. Further experimental validation in a zebrafish model indicated that KR could regulate the expressions of critical targets (AKT1, P65, MAPK14, JUN, TNF-α, and MMP9). This study provides a systemic perspective of the relationships between the active ingredients of KR and their multi-targets in OP, thereby constructing a pharmacological network to clarify the mechanisms by which KR ameliorates OP. Full article

Iron (Fe) deficiency is a pervasive agricultural concern on a global scale. Intercropping plays a pivotal role in activating soil nutrient cycling and crop nutrient uptake and utilization. This study integrates plant physiology, soil physicochemical determination, high-throughput sequencing, and metabolomics techniques to conduct pot experiments using field-collected soils with soybean and maize plants. This study aims to investigate the mechanisms through which microorganisms in a soybean–maize intercropping system regulate Fe deficiency adaptation. The results revealed that intercropping enhances the resilience of soybean and maize in Fe-deficient environments, facilitates nutrient absorption by plants, and enriches soil nutrient content. Moreover, intercropping fostered more intricate microbial interactions in comparison to monocropping. The dominant microorganisms in the rhizosphere of intercropped soybean and maize included genera Microbacterium, Sphingomonas, Shinella, and Rhizobium. Microbacterium, Sphingomonas, Shinella, and Rhizobium have the potential to produce Fe chelators or enhance plant Fe absorption. Additionally, intercropping notably modified the composition of root exudates derived from soybean and maize. The soybean and maize rhizosphere exhibited significant enrichment with oleamide, coumestrol, glycitein, and daidzein. Coumestrol may have an effect of promoting Fe absorption, and it is significantly positively correlated with the genus Nakamurella in the maize rhizosphere and the genus Pirellula in the soybean rhizosphere. Consequently, these findings suggested that the rhizosphere of intercropped soybean and maize significantly enriches specific microbial communities and root exudates, thereby enhancing microecosystem stability and improving plant tolerance to Fe deficiency. Full article

Phytoestrogens are components naturally occurring in plants and include many foods that are part of the regular diet of animals and humans. Phytoestrogens are xenoestrogens of plant origin that are not produced in the endocrine system. Phytoestrogens can act as either agonists or antagonists, depending on their tissue concentrations and the levels of endogenous estrogens at various life stages. The aim was to evaluate the intake of phytoestrogens and the estrogenic effect of the diet of women at university in Chihuahua (Mexico). In total, 400 female university students individually filled out a food frequency questionnaire (FFQ) that included 120 foods. Estimates of the intake of phytoestrogen (genistein, daidzein, biochanin A, formononetin, matairesinol, coumestrol, enterolactone, secoisoresinol, enterodiol) in the subjects’ daily diet were based on published reports. Quantification of phytoestrogens was expressed in µg day⁻¹. The estrogenic effect of those compound identified according to the foods consumed was estimated using the in vitro E-SCREN test. SPSS v.22.0 (IBM, Chicago, IL, USA) was applied for statistical analysis following descriptive analysis and stepwise regression. p < 0.050 was taken as significant. The results of intake show that the majority of isoflavones are formononetin (median 110.60 (μg day⁻¹) and their estrogenic activity is 4.11 Eq. E2 (pmol day⁻¹); the majority of lignans are enterolactone (median 147.24 (μg day⁻¹), and their estrogenic activity is 4.94 Eq. E2 (pmol day⁻¹). The total phytoestrogen estrogenic effect is measured in pM of E2, with a mean of 28.28 (SD = 23.97) and median of 21.50. The mean consumption of phytoestrogens in Mexican university students is similar to the consumption found in similar studies in the United States, England, Germany, and Spain (<1 mg day⁻¹). Phytoestrogens can be beneficial in adult women during perimenopause and menopause due to their estrogenic effects, but they are less recommended for women in the fertile stage, as, for example, in the study presented here, because they could function as endocrine disruptors. They are not recommended as dietary supplements for young women or pregnant women. Full article

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors globally, significantly affecting liver functions, thus necessitating the identification of biomarkers and effective therapeutics to improve HCC-based disabilities. This study aimed to identify prognostic biomarkers, signaling cascades, and candidate drugs for the treatment of HCC through integrated bioinformatics approaches such as functional enrichment analysis, survival analysis, molecular docking, and simulation. Differential expression and functional enrichment analyses revealed 176 common differentially expressed genes from two microarray datasets, GSE29721 and GSE49515, significantly involved in HCC development and progression. Topological analyses revealed 12 hub genes exhibiting elevated expression in patients with higher tumor stages and grades. Survival analyses indicated that 11 hub genes (CCNB1, AURKA, RACGAP1, CEP55, SMC4, RRM2, PRC1, CKAP2, SMC2, UHRF1, and FANCI) and three transcription factors (E2F1, CREB1, and NFYA) are strongly linked to poor patient survival. Finally, molecular docking and simulation identified seven candidate drugs with stable complexes to their target proteins: tozasertib (−9.8 kcal/mol), tamatinib (−9.6 kcal/mol), ilorasertib (−9.5 kcal/mol), hesperidin (−9.5 kcal/mol), PF−562271 (−9.3 kcal/mol), coumestrol (−8.4 kcal/mol), and clofarabine (−7.7 kcal/mol). These findings suggest that the identified hub genes and TFs could serve as valuable prognostic biomarkers and therapeutic targets for HCC-based disabilities. Full article

Emerging pollutants, like phytoestrogens, are gaining attention in the scientific community for their impact on aquatic organisms. Nevertheless, there is a paucity of studies examining their effects on tropical aquatic species. In this context, the objective of this study was to (i) conduct chronic ecotoxicological assays with the sea urchin Echinometra lucunter with two phytoestrogens, namely genistein and daidzein (both derived from soy plant), and compare the results to the synthetic estrogen ‘estradiol valerate’; (ii) predict the potential risks of these phytoestrogens through an ecological risk assessment; and (iii) create a prioritization list of the most hazardous phytoestrogens using environmental persistence, bioaccumulation, and toxicity (PBT criteria). The results of chronic exposure demonstrated the following order of toxicity: daidzein (IC₅₀ = 2.60 mg/L); genistein (IC₅₀ = 3.37 mg/L); and estradiol valerate (IC₅₀ = 28.40 mg/L). The results classify genistein and daidzein as “toxic” and estradiol valerate as “harmful” to the sea urchin. The final ranking of the PBT approach in coastal waters was as follows: biochanin A (the highest priority), followed by formononetin, genistein, enterolactone, daidzein, estradiol valerate, coumestrol, and 8-prenylnaringenin. The dataset highlights the importance of environmental monitoring to track phytoestrogens in Latin American coastal areas, particularly in developing countries. Full article

(1) Background: HASPIN kinase is involved in regulating spindle function and chromosome segregation, as well as phosphorylating histone H3 at Thr3 in mitotic cells. Several HASPIN inhibitors suppress cancer cell proliferation. It was recently reported that coumestrol from bean sprouts inhibits HASPIN, and a cultivation method for bean sprouts containing large amounts of coumestrol has been established. Here, we showed the effects of bean sprout ingestion on intestinal polyp development, cachexia, and hypogonadism in a mouse model of familial adenomatous polyposis (Apc^Min/+). (2) Methods: Apc^Min/+ mice were randomized into control and treatment groups. Mice in the control group were given the standard diet, while those in the treatment group were given the same standard diet with the addition of 15% bean sprouts. Treatments were commenced at 7 weeks old and analyses were performed at 12 weeks old. (3) Results: ingesting bean sprouts suppressed the development of intestinal polyps, cachexia, and hypogonadism, and also increased serum levels of testosterone in male wild-type and Apc^Min/+ mice. (4) Conclusions: ingesting bean sprouts helps prevent cancer and increases serum levels of testosterone in a mouse model. These results are expected to be applicable to humans. Full article

The role of estrogens in prostate cancer (PCa) is shrouded in mystery, with its actions going from angelic to devilish. The findings by Huggins and Hodges establishing PCa as a hormone-sensitive cancer have provided the basis for using estrogens in therapy. However, despite the clinical efficacy in suppressing tumor growth and the panoply of experimental evidence describing its anticarcinogenic effects, estrogens were abolished from PCa treatment because of the adverse secondary effects. Notwithstanding, research work over the years has continued investigating the effects of estrogens, reporting their pros and cons in prostate carcinogenesis. In contrast with the beneficial therapeutic effects, many reports have implicated estrogens in the disruption of prostate cell fate and tissue homeostasis. On the other hand, epidemiological data demonstrating the lower incidence of PCa in Eastern countries associated with a higher consumption of phytoestrogens support the beneficial role of estrogens in counteracting cancer development. Many studies have investigated the effects of phytoestrogens and the underlying mechanisms of action, which may contribute to developing safe estrogen-based anti-PCa therapies. This review compiles the existing data on the anti- and protumorigenic actions of estrogens and summarizes the anticancer effects of several phytoestrogens, highlighting their promising features in PCa treatment. Full article

Drought limits the growth and development of Phaseolus vulgaris L. (known as common bean). Common bean plants contain various phenylpropanoids, but it is not known whether the levels of these metabolites are altered by drought. Here, BT6 and BT44, two white bean recombinant inbred lines (RILs), were cultivated under severe drought. Their respective growth and phenylpropanoid profiles were compared to those of well-irrigated plants. Both RILs accumulated much less biomass in their vegetative parts with severe drought, which was associated with more phaseollin and phaseollinisoflavan in their roots relative to well-irrigated plants. A sustained accumulation of coumestrol was evident in BT44 roots with drought. Transient alterations in the leaf profiles of various phenolic acids occurred in drought-stressed BT6 and BT44 plants, including the respective accumulation of two separate caftaric acid isomers and coutaric acid (isomer 1) relative to well-irrigated plants. A sustained rise in fertaric acid was observed in BT44 with drought stress, whereas the greater amount relative to well-watered plants was transient in BT6. Apart from kaempferol diglucoside (isomer 2), the concentrations of most leaf flavonol glycosides were not altered with drought. Overall, fine tuning of leaf and root phenylpropanoid profiles occurs in white bean plants subjected to severe drought. Full article

Legumes, one of the first crops of humanity, inherently constitute a staple nutritional source for mankind, attracting significant research attention that has been afforded to the development of numerous cultivars. The study herein concerns the exploitation of the nutritional and bio-functional content of beans harvested from eleven Greek cultivars belonging to five different species, namely Cicer arietinum L., Pisum sativum L., Vicia faba L., Lens culinaris L., and Phaseolus vulgaris L. The final goal is to define their varietal identity and correlate their phytochemical content with their potential utilization as functional foods and/or feed of high nutritional value. In this respect, their extracts were screened against the presence of 27 fatty acids and 19 phenolic compounds, revealing the presence of 22 and 15 molecules, respectively. Specifically, numerous fatty acids were detected in significant amounts in all but C. arietinum extract, while significant polyphenolic content was confirmed only in P. vulgaris. Among individual compounds, linoleic acid was the major fatty acid detected in amounts averaging more than 150 mg/g, followed by oleic acid, which was present as a major compound in all extracts. Among the nine polyphenols detected in P. vulgaris, the molecules of genistein (3.88 mg/g) and coumestrol (0.82 mg/g) were the most abundant. Their antioxidant properties were evaluated through DPPH and FRAP assays, which were highlighted as most potent in both tests of the V. faba extract, while C. arietinum was determined as totally inactive, indicating a potential correlation between the phenolic content of the plant species and antioxidant activity. These results are indicative of the significant advances achieved for the cultivars investigated and reveal their important role as nutritional crops for human and animal consumption. Full article

Ovulation and artificial insemination rates have been observed to decrease in sheep and cows when exposed to dietary phytoestrogens at concentrations greater than 25 mg/kg DM. A grazing trial was undertaken to investigate the effects of coumestrol and other key phytoestrogens on the superovulatory response, embryo numbers and quality in beef cows grazing legume pastures. A 7-week controlled grazing trial was conducted with legume and ryegrass pasture treatments, with cows exposed to legumes at two timed treatments, 4 and 7 weeks. Twenty Angus cows were subjected to a conventional estrus synchronization and superovulation protocol. Embryos were recovered via conventional uterine body flushing 7 days post artificial insemination (AI). Numerous phytoestrogens were identified in both pasture and plasma samples, including coumestrol and formononetin. Concentrations of phytoestrogens in the pasture ranged from 0.001 to 47.5 mg/kg DM and 0 to 2.6 ng/mL in plasma. Approximately 50% of cows produced viable embryos 7 days post AI. A significant interaction between the effect of treatment groups on the embryo stage was observed (p < 0.05). The results suggest that concentrations of >25 mg/kg DM of phytoestrogens less than 20 days preceding AI may negatively affect oocyte developmental competence, reduce progesterone production and thus contribute to early embryonic loss. Full article

Isoflavones, belonging to polyphenolic compounds, show structural similarity to natural estrogens, and in this context, they have been extensively studied. Some of them are also applied as cosmetic additives; however, little is known regarding their effects on skin cells. In this investigation, common isoflavones, including genistein, daidzein, glycitein, formononetin, and biochanin A, as well as coumestrol, were evaluated for antioxidant activity and their impact on human skin fibroblasts and keratinocytes. Antioxidant effects were assessed using DPPH, ABTS, and FRAP tests, and the ability to scavenge reactive oxygen species (ROS) was tested in cells with H₂O₂-provoked oxidative stress. The impact on the activity of antioxidant enzymes (SOD, CAT, GSH) and lipid peroxidation (MDA) was also explored. As shown by Alamar Blue and neutral red uptake assays, the compounds were not toxic within the tested concentration range, and formononetin and coumestrol even demonstrated a stimulatory effect on cells. Coumestrol and biochanin A demonstrated significant antioxidative potential, leading to a significant decrease in ROS in the cells stimulated by H₂O₂. Furthermore, they influenced enzyme activity, preventing depletion during induced oxidative stress, and also reduced MDA levels, demonstrating protection against lipid peroxidation. In turn, genistein, daidzein, and glycitein exhibited low antioxidant capacity. Full article

The thrip (Megalurothrips usitatus) damages the flowers and pods of the cowpea, causing “black-heads and black-tails” (BHBT) symptoms and negatively affecting its economic value. However, the mechanism by which BHBT symptoms develop is still unknown. Our results showed that the microstructure of the pod epidermis was altered and the content of the plant’s resistance-related compounds increased after a thrip infestation. However, the contents of protein and free amino acids did not change significantly, suggesting that the nutritional value was not altered. Pathogens were found not to be involved in the formation of BHBT symptoms, as fungi and pathogenic bacteria were not enriched in damaged pods. Two herbivory-induced flavonoids—7,4′-dihydroxyflavone and coumestrol—were found to exert insecticidal activity. Our study clarified that BHBT symptoms are directly caused by the thrip. Thresholds for pest control need to be reconsidered as thrip herbivory did not degrade cowpea nutrition. Full article

There is a longstanding interest in the relationship between diet and hot flash symptoms during midlife, especially in whether phytoestrogens ease menopausal symptoms. The purpose of this study was to examine hot flashes, night sweats, trouble sleeping, and vaginal dryness in relation to the intake of foods rich in phytoestrogens among Bangladeshi women aged 35 to 59 years who were living either in Sylhet, Bangladesh (n = 157) or as migrants in London (n = 174). Consumption ranges for phytoestrogens were constructed from food frequencies. We hypothesized that diets rich in isoflavones, lignans, and coumestrol would be associated with lower symptom frequencies. However, adjusted logistic regression results showed that with each incremental increase in general phytoestrogen consumption (scale of 0 to 10), the likelihood of hot flashes increased by 1.4%. Each incremental increase in lignan consumption raised the likelihood of hot flashes by 1.6%. In contrast, the odds of vaginal dryness decreased by 2%, with each incremental increase in phytoestrogen and lignan consumption, and by 4%, with each incremental increase in isoflavone consumption. Night sweats and trouble sleeping were not associated with phytoestrogen intake in logistic regressions. Our findings add to the conflicting data on relationships between phytoestrogens and symptoms associated with menopause. Full article

The intensive use of plant materials as a sustainable alternative for fish feed production, combined with their phytochemical content, which affects the growth and production characteristics of farmed fishes, necessitates their monitoring for the presence of raw materials of plant origin. This study reported herein concerns the development, validation and application of a workflow using high-performance liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) for the quantification of 67 natural phytoestrogens in plant-derived raw materials that were used to produce fish feeds. Specifically, we verified the presence of 8 phytoestrogens in rapeseed meal samples, 20 in soybean meal samples, 12 in sunflower meal samples and only 1 in wheat meal samples in quantities enabling their efficient incorporation into clusters. Among the various constituents, the soybean phytoestrogens daidzein, genistein, daidzin, glycitin, apigenin, calycosin and coumestrol, as well as the sunflower neochlorogenic, caffeic and chlorogenic phenolic acids, displayed the highest correlations with their origin descriptions. A hierarchical cluster analysis of the studied samples, based on their phytoestrogen contents, led to the efficient clustering of raw materials. The accuracy and efficiency of this clustering were tested through the incorporation of additional samples of soybean meal, wheat meal and maize meal, which verified the utilization of the phytoestrogen content as a valuable biomarker for the discrimination of raw materials used for fish feed production. Full article