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Stem Cell Reviews and Reports Dec 2022Female germline stem cells (FGSCs) have been successfully isolated and characterized from postnatal mammalian and human ovarian tissues. However, the effects and...
Female germline stem cells (FGSCs) have been successfully isolated and characterized from postnatal mammalian and human ovarian tissues. However, the effects and mechanisms of action of natural small-molecule compounds on FGSCs are largely unknown. Here, we found that daidzein promoted the viability and proliferation of FGSCs. To elucidate the mechanism underlying this, we performed RNA-Sequence in daidzein-treated FGSCs and controls. The results showed that there were 153 upregulated and 156 downregulated genes in daidzein treatment. We confirmed the expression of some genes related to cell proliferation in the sequencing results by RT-PCR, such as Type C lectin domain family 11 member a (Clec11a), Mucin1 (Muc1), Glutathione peroxidase 3 (Gpx3), and Tet methylcytosine dioxygenase 1 (Tet1). The high expression of Clec11a at the protein level after daidzein treatment was also confirmed by western blotting. Furthermore, recombinant mouse Clec11a (rmClec11a) protein was shown to promote the viability and proliferation of FGSCs. However, knockdown of Clec11a inhibited the viability and proliferation of FGSCs, which could not be rescued by the administration of daidzein. These results indicate that daidzein promoted the viability and proliferation of FGSCs through Clec11a. In addition, both daidzein and rmClec11a activated the Akt signaling pathway in FGSCs. However, Clec11a knockdown inhibited this pathway, which could not be rescued by daidzein administration. Taken together, our findings revealed that daidzein activates the Akt signaling pathway to promote cell viability and proliferation through upregulating Clec11a. This study should deepen our understanding of the developmental mechanism of FGSCs and female infertility.
Topics: Animals; Female; Humans; Mice; Cell Proliferation; Isoflavones; Mammals; Mixed Function Oxygenases; Oogonial Stem Cells; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Hematopoietic Cell Growth Factors; Lectins, C-Type; Up-Regulation
PubMed: 35655001
DOI: 10.1007/s12015-022-10394-0 -
Animal Biotechnology Feb 2022Isoflavones possess a wide range of physiological effects. However, it is still unclear whether isoflavones can promote milk synthesis in mammary gland. This study aimed...
Isoflavones possess a wide range of physiological effects. However, it is still unclear whether isoflavones can promote milk synthesis in mammary gland. This study aimed to determine the effects of a main soy isoflavone, daidzein, on milk synthesis and proliferation of mammary epithelial cells (MECs) and reveal the underlying molecular mechanism. Primary bovine MECs were treated with different concentrations of daidzein (0, 5, 10, 20, 40, and 80 μM). Daidzein dose-dependently promoted α- and β-casein and lipid synthesis, cell cycle transition, and cell amount, with the best stimulatory effect at 20 μM. Daidzein also stimulated mTOR activation and Cyclin D1 and SREBP-1c expression. Daidzein induced the expression and nuclear localization of estrogen receptor α (ERα), and ERα knockdown blocked the stimulation of daidzein on these above signaling pathways. ERα knockdown also abolished the stimulation of daidzein on NFκB1 expression and phosphorylation, and NFκB1 was required for daidzein to enhance the mTOR, Cyclin D1 and SREBP-1c signaling pathways. In summary, our findings reveal that daidzein stimulates milk synthesis and proliferation of MECs via the ERα-dependent NFκB1 activation.
Topics: Animals; Cattle; Cell Proliferation; Epithelial Cells; Estrogen Receptor alpha; Isoflavones; Mammary Glands, Animal; Milk
PubMed: 32401613
DOI: 10.1080/10495398.2020.1763376 -
Food Chemistry Dec 2020The self-microemulsifying delivery system was fabricated by whey protein isolate (WPI), daidzein (Dai) and surfactants, the interaction of WPI, Dai and D-α-Tocopherol...
The self-microemulsifying delivery system was fabricated by whey protein isolate (WPI), daidzein (Dai) and surfactants, the interaction of WPI, Dai and D-α-Tocopherol polyethylene glycol succinate (TPGS) was hereby studied in the absence or presence of Tween 20. The increase of surfactant concentration led to the decrease of the modulus and changes of protein interfacial conformation, which allowed the formation of a strong intermolecular network. The environment and structure of WPI and daidzein could be changed by TPGS, and the addition of Tween 20 could further enhance the interaction between the components by changing TPGS structure. With the increase of surfactants and oil phase, Ksv and Ka values of WPI-Dai increased first and then decreased. Therefore, the interaction between the components was also dependent on the WPI-surfactant ration. These findings provide a potential strategy for designing microemulsion food system based on the understanding of the interactions among individual composition of microemulsions.
Topics: Animals; Cattle; Emulsions; Isoflavones; Polyethylene Glycols; Polysorbates; Surface-Active Agents; Whey Proteins
PubMed: 32659698
DOI: 10.1016/j.foodchem.2020.127461 -
Annales D'endocrinologie Feb 2015With 13 million new cases worldwide every year, prostate cancer is as a very real public health concern. Prostate cancer is common in over-50s men and the sixth-leading... (Review)
Review
With 13 million new cases worldwide every year, prostate cancer is as a very real public health concern. Prostate cancer is common in over-50s men and the sixth-leading cause of cancer-related death in men worldwide. Like all cancers, prostate cancer is multifactorial - there are non-modifiable risk factors like heredity, ethnicity and geographic location, but also modifiable risk factors such as diet. Diet-cancer linkages have risen to prominence in the last few years, with accruing epidemiological data pointing to between-population incidence differentials in numerous cancers. Indeed, there are correlations between fat-rich diet and risk of hormone-dependent cancers like prostate cancer and breast cancer. Diet is a risk factor for prostate cancer, but certain micronutrients in specific diets are considered protective factors against prostate cancer. Examples include tomato lycopene, green tea epigallocatechin gallate, and soy phytoestrogens. These micronutrients are thought to exert cancer-protective effects via anti-oxidant pathways and inhibition of cell proliferation. Here, we focus in on the effects of phytoestrogens, and chiefly genistein and daidzein, which are the best-researched to date. Soy phytoestrogens are nonsteroid molecules whose structural similarity lends them the ability to mimic the effects of 17ß-estradiol. On top of anti-oxidant effects, there is evidence that soy phytoestrogens can modulate the epigenetic modifications found in prostate cancer. We also studied the impact of phytoestrogens on epigenetic modifications in prostate cancer, with special focus on DNA methylation, miRNA-mediated regulation and histone modifications.
Topics: Adult; Antioxidants; DNA Methylation; Diet; Epigenesis, Genetic; Genistein; Histone Code; Humans; Isoflavones; Male; MicroRNAs; Middle Aged; Phytoestrogens; Prostatic Neoplasms; Risk Factors; Glycine max
PubMed: 25592466
DOI: 10.1016/j.ando.2014.09.001 -
Nanoscale Research Letters Oct 2019In this study, daidzein long-circulating liposomes (DLCL) were prepared using the ultrasonication and lipid film-hydration method. The optimized preparation conditions...
In this study, daidzein long-circulating liposomes (DLCL) were prepared using the ultrasonication and lipid film-hydration method. The optimized preparation conditions by the orthogonal design was as follows: 55 to 40 for the molar ratio of soybean phosphatidylcholine (SPC) to cholesterol, 1 to 10 for the mass ratio of daidzein to total lipid (SPC and cholesterol) (w:w), the indicated concentration of 5% DSPE-mPEG2000 (w:w), 50 °C for the hydration temperature, and 24 min for the ultrasonic time. Under these conditions, the encapsulation efficiency and drug loading of DLCL were 85.3 ± 3.6% and 8.2 ± 1.4%, respectively. The complete release times of DLCL in the medium of pH 1.2 and pH 6.9 increased by four- and twofold of that of free drugs, respectively. After rats were orally administered, a single dose of daidzein (30 mg/kg) and DLCL (containing equal dose of daidzein), respectively, and the MRT (mean residence time, which is the time required for the elimination of 63.2% of drug in the body), t (the elimination half-life, which is the time required to halve the plasma drug concentration of the terminal phase), and AUC (the area under the plasma drug concentration-time curve, which represents the total absorption after a single dose and reflects the drug absorption degree) of daidzein in DLCL group, increased by 1.6-, 1.8- and 2.5-fold as compared with those in the free group daidzein. Our results indicated that DLCL could not only reduce the first-pass effect of daidzein to promote its oral absorption, but also prolong its mean resident time to achieve the slow-release effect.
PubMed: 31617108
DOI: 10.1186/s11671-019-3164-y -
Critical Reviews in Toxicology Sep 2014Chemicals with estrogenic activity are derived from many different natural and synthetic processes and products, including endogenous production (e.g., estradiol,... (Review)
Review
Chemicals with estrogenic activity are derived from many different natural and synthetic processes and products, including endogenous production (e.g., estradiol, conjugated estrogens), drugs (e.g., ethinyl estradiol, conjugated estrogens), plants used as foods (phytoestrogens such as genistein, daidzein, S-equol), and man-made chemicals (xenoestrogens such as bisphenol A). Human exposure to low doses of endogenous estrogens, estrogenic drugs, phytoestrogens, and xenoestrogens has the potential to improve health or disrupt normal endocrine activity, as well as impact the diverse systems with which estrogens interact, including the cardiovascular system, and lipid and carbohydrate metabolism. Mechanisms of action and diversity of adverse and non-adverse effects following human exposure to low doses of estrogen active chemicals (EACs, defined as chemicals which interact with an estrogen receptor [ER]) are poorly understood. This review summarizes our current understanding of the pharmacological action with a focus on pharmacokinetics (PK) and toxicokinetics (TK) of several representative EACs in both physiological and pathological processes. The goal of this review is to assess the current state-of-the-science on: (i) the potential for EACs to interfere with endocrine activity, (ii) factors which contribute to endocrine-related clinical outcomes, and (iii) existing knowledge gaps. While classical PK approaches (compartmental or non-compartmental) can be used to characterize absorption, distribution, metabolism, and elimination of EACs, many of the detailed pharmacological characteristics necessary to understand benefit-risk balance have not yet been clarified. Pharmacological complexities mirror the complexity of determining whether and under what conditions exposure to estrogens in drugs, foods or to xenoestrogenic chemicals are beneficial or harmful to human health.
Topics: Animals; Endocrine Disruptors; Environmental Exposure; Estrogens; Humans; Phytoestrogens; Receptors, Estrogen; Toxicokinetics; Xenobiotics
PubMed: 25099693
DOI: 10.3109/10408444.2014.930813 -
Molecules (Basel, Switzerland) Feb 2023Herbal drugs have been attracting much scientific interest in the last few decades and nowadays, phytoconstituents-based research is in progress to disclose their... (Review)
Review
Herbal drugs have been attracting much scientific interest in the last few decades and nowadays, phytoconstituents-based research is in progress to disclose their unidentified medicinal potential. Daidzein (DAI) is the natural phytoestrogen isoflavone derived primarily from leguminous plants, such as the soybean and mung bean, and its IUPAC name is 4',7-dihydroxyisoflavone. This compound has received great attention as a fascinating pharmacophore with remarkable potential for the therapeutic management of several diseases. Certain pharmacokinetic properties of DAI such as less aqueous solubility, low permeability, and poor bioavailability are major obstacles restricting the therapeutic applications. In this review, distinctive physicochemical characteristics and pharmacokinetics of DAI has been elucidated. The pharmacological applications in treatment of several disorders like oxidative stress, cancer, obesity, cardiovascular, neuroprotective, diabetes, ovariectomy, anxiety, and inflammation with their mechanism of action are explained. Furthermore, this review article comprehensively focuses to provide up-to-date information about nanotechnology-based formulations which have been investigated for DAI in preceding years which includes polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carrier, polymer-lipid nanoparticles, nanocomplexes, polymeric micelles, nanoemulsion, nanosuspension, liposomes, and self-microemulsifying drug delivery systems.
Topics: Drug Delivery Systems; Nanotechnology; Nanoparticles; Isoflavones; Micelles; Polymers
PubMed: 36838751
DOI: 10.3390/molecules28041765 -
The Journal of Steroid Biochemistry and... Jul 2018Endometriosis is an estrogen-dependent disease, and isoflavones interact with estrogen receptors. The purposes of this study are to investigate the in vitro and in vivo...
Endometriosis is an estrogen-dependent disease, and isoflavones interact with estrogen receptors. The purposes of this study are to investigate the in vitro and in vivo effects of daidzein-rich isoflavone aglycones (DRIAs), dietary supplements, on cellular proliferation in endometriosis. Stromal cells isolated from ovarian endometrioma (OESCs) and normal endometrium (NESCs) were cultured with DRIAs, i.e., each of the DRIA components (daidzein, genistein, or glycitein), or isoflavone glycosides (IG; DRIA precursors). A mouse model of endometriosis was established by transplanting donor-mouse uterine fragments into recipient mice. Our results showed that DRIAs (0.2-20 μM) inhibited the proliferation of OESCs (P < 0.05 for 0.2 μM; P < 0.01 for 2 and 20 μM) but not of NESCs. However, daidzein, genistein, glycitein, and IG did not inhibit their proliferation. DRIA-induced suppression was reversed by inhibition of the estrogen receptor (ER)β by an antagonist, PHTPP, or by ERβ siRNA (P < 0.05), but not by MPP, an ERα antagonist. In OESCs, DRIAs led to reduced expression of IL-6, IL-8, COX-2, and aromatase, as well as reduced aromatase activity, serum glucocorticoid-regulated kinase levels, and PGE levels (P < 0.05). Western blot and immunofluorescence assays revealed that DRIAs inhibited TNF-α-induced IκB phosphorylation and p65 uptake into the nuclei of OESCs. In the mouse model, a DRIA-containing feed significantly decreased the number, weight, and Ki-67 proliferative activity of endometriosis-like lesions compared to in mice fed with an IG-containing feed and the control feed (P < 0.01). In conclusion, DRIAs inhibit cellular proliferation in endometriosis, thus representing a potential therapeutic option for the management of endometriosis.
Topics: Animals; Cell Proliferation; Endometriosis; Female; Humans; Inflammation; Isoflavones; Mice; Phosphorylation; Phytoestrogens; Signal Transduction
PubMed: 29679753
DOI: 10.1016/j.jsbmb.2018.04.004 -
Bioscience, Biotechnology, and... Jun 2023Soy isoflavones have been shown to have anti-inflammatory properties; however, the anti-inflammatory effects of isoflavone metabolites produced during soybean...
Soy isoflavones have been shown to have anti-inflammatory properties; however, the anti-inflammatory effects of isoflavone metabolites produced during soybean germination remain unclear. We found that the daidzein and genistein derivatives, 8-prenyl daidzein (8-PD) and 8-prenyl genistein (8-PG), demonstrated a more potent effect than daidzein and genistein on repressing inflammatory responses in macrophages. Although IkB protein levels were unaltered, 8-PD and 8-PG repressed nuclear factor kappa B (NF-κB) activation, which was associated with reduced ERK1/2, JNK, and p38 MAPK activation and suppressed mitogen- and stress-activated kinase 1 phosphorylation. Inflammatory responses induced by the medium containing hypertrophic adipocyte secretions were successfully suppressed by 8-PD and 8-PG treatment. In the ex vivo study, 8-PD and 8-PG significantly inhibited proinflammatory C-C motif chemokine ligand 2 (CCL2) secretion from the adipose tissues of mice fed a long-term high-fat diet. The data suggest that 8-PD and 8-PG could regulate macrophage activation under obesity conditions.
Topics: Mice; Animals; Genistein; Glycine max; Isoflavones; Macrophages; Anti-Inflammatory Agents
PubMed: 37024261
DOI: 10.1093/bbb/zbad041 -
Environmental Science and Pollution... Dec 2023Acute kidney injury (AKI) is a life-threatening complication that accompanies rhabdomyolysis. Daidzein is a dietary isoflavone that has various biological activities....
Acute kidney injury (AKI) is a life-threatening complication that accompanies rhabdomyolysis. Daidzein is a dietary isoflavone that has various biological activities. This study examined the therapeutic potential of daidzein and the underlying mechanisms against AKI induced by glycerol in male rats. Animals were injected once with glycerol (50%, 10 ml/kg, intramuscular) for induction of AKI and pre-treated orally with daidzein (25, 50, and 100 mg/kg) for 2 weeks. Biochemical, histopathological, immunohistopathological, and molecular parameters were assessed to evaluate the effect of daidzein. The results revealed that the model group displayed remarkable functional, molecular, and structural changes in the kidney. However, pre-administration of daidzein markedly decreased the kidney relative weight as well as the levels of urea, creatinine, K, P, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin C. Further, daidzein lessened the rhabdomyolysis-related markers [lactate dehydrogenase (LDH) and creatine kinase (CK)]. Notably, the enhancement of the antioxidant biomarkers [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and reduced glutathione (GSH) is accompanied by a decrease in malondialdehyde (MDA) and nitric oxide (NO) levels. Moreover, upregulated gene expression levels of nuclear factor erythroid 2-related factor 2 (Nfe212) and hemeoxygenase-1 (Hmox1) were exerted by daidzein administration. Rats who received daidzein displayed markedly lower interleukin-1β (IL-1β), tumor nuclear factor-α (TNF-α), myleoperoxidase (MPO), and nuclear factor kappa B (NF-κB) levels together with higher interleukin-10 (IL-10) related to the model group. Remarkably, significant declines were noticed in the pro-apoptotic (Bax and caspase-3) and rises in antiapoptotic (Bcl-2) levels in the group that received daidzein. The renal histological screening validated the aforementioned biochemical and molecular alterations. Our findings support daidzein as a potential therapeutic approach against AKI-induced renal injury via suppression of muscle degradation, oxidative damage, cytokine release, and apoptosis.
Topics: Rats; Male; Animals; Glycerol; Acute Kidney Injury; Kidney; Antioxidants; Oxidative Stress; Isoflavones; Rhabdomyolysis
PubMed: 37919499
DOI: 10.1007/s11356-023-30461-4