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Current Medicinal Chemistry 2017Among naturally occurring isoflavones, soy isoflavones are an important class with various biological activities. Due to their phytoestrogenic structure, their effects... (Review)
Review
Among naturally occurring isoflavones, soy isoflavones are an important class with various biological activities. Due to their phytoestrogenic structure, their effects on the brain are profound thus making the neurobiological effects of these compounds an active area of research. One such compound is daidzein, which has been reported to affect various neurobiological regulatory mechanisms such as behavior, cognition, growth, development and reproduction. These effects are mainly elicited through the interaction of daidzein with different signaling molecules and receptors, thereby offering neuroprotection. In addition, daidzein has also been reported to possess activities against various neuropathological conditions mainly by its interaction with the cerebrovascular system. This review focuses on providing a comprehensive account on the bioavailability and metabolism of daidzein in vivo, and discusses its activities and mechanisms of action in detail, in both physiological and pathological conditions. In addition, the effects of daidzein on other disorders have also been examined briefly in this article.
Topics: Animals; Behavior; Brain; Cognition; Humans; Isoflavones; Reproduction
PubMed: 27804870
DOI: 10.2174/0929867323666161101140214 -
Pharmacokinetics, pharmacodynamics, toxicity, and formulations of daidzein: An important isoflavone.Phytotherapy Research : PTR Jun 2023Daidzein, 7-hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one is a naturally occurring compound present in leguminous plants, especially in soybeans. Chemically it belongs to... (Review)
Review
Daidzein, 7-hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one is a naturally occurring compound present in leguminous plants, especially in soybeans. Chemically it belongs to the isoflavone class and possesses high nutritive value. Daidzein acts on estrogen receptor and is non-steroidal in nature hence it can also be called as non-steroidal phytoestrogenic compound. Daidzein has been studied by many researchers for its pharmacological activities. Daidzein metabolites were also studied in detail for their health benefits. Researchers have developed novel formulations of daidzein in the past few years to improve its aqueous solubility and bioavailability. Self-emulsified daidzein, poly(lactic-co-glycolic) acid daidzein nanoparticles, nanoemulsion, nanoemulsion gel, and co-crystals are a few of them. The present review provides detailed information on the chemistry, drug development aspects, pharmacokinetics, and pharmacodynamics of daidzein. A literature search was performed using various datasets like PubMed, EBSCO, ProQuest Scopus, and selected websites including the National Institutes of Health and the World Health Organization. Daidzein has a wide range of pharmacodynamic properties in the treatment of cancer, neurodegenerative disorders, cardiac disorders, diabetes and its complication, osteoporosis, and skin disorders. The pharmacokinetic, pharmacodynamics, and drug development aspects of daidzein will help researchers to design further research work on daidzein in the future.
Topics: Isoflavones; Glycine max; Phytoestrogens; Biological Availability
PubMed: 37118928
DOI: 10.1002/ptr.7852 -
PeerJ 2023Postmenopausal osteoporosis and osteoporosis-related fractures are world-wide serious public health problem. Recent studies demonstrated that inhibiting caveolin-1 leads...
BACKGROUND
Postmenopausal osteoporosis and osteoporosis-related fractures are world-wide serious public health problem. Recent studies demonstrated that inhibiting caveolin-1 leads to osteoclastogenesis suppression and protection against OVX-induced osteoporosis. This study aimed to explore the mechanism of caveolin-1 mediating bone loss and the potential therapeutic target.
METHODS
Thirty C57BL/6 female mice were allocated randomly into three groups: sham or bilateral ovariectomy (OVX) surgeries were performed for mice and subsequently daidzein or vehicle was administrated to animals (control, OVX + vehicle and OVX + daidzein). After 8-week administration, femurs were harvested for Micro-CT scan, histological staining including H&E, immunohistochemistry, immunofluorescence, TRAP. Bone marrow endothelial cells (BMECs) were cultured and treated with inhibitors of caveolin-1 (daidzein) or EGFR (erlotinib) and then scratch wound healing and ki67 assays were performed. In addition, cells were harvested for western blot and PCR analysis.
RESULTS
Micro-CT showed inhibiting caveolin-1with daidzein alleviated OVX-induced osteoporosis and osteogenesis suppression. Further investigations revealed H-type vessels in cancellous bone were decreased in OVX-induced mice, which can be alleviated by daidzein. It was subsequently proved that daidzein improved migration and proliferation of BMECs hence improved H-type vessels formation through inhibiting caveolin-1, which suppressed EGFR/AKT/PI3K signaling in BMECs.
CONCLUSIONS
This study demonstrated that daidzein alleviates OVX-induced osteoporosis by promoting H-type vessels formation in cancellous bone, which then promotes bone formation. Activating EGFR/AKT/PI3K signaling could be the critical reason.
Topics: Female; Mice; Animals; Osteogenesis; Caveolin 1; Endothelial Cells; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Mice, Inbred C57BL; Osteoporosis; X-Ray Microtomography; ErbB Receptors
PubMed: 37868048
DOI: 10.7717/peerj.16121 -
BioFactors (Oxford, England) Sep 2018Over the last decades, the incidence of type 2 diabetes (T2D) is increasing substantially. Emerging evidences from epidemiological studies have shown the association... (Review)
Review
Over the last decades, the incidence of type 2 diabetes (T2D) is increasing substantially. Emerging evidences from epidemiological studies have shown the association between higher intake of soy isoflavones and reduced risk of T2D and its associated health risks. Daidzein, a soy isoflavone, has been found to have a promising therapeutic potential in managing T2D pathophysiology. Fermented soybean is the major source of daidzein; however, it can also be formed via the consumption of its glycosylated moiety, daidzin with subsequent hydrolysis by intestinal bacterial enzyme. Many studies reported the prophylactic effect of daidzein on the improvement of hyperglycemia, insulin resistance, dislipidemia, obesity, inflammation, and other complications associated with T2D. The molecular mechanisms underlying the action of daidzein include diverged pathways where daidzein has been shown to interact with several signaling molecules and receptors to achieve desirable effect. Although the specific molecular mechanism is still elusive, further studies are thus needed to understand it in detail. In this review, we discuss the antidiabetic potential of daidzein with respect to the evidences from various clinical, preclinical, and cell culture studies and the underlying molecular mechanism in a precise way to have a comprehensive account on this isoflavone with promising therapeutic potential. © 2018 BioFactors, 44(5):407-417, 2018.
Topics: Diabetes Mellitus, Type 2; Glucose; Humans; Hypoglycemic Agents; Inflammation; Insulin Resistance; Isoflavones; Lipid Metabolism; Glycine max
PubMed: 30191623
DOI: 10.1002/biof.1439 -
Life Sciences Jan 2021The present study was designed to check the effect of daidzein in the management of diabetic retinopathy.
AIM
The present study was designed to check the effect of daidzein in the management of diabetic retinopathy.
MAIN METHODS
Streptozotocin at dose 55 mg/kg was used for inducing diabetes in rats. After 28 days of diabetic induction, animals were treated with daidzein at dose 25, 50, and 100 mg/kg for the next 28 days. Electroretinography, estimation of plasma glucose, lactate dehydrogenase, aldose reductase, sorbitol dehydrogenase and oxidative stress parameters were performed at the end of the study. Histopathology of retina was carried out at the end of the study.
KEY FINDINGS
Diabetic control animals showed a significant increase in levels of plasma glucose and plasma lactate dehydrogenase (p < 0.001). Treatment with daidzein at a dose of 50 and 100 mg/kg significantly reduced the elevated level of blood glucose (p < 0.01 and p < 0.01). Whereas, treatment with daidzein at a dose 100 mg/kg significantly reduced the elevated level of lactate dehydrogenase in plasma after 28 days of treatment (p < 0.01). Treatment with daidzein at a dose of 100 mg/kg significantly reduced the level of aldose reductase and sorbitol dehydrogenase (p < 0.01 and p < 0.001 respectively). Electroretinography revealed that daidzein treatment at a dose of 100 mg/kg significantly prevented the change in 'a' and 'b' wave amplitude and latency. Oxidative stress was also found to be significantly reduced after 28 days of daidzein treatment. Histopathological findings showed a reduction in retinal thickness after daidzein treatment.
SIGNIFICANCE
Daidzein treatment protected retina from damage in hyperglycaemic conditions. Thus, Daidzein can be considered as an effective treatment option for diabetic retinopathy.
Topics: Aldehyde Reductase; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Dose-Response Relationship, Drug; Electroretinography; Hypoglycemic Agents; Isoflavones; L-Iditol 2-Dehydrogenase; L-Lactate Dehydrogenase; Lens, Crystalline; Male; Rats; Rats, Sprague-Dawley; Retina
PubMed: 33217441
DOI: 10.1016/j.lfs.2020.118779 -
European Review For Medical and... Feb 2023The aim of this study was to investigate the effect of daidzein against intestinal ischemia-reperfusion injury in rats.
OBJECTIVE
The aim of this study was to investigate the effect of daidzein against intestinal ischemia-reperfusion injury in rats.
MATERIALS AND METHODS
Thirty male Wistar albino rats with a mean weight of 200-250 gr were used. Animals were categorized into sham, ischemia-reperfusion (IR), and IR+Daidzein group. 3-hour ischemia of intestine was created by occluding superior mesenteric artery and then left for 3-hour reperfusion. In IR+daidzein group, after ischemia, 50 mg/kg daidzein was orally administered to the animals. Blood samples were collected for biochemical assays. Intestine tissues were excised for histopathologic and immunohistochemical processing.
RESULTS
Malondialdehyde (MDA) increased, and Catalase (CAT) and Glutathione (GSH) decreased after IR in intestine tissue. Daidzein treatment decreased MDA and increased CAT and GSH level in IR+Daidzein group. Histopathologically, sham group showed normal intestinal tissue histology. In IR group, epithelial and villi degeneration, edema, leukocyte infiltration, vascular dilatation and congestion was observed. After Daidzein treatment, these pathologies were improved. The caspase-6 expression was mainly negative in sham group. After IR, caspase-6 reaction was very high in IR group. Daidzein reduced caspase-6 expression in IR+Daidzein group. Ki67 immune staining was negative in the sham group. In IR group, Ki67 expression was increased in inflammatory cells, deep glandular cells and in some goblet cell nuclei. In IR+Daidzein group, Ki67 expression was decreased due to reduced inflammation.
CONCLUSIONS
IR injury causes oxidative stress, apoptosis and inflammation. Daidzein treatment improved histopathology against intestinal IR.
Topics: Male; Rats; Animals; Rats, Wistar; Caspase 6; Ki-67 Antigen; Intestines; Ischemia; Reperfusion; Reperfusion Injury
PubMed: 36876688
DOI: 10.26355/eurrev_202302_31389 -
European Journal of Pharmacology Mar 2022Myocardial fibrosis is a concomitant bioprocess associated with many cardiovascular diseases (CVDs). Daidzein is an isoflavone that has been used for the treatment of...
Myocardial fibrosis is a concomitant bioprocess associated with many cardiovascular diseases (CVDs). Daidzein is an isoflavone that has been used for the treatment of CVDs. This study aimed to reveal its role in myocardial fibrosis. Our results indicate that daidzein had a nontoxic effect on cardiac fibroblasts and that TGF-β1 and TGFβRI levels were gradually decreased by daidzein in a dose-dependent manner. In the current study, we show that daidzein significantly inhibited TGF-β1-induced mRNA and protein expression of α-SMA, collagen I, and collagen III. Accordingly, immunofluorescence staining of α-SMA was performed. Daidzein also inhibited TGF-β1-induced cardiac fibroblast proliferation and migration. Mechanistically, daidzein inhibited the TGF-β/SMAD signaling pathway induced by TGF-β1 in cardiac fibroblasts. Additionally, daidzein ameliorated MI-induced cardiac dysfunction and cardiac fibrosis in vivo. Based on these findings, we conclude that daidzein reduces TGF-β1-induced cardiac fibroblast activation by partially regulating the TGF-β1/SMAD2/3 signaling pathway.
Topics: Animals; Cardiovascular Diseases; Disease Models, Animal; Dose-Response Relationship, Drug; Fibroblasts; Fibrosis; Growth Inhibitors; Humans; Isoflavones; Male; Mice, Inbred C57BL; Myocardium; Rats; Rats, Sprague-Dawley; Signal Transduction; Smad2 Protein; Transforming Growth Factor beta1; Mice
PubMed: 35151651
DOI: 10.1016/j.ejphar.2022.174805 -
Life Sciences Nov 2021Present study focuses on the effect of daidzein in an experimental model of diabetic cardiomyopathy in rats.
AIM
Present study focuses on the effect of daidzein in an experimental model of diabetic cardiomyopathy in rats.
MATERIALS AND METHODS
Diabetes was induced in male Sprague Dawley rats by a single intraperitoneal injection of STZ at dose 55 mg/kg. Daidzein treatment was started after six weeks of diabetes induction. Animals received daidzein at a dose of 25, 50, and 100 mg/kg orally for the next four weeks.
KEY FINDINGS
Diabetic control animals showed significant prolongation in QT interval, PR interval, and R wave amplitude as compared to normal control animals. Treatment with daidzein at dose 100 mg/kg significantly normalized the QT interval, PR interval, and R wave amplitude. A significant reduction in QRS duration was observed in diabetic animals. Treatment with daidzein significantly improved the QRS duration after treatment. Hemodynamic parameters like systolic pressure (SBP), diastolic pressure (DBP) and mean atrial pressure (MAP) were found to be significantly decreased in diabetic animals. Treatment with daidzein at dose 100 mg/kg significantly improved the SBP, DBP, and MAP. Daidzein treatment prevented the loss of cardiac marker enzyme from heart tissue and also increased the level of AMPK and SIRT1 in plasma. Protein expression of NOX-4 and RAC-1 was also found to be reduced in cardiac tissue of daidzein treated animals. Daidzein treatment improved oxidative defense mechanism and reduced cardiac tissue necrosis and fibrosis.
SIGNIFICANCE
From the results, it can be concluded that daidzein mitigates the progression of diabetic cardiomyopathy by inhibiting NOX-4 induced oxidative stress in cardiac tissue.
Topics: Adenylate Kinase; Animals; Antioxidants; Biomarkers; Blood Glucose; Body Weight; Cardiomegaly; Diabetes Mellitus, Experimental; Electrocardiography; Heart Ventricles; Hemodynamics; Isoflavones; Lipids; Male; Myocardium; NADPH Oxidase 4; Oxidative Stress; Rats, Sprague-Dawley; Sirtuin 1; Troponin I; rac1 GTP-Binding Protein; Rats
PubMed: 34090859
DOI: 10.1016/j.lfs.2021.119664 -
Acta Cirurgica Brasileira 2023Our aim was to investigate protective effects of daidzein treatment on ischemia-reperfusion (I/R) injury-induced ovarian tissue by immunohistochemical techniques.
PURPOSE
Our aim was to investigate protective effects of daidzein treatment on ischemia-reperfusion (I/R) injury-induced ovarian tissue by immunohistochemical techniques.
METHODS
Thirty Sprague Dawley female rats were categorized into three groups as sham, I/R group, and I/R+daidzein groups. Bloods were analyzed for malondialdehyde (MDA), glutathione peroxidase (GSH), and myeloperoxidase (MPO), and ovaries were processed for histological tissue protocol.
RESULTS
Both MDA and MPO values were increased in I/R group compared to sham and I/R+daidzein groups. GSH content was increased in I/R+daidzein group compared to I/R groups. In I/R group, theca and follicular cells were degenerated with apoptosis and dilatation and congestion, edema. In I/R+daidzein group, daidzein improved pathologies. In the I/R group, Bax expression was positive with follicular cells, granulosa cells and inflammatory cells. In the I/R+daidzein group, positive Bax reaction was observed in the epithelial, antral, and inflammatory cells. In I/R group, Bcl-2 reaction was in germinative epithelial cells, cells of antral follicle. In the I/R+daidzein group, Bcl-2 expression level was reduced after daidzein treatment.
CONCLUSIONS
After the I/R procedure, ovarian cells and follicles were degenerated with apoptosis and inflammation. After daidzein treatment, Bax and Bcl-2 signal were decreased. It was observed that daidzein stopped the apoptotic process.
Topics: Rats; Animals; Female; Rats, Sprague-Dawley; Ovary; bcl-2-Associated X Protein; Ischemia; Reperfusion Injury; Proto-Oncogene Proteins c-bcl-2; Reperfusion; Malondialdehyde; Apoptosis
PubMed: 37909594
DOI: 10.1590/acb384423 -
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