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Cell Host & Microbe May 2023Acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury (DILI). The impact of the gut microbiota and associated metabolites on APAP and liver...
Acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury (DILI). The impact of the gut microbiota and associated metabolites on APAP and liver function remains unclear. We show that APAP disturbance is associated with a distinct gut microbial community, with notable decreases in Lactobacillus vaginalis. Mice receiving L. vaginalis showed resistance to APAP hepatotoxicity due to the liberation of the isoflavone daidzein from the diet by bacterial β-galactosidase. The hepatoprotective effects of L. vaginalis in APAP-exposed germ-free mice were abolished with a β-galactosidase inhibitor. Similarly, β-galactosidase-deficient L. vaginalis produced poorer outcomes in APAP-treated mice than the wild-type strain, but these differences were overcome with daidzein administration. Mechanistically, daidzein prevented ferroptotic death, which was linked to decreased expression of farnesyl diphosphate synthase (Fdps) that activated a key ferroptosis pathway involving AKT-GSK3β-Nrf2. Thus, liberation of daidzein by L. vaginalis β-galactosidase inhibits Fdps-mediated hepatocyte ferroptosis, providing promising therapeutic approaches for DILI.
Topics: Animals; Mice; Acetaminophen; beta-Galactosidase; Chemical and Drug Induced Liver Injury; Gastrointestinal Microbiome; Isoflavones; Liver; Mice, Inbred C57BL; NF-E2-Related Factor 2
PubMed: 37100057
DOI: 10.1016/j.chom.2023.04.002 -
International Journal of Molecular... Mar 2021Based on their nutrient composition, soybeans and related foods have been considered to be nutritious and healthy for humans. Particularly, the biological activity and... (Review)
Review
Based on their nutrient composition, soybeans and related foods have been considered to be nutritious and healthy for humans. Particularly, the biological activity and subsequent benefits of soy products may be associated with the presence of isoflavone in soybeans. As an alternative treatment for menopause-related symptoms, isoflavone has gained much popularity for postmenopausal women who have concerns related to undergoing hormone replacement therapy. However, current research has still not reached a consensus on the effects of isoflavone on humans. This overview is a summary of the current literature about the processing of soybeans and isoflavone types (daidzein, genistein, and S-equol) and supplements and their extraction and analysis as well as information about the utilization of isoflavones in soybeans. The processes of preparation (cleaning, drying, crushing and dehulling) and extraction of soybeans are implemented to produce refined soy oil, soy lecithin, free fatty acids, glycerol and soybean meal. The remaining components consist of inorganic constituents (minerals) and the minor components of biologically interesting small molecules. Regarding the preventive effects on diseases or cancers, a higher intake of isoflavones is associated with a moderately lower risk of developing coronary heart disease. It may also reduce the risks of breast and colorectal cancer as well as the incidence of breast cancer recurrence. Consumption of isoflavones or soy foods is associated with reduced risks of endometrial and bladder cancer. Regarding the therapeutic effects on menopausal syndrome or other diseases, isoflavones have been found to alleviate vasomotor syndromes even after considering placebo effects, reduce bone loss in the spine and ameliorate hypertension and in vitro glycemic control. They may also alleviate depressive symptoms during pregnancy. On the other hand, isoflavones have not shown definitive effects regarding improving cognition and urogenital symptoms. Because of lacking standardization in the study designs, such as the ingredients and doses of isoflavones and the durations and outcomes of trials, it currently remains difficult to draw overall conclusions for all aspects of isoflavones. These limitations warrant further investigations of isoflavone use for women's health.
Topics: Animals; Chemical Fractionation; Dietary Supplements; Drug Evaluation, Preclinical; Hot Flashes; Humans; Isoflavones; Menopause; Metabolic Networks and Pathways; Phytoestrogens; Plant Extracts; Glycine max; Spectrum Analysis; Structure-Activity Relationship; Syndrome
PubMed: 33809928
DOI: 10.3390/ijms22063212 -
Nutrients Sep 2019Epidemiological data suggest that regular intake of isoflavones from soy reduces the incidence of estrogen-dependent and aging-associated disorders, such as menopause... (Review)
Review
Epidemiological data suggest that regular intake of isoflavones from soy reduces the incidence of estrogen-dependent and aging-associated disorders, such as menopause symptoms in women, osteoporosis, cardiovascular diseases and cancer. Equol, produced from daidzein, is the isoflavone-derived metabolite with the greatest estrogenic and antioxidant activity. Consequently, equol has been endorsed as having many beneficial effects on human health. The conversion of daidzein into equol takes place in the intestine via the action of reductase enzymes belonging to incompletely characterized members of the gut microbiota. While all animal species analyzed so far produce equol, only between one third and one half of human subjects (depending on the community) are able to do so, ostensibly those that harbor equol-producing microbes. Conceivably, these subjects might be the only ones who can fully benefit from soy or isoflavone consumption. This review summarizes current knowledge on the microorganisms involved in, the genetic background to, and the biochemical pathways of, equol biosynthesis. It also outlines the results of recent clinical trials and meta-analyses on the effects of equol on different areas of human health and discusses briefly its presumptive mode of action.
Topics: Animals; Bacteria; Diet; Equol; Gastrointestinal Microbiome; Health Status; Humans; Isoflavones
PubMed: 31527435
DOI: 10.3390/nu11092231 -
Nutrients Nov 2019Isoflavones have gained popularity as an alternative treatment for menopausal symptoms for people who cannot or are unwilling to take hormone replacement therapy....
Isoflavones have gained popularity as an alternative treatment for menopausal symptoms for people who cannot or are unwilling to take hormone replacement therapy. However, there is still no consensus on the effects of isoflavones despite over two decades of vigorous research. This systematic review aims to summarize the current literature on isoflavone supplements, focusing on the active ingredients daidzein, genistein, and S-equol, and provide a framework to guide future research. We performed a literature search in Ovid Medline using the search terms "isoflavone" and "menopause", which yielded 95 abstracts and 68 full-text articles. We found that isoflavones reduce hot flashes even accounting for placebo effect, attenuate lumbar spine bone mineral density (BMD) loss, show beneficial effects on systolic blood pressure during early menopause, and improve glycemic control in vitro. There are currently no conclusive benefits of isoflavones on urogenital symptoms and cognition. Due to the lack of standardized research protocols including isoflavone component and dosage, outcomes, and trial duration, it is difficult to reach a conclusion at this point in time. Despite these limitations, the evidence thus far favors the use of isoflavones due to their safety profile and benefit to overall health.
Topics: Dietary Supplements; Female; Humans; Isoflavones; Menopause
PubMed: 31689947
DOI: 10.3390/nu11112649 -
Food & Function Sep 2022Heart failure (HF) is a clinical syndrome characterized by typical symptoms that usually occur at the end stage of various heart diseases and lead to death. Daidzein...
Heart failure (HF) is a clinical syndrome characterized by typical symptoms that usually occur at the end stage of various heart diseases and lead to death. Daidzein (DAI), an isoflavone found in soy foods, is widely used to treat menopausal syndrome, prostate cancer, breast cancer, heart disease, cardiovascular disease, and osteoporosis, and has anti-oxidant and anti-inflammatory properties. However, the effects of DAI in HF remain unknown. In this study, doxorubicin (DOX) was used to establish HF models of C57BL/6J mice and H9c2 cells with DAI treatment. Our results showed that DAI markedly improved the DOX-induced decline in cardiac function, and decreased the left ventricular ejection fraction, cardiac inflammation, oxidative stress, apoptosis, and fibrosis. Mechanistically, DAI affects cardiac energy metabolism by regulating SIRT3, and meets the ATP demand of the heart by improving glucose, lipid, and ketone body metabolism as well as restoring mitochondrial dysfunction and . Additionally, DAI can exert an antioxidant function and alleviate HF through the SIRT3/FOXO3a pathway. In conclusion, we demonstrate that DAI alleviates DOX-induced cardiotoxicity by regulating cardiac energy metabolism as well as reducing inflammation, oxidative stress, apoptosis and fibrosis, indicating its potential application for HF treatment.
Topics: Adenosine Triphosphate; Animals; Antioxidants; Apoptosis; Cardiotoxicity; Doxorubicin; Fibrosis; Glucose; Heart Failure; Inflammation; Isoflavones; Ketones; Lipids; Male; Mice; Mice, Inbred C57BL; Myocytes, Cardiac; Oxidative Stress; Signal Transduction; Sirtuin 3; Stroke Volume; Ventricular Function, Left
PubMed: 36000402
DOI: 10.1039/d2fo00772j -
Current Medicinal Chemistry 2021Over the past several decades, plant-derived products (phytochemicals) have been suggested to possess immense therapeutic potential. Among these phytochemicals,... (Review)
Review
Over the past several decades, plant-derived products (phytochemicals) have been suggested to possess immense therapeutic potential. Among these phytochemicals, different flavonoids have been reported for their potent anticancer activity. To exhibit their anticancer potential, these flavonoids modulate different signaling pathways. Among these pathways, the mammalian target of rapamycin (mTOR) and associated phosphatidyl-inositol 3-kinase (PI3K)/protein kinase B (Akt) signaling cascade have been reported as a pivotal modulator of cell survival, proliferation, and death/apoptosis. Hence, targeting this cascade could be an ideal strategy to alleviate apoptosis and inhibit proliferation in different forms of cancer. The targeting of PI3K/Akt/mTOR by flavonoids have been well documented in the scientific literature. In the current study, we have studied the anticancer potential of various flavonoids, especially flavones, flavonols, and isoflavones that include apigenin, luteolin, baicalein, tangeretin, epigallocatechin- 3-gallate, genistein, and daidzein especially dealing with mTOR targeting.
Topics: Chemoprevention; Flavonoids; Humans; Neoplasms; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; TOR Serine-Threonine Kinases
PubMed: 33167824
DOI: 10.2174/0929867327666201109122025 -
Journal of Food Biochemistry Feb 2022Puerarin (PUE) and daidzein (DAI) are polyphenols with extensive biological activities. In the present study, the interactions between PUE/DAI and micellar casein (MC)...
Puerarin (PUE) and daidzein (DAI) are polyphenols with extensive biological activities. In the present study, the interactions between PUE/DAI and micellar casein (MC) were investigated, and the physicochemical properties of their complexes were analyzed. The results of fluorescence spectrum analysis and molecular docking revealed that the main interactions between DAI and MC were hydrophobic forces, while that between PUE and MC was hydrogen bonding. The FTIR and XRD analyses confirmed the formation of complexes between MC and PUE/DAI. After binding to PUE/DAI, the size of MC increased. The weight loss rate of MC decreased after complexing with PUE/DAI, but its morphology was not extensively modified. The DPPH radical scavenging capacities of PUE-MC and DAI-MC complexes were higher than those of free PUE/DAI in both water and ethanol. In vitro release experiments showed that the release rate of PUE/DAI was inhibited by MC under simulated intestinal conditions. PRACTICAL APPLICATIONS: The low water solubility and poor bioavailability of PUE and DAI limit their application. Micellar casein has high affinity for PUE and DAI. After encapsulated by micellar casein, the release rates of PUE and DAI were prolonged during simulated intestinal digestion. The results would provide useful information for improving the solubility and bioavailability of PUE and DAI, and broadening the use of them in the food and pharmaceutical industry.
Topics: Caseins; Isoflavones; Micelles; Molecular Docking Simulation
PubMed: 34981538
DOI: 10.1111/jfbc.14048 -
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 -
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