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Die Pharmazie Feb 2021Daidzein is a secondary metabolite derived from plants, has a flavonoid structure and is known for its protective activity in gastrointestinal disorders. The current...
Daidzein is a secondary metabolite derived from plants, has a flavonoid structure and is known for its protective activity in gastrointestinal disorders. The current work determines the preventive effect of daidzein against injury in the esophagus mucosa induced by esophageal reflux (RE) in an animal model. Adult male Wistar rats were classified into six groups: normal control, ER + different doses of daidzein and ER + omeprazole. RE was induced in all animals except controls and supplemented with daidzein and standard drugs orally for 6 hours. Serum and tissue were used for further biochemical parameters. Daidzein as a flavonoid has antioxidant properties and shows antioxidant activity. The outcomes also reveal an elevation in lipid peroxidation and a decline in the levels of sulphhydryl groups and glutathione, along with the depletion in the activities of enzymatic antioxidants in the oxidative stress state. In a dose-dependent manner daidzein and omeprazole amended all macroscopic and biochemical variations and protected against the raised level of hydrogen peroxide (H₂O₂), calcium and free iron levels in esophageal tissue induced during RE. It also improved the expression and level of proinflammatory cytokines. : The finding reports that daidzein has a potential to show a shielding effect against esophagus damage induced by RE in rats, at least in part alteration of inflammatory cytokines.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cell Survival; Claudin-4; Claudin-5; Cytokines; Disease Models, Animal; Esophageal Mucosa; Esophagus; Gastroesophageal Reflux; Glutathione; Isoflavones; Lipid Peroxidation; Lipopolysaccharides; Male; Mice; Oxidative Stress; RAW 264.7 Cells; Rats; Rats, Wistar
PubMed: 33714284
DOI: 10.1691/ph.2021.01003 -
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 -
European Journal of Pharmacology Oct 2020Endotoxin-induced acute liver injury (ALI) is a severe disease associated with a poor prognosis. Therefore, it is urgent to discover new effective therapies to prevent...
Endotoxin-induced acute liver injury (ALI) is a severe disease associated with a poor prognosis. Therefore, it is urgent to discover new effective therapies to prevent ALI. Daidzein, extracted from leguminous plants, possess anti-inflammatory and antioxidative bioactivities. However, little is known about whether daidzein could attenuate lipopolysaccharide (LPS)-induced ALI. We investigated the effects of daidzein on hepatocyte injury and its underlying mechanisms. In LPS-induced hepatocyte supernatant, 100 μM daidzein decreased ALT and AST expression levels by 49.3% ± 5.6% and 39.3% ± 3.5%, respectively, with no cytotoxicity. In addition, the expression of inflammatory factors, including interleukin-1β (IL-lβ), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were decreased by 100 μM daidzein (73.8% ± 5.3%, 58.8 ± 9.0% and 55.5% ± 7.2%, respectively) in LPS-treated hepatocytes. Western blot analysis showed that daidzein inhibited LPS-induced p-ERK1/2, p-IκBα and p-p65 expression levels. Moreover, 100 μM daidzein reduced the LPS-induced production of Reactive oxygen species by 23.9 ± 7.8% and increased SOD activity by 88.4% ± 18.9% by downregulating Keap-1 and upregulating Nrf2 expression. In conclusion, these data indicate that daidzein ameliorates LPS-induced hepatocyte injury by inhibiting inflammation and oxidative stress.
Topics: Alanine Transaminase; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Cytokines; Estrogens, Non-Steroidal; Hepatocytes; Isoflavones; Lipopolysaccharides; MAP Kinase Signaling System; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Primary Cell Culture; Transcription Factor RelA
PubMed: 32712091
DOI: 10.1016/j.ejphar.2020.173399 -
Animal Biotechnology Oct 2022Fat deposition in skeletal muscle is an important aspect of improving meat quality. Isoflavones can promote animal anabolism, but whether and how they regulate muscle...
Fat deposition in skeletal muscle is an important aspect of improving meat quality. Isoflavones can promote animal anabolism, but whether and how they regulate muscle fat deposition remain largely unclear. In this study, we explored the role and corresponding molecular mechanism of one of the major isoflavones, daidzein, in fat deposition in C2C12 myoblast cells. In the absence of fatty acids (FAs), daidzein did not promote triglyceride synthesis and lipid droplet formation in cells but increased sterol regulatory element-binding protein 1c (SREBP-1c) expression and maturation. In the presence of FAs, daidzein enhanced FAs-induced fat deposition and the SREBP-1c signaling. Daidzein promoted FAs-induced nuclear factor κB1 (NFκB1) phosphorylation and activated the SREBP-1c signaling in a PI3K-dependent manner. G protein-coupled receptor 30 (GPR30) knockdown but not estrogen receptor α (ERα) knockdown blocked the stimulation of daidzein on the PI3K-NFκB1-SREBP-1c signaling pathway, while both knockdown did not affect the stimulation of FAs on this signaling. qRT-PCR and ChIP-qPCR further detected that daidzein stimulated NFκB1-targeted transcription. Daidzein did not affect ERα expression in cells, but it stimulated GPR30 expression and cytoplasmic localization. These results reveal that daidzein promotes FAs-induced fat deposition through the GPR30 signaling in C2C12 myoblast cells.
Topics: Animals; Estrogen Receptor alpha; Fatty Acids; Isoflavones; Myoblasts; Phosphatidylinositol 3-Kinases; Receptors, G-Protein-Coupled; Sterol Regulatory Element Binding Protein 1; Sterols; Triglycerides
PubMed: 33164657
DOI: 10.1080/10495398.2020.1842749 -
Naunyn-Schmiedeberg's Archives of... Aug 2022Reactive oxygen species via NADPH oxidase (NOX) activation are involved in the pathogenesis of many disease conditions such as diabetes and its complications. In the...
Reactive oxygen species via NADPH oxidase (NOX) activation are involved in the pathogenesis of many disease conditions such as diabetes and its complications. In the present study, we have examined the effect of daidzein in the management of diabetic cystopathy. Diabetes was induced in male Sprague Dawley rats via intraperitoneal injection of streptozotocin (STZ) at a dose of 55 mg/kg. After 6 weeks of diabetes induction, animals were treated with daidzein orally at a dose of 25, 50, and 100 mg/kg for 4 weeks. Diabetic animals showed increase (p < 0.001) in bladder capacity (4.32 ± 0.43 mL) and residual volume (2.53 ± 0.19 mL) when compared with normal control animals (2.10 ± 0.40 mL and 0.51 ± 0.12 mL res). Treatment with daidzein at dose of 50 and 100 mg/kg significantly reduced the elevated bladder capacity (2.91 ± 0.11 mL, p < 0.01 and 2.65 ± 1.13 mL, p < 0.001) and residual volume (1.40 ± 0.15 mL, p < 0.001 and 1.15 ± 0.05 mL, p < 0.001). Daidzein-treated animals also showed improvement in voiding efficiency. Elevated threshold and baseline pressure were also found to be reduced in diabetic animals after 4 weeks of daidzein treatment. Daidzein treatment also prevented the loss of antioxidant enzymes in the urinary bladder and also reduced the expression of NOX-4 and RAC-1 in the bladder. From the results, it can be concluded that daidzein showed a beneficial effect on urinary bladder dysfunction in diabetic animals.
Topics: Animals; Diabetes Mellitus, Experimental; Isoflavones; Male; Rats; Rats, Sprague-Dawley; Streptozocin; Urinary Bladder
PubMed: 35538367
DOI: 10.1007/s00210-022-02246-y -
International Journal of Pharmaceutics Mar 2016Daidzein is one of the most effective candidates for treating cardiovascular and cerebrovascular disease. However, considering its poor oral absorption and limited...
Daidzein is one of the most effective candidates for treating cardiovascular and cerebrovascular disease. However, considering its poor oral absorption and limited bioavailability, daidzein-loaded nanostructured lipid carriers-PLGA nanofibers were designed to handle the drawbacks. Daidzein-NLCs were successfully prepared by an emulsification and low-temperature solidification method. The physicochemical characteristics of NLCs were evaluated afterwards. Based on the preparation of daidzein-loaded NLCs, Daidzein-NLCs-nanofibers were optimized by electrospinning and were observed under Scanning Electron Microscope to capture the appearance. The sustained release profile of daidzein from Daidzein-NLCs-nanofibers in vivo was best fitted to the Kormeyer-Peppas equation. The in vitro skin permeable behavior showed the cumulative amount of daidzein from Daidzein-NLCs-nanofibers reached 21.71 μg cm(-2) at 60 h, which was 3.78 times higher than pure daidzein solution. It demonstrated that the Daidzein-NLCs-nanofibers could significantly enhance the transported amount of drug. Confocal Laser Scanning Microscopy resulting images revealed a more effective content accumulation of Daidzein-NLCs-nanofibers than Daidzein-NLCs in epidermis. In vivo study indicated that Daidzein-NLCs-nanofibers had better skin retention than Daidzein-NLCs in the long term. The skin irritation experiment showed a positive result with no obvious stimulus observed. These results suggested that Daidzein-NLCs-nanofibers could be a potential candidate for transdermal delivery.
Topics: Administration, Cutaneous; Animals; Azepines; Drug Carriers; Drug Liberation; In Vitro Techniques; Isoflavones; Lactic Acid; Lipids; Male; Nanofibers; Nanostructures; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rats, Sprague-Dawley; Skin; Skin Absorption; Skin Irritancy Tests
PubMed: 26851353
DOI: 10.1016/j.ijpharm.2016.02.003 -
Comparative Biochemistry and... Aug 2022This study investigates the therapeutic activity of daidzein, an isoflavone that occurs naturally in plants and herbs, against gentamicin-induced nephrotoxicity in...
This study investigates the therapeutic activity of daidzein, an isoflavone that occurs naturally in plants and herbs, against gentamicin-induced nephrotoxicity in Madin-Darby canine kidney (MDCK) cells in-vitro and zebrafish model in-vivo. The in-vitro studies revealed that daidzein protected MDCK cells from gentamicin-induced inflammation by suppressing oxidative stress and apoptosis. The zebrafish were divided into groups and injected with gentamicin (140 mg/mL) to induce nephrotoxic conditions. After injection, renal dysfunction, nitric oxide production, antioxidant consumption, exaggerated apoptosis, and inflammation were all observed in the zebrafish model. We also observed that during kidney inflammation in zebrafish, pro-inflammatory cytokines such as cyclooxygenase (COX-2), tumor necrosis factor (TNF-α), and interleukin-1β (IL-1β) are upregulated. Furthermore, daidzein treatment after gentamicin injection showed a strong protective anti-inflammatory effect. Daidzein activity was associated with an increase in antioxidant biomarkers such as superoxide dismutase (SOD) and glutathione reductase (GSH), whereas lipid peroxidation (LPO) and nitric oxide (NO) production were decreased in a dose-dependent factor. Moreover, histopathological alteration caused by gentamicin in zebrafish kidneys was normalized due to daidzein treatment. Daidzein also downregulated the pro-inflammatory cytokines gene expression in gentamicin-induced kidney inflammation in zebrafish. These results revealed that daidzein could potentially prevent nephrotoxic conditions through pro-inflammatory cytokines inhibition and its antioxidant property.
Topics: Animals; Antioxidants; Cytokines; Dogs; Gentamicins; Inflammation; Isoflavones; Kidney; Nitric Oxide; Oxidative Stress; Tumor Necrosis Factor-alpha; Zebrafish
PubMed: 35523404
DOI: 10.1016/j.cbpc.2022.109364 -
Journal of Biochemical and Molecular... Feb 2022Parkinson's disease (PD) ranks as the second most neurodegenerative disease characterized by loss of neurons, bradykinesia, anosmia, sleep disorder, and motor deficiency...
Parkinson's disease (PD) ranks as the second most neurodegenerative disease characterized by loss of neurons, bradykinesia, anosmia, sleep disorder, and motor deficiency with increased global prevalence. Here, we have analyzed daidzein's neuroprotective functions in in vitro and in vivo models of PD. BV2 microglial cells induced with lipopolysaccharide (LPS) and C57BL6 mice induced with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) were used in this study to investigate neuroprotective functions of daidzein. BV2 cells induced with LPS do not exert and significant (p < 0.05) reduction in cell viability up to concentration range (5-100 µM/ml). Furthermore, LPS exposed BV2 microglia exhibited significantly (p < 0.05) increased NO production, pro-inflammatory mediators PGE2, interleukin-6 (IL6), and interleukin-1β (IL-1β) levels. Treatment with daidzein (10, 25, and 50 µM/ml) to LPS-induced BV2 microglia exhibited significantly (p < 0.05) decreased NO, pro-inflammatory mediators PGE2, IL6, and IlL-1β. Similar to the in vitro results, C57BL6 mice induced with MPTP showed defects in motor functions as observed from altered forelimb and hindlimb footprint analyses, grip strength, and perturbed motor coordination observed via rotarod tests. Additionally, levels of dopamine were significantly reduced, and pro-inflammatory mediators tumor necrosis factor alpha (TNF-α), IL-1β, IL6 were found to be increased in MPTP-induced C57BL6 PD mice. Administering daidzein significantly restored the functional levels of dopamine and pro-inflammatory mediators TNF-α, IL-1β, IL6 to near normal physiology as seen in healthy C57BL6 mice controls. Similarly, daidzein treatment to PD mice also restored the histological architecture to near normal levels as in control mice. Together, our results collectively endorse the neuroprotective functions of daidzein as observed from our initial studies, and further studies aimed at investigating daidzein's ability in regulating the catecholamine synthesis pathway to protect substantia nigra pars compacta (SNpc) neurons are in focus.
Topics: Animals; Isoflavones; Lipopolysaccharides; Male; Mice; Microglia; Neuroprotective Agents; Parkinsonian Disorders
PubMed: 34850494
DOI: 10.1002/jbt.22949 -
Molecules (Basel, Switzerland) Dec 2022The intestinal epithelium provides an important barrier against bacterial endotoxin translocation, which can regulate the absorption of water and ions. The disruption of...
The intestinal epithelium provides an important barrier against bacterial endotoxin translocation, which can regulate the absorption of water and ions. The disruption of epithelial barrier function can result in water transport and tight junction damage, or further cause diarrhea. Therefore, reducing intestinal epithelial barrier injury plays an important role in diarrhea. Inflammatory response is an important cause of intestinal barrier defects. Daidzein improving the barrier integrity has been reported, but the effect on tight junction proteins and aquaporins is not well-described yet, and the underlying mechanism remains indistinct in the human intestinal epithelium. This study aimed to investigate the effects and mechanisms of daidzein on intestinal epithelial barrier injury induced by LPS, and a barrier injury model induced by LPS was established with human colorectal epithelial adenocarcinoma cell line Caco-2 cells. We found that daidzein protected the integrity of Caco-2 cell monolayers, reversed LPS-induced downregulation of ZO-1, occludin, claudin-1, and AQP3 expression, maintained intercellular junction of ZO-1, and suppressed NF-κB and the expression of inflammatory factors (TNF-α, IL-6). Furthermore, we found that daidzein suppressed the phosphorylation of the PI3K/AKT and P38 pathway-related proteins and the level of the related genes, and the PI3K/AKT and P38 pathway inhibitors increased ZO-1, occludin, claudin-1, and AQP3 expression. The study showed that daidzein could resist LPS-induced intestinal epithelial barrier injury, and the mechanism is related to suppressing the PI3K/AKT and P38 pathways. Therefore, daidzein could be a candidate as a dietary supplementation or drug to prevent or cure diarrhea.
Topics: Humans; Caco-2 Cells; Lipopolysaccharides; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Occludin; Claudin-1; Intestinal Mucosa; Tight Junction Proteins; Diarrhea; Tight Junctions; Epithelial Cells
PubMed: 36558058
DOI: 10.3390/molecules27248928 -
Virus Research Jun 2021MicroRNAs are emerging as critical endogenous regulators of gene function. Aberrant regulation of microRNAs is associated with various human diseases, most importantly...
MicroRNAs are emerging as critical endogenous regulators of gene function. Aberrant regulation of microRNAs is associated with various human diseases, most importantly cancer. MicroRNA-122 (miR-122), a liver-specific microRNA, has been implicated in the control of hepatitis C virus (HCV) RNA replication and its response to interferon (IFN) in human hepatoma cells. Here, we report that daidzein, a naturally occurring plant isoflavone, inhibits HCV replication and enhances the antiviral effect of IFN-α on HCV therapy by decreasing microRNA-122 levels in vitro without significantly affecting cell growth. Moreover, daidzein was found to inhibit the expression of miR-122 and miR-21 by down-regulating the expression of TRBP, indicating that daidzein is possibly a general inhibitor of the miRNA pathway. Thus, daidzein provides new insights for drug discovery and HCV prevention.
Topics: Antiviral Agents; Hepacivirus; Hepatitis C; Humans; Interferon-alpha; Isoflavones; MicroRNAs; Virus Replication
PubMed: 33775754
DOI: 10.1016/j.virusres.2021.198404