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Indian Journal of Pharmacology 2017The objective of the study was to investigate the effect of daidzein flavonoid on cisplatin (CP)-induced hematotoxicity and hepatotoxicity in experimental rats.
OBJECTIVE
The objective of the study was to investigate the effect of daidzein flavonoid on cisplatin (CP)-induced hematotoxicity and hepatotoxicity in experimental rats.
MATERIALS AND METHODS
The Wistar rats were randomly divided into four equal groups: Normal (saline 1 ml p.o.), CP (7.5 mg/kg once intraperioteneally on 16 day), test group of low dose (combination of CP and daidzein 20 mg/kg p.o. for 21 days), and test group of high dose (combination of CP and daidzein 40 mg/kg p.o. for 21 days). Blood samples were collected on 22 day from each rat and subjected for evaluation of hematological parameters such as red blood corpuscles (RBC), white blood corpuscles, hemoglobin (Hb) and platelets, and serum biomarkers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Liver of each rat was excised and subjected for antioxidants evaluation such as malonyl dialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase, and histopathological study.
RESULTS
Daidzein had a significant ( < 0.001) beneficial role in CP-induced hemotoxicity by increasing RBC, Hb, packed cell volume, and platelets. Daidzein also exhibited a significant ( < 0.001) protection against CP-induced hepatotoxicity by decreasing ALT, AST, ALP, and MDA level and by elevating the GSH, SOD, and catalase.
CONCLUSIONS
Daidzein attenuates CP-induced oxidative stress on blood cells and antioxidants in rats.
Topics: Alanine Transaminase; Animals; Antineoplastic Agents; Antioxidants; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Cisplatin; Dose-Response Relationship, Drug; Female; Glutathione; Isoflavones; Male; Oxidative Stress; Rats; Rats, Wistar; Superoxide Dismutase
PubMed: 28458422
DOI: 10.4103/0253-7613.201022 -
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 -
Archives of Toxicology Sep 2018Daidzein, one of the major soy isoflavones, has a number of beneficial bioactivities for human health. It is mainly metabolized into 7- and/or 4'-glucuronides by...
Daidzein, one of the major soy isoflavones, has a number of beneficial bioactivities for human health. It is mainly metabolized into 7- and/or 4'-glucuronides by UDP-glucuronosyltransferase (UGT) enzymes in mammals, including humans. The present study was conducted to examine the regioselective glucuronidation of daidzein at the 7- and 4'-hydroxyl groups in the liver and intestinal microsomes of humans, monkeys, rats, and mice. Daidzein glucuronidation activities at substrate concentrations of 1.0-200 µM were assessed, and Eadie-Hofstee plots were constructed. The kinetics for 7- and 4'-glucuronidation in the liver microsomes fit the Michaelis-Menten model, except for an atypical model for 7-glucuronidation in rats and a biphasic model for 4'-glucuronidation in monkeys. These kinetics in the intestinal microsomes followed the Michaelis-Menten model, except for a biphasic model for 7-glucuronidation in mice. The CL values for 7-glucuronidation were in the order of monkeys (49) ≫ rats (5.3) > humans (1.0) > mice (0.7) for liver microsomes, and rats (2.4) ≥ monkeys (2.2) > humans (1.0) ≥ mice (0.8) for intestinal microsomes. On the other hand, the CL values for 4'-glucuronidation were in the order of monkeys (4.0) > mice (1.0) ≈ humans (1.0) > rats (0.4) for liver microsomes, and humans (1.0) ≫ monkeys (0.08) ≥ mice (0.07) > rats (0.05) for intestinal microsomes. These results demonstrated that the metabolic abilities of UGT enzymes toward daidzein in the liver and intestines markedly differed among humans, monkeys, rats, and mice, and suggest that species and regioselective differences are closely associated with the bioactivities of soy isoflavones.
Topics: Adolescent; Adult; Aged; Animals; Glucuronosyltransferase; Humans; Intestinal Mucosa; Intestines; Isoflavones; Macaca fascicularis; Mice, Inbred Strains; Microsomes; Microsomes, Liver; Middle Aged; Rats, Sprague-Dawley
PubMed: 30014295
DOI: 10.1007/s00204-018-2265-1 -
Food & Function Mar 2024Daidzein, an isoflavone found abundantly in legumes, may benefit from bypassing upper gut absorption to reach the colon where it can be metabolized into the potent...
Daidzein, an isoflavone found abundantly in legumes, may benefit from bypassing upper gut absorption to reach the colon where it can be metabolized into the potent estrogen equol by the gut microbiome. To achieve this, we developed mucin coated protein-tannin multilayer microcarriers. Highly porous functionalized calcium carbonate (FCC) microparticles efficiently absorbed daidzein from a dimethyl sulfoxide solution, with a loading capacity of 21.6 ± 1.8 wt% as measured by ultra-high pressure liquid chromatography - mass spectrometry (UPLC-MS). Daidzein-containing FCC microparticles were then coated with a bovine serum albumin (BSA)-tannin -layer film terminated with mucin ((BSA-TA)-mucin) by layer-by-layer deposition from corresponding aqueous solutions followed by FCC decomposition with HCl. Raman spectroscopy confirmed mucin-tannin complexation involving both hydrophobic interactions and hydrogen bonding. The resulting multilayer microcarriers contained 54 wt% of nanocrystalline daidzein as confirmed by X-ray diffraction and UPLC-MS. Preliminary screening of several types of mucin coatings using an INFOGEST digestion model demonstrated that mucin type III from porcine stomach provided the highest protection against upper intestinal digestion. (BSA-TA)-mucin and (BSA-TA)-mucin microcarriers retained 71 ± 16.4% and 68 ± 4.6% of daidzein, respectively, at the end of the small intestinal phase. Mucin-free (BSA-TA) retained a lower daidzein amount of 46%. Daidzein release and further conversion into equol were observed during colonic studies with fecal microbiota from a healthy non-equol-producing donor and . The developed approach has potential for encapsulating other hydrophobic nutraceuticals or therapeutics, enhancing their bioaccessibility in the colon.
Topics: Equol; Chromatography, Liquid; Mucins; Tannins; Tandem Mass Spectrometry; Isoflavones; Polyphenols
PubMed: 38362621
DOI: 10.1039/d3fo03356b -
Chemical Biology & Drug Design Oct 2023In the present study, a series of derivatives and analogs of daidzein were designed and synthesized to investigate cholinesterase inhibition and blood-brain barrier...
In the present study, a series of derivatives and analogs of daidzein were designed and synthesized to investigate cholinesterase inhibition and blood-brain barrier permeability. The enzyme assay showed that most of the compounds containing a tertiary amine group exhibit moderate cholinesterase inhibition, 7-hydroxychromone derivatives (absence of B ring of daidzein scaffold) only have a weaker bioactivity, while those compounds without the tertiary amine group have no bioactivity. Among them compound 15a (4'-N,N-dimethylaminoethoxy-7-methoxyisoflavone) appeared the best inhibitory activity (IC : 2.14 ± 0.31 μmol/L) and higher selectivity for AChE over BuChE (Ratio: 7.07). It was selected for the further investigation by UPLC-MS/MS. The results show that C of compound 15a in mice was more than 2.87 within 240 min. This discovery may provide worthy information for the future development of central nervous drugs including but not limited to cholinesterase inhibitors.
Topics: Mice; Animals; Structure-Activity Relationship; Blood-Brain Barrier; Chromatography, Liquid; Molecular Docking Simulation; Tandem Mass Spectrometry; Cholinesterase Inhibitors; Brain; Acetylcholinesterase; Amines; Permeability; Molecular Structure; Drug Design
PubMed: 37291745
DOI: 10.1111/cbdd.14279 -
Scientific Reports Feb 2021Soybean meal-induced enteropathy (SBMIE) is prevalent in aquaculture. The aim of this study is to evaluate the role of daidzein on SBMIE of juvenile turbot (Scophthalmus...
Soybean meal-induced enteropathy (SBMIE) is prevalent in aquaculture. The aim of this study is to evaluate the role of daidzein on SBMIE of juvenile turbot (Scophthalmus maximus L.) by feeding with fish meal diet (FM), soybean meal diet (SBM, 40% fish meal protein in FM replaced by soybean meal protein) and daidzein diet (DAID, 40 mg/kg daidzein supplemented to SBM) for 12 weeks. We found that daidzein supplementation elevated the gene expression of anti-inflammatory cytokine TGF-β, decreased gene expression of pro-inflammatory cytokines TNF-α and signal molecules p38, JNK and NF-κB. SBM up-regulated the genes expression related to oxidative stress and apoptosis, but dietary daidzein restored it to the similar level with that in FM group. Moreover, dietary daidzein up-regulated gene expression of tight junction protein, and modified the intestinal microbial profiles with boosted relative abundance of phylum Proteobacteria and Deinococcus-Thermus, genera Sphingomonas and Thermus, species Lactococcus lactis, and decreased abundance of some potential pathogenic bacteria. In conclusion, dietary daidzein could ameliorate SBM-induced intestinal inflammatory response, oxidative stress, mucosal barrier injury and microbiota community disorder of turbot. Moreover, p38, JNK and NF-κB signaling might be involved in the anti-inflammatory process of daidzein, and daidzein itself might act as an antioxidant to resist SBM-induced oxidative damage.
Topics: Animal Feed; Animals; Fish Diseases; Fish Proteins; Flatfishes; Gene Expression Regulation; Isoflavones; Signal Transduction; Soybean Proteins
PubMed: 33558631
DOI: 10.1038/s41598-021-82866-1 -
Inflammopharmacology Aug 2023Paclitaxel (PTX) is an anti-microtubule agent, used for the treatment of various types of cancers; however, it produces painful neuropathy which limits its use. Many...
Paclitaxel (PTX) is an anti-microtubule agent, used for the treatment of various types of cancers; however, it produces painful neuropathy which limits its use. Many neuroprotective agents have been introduced to mitigate PTX-induced neuropathic pain (PINP), but they pose many adverse effects. The purpose of this study was to evaluate the pharmacological characteristics of soy isoflavone, and daidzein (DZ) in attenuating PINP. At the beginning of the investigation, the effect of DZ was confirmed through behavioral analysis, as it reduced pain hypersensitivity. Moreover, changes in the histological parameters were reversed by DZ administration along with vascular permeability. PTX administration upregulated transient receptor potential vanilloid 1 (TRPV1) channels and purinergic receptors (P2Y), contributing to hyperalgesia; but administration of DZ downregulated the TRPV1 and P2Y, thus reducing hyperalgesia. DZ increased nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), playing a pivotal role in the activation of the antioxidant pathway. DZ also decreased neuronal apoptosis by decreasing caspase-3 and Bcl2-associated X-protein (Bax), while simultaneously, increasing Bcl-2. PTX administration produced severe DNA damage, which was mitigated by DZ. Similarly, DZ administration resulted in inhibition of neuroinflammation by increasing antioxidant enzymes and reducing oxidative stress markers. PTX caused increased in production of pro-inflammatory mediators such as the cytokines production, while DZ inhibited the pro-inflammatory mediators. Additionally, in silico pharmacokinetic and toxicodynamic study of DZ was also conducted. In summary, DZ demonstrated significant neuroprotective activity against PTX induced neuropathic pain.
Topics: Humans; Paclitaxel; Hyperalgesia; NF-E2-Related Factor 2; Heme Oxygenase-1; Up-Regulation; Down-Regulation; Antioxidants; Neuralgia; Antineoplastic Agents; Isoflavones; Inflammation Mediators; Oxidative Stress; TRPV Cation Channels
PubMed: 37145202
DOI: 10.1007/s10787-023-01225-w -
Clinical Nutrition (Edinburgh, Scotland) Oct 2018To evaluate the relationship between phytoestrogen and colon cancer risk, we quantified plasma isoflavones (Genistein and Daidzein) and lignan (enterolactone) in a...
BACKGROUND & AIMS
To evaluate the relationship between phytoestrogen and colon cancer risk, we quantified plasma isoflavones (Genistein and Daidzein) and lignan (enterolactone) in a Korean nested case-control study and conducted replication study in a Vietnamese case-control study.
METHODS
Study populations of 101 cases and 391 controls were selected from the Korean Multicenter Cancer Cohort which was constructed from 1993 to 2004. For replication study, Vietnamese hospital-based case-control subjects of 222 cases and 206 controls were selected from 2003 to 2007. The concentrations of plasma genistein, daidzein, and enterolactone were quantified by liquid chromatography-mass spectrometry. Logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs), and meta-analysis was conducted to estimate combined ORs (CORs) and 95% Cis of Korean and Vietnamese population in 2014.
RESULTS
Genistein showed a continual decrease in colorectal cancer risk according to level up of the concentration categories in Korean and Vietnamese population (P for trend = 0.032, and 0.001, respectively) and a significantly decreased risk was found at the highest concentration of genistein and daidzein (for the highest category compared to the lowest: COR (95% CI) = 0.46 (0.30-0.69), and COR (95% CI) = 0.54 (0.36-0.82)). When the study population was stratified, the beneficial relationship of genistein with colorectal cancer was observed regardless of sex and anatomical subtype. However, enterolacton level was not associated with colorectal cancer risk.
CONCLUSIONS
High plasma levels of isoflavones had relationship with a decreased risk of colorectal cancer, regardless of different ethnic background.
Topics: 4-Butyrolactone; Adult; Aged; Asian People; Case-Control Studies; Colorectal Neoplasms; Female; Genistein; Humans; Isoflavones; Lignans; Male; Middle Aged; Phytoestrogens; Republic of Korea; Risk Factors; Vietnam
PubMed: 28778370
DOI: 10.1016/j.clnu.2017.07.014 -
Psychopharmacology Jul 2021Cocaine addiction is a chronic relapsing disorder that lacks of an effective treatment. Isoflavones are a family of compounds present in different plants and vegetables...
RATIONALE
Cocaine addiction is a chronic relapsing disorder that lacks of an effective treatment. Isoflavones are a family of compounds present in different plants and vegetables like soybeans that share a common chemical structure. Previous studies have described that synthetic derivatives from the natural isoflavone daidzin can modulate cocaine addiction, by a mechanism suggested to involve aldehyde-dehydrogenase (ALDH) activities.
OBJECTIVES
Based on these previous studies, we investigated the effects of three natural isoflavones, daidzin, daidzein, and genistein, on the modulation of the cocaine reinforcing effects and on cue-induced reinstatement in an operant mouse model of cocaine self-administration.
RESULTS
Chronic treatment with daidzein or genistein decreased operant responding to obtain cocaine intravenous infusions. On the other hand, daidzein and daidzin, but not genistein, were effective in decreasing cue-induced cocaine reinstatement. Complementary studies revealed that daidzein effects on cocaine reinforcement were mediated through a mechanism that involved dopamine type-2/3 receptors (DA-D2/3) activities.
CONCLUSIONS
Our results suggest that these natural compounds alone or in combination can be a potential therapeutic approach for cocaine addiction. Further clinical studies are required in order to ascertain their potential therapeutic use.
Topics: Animals; Cocaine; Cocaine-Related Disorders; Conditioning, Operant; Cues; Dopamine Uptake Inhibitors; Dose-Response Relationship, Drug; Extinction, Psychological; Isoflavones; Locomotion; Male; Mice; Phytoestrogens; Reinforcement, Psychology; Self Administration
PubMed: 33839903
DOI: 10.1007/s00213-021-05820-z -
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