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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 -
The Journal of Nutrition Jan 2012Intestinal conversion of the isoflavone daidzein to the bioactive equol is exclusively catalyzed by gut bacteria, but a direct role in equol formation under in vivo...
Intestinal conversion of the isoflavone daidzein to the bioactive equol is exclusively catalyzed by gut bacteria, but a direct role in equol formation under in vivo conditions has not yet been demonstrated. Slackia isoflavoniconvertens is one of the few equol-forming gut bacteria isolated from humans and, moreover, it also converts genistein to 5-hydroxy-equol. To demonstrate the isoflavone-converting ability of S. isoflavoniconvertens in vivo, the metabolization of dietary daidzein and genistein was investigated in male and female rats harboring a simplified human microbiota without (control) or with S. isoflavoniconvertens (SIA). Feces, urine, intestinal contents, and plasma of the rats were analyzed for daidzein, genistein, and their metabolites. Equol and 5-hydroxy-equol were found in intestinal contents, feces, and urine of SIA rats but not in the corresponding samples of the control rats. 5-Hydroxy-equol was present at much lower concentrations than equol and the main metabolite produced from genistein was the intermediate dihydrogenistein. The plasma of SIA rats contained equol but no 5-hydroxy-equol. Equol formation had no effect on plasma concentrations of the insulin-like growth factor I. The concentrations of daidzein and genistein were considerably lower in all samples of the SIA rats than in those of the control rats. Male SIA rats had higher intestinal and fecal concentrations of the isoflavones and their metabolites than female SIA rats. The observed activity in the rat model indicates that S. isoflavoniconvertens is capable of contributing in vivo to the bioactivation of daidzein and genistein by formation of equol and 5-hydroxy-equol.
Topics: Actinobacteria; Animals; Chromatography, High Pressure Liquid; Colony Count, Microbial; Equol; Female; Genistein; Germ-Free Life; Humans; Insulin-Like Growth Factor I; Intestinal Mucosa; Intestines; Isoflavones; Male; Rats; Real-Time Polymerase Chain Reaction
PubMed: 22113864
DOI: 10.3945/jn.111.148247 -
Frontiers in Endocrinology 2019This study is a analysis of steroid hormones before and after administration of pharmacological doses of soy isoflavones in a large cohort of men and women from two...
This study is a analysis of steroid hormones before and after administration of pharmacological doses of soy isoflavones in a large cohort of men and women from two independent studies. Isoflavones are reported to inhibit mineralo- and glucocorticoid hormone production as well as reproductive steroids and . We focused on cytochrome P450 17α-hydroxylase (CYP17A1) which catalyses the production of dehydroepiandrosterone (DHEA), in the androgen biosynthesis pathway to elucidate effects on sex steroids . Effects of soy isoflavones on steroid levels in two studies comprising 400 patients were examined: 200 men (study 1; 3 months duration) and 200 postmenopausal women (study 2; 6 months duration), randomized to consume 15 g soy protein with 66 mg isoflavones (SPI) or 15 g soy protein alone without isoflavones (SP) daily. Effects of genistein and daidzein on steroid metabolism were determined , in HEK293 cells expressing CYP17A1 and in the human adrenocortical carcinoma H295R cell model. SPI decreased serum dehydroepiandrosterone sulfate (DHEAS) levels in both men and women ( < 0.01), with decreased androstenedione (A4) ( < 0.01) in women not observed in men ( < 0.86). Cortisol, cortisone, 11-deoxycortisol, aldosterone, testosterone (T), or estradiol (E2) levels were unchanged. The dual hydroxylase and lyase activity of CYP17A1, which catalyses the biosynthesis of androgen precursors, and 3β-hydroxysteroid dehydrogenase (3βHSD2) were investigated . In transiently transfected HEK293 cells, only the lyase activity was inhibited by both genistein, 20% ( < 0.001) and daidzein, 58% ( < 0.0001). In forskolin-stimulated H295R cells DHEA production was decreased by daidzein ( < 0.05) and genistein, confirming inhibition of the lyase activity by the isoflavones. clinical data suggested inhibition of CYP17A1 17,20 lyase within the adrenal in men and within the ovary and adrenal in females. This was confirmed with inhibition of the lyase activity by both genistein and daidzein. In addition, 3βHSD2 was inhibited perhaps accounting for decreased A4 levels observed in females. The decreased DHEAS and A4 levels together with the inhibition of the 17,20 lyase activity of CYP17A1, may impact production of androgens in clinical conditions associated with androgen excess. ISRCTN number: ISRCTN55827330 ISRCTN number: ISRCTN 90604927.
PubMed: 31031706
DOI: 10.3389/fendo.2019.00229 -
Royal Society Open Science Jan 2021Novel daidzein napsylates (DD4 and DD5) were synthesized by microwave irradiation, according to structural modification of daidzein (DAI) using the principle of...
Novel daidzein napsylates (DD4 and DD5) were synthesized by microwave irradiation, according to structural modification of daidzein (DAI) using the principle of pharmacokinetic transformation. The pharmacological properties of DD4 and DD5 were evaluated via high performance liquid chromatography (HPLC) and calculated based on the drug design software ChemAxon 16.1.18. The cell uptake changes of DD4 and DD5 were investigated to analyse the structure-property relationship. The metabolisms of DD4 and DD5 were analysed by HPLC-mass spectrometry in human aortic vascular smooth muscle cells (HAVSMCs) and their possible metabolic pathways were inferred . The results showed that the solubility of DD4 and DD5 was increased by 2.79 × 10 and 2.16 × 10 times compared to that of DAI, separately, in ethyl acetate. The maximum absorption rates of DD4 and DD5 were enhanced by 4.3-4.5 times relative to DAI. Preliminary studies on metabolites of DD4 and DD5 in HAVSMCs showed that DD4 and DD5 were hydrolysed into DAI under the action of intracellular hydrolase in two ways, ester hydrolysis or ether hydrolysis. Then, DAI was combined with glucuronic acid to form daidzein monoglucuronate under the action of uridine diphosphate (UDP)-glucuronidase. Meanwhile, it was also found that metabolite M5 of DD5 could undergo glucuronidation under the action of UDP-glucuronosyltransferase and competitive sulphation under the action of sulphotransferase to produce its sulfate conjugate M7. Analysis of structure-property relationships indicated that the absorption and utilization of drugs is closely relative to the physical properties and could be improved by adjusting the liposolubility. The pharmaceutical properties were optimized comprehensively after DAI was modified by naphthalene sulphonate esterification. This indicates that this kind of derivatives may have relatively good absorption and transport characteristics and biological activities . The research on biological activities of the new derivatives (DD4 and DD5) is ongoing in our laboratory.
PubMed: 33614082
DOI: 10.1098/rsos.201475 -
Molecules (Basel, Switzerland) Apr 2020Soy isoflavones are popular ingredients with anti-adipogenic and anti-lipogenic properties. The anti-adipogenic and anti-lipogenic properties of genistein are...
Soy isoflavones are popular ingredients with anti-adipogenic and anti-lipogenic properties. The anti-adipogenic and anti-lipogenic properties of genistein are well-known, but those of genistin and glycitein remain unknown, and those of daidzein are characterized by contrasting data. Therefore, the purpose of our study was to investigate the effects of daidzein, glycitein, genistein, and genistin on adipogenesis and lipogenesis in 3T3-L1 cells. Proliferation of 3T3-L1 preadipocytes was unaffected by genistin and glycitein, but it was affected by 50 and 100 µM genistein and 100 µM daidzein for 48 h. Among the four isoflavones, only 50 and 100 µM genistin and genistein markedly suppressed lipid accumulation during adipogenesis in 3T3-L1 cells through a similar signaling pathway in a dose-dependent manner. Genistin and genistein suppress adipocyte-specific proteins and genes, such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα), and adipocyte binding protein 2 (aP2)/fatty acid-binding protein 4 (FABP4), and lipogenic enzymes such as ATP citrate lyase (ACL), acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FAS). Both isoflavones also activate AMP-activated protein kinase α (AMPKα), an essential factor in adipocyte differentiation, and inhibited sterol regulatory element-binding transcription factor 1c (SREBP-1c). These results indicate that genistin is a potent anti-adipogenic and anti-lipogenic agent.
Topics: 3T3-L1 Cells; AMP-Activated Protein Kinases; ATP Citrate (pro-S)-Lyase; Acetyl-CoA Carboxylase; Adipocytes; Adipogenesis; Animals; Anti-Obesity Agents; CCAAT-Enhancer-Binding Protein-alpha; Cell Survival; Fatty Acid Synthases; Fatty Acid-Binding Proteins; Gene Expression Regulation; Isoflavones; Lipogenesis; Mice; PPAR gamma; Glycine max; Sterol Regulatory Element Binding Protein 1
PubMed: 32349444
DOI: 10.3390/molecules25092042 -
Poultry Science Jun 2021This experiment examined the separate and combined effects of daidzein (Da) and Chinese herbs (CH) on laying performance and egg quality of post-peak laying hens....
Dietary supplementation with daidzein and Chinese herbs, independently and combined, improves laying performance, egg quality and plasma hormone levels of post-peak laying hens.
This experiment examined the separate and combined effects of daidzein (Da) and Chinese herbs (CH) on laying performance and egg quality of post-peak laying hens. Additionally, we explored potential mechanisms of action for these 2 additives by examining plasma hormone levels. After 4 wk of acclimation to caging, 60-week-old Hyline Brown hens (360) were selected and randomly divided into 4 groups with 6 replicates and 15 chickens per replicate. The following 4 dietary groups were utilized: 1) control group (basal diet); 2) Da group (basal diet + 0.03 kg/t DA); 3) CH group (basal diet +0.6 kg/t CH); 4) Da + CH group (basal diet + 0.03 kg/t Da + 0.6 kg/t CH). Data were analyzed in a completely randomized design with a 2×2 factorial arrangement of treatments. Egg production and FCR treatment averages were analyzed in the following 3 phases: wk 1-4, 5-8, and 1-8 of treatment administration. Results revealed that Da increased egg production but decreased FCR (P < 0.05) for wk 1-8 and especially during wk 5-8 (P < 0.05). CH decreased FCR in wk 1-4 and 5-8 (P < 0.05), but increased egg production only during wk 5-8 (P < 0.05). Da increased Haugh units (P < 0.05) on wk 4 and 8; CH increased Haugh units (P < 0.05) but decreased yolk ratio (P < 0.05) on wk 4 and 8. Da increased the plasma levels of T3, PROG, FSH, LH and E2 (P < 0.05); CH increased the plasma level of T3 (P < 0.05). Additionally, Da x CH interactions existed for albumen height, Haugh units, albumen ratio and the level of T3 on wk 8 (P < 0.05), indicating that the combination of Da and CH was more effective than administration of either of these dietary components independently. In conclusion, Da and CH, both independently and in combination, increase laying performance, egg quality and plasma hormones levels in post-peak laying hens. Therefore, these treatments may be able to provide prolonged economic benefits to aged laying hens.
Topics: Animal Feed; Animals; Chickens; China; Diet; Dietary Supplements; Female; Hormones; Isoflavones
PubMed: 33975040
DOI: 10.1016/j.psj.2021.101115 -
Postepy Dermatologii I Alergologii Dec 2019Genistein and daidzein are typical soy isoflavones with known estrogenic properties to provide protection against skin ageing in postmenopausal women and female rats....
INTRODUCTION
Genistein and daidzein are typical soy isoflavones with known estrogenic properties to provide protection against skin ageing in postmenopausal women and female rats. However their effect on male skin was very rarely studied.
AIM
This study was designed to evaluate the effect of a mixture of genistein and daidzein on male rats' skin.
MATERIAL AND METHODS
Male rats were administered this mixture in a dose of 2 or 20 mg/kg body weight (bw) per day for 5 days weekly mixed with regular rat chow, from prenatal life until sexual maturity. The female and male rats of the control group received regular rat chow. The skin epidermis thickness, number of fibroblasts in the dermis and diameter of collagen fibers in the dermis were measured using morphometric assay. The isoflavone effects on activities of antioxidant enzymes, lipid peroxides, and glutathione concentration in the skin were measured with commercially available kits.
RESULTS
The thickness of the skin epidermis and collagen fibers in the dermis and amount of elastic fibers were significantly greater in the isoflavone-treated groups. Isoflavones significantly decreased catalase activity in the skin homogenates and at a higher dose inhibited lipid peroxides formation.
CONCLUSIONS
Our results provide further support for the contribution of isoflavones to defence mechanisms against oxidative stress in the skin and suggest that genistein and daidzein supplementation may provide protection against skin ageing in males.
PubMed: 31998007
DOI: 10.5114/ada.2019.87280 -
Iranian Journal of Veterinary Research 2023Renin-angiotensin system (RAS) is prominently associated with renal pathophysiology in postmenopausal women. Long non-coding RNAs (lncRNAs) H19, GAS5, MIAT, and Rian...
BACKGROUND
Renin-angiotensin system (RAS) is prominently associated with renal pathophysiology in postmenopausal women. Long non-coding RNAs (lncRNAs) H19, GAS5, MIAT, and Rian have been linked to the pathogenesis of renal injury.
AIMS
This study aimed to evaluate the beneficial effects of daidzein on unilateral ureteral obstruction (UUO) induced-renal injury in ovariectomized (OVX) rats through interaction with angiotensin AT1, Mas receptors, and lncRNAs.
METHODS
84 female rats were ovariectomized (OVX) two weeks before performing obstruction of the left kidney ureter (UUO). The animals were then randomly divided into four main groups (n=21): Sham+DMSO, UUO+DMSO, UUO+17β-Estradiol (E2) (positive control), and UUO+daidzein. Each main group comprised three subgroups (n=7) and were treated with saline, A779 (MasR antagonist), or losartan (AT1R antagonist) for 15 days. On day 16, the animals were euthanized, and the left kidneys were harvested for histopathology and lncRNAs expression assays.
RESULTS
UUO significantly increased kidney tissue damage score (KTDS) in the UUO rats, increased the expression of H19 and MIAT, and decreased the expression of GAS5 and Rian. Daidzein alone and in co-treatment with losartan or A779 reversed these effects. Daidzein with 1 mg/kg dose was more effective than E2.
CONCLUSION
Daidzein alone and in co-treatment with A779 and losartan improved renal injury in UUO rats and recovered dysregulated expression of UUO-related lncRNAs through modulating MasR and AT1R receptors, associating with modulation of the expression of lncRNAs. Daidzein could be considered a renoprotective phytoestrogen substitute for E2 therapy in postmenopausal women suffering from renal diseases.
PubMed: 37378389
DOI: 10.22099/IJVR.2023.43460.6357 -
FEMS Microbiology Letters Jul 2021Equol is the isoflavone-derived metabolite with the greatest estrogenic and antioxidant activity. It is produced from daidzein by fastidious and oxygen-susceptible...
Equol is the isoflavone-derived metabolite with the greatest estrogenic and antioxidant activity. It is produced from daidzein by fastidious and oxygen-susceptible intestinal bacteria, which hinders their use at an industrial scale. Therefore, expressing the equol production machinery into easily-cultivable hosts would expedite the heterologous production of this compound. In this work, four genes (racemase, tdr, ddr and dzr) coding for key enzymes involved in equol production in Adlercreutzia equolifaciens DSM19450T were synthesized and cloned in a pUC-derived vector (pUC57-equol) that was introduced in Escherichia coli. Recombinant clones of E. coli produced equol in cultures supplemented with daidzein (equol precursor) and dihydrodaidzein (intermediate compound). To check whether equol genes were expressed in Gram-positive bacteria, the pUC57-equol construct was cloned into the low-copy-number vector pIL252, and the new construct (pIL252-pUC57-equol) introduced into model strains of Lacticaseibacillus casei and Lactococcus lactis. L. casei clones carrying pIL252-pUC57-equol produced a small amount of equol from dihydrodaidzein but not from daidzein, while L. lactis recombinant clones produced no equol from either of the substrates. This is the first time that A. equolifaciens equol genes have been cloned and expressed in heterologous hosts. E. coli clones harboring pUC57-equol could be used for biotechnological production of equol.
Topics: Actinobacteria; Bacterial Proteins; Cloning, Molecular; Equol; Escherichia coli; Gene Expression; Isoflavones
PubMed: 34173644
DOI: 10.1093/femsle/fnab082 -
Nutrition Research (New York, N.Y.) Aug 2019Soy isoflavones are potentially beneficial phytoestrogens, but their tissue-selective effects in women are poorly understood. We tested the hypothesis that soy... (Comparative Study)
Comparative Study Randomized Controlled Trial
Daidzein and genistein have differential effects in decreasing whole body bone mineral density but had no effect on hip and spine density in premenopausal women: A 2-year randomized, double-blind, placebo-controlled study.
Soy isoflavones are potentially beneficial phytoestrogens, but their tissue-selective effects in women are poorly understood. We tested the hypothesis that soy isoflavones affect bone mineral density (BMD), which may be influenced by individual differences in isoflavone metabolism and serum calcium levels. Ninety-nine healthy premenopausal women were randomized to isoflavones (136.6 mg aglycone equivalence) and 98 to placebo for 5 days per week for up to 2 years. BMD, serum calcium, and urinary excretion of daidzein and genistein were measured before and during treatment. In 129 adherent subjects, we found that isoflavone exposure, determined by urinary excretion levels, but not by dose assignment, interacted with serum calcium in affecting whole body BMD, but not hip and spine BMD. The regression coefficient was -0.042 for genistein excretion (GE) and 0.091 for the interaction between GE and serum calcium (all P < .05). Daidzein excretion had similar but marginal effect. Genistein significantly decreased whole body BMD only at low normal serum calcium levels but increased whole body BMD at higher serum calcium levels. Comparing maximum to minimum GE, mean changes in whole body BMD were +0.033 and -0.113 g/cm at serum calcium levels of 10 and 8.15 mg/dL, respectively. These associations were not evident by intention-to-treat analysis, which could not model for inter-individual differences in isoflavone metabolism. In summary, soy isoflavones decrease whole body BMD only when serum calcium is low. Isoflavones are dietary substances that may influence calcium homeostasis by releasing calcium from bone while sparing the common fracture risk sites hip and spine.
Topics: Absorptiometry, Photon; Adult; Bone Density; Calcium; Double-Blind Method; Female; Genistein; Humans; Isoflavones; Lumbar Vertebrae; Pelvic Bones; Phytoestrogens; Placebos; Premenopause
PubMed: 31421395
DOI: 10.1016/j.nutres.2019.06.007