Administration Of Genistein Research Articles

Effect of Genistein Supplementation on Exercise-Induced Inflammation and Oxidative Stress in Mice Liver and Skeletal Muscle.

Background and objectives: The purpose of this study was to investigate the influences of oral high-dose genistein (GE) administration on exercise-induced oxidative stress, inflammatory response and tissue damage. Materials and Methods: Thirty-two mice were randomly divided into control group (Con; sedentary/0.5% CMC-Na), GE administrated group (GE; sedentary/GE dosed), exercise group (Ex; exercise/0.5% CMC-Na), or GE administrated plus exercise group (GE + Ex; exercise/GE dosed), mice in the GE and GE + Ex group were given GE orally at the dose of 200 mg/kg weight. Results: Plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels, liver interleukin (IL)-6, IL-1β, superoxide dismutase 1 (SOD1), catalase (CAT), hemeoxygenase-1 (HO-1) gene expression levels and skeletal muscle IL-6, nuclear factor erythroid 2-related factor (Nrf2), and HO-1 gene expression levels increased immediately after exhaustive exercise. GE supplementation increased liver protein carbonyl concentrations. On the other hand, GE supplementation significantly decreased SOD1, CAT gene expression levels in the liver and Nrf2, and HO-1 gene expression levels in the skeletal muscles. Conclusions: Acute exercise induced organ damage, inflammation, and oxidative stress in skeletal muscles and the liver. However, a single dose of GE supplementation before exercise did not lead to favorable antioxidant and anti-inflammatory effects in this study.

The effect of genistein on insulin resistance, inflammatory factors, lipid profile, and histopathologic indices in rats with polycystic ovary syndrome.

ObjectivePolycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, irregular menstruation, ovulatory dysfunction, and insulin resistance. Recent studies have reported the possible role of phytoestrogens in PCOS. This animal study aimed to evaluate the effects of genistein on insulin resistance, inflammatory factors, lipid profile, and histopathologic indices on PCOS.MethodsPCOS was induced by 1 mg/kg of letrozole in adult Sprague-Dawley rats. The rats then received normal saline (PCOS group), 150 mg/kg of metformin, or 20 mg/kg of genistein dissolved in 1% methylcellulose solution for 42 days. Body weight, the glycemic and lipid profile, and inflammatory, antioxidative, and histopathological parameters were assessed at the end of the intervention.ResultsTreatment with genistein significantly alleviated the increased level of fasting blood insulin (p=0.16) and the homeostatic model assessment of insulin resistance (p=0.012). In addition, the genistein group had significantly lower levels of serum malondialdehyde (p=0.039) and tumor necrosis factor-alpha (p=0.003), and higher superoxide dismutase enzyme activity (p<0.001). Furthermore, the histopathological analysis indicated that genistein administration led to an increase in luteinization and the development of fewer cysts (p<0.05).ConclusionBiochemical and histopathological analyses indicated that genistein administration to rats with PCOS induced significant remission in oxidative, inflammatory, and glycemic and histopathologic parameters.

Early Postnatal Genistein Administration Affects Mice Metabolism and Reproduction in a Sexually Dimorphic Way.

The phytoestrogen genistein (GEN) may interfere with permanent morphological changes in the brain circuits sensitive to estrogen. Due to the frequent use of soy milk in the neonatal diet, we aimed to study the effects of early GEN exposure on some physiological and reproductive parameters. Mice of both sexes from PND1 to PND8 were treated with GEN (50 mg/kg body weight, comparable to the exposure level in babies fed with soy-based formulas). When adult, we observed, in GEN-treated females, an advanced pubertal onset and an altered estrous cycle, and, in males, a decrease of testicle weight and fecal testosterone concentration. Furthermore, we observed an increase in body weight and altered plasma concentrations of metabolic hormones (leptin, ghrelin, triiodothyronine) limited to adult females. Exposure to GEN significantly altered kisspeptin and POMC immunoreactivity only in females and orexin immunoreactivity in both sexes. In conclusion, early postnatal exposure of mice to GEN determines long-term sex-specific organizational effects. It impairs the reproductive system and has an obesogenic effect only in females, which is probably due to the alterations of neuroendocrine circuits controlling metabolism; thus GEN, should be classified as a metabolism disrupting chemical.

Genistein Inhibits Colonic Goblet Cell Loss and Colorectal Inflammation Induced by Salmonella Typhimurium Infection.

Salmonella is the main food-borne pathogen, which can infect intestinal epithelial cells and causes colitis. Genistein has a variety of biological activities that alleviates colitis induced by sodium dextran sulfate in a variety of ways, but its protective effects on colitis caused by pathogenic bacteria are still unknown. This study explores the protective effect of genistein in reducing colitis caused by Salmonella infection. Salmonella causes colon inflammation through activating cyclooxygenase-2/prostaglandin E2, and genistein inhibits colitis caused by Salmonella typhimurium infection. Salmonella infection increases colonic mucosal damage, proliferating cells, and goblet cell loss, while the administration of genistein solves these pathological changes. In addition, it is further proved that Salmonella causes severe colitis related to goblet cell loss and activates the host crypt stem cells to repair the damaged epithelium. Salmonella infection inhibites the host mammalian target of rapamycin, activates light chain 3 II pathways to induce autophagy to eliminate pathogenic bacteria. Genistein increases Lactobacillus in feces and reduces Salmonella colonization to inhibit colitis induces by Salmonella infection. This study demonstrates genistein alleviated colitis and inhibites the goblet cell loss causes by Salmonella infection through regulating the gut bacteria and intestinal stem cell development.

Alterations in the Intestinal Morphology, Gut Microbiota, and Trace Mineral Status Following Intraamniotic Administration (Gallus gallus) of Genistein

Abstract Objectives Assess the effects of intraamniotic genistein administration on brush border membrane (BBM) functionality, intestinal morphology, cecal microbiome and Fe status in-vivo (Gallus gallus). Methods Broiler chickens (Gallus gallus, n = 39) were injected in ovo (day 17 of embryonic incubation) with varying concentrations of 1 mL pure genistein in 18 Ω H2O. Two treatment groups (1.25, 2.5%), two controls (water and non-injected), and a positive control (5% inulin) were administered. Upon hatch, blood was taken for hemoglobin determination and chicks were then euthanized. Nutritional status was assessed using pectoral muscle glycogen storage and body weight analysis. Duodenal and cecal tissues were excised for BBM morphometric analysis, mRNA gene expression of relevant BBM Fe transporter proteins, and 16S rRNA gene sequencing was done to evaluate gut microbiota modulation in the intestinal cecum. Results Preliminary results reveal significant increase in body weight, decrease of cecum weight, and increase in villus surface area with the higher dose of genistein administration (P &amp;lt; 0.05) compared to controls. Blood hemoglobin was found to be increased in the genistein-treated groups when compared to the controls (P &amp;lt; 0.05). Additionally, genistein administration downregulated the expression of duodenal cytochrome B (DcytB) and divalent metal transporter 1 (DMT1) and upregulated the expression of ferroportin with a dose responsive effect, indicating improved Fe physiological status. Further, administration of genistein altered the composition and function of cecal microbiota. Conclusions Genistein is a compound present in multiple staple food crops, including soybeans and chickpeas, and may be extracted and potentially used to enhance dietary Fe bioavailability and improve Fe deficiency in vulnerable populations. Recent evidence suggests a physiological role for genistein administration in improving the functionality and development of the BBM, improving Fe status, affecting the intestinal microbiome, as well as improving physiological status. Funding Sources N/A.

Involvement of SIRT1 in amelioration of schistosomiasis-induced hepatic fibrosis by genistein

Previous study revealed that genistein alleviate the extent of hepatic fibrosis in schistosomiasis-infected mice, however, the potential mechanism is still incomplete. Present study was, therefore, carried out to investigate the underlying mechanism of ameliorating schistosomiasis-induced hepatic fibrosis by genistein. α-smooth muscle actin (α-SMA) expression, as a critical fibrotic marker, was markedly upregulated in Schistosoma japonicum (S. japonicum) egg-induced liver fibrosis, and gradually inhibited by genistein administration in infected mice. Contrary to the changes of α-SMA expression, hepatic SIRT1 expression and activity was greatly inhibited in mice upon S. japonicum infection, and the repression was reversed in liver tissues after receiving 25 mg/kg genistein. 50 mg/kg genistein treatment gave rise to the higher SIRT1 expression and activity than that of the control group. In hepatic stellate cells (HSCs), genistein (5, 10, 20 μM) treatment resulted in the increases of SIRT1 expression and activity in concentration-dependent manner. Moreover, to mimic the fibrogenesis in vivo, macrophage was treated with soluble egg antigen (SEA) to obtain macrophage-conditioned medium (MφCM), which was used to stimulate HSCs. Intriguingly, SIRT1 overexpression decreased fibrosis associated gene expression in HSCs exposed to MφCM or not. Additionally, MφCM gave rise to high levels of α-SMA and p-Smad3 and the increments were reversed upon genistein treatment in HSCs. Furthermore, EX527, SIRT1 specific inhibitor, abrogated the inhibitory effects of genistein on HSCs activation. Together, the results support the notion that the strong elevation of SIRT1 expression and activity may represent a potential mechanism of protection against schistosomiasis-induced hepatic fibrosis by genistein.

Genistein during Development Alters Differentially the Expression of POMC in Male and Female Rats.

Phytoestrogens are considered beneficial for health, but some studies have shown that they may cause adverse effects. This study investigated the effects of genistein administration during the second week of life on energy metabolism and on the circuits regulating food intake. Two different genistein doses, 10 or 50 µg/g, were administered to male and female rats from postnatal day (P) 6 to P13. Physiological parameters, such as body weight and caloric intake, were then analyzed at P90. Moreover, proopiomelanocortin (POMC) expression in the arcuate nucleus (Arc) and orexin expression in the dorsomedial hypothalamus (DMH), perifornical area (PF) and lateral hypothalamus (LH) were studied. Our results showed a delay in the emergence of sex differences in the body weight in the groups with higher genistein doses. Furthermore, a significant decrease in the number of POMC-immunoreactive (POMC-ir) cells in the Arc in the two groups of females treated with genistein was observed. In contrast, no alteration in orexin expression was detected in any of the structures analyzed in either males or females. In conclusion, genistein can modulate estradiol’s programming actions on the hypothalamic feeding circuits differentially in male and female rats during development.

Local administration of genistein as a local anesthetic agent inhibits the trigeminal nociceptive neuronal activity in rats

A modulatory role has been reported for the isoflavone, genistein, on voltage-gated Na+ channels in the trigeminal ganglion in vitro. However, the acute effects of genistein in vivo, particularly on nociceptive transmission in the trigeminal system, remain to be determined. The aim of the present study was to examine whether acute local genistein administration to rats attenuates the excitability of wide-dynamic range (WDR) spinal trigeminal nucleus caudalis (SpVc) neurons in response to nociceptive and non-nociceptive mechanical stimulation in vivo.Extracellular single unit recordings were made from SpVc WDR neurons in response to orofacial non-noxious and noxious mechanical stimulation of pentobarbital-anesthetized rats. The effects of local administration of genistein, lidocaine, and lidocaine with genistein to the receptive field on the discharge frequency of SpVc neurons were evaluated. The mean firing frequency of SpVc WDR neurons in response to both non-noxious and noxious mechanical stimuli was significantly and dose-dependently (0.1−10 mM) inhibited by genistein, and maximum inhibition of the discharge frequency of both non-noxious and noxious mechanical stimuli was seen within 10 min. The inhibitory effect of genistein lasted for 20 min and was reversible. No significant difference was seen between the relative magnitude of inhibition by genistein on the SpVc WDR neuronal discharge frequency for noxious and non-noxious stimulation. The mean magnitude of inhibition by genistein (10 mM) on SpVc neuronal discharge frequency was almost equal to that of the local anesthetic, 1 % lidocaine (37 mM). Local injection of half-dose of lidocaine replaced the half-dose of genistein. These results suggest that local injection of genistein into the peripheral receptive field suppresses the excitability of SpVc neurons, possibly via inhibition of voltage-gated Na+ channels in the nociceptive nerve terminals of trigeminal ganglion. Therefore, administration of genistein as a local anesthetic may provide relief from trigeminal nociceptive pain without side effects, thus contributing to the area of complementary and alternative medicines.

Protective effect of swimming and genistein on the expression of microRNA 132, insulin growth factor 1, and brain-derived neurotrophic factor genes, as well as spatial memory, in the hippocampus of diabetic ovariectomized rats

Background and Objective: The present study aimed to assess the effects of the combined use of exercise and genistein on the hippocampal expression of microRNA-132, IGF-1, and BDNF in type 2 diabetic ovariectomized rats. Materials and Methods: Wistar female rats in the weight range of 180-220 gr (n=10) were assigned to six groups: sham, ovariectomy, ovariectomized diabetic, ovariectomized diabetic treated with genistein for eight weeks, diabetic ovariectomized treated with swimming for eight weeks, and a group that was treated with both genistein and swimming for eight weeks. The effect of those treatments was assessed by the determination of microRNA-132, insulin growth factor 1 (IGF-1), and brain-derived neurotrophic factor (BDNF) expression levels within the hippocampus. These genes were evaluated by real-time-polymerase chain reaction (RT-PCR) and spatial memory was assessed by the Morris water maze. Results: Ovariectomy demonstrated a decrease in the expression of microRNA-132, IGF-1, and BDNF in the hippocampus, as well as spatial memory, in diabetic ovariectomized rats, which showed a greater reduction in the expression of those genes in rats (P&lt;0.05). Nevertheless, genistein administration, swimming training, and a combination of them significantly up-regulated microRNA-132, BDNF, and IGF-1 expression, as well as spatial memory (P&lt;0.05). Conclusions: As evidenced by the obtained results, the combined use of genistein and swimming could prevent estrogen deficiency effects in the hippocampus of ovariectomized diabetic rats

Genistein Blunted Detrimental Effects of Polycystic Ovary Syndrome on the Ovarian Tissue of Rats by Improving Follicular Development and Gonadotropin Secretion.

ObjectivePolycystic ovary syndrome (PCOS) is a common cause of female infertility worldwide. It has been shown that genistein, a natural isoflavone, may influence follicular competence via the production of gonadotropins in women with PCOS. The current study aims to evaluate the effects of genistein on the ovarian tissue of rats with PCOS.MethodsThirty female Wistar rats were randomly divided into the following four groups: Control; PCOS (rats received 2 mg/kbW estradiol valerate); Genistein (rats given 1 mg/kg BW of genistein for 14 days); and Genistein + PCOS. All animals were slaughtered under anesthesia and blood samples were collected for biochemical analysis. Follicular morphology was analyzed based on histologic examination.ResultsHistologic examination exhibited enhanced follicular atresia at various stages in the rats with PCOS compared to controls (p<0.001). Induction of PCOS caused significant reduction in gonadotropin levels and steroid hormone levels consistent with insulin resistance (p<0.01). Data showed that 14-day administration of genistein might improve follicular morphology in rats with PCOS (p<0.001). Genistein treatment increased the production of gonadotropins and steroid hormones and alleviated insulin resistance in Rats with PCOS (p<0.001).ConclusionsThis study indicated that genistein treatment exerted a beneficial effect on the ovarian tissue of rats with PCOS by improving follicular growth and hormone balance.

Genistein Modulated Lipid Metabolism, Hepatic PPARγ, and Adiponectin Expression in Bilateral Ovariectomized Rats with Nonalcoholic Steatohepatitis (NASH).

The aim of this study was to evaluate the protective effects of genistein on lipid accumulation and apoptosis in estrogen deficient rats with NASH. Female Sprague–Dawley rats (n = 48) were divided into ovariectomized (OVX) and non-OVX groups. Each group was then sub-divided into 3 subgroups; control, NASH (rats fed with a high-fat, high-fructose (HFHF) diet), and NASH+Gen (rats fed with HFHF diet plus daily genistein at 16 mg/kg BW). Results showed that HFHF diet induced liver fat accumulation in both non-OVX and OVX rats, which was evidenced by hepatic steatosis on liver pathology and increased hepatic free fatty acid (FFA) and triglyceride levels. Hepatic fat accumulation was significantly more severe in NASH rats with OVX than non-OVX. Hepatocyte apoptosis was more severe in NASH groups compared with that in control groups. Genistein administration significantly improved histopathology of NASH in both non-OVX and OVX rats and attenuated hepatic lipid accumulation, oxidative stress, and hepatocyte apoptosis. Genistein also down-regulated PPARγ and up-regulated adiponectin expression. In summary, NASH could be worsened by estrogen deficiency, indicating the protective action of estrogen on NASH. Genistein administration alleviated hepatic steatosis and apoptosis through the down-regulation of PPARγ and up-regulation of adiponectin expression.

Effect of genistein on the gene and protein expressions of CXCL-12 and EGR-1 in the rat ovary.

The effect of genistein (GEN) on the gene expression level of stromal cell-derived factor-1/CXCL-12 and early growth response gene-1 was studied in ovarian tissue of young and initially ageing (early stages in the ageing process) female rats. Forty, young female Sprague Dawley (SD) rats of 2-3months old (200±20g) and forty, initially ageing female SD rats of 10-12months (490±20g) old were selected. According to the weight, rats were divided into control group, low-dose group (L), medium-dose group (M) and a high-dose group (H) and were given 15, 30 and 60mg/kg GEN respectively. The positive control (Oestrogen) group was given 0.5mg/kg diethylstilbestrol. The treatment lasted for 30days. The mRNA expression of C-X-C motif chemokine ligand 12 (CXCL-12) and early growth response factor-1 (EGR-1) was measured by real-time PCR, and protein expression of EGR-1 was detected by Western blot. When compared to the negative control group (NC), the ovary/body weight ratio in the young rats decreased in the GEN group, but the difference was not significant. Similarly, compared with NC, the ovary/body weight ratio in the initially ageing rats also decreased with the increase in GEN concentration, but the decrease was significant in M and H groups (p<.01). The administration of GEN enhanced both the gene and protein expression levels of CXCL-12 and EGR-1 in the ovary. Pearson's correlation analysis showed a synergistic effect between CXCL-12 and EGR-1. Thus, we conclude that the effect of GEN on CXCL-12 and EGR-1 in the initially ageing group was obvious than that in the younger group.

Genistein Improves Bone Healing via Triggering Estrogen Receptor Alpha-Mediated Expressions of Osteogenesis-Associated Genes and Consequent Maturation of Osteoblasts.

Osteoporosis-associated fractures may cause higher morbidity and mortality. Our previous study showed the effects of genistein, a phytoestrogen, on the induction of estrogen receptor alpha (ERα) gene expression and stimulation of osteoblast mineralization. In this study, rat calvarial osteoblasts and an animal bone defect model were used to investigate the effects of genistein on bone healing. Treatment with genistein caused a time-dependent increase in alkaline phosphatase (ALP) activity in rat osteoblasts. Levels of cytosolic and nuclear ERα significantly augmented following exposure to genistein. Subsequently, genistein elevated levels of ALP mRNA and protein in rat osteoblasts. Moreover, genistein induced other osteogenesis-associated osteocalcin and Runx2 mRNA and protein expressions. Knocking-down ERα using RNA interference concurrently inhibited genistein-induced Runx2, osteocalcin, and ALP mRNA expression. Attractively, administration of ICR mice suffering bone defects with genistein caused significant increases in the callus width, chondrocyte proliferation, and ALP synthesis. Results of microcomputed tomography revealed that administration of genistein increased trabecular bone numbers and improved the bone thickness and volume. This study showed that genistein can improve bone healing via triggering ERα-mediated osteogenesis-associated gene expressions and subsequent osteoblast maturation.

Genistein Induces Adipogenic and Autophagic Effects in Rainbow Trout (Oncorhynchus mykiss) Adipose Tissue: In Vitro and In Vivo Models.

Soybeans are one of the most used alternative dietary ingredients in aquafeeds. However, they contain phytoestrogens like genistein (GE), which can have an impact on fish metabolism and health. This study aimed to investigate the in vitro and in vivo effects of GE on lipid metabolism, apoptosis, and autophagy in rainbow trout (Oncorhynchus mykiss). Primary cultured preadipocytes were incubated with GE at different concentrations, 10 or 100 μM, and 1 μM 17β-estradiol (E2). Furthermore, juveniles received an intraperitoneal injection of GE at 5 or 50 µg/g body weight, or E2 at 5 µg/g. In vitro, GE 100 μM increased lipid accumulation and reduced cell viability, apparently involving an autophagic process, indicated by the higher LC3-II protein levels, and higher lc3b and cathepsin d transcript levels achieved after GE 10 μM. In vivo, GE 50 µg/g upregulated the gene expression of fatty acid synthase (fas) and glyceraldehyde-3-phosphate dehydrogenase in adipose tissue, suggesting enhanced lipogenesis, whereas it increased hormone-sensitive lipase in liver, indicating a lipolytic response. Besides, autophagy-related genes increased in the tissues analyzed mainly after GE 50 µg/g treatment. Overall, these findings suggest that an elevated GE administration could lead to impaired adipocyte viability and lipid metabolism dysregulation in rainbow trout.

Protective effect of genistein in a rat model of ischemic acute kidney injury.

This study determined the possible anti-inflammatory and antioxidant renal protective effect of genistein, a soy isoflavone, against kidney damage and functional disorders following renal ischemia/reperfusion (I/R) in male rats. The animals were dedicated to five groups (n=7 per group): Sham, Sham+Geni (genistein, 15mg/kg in 1ml 1% DMSO, i.p.), Sham+DMSO (1ml 1% DMSO, i.p.), I/R (bilateral renal ischemia for 45min followed by 24h reperfusion), I/R+Geni (genistein, 15mg/kg). 24-h urine samples, blood and tissue samples of the kidney were collected at the end of 24h reperfusion period. Compared to sham, sham+Geni and sham+DMSO groups, IR injury (IRI) ended in kidney dysfunction (decreased creatinine clearance, and increased fractional excretion of sodium), increased levels of malondialdehyde, decreased activities of antioxidant enzymes (superoxide dismutase, gluthatione peroxidase, and catalase), increased gene expression levels of TLR4 (Toll-like receptor 4) and TNF-α (tumor necrosis factor-alpha), as well as histological damages in kidney tissue. Genistein administration decreased all the changes. Therefore, genistein apparently protects the kidney against IRI by mitigating both oxidative stress and inflammation. The antioxidant and anti-inflammatory properties of genistein probably exert important roles in improving functional disorders and offer renal protection against IRI.

Inhibition of esophageal-carcinoma cell proliferation by genistein via suppression of JAK1/2-STAT3 and AKT/MDM2/p53 signaling pathways.

Esophageal carcinoma (EsC) is a clinically challenging neoplastic disease. Genistein, a natural isoflavone product, has anti-tumor properties. Through in vitro and in vivo studies, we found that genistein suppressed EsC cell proliferation in a time- and concentration-dependent manner. In addition, genistein markedly promoted apoptosis and arrested cell cycle at the G0/G1 phase in a concentration-dependent manner. Furthermore, high concentrations of genistein have no adverse effect on normal esophageal epithelial cells. Mechanistically, genistein treatment strikingly reduced the expression of cell cycle-associated genes, and up-regulated the expression of cell apoptosis-related genes in EsC cells. Additionally, genistein dramatically decreased epidermal growth factor receptor (EGFR) expression and attenuated its down-stream signaling molecules STAT3, MDM2, Akt and JAK1/2 phosphorylation, resulting in inhibited nuclear translocation of STAT3 and MDM2, thereby inhibiting the JAK1/2-STAT3 and AKT/MDM2/p53 signaling pathways. In xenograft nude mice, genistein administration strikingly impaired tumor growth in a dose-dependent manner. Moreover, similar disturbances in molecular mechanisms were observed in vivo. Taken together, genistein suppressed the JAK1/2-STAT3 and AKT/MDM2/p53 signaling pathways by decreasing EGFR expression, leading to cell apoptosis, cell cycle arrest, and proliferation inhibition in EsC cells. Our findings suggest that genistein may be a promising alternative adjuvant therapy for patients with EsC.

Genistein Prevents Single Prolonged Stress-Induced Cognitive Impairment in a Post-Traumatic Stress Disorder Rat Model via Activation of the Serotonergic System.

Post-traumatic stress disorder (PTSD) is a stress-associated mental disorder characterized by an imbalance of neurotransmitters in response to traumatic events or fear. Genistein (GEN), a natural isoflavone, has been shown to exhibit neuroprotective effects. Here, we used the Morris water maze (MWM) and object recognition task (ORT) tests to examine the effects of GEN on cognitive impairment in rats after exposure to single prolonged stress (SPS), and its interaction with the serotonergic system. After exposure to SPS, male rats received GEN (2, 4, and 10 mg/kg, i.p.) for 14 days. Daily GEN administration significantly improved cognitive function in the ORT and MWM tests. GEN treatment also inhibited SPS-induced decreases in serotonin (5-HT) levels in the medial prefrontal cortex and hippocampus. These increased 5-HT concentrations in response to GEN treatment could be partially attributed to the ratio of 5-hydroxyindoleacetic acid/5-HT in the hippocampus. Our findings suggest that GEN significantly attenuates SPS-induced memory deficits in rats and may represent an effective therapeutic option for the treatment of PTSD.

Protective Effect of Genistein on the Morphine-Induced Kidney Disorders in Male Mice

Background: Morphine is a member of the naturally occurring phenanthrene alkaloids of opium. Genistein is a phytoestrogen, present in soy products. This study was designed to evaluate protective effects of genistein against morphine induced damages to the kidneys of mice. Methods: In this study, 48 male mice were randomly assigned to 8 groups: control (saline), morphine treated group (10 mg/kg/day); genistein groups (1, 2, 4 mg/kg/day) and morphine plus genistein treated group. Drugs were administrated intraperitoneally for 30 consequent days. Weight of animals and kidneys, glomeruli characteristics, kidney function markers and blood serum nitric oxide level has been studied. Result: The results indicated that morphine administration significantly increased Lactate dehydrogenase (LDH), Blood urea nitrogen (BUN), creatinine and nitric oxide levels compared to the control ( saline) group (P<0.05). Genistein in all doses and genistein plus morphine at the dose of 4 mg/kg significantly decreased LDH, BUN, creatinine, glomerular diameter and nitric oxide levels compared to the control and morphine groups (p<0.05). Conclusion: It seems that genistein administration improved kidney damages induced by morphine in mice.

Protective effects of Genistein on the cognitive deficits induced by chronic sleep deprivation

Sleep deprivation has been widely reported to cause cognitive dysfunction, and elevation in oxidative stress and inflammation in the body, including the brain, have been suggested as the main factors. Genistein (GE) is an isoflavone widely present in leguminous plants, and it was found to exert a wide spectrum of biological activities, including antioxidant, anti-inflammatory, hepatoprotective, neuroprotective, and antimetastatic effects. In this study, the protective effect of GE on chronic sleep deprivation (CSD)-induced cognitive dysfunction was investigated. The mice were subjected to the sleep interruption apparatus and continuously sleep deprived for 25 days. GE was orally administrated (10, 20, and 40 mg/kg) during the sleep deprivation process totally for 25 days. Cognitive behavioral tests were conducted to study the learning and memory using the object location recognition (OLR) task, novel object recognition (NOR) test, and the Morris water maze (MWM) task. Additionally, the cortex and hippocampus were dissected to measure the oxidative stress markers and the antioxidant element nuclear erythroid-2-related factor 2 (Nrf2) and its downstream targets, including glutamate cysteine ligase catalytic, glutamate cysteine ligase modifier, heme oxygenase 1, and quinone oxidoreductase 1, as well as nuclear factor kappa B (NF-κB) p65, nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2) protein expression. Moreover, the pro-inflammatory cytokines (TNF-α, interleukin [IL]-6, and IL-1β) level was examined in the serum. The current results showed that GE could dose-dependently ameliorate the cognitive deficits of CSD-treated mice in the OLR, NOR, and MWM tasks. In addition, GE treatment significantly elevated the activities of total antioxidant capacity and superoxide dismutase and the level of glutathione and lowered the content of malondialdehyde in the cortex and hippocampus of CSD-treated mice. Furthermore, GE administration effectively activated the antioxidant element Nrf2 and its downstream targets in the cortex and hippocampus of CSD-treated mice. Moreover, GE treatment significantly suppressed CSD-induced NF-κB p65, iNOS, and COX-2 activation in the cortex and hippocampus, as well as inhibited CSD-induced pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) release in the serum. Taken together, all these results suggested that GE has substantial potential as a therapeutic intervention for the alleviation of CSD-induced deleterious effects.

Genistein improves the vaginal epithelium thickness in a rat model of vaginal atrophy through modulation of hormone and heat shock protein 70 levels

Objective: To investigate whether administration of genistein can improve hormonal changes (estradiol and follicle stimulating hormone (FSH)] , heat shock protein 70 (Hsp70) expression, and thickness of vaginal epithelial cells in a rat model of vaginal atrophy. Methods: Twenty-five multiparous female rats were divided into five groups, namely the control group (without ovariectomy), the ovariectomy only group, and the ovariectomy groups 1, 2 and 3 receiving genistein at the doses of 0.045, 0.090 and 0.180 mg/kg body weight/day, respectively. Estradiol, FSH, and Hsp70 expression were analyzed by using the immunoassay technique. Analysis of the thickness of the vaginal epithelium was performed by histology. Results: Ovariectomy significantly decreased estradiol levels compared to the control group (P 0.05). Ovariectomy significantly increased parabasal cell Hsp70 expression compared to the control group (P 0.05). Conclusions: Genistein is able to increase the thickness of the vaginal epithelium through hormone modulation and cellular stress suppression. Genistein is beneficial in the form of a herbal or alternative food for improvement of vaginal atrophy due to menopause.