Soy Isoflavones Research Articles

S-equol, a metabolite of dietary soy isoflavones, alleviates lipopolysaccharide-induced depressive-like behavior in mice by inhibiting neuroinflammation and enhancing synaptic plasticity.

Systemic injection with lipopolysaccharide can lead to depressive-like behavior in experimental animals by inducing neuroinflammation and is considered to be a classic model of depression. S-equol is a major metabolite of dietary soy isoflavones with antioxidant and anti-inflammatory effects, and it has many beneficial effects on human health, including alleviation of menopausal symptoms, osteoporosis, cancer, obesity, chronic kidney disease, and cognitive dysfunction. A recent study reported that S-equol inhibited lipopolysaccharide-stimulated neuroinflammation in astrocytes. However, there is no research on the antidepressant-like effects of S-equol. Therefore, the present study was conducted to evaluate the antidepressant-like effects of S-equol in a lipopolysaccharide-induced depression model in mice and explore its underlying mechanisms. Our results demonstrated that treatment with S-equol (10, 20 and 40 mg kg-1) for 19 days markedly reversed the behavior of acute LPS (1.0 mg kg-1) treated mice in sucrose preference, tail suspension and forced swimming tests, exerting antidepressant-like effects. In addition, S-equol administration significantly decreased the levels of pro-inflammatory cytokines (tumor necrosis factor, interleukin-6, interleukin-10, interleukin-1β), increased the levels of 5-hydroxytryptamine and norepinephrine, and normalized the release of tryptophan and kynurenine in the hippocampi of lipopolysaccharide-treated mice. Moreover, treatment with S-equol significantly up-regulated the expression of synaptic plasticity-related proteins (phospho synapsin, synapsin, postsynaptic density-95) and down-regulated the toll-like receptor 4/nuclear factor kappa B signaling pathway in the hippocampi of lipopolysaccharide-treated mice. These findings demonstrated that S-equol significantly alleviated the depressive-like behavior induced by acute systemic injection of LPS, and its antidepressant action was related to mediation of neuroinflammation via the TLR4/NF-κB signaling pathway, normalization of the monoamine neurotransmitter levels, reversal of tryptophan metabolism dysfunction, and enhancement of synaptic plasticity. The current study provides insight into the potential of S-equol in the prevention of depression.

Health Promotion Effects of Soy Isoflavones.

Soybeans contain several physiologically active ingredients, such as soy phytosterol, soyasaponin, soy protein, and lecithin, and are therefore expected to express the functionalities of said ingredients. Among them, soy isoflavones have been studied in recent years for their various functions, including their obesity-preventing effect, blood glucose level reducing effect, osteoporosis and breast cancer risk reduction, and anti-oxidative effect, and several health promoting effects and disease preventing effects are expected. For example, it has been determined that soy isoflavones reduce body and fat weight in experiments in which mice were fed a diet containing soy isoflavones in studies on anti-obesity. Epidemiologic studies with humans have also shown that women who consume more soybeans have lower BMI than those who consume less. We previously found that soy isoflavones may have anti-obesity effects in myoblasts through the activation of transcriptional coactivator PGC-1β, which increases energy expenditure. In recent studies, a decrease in blood glucose level due to soy isoflavone was seen in an experiment in which diabetic model mice were fed a diet containing soy isoflavone. It has also been suggested that soy isoflavone intake may increase bone mineral density in postmenopausal women and reduce the risk of breast cancer. This review focuses on the actions of soy isoflavones known to date, including their anti-obesity and anti-diabetic effects, bone loss preventing effects, and cancer risk reduction effects, and introduces reports on the health promotion and disease prevention effects of soy isoflavones.

Administration of Cholic Acid Inhibits Equol Production from Daidzein in Mice.

Equol (Eq) is a metabolite of soy isoflavone daidzein (De) produced by the intestinal microbiota. The clinical effectiveness of soy isoflavone is considered to depend on the individual ability of Eq production. Previous studies have demonstrated that habitual dietary patterns may influence the production of Eq. For example, high Eq producers consumed less fat as a percentage of energy than low Eq producers. However, the inhibitory factors of Eq production are unknown. Recently, it was reported that bile acids induced by high-fat diet consumption may be a host-related factor controlling the composition of the intestinal microbiota. In this study, we investigated the effect of cholic acid (CA) administration, a mimic of the microbiota altered by a high-fat diet, on Eq production in mice. CA administration significantly decreased the levels of the De metabolites Eq, dihydrodaidzein, and O-desmethylangolensin in the serum of mice. However, CA administration did not affect the total molar concentration of De and its metabolites. Moreover, CA administration increased the levels of secondary bile acids, particularly deoxycholic acid (DCA), which has strong antibacterial activity in the cecum contents of mice. Thus, CA administration may increase the levels of DCA, a secondary bile acid, resulting in inhibition of Eq production. These findings may help to reveal the factors inhibiting Eq production and enhance the clinical effectiveness of isoflavone intake.

Effect of Soy Isoflavones on the Performance of Cerebral Neurotransmitter Systems in Adult and Aged Male Rats

Effect of Soy Isoflavones on the Performance of Cerebral Neurotransmitter Systems in Adult and Aged Male Rats

Release of Soybean Isoflavones by Using a β-Glucosidase from Alicyclobacillus herbarius.

β‐Glucosidases are used in the food industry to hydrolyse glycosidic bonds in complex sugars, with enzymes sourced from extremophiles better able to tolerate the process conditions. In this work, a novel β‐glycosidase from the acidophilic organism Alicyclobacillus herbarius was cloned and heterologously expressed in Escherichia coli BL21(DE3). AheGH1 was stable over a broad range of pH values (5–11) and temperatures (4–55 °C). The enzyme exhibited excellent tolerance to fructose and good tolerance to glucose, retaining 65 % activity in the presence of 10 % (w/v) glucose. It also tolerated organic solvents, some of which appeared to have a stimulating effect, in particular ethanol with a 1.7‐fold increase in activity at 10 % (v/v). The enzyme was then applied for the cleavage of isoflavone from isoflavone glucosides in an ethanolic extract of soy flour, to produce soy isoflavones, which constitute a valuable food supplement, full conversion was achieved within 15 min at 30 °C.

Equol-producing status affects exercise training-induced improvement in arterial compliance in postmenopausal women.

Central arterial compliance decreases drastically after menopause. Regular intake of soy isoflavone and aerobic exercise increase arterial compliance. The equol is a metabolite of isoflavone daidzein by gut microbiome. We determined whether the equol-producing status affects aerobic exercise-induced improvement in carotid arterial compliance. Forty-three postmenopausal women were assigned to two intervention groups: 1) exercise and isoflavone (Ex+Iso, n = 27 females) or 2) isoflavone interventions (Iso; n = 16 females). Participants of the Ex+Iso intervention group completed an 8-wk aerobic exercise training, and all participants were administered with oral isoflavone supplements during the interventions. The equol-producing status (equol producers or nonproducers) was determined from urine equol concentrations after a soy challenge. In the Ex+Iso intervention group, carotid arterial compliance increased in the equol producers (0.084 ± 0.030→0.117 ± 0.035 mm2/mmHg), but not in the nonproducers (0.089 ± 0.028→0.097 ± 0.026 mm2/mmHg) after the intervention (interaction effect; P < 0.05). The magnitude of increases in carotid arterial compliance was significantly greater in the equol producers than in the non-equol producers (P < 0.05). In the isoflavone intervention group, there were no changes in any parameters after the intervention irrespective of the equol status. These results suggest that equol-producing status is obligatory to aerobic exercise training-induced improvements in central arterial compliance in postmenopausal women.NEW & NOTEWORTHY Isoflavone intake and aerobic exercise increase central artery compliance. Equol, a metabolite of isoflavone daidzein by gut microbiome, has beneficial effects on vascular function. We demonstrated for the first time that the interaction of aerobic exercise and equol production status plays an essential role in improvements in central artery compliance in postmenopausal women. More specifically, the equol-producing status was obligatory to exercise training-induced improvements in central arterial compliance in postmenopausal women.

Assessment of the skin efficacy and acceptability of a cosmetic product in the treatment of the forearm hypertrichosis in female patients.

Treatment of unwanted body hair is a challenging area in cosmetic dermatology. Topical soy isoflavones and derivatives or eflornithine have been utilized in dermatocosmetology for their estrogenic and antiandrogenic activity. To evaluate the efficacy of a formulation containing capryloyl glycine 4% in decreasing hair growth on the forearms after topical application for 120days vs placebo. A total of 69 female patients entered the study (age 37±6). Hair growth was quantified using TrichoScan software on both forearms at 20-fold magnification (analyzed area 0.651 cm2). Hair density (number of hairs/cm2 ), density vellus hair, density terminal hair, and median length of hairs were evaluated. The data were analyzed using ANOVA for repeated measures to evaluate changes during the treatment (T0, T60, and T120) and Student's t test (placebo vs active). There was a significant decrease on hair density, median, and terminal hair at the end of the treatment in the active-treated site (P<.001) as measured by TrichoScan software. Direct comparison between active and placebo-treated sites showed no significant differences at T0, but highly significant differences at T120 (P<.001). The study shows that a cosmetic formulation based on capryloyl glycine 4% is highly effective in reducing several parameters related to hair growth and hair thickness vs placebo, thus showing efficacy in the treatment of hypertrichosis.

From Proteomics to Personalized Medicine: The Importance of Isoflavone Dose and Estrogen Receptor Status in Breast Cancer Cells.

Continuing efforts are directed towards finding alternative breast cancer chemotherapeutics, with improved safety and efficacy profiles. Soy isoflavones represent promising agents but, despite extensive research, limited information exists regarding their impact on the breast cancer cell proteome. The purpose of this study was to compare the proteomic profiles of MCF-7 (estrogen responsive) and MDA-MB-231 (estrogen non-responsive) breast cancer cells exposed to different concentrations of genistein, daidzein, and a soy seed extract, using a high throughput LC–UDMSE protein profiling approach. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay confirmed the dual activity of soy isoflavones on MCF-7 cells and the inhibitory effect on MDA-MB-231 cells. Proteome profiling of paramagnetic beads prepared peptides by nano-LC UDMSE and pathway enrichment analysis revealed that isoflavones affected distinct molecular pathways in MCF-7 and MDA-MB-231 cells, such as tyrosine kinases signaling pathway, cytoskeleton organization, lipid and phospholipid catabolism, extracellular matrix degradation and mRNA splicing. Also, in MCF-7 cells, low and high isoflavone doses induced different changes of the proteome, including cell cycle alterations. Therefore, the expression of estrogen receptors and the isoflavone dose are determinant factors for the molecular impact of isoflavones and must be taken into account when considering adjuvant breast cancer therapy towards personalized medicine.

Scientific Evidence Supporting the Beneficial Effects of Isoflavones on Human Health.

Isoflavones are phenolic compounds with a chemical structure similar to that of estradiol. They are present in several vegetables, mainly in legumes such as soy, white and red clover, alfalfa and beans. The most significant food source of isoflavones in humans is soy-derived products. Isoflavones could be used as an alternative therapy for pathologies dependent on hormonal disorders such as breast and prostate cancer, cardiovascular diseases, as well as to minimize menopausal symptoms. According to the results gathered in the present review, it can be stated that there is scientific evidence showing the beneficial effect of isoflavones on bone health and thus in the prevention and treatment of osteoporosis on postmenopausal women, although the results do not seem entirely conclusive as there are discrepancies among the studies, probably related to their experimental designs. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. Regarding cancer, scientific evidence suggests that isoflavones could be useful in reducing the risk of suffering some types of cancer, such as breast and endometrial cancer, but further studies are needed to confirm these results. Finally, isoflavones could be useful in reducing hot flushes associated with menopause. However, a limitation in this field is that there is still a great heterogeneity among studies. Lastly, with regard to isoflavone consumption safety, it seems that they are safe and that the most common adverse effect is mild and occurs at the gastrointestinal level.

Efficacy and Safety of Nutraceutical on Menopausal Symptoms in Post-Menopausal Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Background Menopausal symptoms severely reduce the quality of life of post-menopausal women worldwide. Nutraceuticals are widely prescribed as a viable and safer alternative and complementary approach to standard therapies. The aim of this study was to evaluate the clinical efficacy and safety of a nutraceutical in post-menopausal women. Methods The study was designed as a randomized, double-blinded, placebo-controlled clinical trial. Post-menopausal women aged 45–60 years old were enrolled and randomly assigned to either treatment (n = 50) or placebo group (n = 51). The intervention, a proprietary combination of soy isoflavone, black cohosh, chasteberry and evening primrose oil extracts, and the placebo, were administered to each group for total of 12 weeks. Menopausal symptoms, endocrine profiles, and blood chemistry were evaluated at baseline, 6 weeks, and 12 weeks of the study. Results Nutraceutical supplementation demonstrated a statistically significant reduction in hot flushes and sweating (p < 0.0001), sleep problems (p < 0.0005), depressed mood (p = 0.0004) and irritability symptoms (p < 0.0003) compared with the placebo group. There were no significant differences in hormonal levels between the test and placebo groups, however levels of C-reactive protein were significantly decreased. Moreover, serum LDL-C and triglyceride levels were significantly lower than baseline levels in the treatment group at 6- and 12-week timepoints. No adverse effects were reported during the treatment. Conclusion These data indicate that a nutraceutical containing a combination of four medicinal herbs effectively and safely improved menopausal symptoms, as well as general health indicators, in post-menopausal women.

Soy Intake and Possible Adverse Health Effects in Nordic Children and Pregnant Women (Unborn Children)

Aim: To explore possible adverse health effects of high soy intake among children and pregnant women (unborn children) in the Nordic countries. Methods: A dietary exposure scenario with a high soy ...

Soy Food Intake Is Inversely Associated with Newly Diagnosed Nonalcoholic Fatty Liver Disease in the TCLSIH Cohort Study

Animal studies have shown that soy protein and isoflavones can increase antioxidant capacity and improve insulin resistance, and thus ameliorate nonalcoholic fatty liver disease (NAFLD). However, only limited epidemiological studies have examined the association of soy food intake with NAFLD. We investigated the association between soy food intake and NAFLD in a Chinese cohort. A total of 24,622 participants aged 20-90 y were included in the study. Diet information was collected using a validated 100-item FFQ. NAFLD was defined as having fatty liver diagnosed by ultrasonography and excluding men and women who consumed>210g alcohol/wk and>140g/wk, respectively. Logistic regression analysis was used to assess the association of soy food intake with NAFLD. After adjustment for potential confounders, and taking those with<1time/wk soy food intake as the reference group, the ORs for NAFLD across soy food intake frequency were 0.94 (95% CI: 0.83, 1.07) for 1 time/wk, 0.88 (95% CI: 0.78, 0.99) for 2-3 times/wk, and 0.75 (95% CI: 0.65, 0.87) for≥4 times/wk (P-trend<0.0001). The results were similar when participants were categorized by the energy-adjusted soy food intake (grams per 1000kilocalories) quartiles (OR=0.80; 95% CI: 0.71, 0.91; comparing extreme quartiles). Higher soy food intake was associated with a lower prevalence of NAFLD in Chinese adults. Further prospective studies and randomized clinical trials are necessary to confirm if soy food intake is inversely related to the risk of NAFLD.

52 Alterations of fecal microbiome characteristics by dietary soy isoflavone ingestion in growing pigs infected with porcine reproductive and respiratory syndrome virus

Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically-important disease and ingestion of soy isoflavones (ISF) may benefit PRRSV-infected pigs due to demonstrated anti-inflammatory and anti-viral properties. The objective of this study was to quantify long-term effects of ISF consumption on fecal microbiome characteristics under disease challenge. In total, 96 weaned barrows were group-housed in a BSL-2 containment facility and allotted to 1 of 3 experimental treatments that were maintained throughout the wean-to-finish study: non-infected pigs receiving an ISF-devoid control diet (NC, n=24), and infected pigs receiving either the control diet (PC, n=36) or that supplemented with total ISF in excess of 1,600 mg/kg (ISF, n=36) (Table 1). Following a 7-day adaptation, pigs were inoculated intranasally with either a sham-control (PBS) or live PRRSV (1×105 TCID50/mL, strain NADC20). Fecal samples were collected from 48 individual pigs at pre-infection (-2 days post-inoculation, DPI), peak-infection (10 DPI), and post-infection (144 DPI) time-points and extracted DNA was used for 16S bacterial rRNA sequencing. Differences in bacterial communities among diet groups were evaluated using UniFrac distance matrices (weighted and unweighted) in QIIME. All other data were analyzed by one-way ANOVA performed on transformed data using R. Across all time-points, only minimal differences were observed due to ISF alone. At 10 DPI, PRRSV infection reduced Prevotella 9 genera abundance from approximately 20% to less than 10%, but the specific function of this variety in pigs is unclear. The most notable finding was decreased relative abundance of Actinobacteria at 144 DPI between non-infected and infected treatments (P &amp;lt; 0.05), which is consistent with various dysbioses observed in other disease models. Our findings indicate that differences present were mainly due to PRRSV infection and not strongly influenced by ISF ingestion, which implies previously observed performance benefits conferred by dietary ISF are not likely due to changes in microbiome composition.

Genistein Ameliorates Renal Fibrosis Through Regulation Snail via m6A RNA Demethylase ALKBH5.

Renal tubule-interstitial fibrosis is related to chronic kidney disease progression and a typical feature of the aging kidney. Epigenetic modifications of fibrosis-prone genes regulate the development of renal fibrosis. As a kind of “epigenetic diet”, soy isoflavone genistein was reported to have renal protective action and epigenetic-modulating effects. However, its renal protection role and underlying mechanisms are yet to be fully clarified. Herein, we showed that genistein exhibits a demonstrable anti-fibrotic effect on kidney in vivo UUO (unilateral ureteral occlusion) model and renal epithelial cells in vitro model. The mechanism is strongly associated with epithelial-to-mesenchymal transition and m6A RNA demethylase ALKBH5. Mouse fibrotic kidneys induced by UUO exhibited adverse expression of renal fibrosis-related proteins and significant increases in the total m6A level. As an eraser, ALKBH5 showed severer suppression in the renal fibrosis process. However, genistein pretreatment restored ALKBH5 loss remarkably and reduced renal fibrosis, abnormal protein, and inflammatory markers. The examination of possible mechanisms revealed that genistein promoted ALKBH5 and maybe induced the level of mRNA m6A methylation in some epithelial-to-mesenchymal transition-related transcription factors. We found snail was the critical regulator and critical for the protective role of genistein. To verify the relationship between ALKBH5 and snail, we generated knockdown and overexpression of ALKBH5 cells in vitro. ALKBH5 knockdown enhanced the mesenchymal phenotype marker α-smooth muscle actin and snail expression. In agreement, overexpression ALKBH5 increased epithelial adhesion molecule E-cadherin and reduced snail expression. In conclusion, genistein increased renal ALKBH5 expression in UUO-induced renal fibrosis and reduced RNA m6A levels and ameliorates renal damages.

Soy isoflavones ameliorate the cognitive dysfunction of Goto-Kakizaki rats by activating the Nrf2-HO-1 signalling pathway.

Soy isoflavones (SIF) are soybean phytochemicals that are considered to be biologically active components that protect from neurodegenerative diseases. In this study, the therapeutic effect of SIF was evaluated in a diabetic Goto-Kakizaki (GK) rat model. Twenty male GK rats were randomly divided into diabetes mellitus (DM) model group and SIF+DM group (n=10 in each group). Twenty age-matched male Wistar rats were randomly divided into control group (CON group) and CON+SIF group, with 10 rats in each group. The learning and memory functions of the animals were determined by the Morris water maze (MWM) test. Hematoxylin-eosin staining (HE) was performed to examine pyramidal neuron loss in the CA1 area of the hippocampus. Markers of oxidative stress (OS) were measured to evaluate oxidative stress-mediated injury. RT-PCR and western blotting were used to analyze the expression of nuclear factorerythroid2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone1 (NQO1). Treatment with SIF for 4 weeks alleviated the cognitive dysfunction of the GK rats as determined by the MWM test. Moreover, SIF treatment also reduced diabetes-related oxidative reactions. In addition, SIF enhanced the expression of Nrf2, HO-1 and NQO1, suggesting a potential antioxidation mechanism for the effect of SIF. These findings suggest that SIF can be considered candidates for inhibiting the progression of diabetes-induced cognitive dysfunction, provide novel insights into the antioxidant effect of SIF and further strengthen the link between oxidative stress and diabetes.

Bioconversion and bioaccessibility of isoflavones from sogurt during in vitro digestion

This study investigated the bioconversion and bioaccessibility of soy isoflavones produced in sogurt fermented with S. thermophilus and L. bulgaricus during in vitro digestion. The highest survivability of S. thermophilus (6.49 log cfu/mL) and L. bulgaricus (6.48 log cfu/mL) was in oral phase. In gastric phase, the total aglycones of sogurt (26.73 g/L) increased up to 20 times than control (1.21 g/L), with a significant increase in daidzein (17.05 g/L) and genistein (9.68 g/L). Addition of 8U of β-glucosidase into soymilk significantly increased the conversion of isoflavone in ENTII (daidzein: 0.46 g/L; genistein: 0.18 g/L) than in ENTI (daidzein: 0.33 g/L; genistein: 0.20 g/L). The particle size analysis and confocal micrographs of digesta also suggest the size of fat and protein in gastric phase to be smaller than in intestinal phase. The results indicate the prospective to develop soy-based fermented products capable of releasing high isoflavone in the digestive system.

Recent advances on the synthesis of flavans, isoflavans, and neoflavans

AbstractHeterocyclic compounds are the omnipresent structural cores comprising many natural and pharmaceutical products of biological significance. Significantly, heterocyclic compounds are widely distributed in nature, and also have applications in agrochemicals, sanitizers, as dyestuff, as copolymers, etc. Among heterocyles, flavonoids are a class of compounds that are highly interesting and constitute many natural products. In general, all flavanoids contains a basic core of C6‐C3‐C6 of phenyl‐benzopyran backbone. The relative placement of the phenyl group on to the benzopyran core makes further classification into flavanoids, isoflavanoids and neoflavanoids. Flavans (2‐aryl chroman) are subclass of anthoxanthanes exhibits a broad spectrum of biological properties such as anti‐inflammatory, anti‐oxidant, and anti‐malarial properties. Some representative naturally occurring products possessing flavan core are apigenin, luteolin, tangeretin, scutellarein, etc. On the other hand, some of the notable isoflavan‐based natural products are glabridin and (S)‐(−)‐equol. Glabridin is isolated from Licorice roots, which regulates paraoxonase (PON2) levels. While the simple isoflavan (S)‐(−)‐equol, is produced from soy isoflavone intake. Also, natural products such as dalbergichromene, centchroman, and (+)‐myristinin A possess neoflavan (4‐aryl‐3,4‐dihydro‐2H‐chromenes) core structure. Owing to their broad biological and pharmacological properties, synthetic chemists are fascinated in developing new routes toward their synthesis. As a result, a decent number of reports have been established in the literature. Thus, for the past 5 years of time frame, many new methodologies have been witnessed, for the synthesis of various flavan systems. This review emphasizes most of the significant methods on accomplishing flavans, isoflavans and neoflavans and also focused on their applications to the synthesis of relevant natural as well as biologically active products.

Effects of resveratrol combined with soy isoflavones on apoptosis induced by oxidative stress in hippocampus of aging model rats

To investigate the effect of resveratrol(Res) combined with soy isoflavones(SIF) on apoptosisinduced by oxidative stress in hippocampus in aging model rats. Sixty female SD rats were randomly divided into the Sham control group, aging model group, Res treatment group, SIF treatment group, Res combined with SIF treatment group and estrogen replacement therapy group(ERT group). Rats with aging were induced by bilateral ovariectomy combined with intraperitoneal injection of D-galactose. TUNEL and transmission electron microscopy were used to observe apoptosis and ultrastructural changes of mitochondrion in hippocampus, respectively. The activities of superoxide dismutase(SOD), catalase(CAT), glutathione peroxidase(GSH-Px) and content of Malonaldehyde(MDA) were detected in the hippocampal homogenate. The protein expressions of cytochrome C oxidase(COX) Ⅰ, Bcl-2 associated X protein(Bax)、B-cell leukemia/lymphoma 2(Bcl-2) and cytochrome C were detected by Western blot. Compared with the Sham control group, the number of TUNEL-positive cells and the apoptotic index(AI) in the model group increased. Marked increase of mitochondrial swelling and vacuolation, decrease of mitochondrial integrity were also observed in the model group. Additionally, the levels of SOD, CAT and GSH-Px were decreased and the level of MDA was increased in the model group in the hippocampus, Bax and cytochrome C protein expression increased, and the COX Ⅰ protein expression and the ratio of Bcl-2/Bax decreased(P&lt;0. 05). In compared with the model group, the number of TUNEL-positive cells and AI significantly decreased, mitochondrial integrity improved in all of the treatment groups, the COX Ⅰ protein expression significantly up-regulated, Bax and cytochrome C protein expression down-regulated, and the protein expression ratio of Bcl-2/Bax increased(P&lt;0. 05 or P&lt;0. 01). Compared with the Res alone and SIF alone treatment group, Res combined SIF treatment decreased the AI and Bax, cytochrome C protein expression, moreover, increased the mitochondrial integrity rate, COX Ⅰ and Bcl-2/Bax protein expression ratio(P&lt;0. 05). There was no statistically significant difference in Bcl-2 protein expression among all the groups(P&gt;0. 05). Res and SIF alone and in combination decreased apoptosisinduced by oxidative stress in hippocampus of aging model rats, and beneficial effect in the Res combined SIF treatment group is more significant than that in the alone administration. Improving the antioxidant capacity, increasing the protein expressions of COX Ⅰ andthe ratio of Bcl-2 and Bax, and inhibiting the release of cytochrome C may be the mechanisms by which Res and SIF improve apoptosis in aging rats.

Non-hormonal Treatments For Menopausal Symptoms and Sleep Disturbances: A Comparison Between Purified Pollen Extracts and Soy Isoflavones.

Besides hot-flushes, sleep disturbances increase around menopause, impacting on the quality of life. When hormone replacement therapy is contraindicated, it is necessary to provide alternative treatments. This study aimed to observe the effects of an herbal remedy from pollen extracts and soy isoflavones for menopausal complaints, particularly on sleep disorders. A six-month prospective observational study was performed in women in natural menopause suffering from menopausal symptoms and sleep disturbances. Three groups were compared: 57 women receiving two tablets/ day containing herbal remedy from pollen extracts (group A), 60 women receiving one tablet/day containing isoflavones 60 mg (group B), 47 women not receiving any treatment (group C). At 3 (T3) and 6 months (T6), the daily number of hot-flushes, Kupperman index for menopausal symptoms, the Pittsburgh Sleep Quality Index (PSQI) test were assessed. Both groups A and B showed a significant improvement of hot flushes (p<0.001) and Kuppermann Index (p<0.001) from T0 to T3 and from T0 to T6. No significant differences between treatment groups were found at T3, while at T6 group A showed greater decrease of daily hot flashes and better improvement of Kupperman Index as compared to group B (respectively, -48.8% versus -18.4% and -24.4% versus -15.4%; p<0.001). Improvement of global sleep quality was more evident in the pollen treated group compared to isoflavones group at both three (-24.7% versus -9.3%, p<0.001) and six (-52.9% vs -4.0%; p<0.001) months, mainly for the scores related to subjective sleep quality, sleep latency and habitual sleep efficiency. Non-hormonal treatments can effectively be used in symptomatic menopausal women: among these, after six months of treatment, pollen extracts might achieve a better improvement of hot flushes, sleep disturbances and menopause-related symptoms than soy isoflavones. Herbal remedy from pollen extracts is mainly effective when the quality of sleep is the most disturbing complaint.

Genistein attenuates amyloid-beta-induced cognitive impairment in rats by modulation of hippocampal synaptotoxicity and hyperphosphorylation of Tau

Alzheimer's disease is a progressive neurodegenerative disorder characterized by extracellular accumulation of amyloid-beta (Aβ) peptide, which induces synaptic dysfunction, alteration of intracellular signaling pathways, hyperphosphorylation of the Tau protein, and cognitive impairment. Genistein, one of the major isoflavones present in soy and soy products, has been shown to modulate some of the pathogenic events associated with the neurodegeneration process. However, its underlying mechanisms remain to be clarified. Therefore, the objectives of the present study were to evaluate the ability of genistein to protect against Aβ1–42-induced cognitive impairment in rats and to elucidate some of the possible mechanisms involved in its neuroprotective effects in the hippocampus. Male Wistar rats received bilateral intracerebroventricular infusions of Aβ1–42 (2 nmol) and genistein 10 mg/kg orally for 10 days. The Aβ-infused animals showed significant impairment of memory, which was accompanied by the following neurochemical alterations in the hippocampus: decreased levels of the synaptic proteins synaptophysin and postsynaptic density protein 95 (PSD-95), hyperphosphorylation of Tau with increased activation of glycogen synthase kinase-3β and c-Jun N-terminal kinase, and inactivation of ERK. Treatment with genistein improved Aβ-induced cognitive impairment by attenuation of synaptotoxicity, hyperphosphorylation of Tau, and inactivation of ERK. Furthermore, treatment with this soy isoflavone did not cause systemic toxicity. These findings provide further evidence of the neuroprotective effect of genistein in an in vivo model of Aβ toxicity and, importantly, extend the current knowledge concerning the mechanisms associated with the neuroprotective effects of this compound in the hippocampus.