Isoflavone Group Research Articles

Molecular insights into genistein-NSAID hybrids—synthesis, characterisation and DFT study

AbstractGenistein (GEN) is one of the pharmaceutically valuable phenolic compounds, which belongs to the isoflavone group of flavonoids and is a natural phytohormone found mainly in soybeans and red clover. It affects estrogen receptors, functioning as a selective estrogen receptor modulator (SERM) with anti-inflammatory and antioxidant activity. The presence of reactive phenolic groups in genistein provides an opportunity to expand its structure by introducing components responsible for anti-inflammatory properties. Such an innovative combination of a compound with anticancer and antioxidant potential with an anti-inflammatory compound (NSAID) may lead to interesting new derivatives with dual mechanisms of biological action. The synthesis and characterisation of genistein-NSAID hybrid compounds (ibuprofen, ketoprofen, naproxen, flurbiprofen) was conducted, together with a comprehensive structural and quantum chemistry DFT (density functional theory) computational analysis allowing the description of 1H-NMR and 13C-NMR spectroscopic properties of the starting compounds and the resulting hybrids. The study resulted in the formation of seven hybrid GEN-NSAID derivatives. In the case of ibuprofen, ketoprofen and flurbiprofen, a mixture of isomeric hybrid GEN-4’-NSAID and GEN-7-NSAID derivatives was obtained, whereas, for naproxen, only GEN-4’-NSAID was formed. The structural characteristics of the resulting compounds were determined using MS, IR, 1H-NMR and 13C-NMR spectroscopic methods. The most accurate DFT computational methods for predicting 1H-NMR and 13C-NMR spectra were also established with statistical parameters to assess their accuracy.

Effect of Isoflavone on Muscle Atrophy in Ovariectomized Mice.

Sarcopenia, characterized by muscle mass decline due to aging or other causes, is exacerbated by decreased estrogen levels after menopause in women. Isoflavones, a class of flavonoids acting on estrogen receptors, may have beneficial effects on metabolic disorders. We examined these effects in ovariectomized mice fed a high-fat, high-sucrose diet (HFHSD). At 7 weeks old, female C57BL6/J mice (18-20 g, n = 12) underwent bilateral ovariectomy (OVX), and were then fed a high-fat, high-sucrose diet starting at 8 weeks of age. Half of the mice received isoflavone water (0.1%). Metabolic analyses, including glucose and insulin tolerance tests, were conducted. Muscle analysis involved grip strength assays, next-generation sequencing, quantitative RT-PCR, and western blotting of skeletal muscle after euthanizing the mice at 14 weeks old. Additionally, 16S rRNA gene sequence analysis of the gut microbiota was performed. The results demonstrated that isoflavone administration did not affect body weight, glucose tolerance, or lipid metabolism. In contrast, isoflavone-treated mice had higher grip strength. Gene expression analysis of the soleus muscle revealed decreased Trim63 expression, and western blotting showed inactivation of muscle-specific RING finger protein 1 in isoflavone-treated mice. Gut microbiota analysis indicated higher Bacteroidetes and lower Firmicutes abundance in the isoflavone group, along with increased microbiota diversity. Gene sets related to TNF-α signaling via NF-κB and unfolded protein response were negatively associated with isoflavones. Isoflavone intake alters gut microbiota and increases muscle strength, suggesting a potential role in improving sarcopenia in menopausal women.

The effect of soy isoflavones supplementation on metabolic status in patients with non-alcoholic fatty liver disease: a randomized placebo controlled clinical trial

BackgroundNon-alcoholic fatty liver disease (NAFLD) accounts as a crucial health concern with a huge burden on health and economic systems. The aim of this study is to evaluate the effect of soy isoflavones supplementation on metabolic status in patients with NAFLD.MethodsIn this randomized clinical trial, 50 patients with NAFLD were randomly allocated to either soy isoflavone or placebo groups for 12 weeks. The soy isoflavone group took 100 mg/d soy isoflavone and the placebo group took the similar tablets containing starch. Anthropometric indices, blood lipids, glycemic parameters and blood pressure were measured at the beginning and at the end of the study.ResultsAt the end of week 12 the level of serum triglyceride (TG), low density lipoprotein (LDL) and total cholesterol (TC) was significantly decreased only in soy isoflavone group compared to baseline (P < 0.05). Although waist circumference (WC) decreased significantly in both groups after 12 weeks of intervention (P < 0.05), hip circumference (HC) decreased significantly only in soy isoflavone group (P = 0.001). No significant changes observed regarding high density lipoprotein (HDL) and blood pressure in both groups. At the end of the study, serum glucose level was significantly decreased in the placebo group compared to baseline (P = 0.047). No significant changes demonstrated in the soy isoflavone group in regard to glycemic parameters (P > 0.05).ConclusionsThis study revealed that soy isoflavones could significantly reduce TG, LDL TC, WC and HC in NAFLD patients.Trial registrationThe Ethics committee of Ahvaz Jundishapur University of Medical Sciences approved the protocol of the present clinical research (IR.AJUMS.REC.1401.155). The study was in accordance with the Declaration of Helsinki. This study’s registered number and date are IRCT20220801055597N1 and 20.09.2022, respectively at https://fa.irct.ir.

The effect of soy isoflavones on non-alcoholic fatty liver disease and the level of fibroblast growth factor-21 and fetuin A

A two-arm randomized open labeled controlled clinical trial was conducted on 50 patients with non-alcoholic fatty liver disease (NAFLD). Subjects were randomized to either receive two tablets of soy isoflavone (100 mg/day) or placebo. At week 12, the serum levels of alanine amino transferase (ALT), aspartate amino transferase (AST) and controlled attenuation parameter (CAP) score were significantly decreased only in the soy isoflavone group (P < 0.05). A significant decline in the gamma glutamyl transferase (GGT) level was observed only in the placebo group (P = 0.017). A significant increase in the serum level of fetuin A was shown in both groups at the end of the trial with a significantly greater increment in the soy isoflavone group compared to the placebo group (P < 0.05). The changes in the serum level of FGF-21 were not significant in any of the two groups. Steatosis grade significantly improved only in the soy isoflavone group (P = 0.045). There was no significant change in the fibrosis grade in the groups. Soy isoflavone intake led to a decrease in ALT, AST, CAP score, steatosis grade and an increase in the level of fetuin A. However, no significant changes were observed in the fibrosis grade and serum levels of GGT and FGF-21.

Flavonoids from Extract Butanol of Twigs Erythrina crista-galli Against the Breast Cancer Cell Line Within In Silico Method

Breast cancer is one of the most serious health problems in the world. The common treatments for breast cancer have side effects and resistance, so the search for cancer drugs from natural products that are more effective is still a concern for researchers. Flavonoids from Erythrina crista-galli, which is one of the natural products, have the potential as anticancer drugs based on their phytoestrogen activity that has been reported. The aim of this research is to isolate flavonoids from extract butanol of E. crista-galli with column chromatography and determine their anticancer activity by the in silico molecular docking method. Two flavonoid compounds with the names 6,8-diprenylgenistein from the isoflavone group and phaseolin from the pterocarpan group were isolated. Molecular docking analysis showed that the highest binding affinity values for compounds 1 and 2 were to CDK-2 protein with values of −10.14 and −8.8 kcal/mol, respectively. However, it is also possible to suggest inhibition through ER protein, especially in compound 1, with a value of −10.66 kcal/mol. Therefore, inhibition of the target CDK-2 enzyme is the most promising for the development of new drugs. HIGHLIGHTS Flavonoids have been isolated from butanol extract 6,8-diprenylgenistein and phaseolin were first reported from the species Erythrina crista-galli 6,8-diprenylgenistein has the potential as a new drug candidate with the highest stability based on its ΔG value by targeting the CDK-2 protein within in silico method GRAPHICAL ABSTRACT

Production of Boeravinone-B, total phenolic, flavonoid content and antioxidant activity from callus cultures of Punarnava (Boerhavia diffusa L.)

Boerhavia diffusa L. (Punarnava) is a medicinal herb, rich in diversified plant secondary metabolites used in curing various health ailments. Boeravinone-B is one of the important phytochemicals reported in Punarnava, possessing various pharmacological activities. It belongs to the family of rotenoids, belonging to the isoflavone group. Production of Boeravinone-B from the Punarnava through conventional propagation is comparatively very low, and alternative interventions are of utmost importance to meet the growing demand. In view of this, the present study aims to develop biotechnological approaches like cell/tissue culture as a substitute strategy for the accumulation of biomass and Boeravinone-B biosynthesis. Callus was established from leaf explants of Boerhavia diffusa L. when cultured on MS semi solid medium fortified with varied concentrations and combinations of auxins and cytokinins. The callus induced on Murashige and Skoog medium (MS medium) supplemented with 5.0 ppm 2,4-Dichlorophenoxyacetic acid (2,4-D) favored the highest production of Boeravinone-B analyzed through High-performance Liquid chromatography (HPLC) and it was found to be 673.95 ?g g-1 Dry weight (DW). The total phenolic and flavonoid content were determined for the callus extracts and the results showed that callus induced on 5.0 ppm 2,4-D medium showed the highest phenolic and flavonoid content, which was 63.48 mg g-1 Gallic acid equivalent (GAE) Dry weight (DW), and 30.22 mg g-1 Quercetin equivalent (QE) DW. Similarly, antioxidant activities (radical scavenging, metal chelating, and reducing power) were performed, and it was found that callus induced on 5.0 ppm 2,4-D showed the highest anti-oxidant potential. Radical scavenging activity was found to be 91.1%, and 74% of metal chelating activity was recorded, and a similar trend was observed with respect to reducing power as well. The results of the present study lay foundation for optimization and subsequent large-scale production of Boeravinone-B from callus/cell suspension cultures.

A Systematic Review: Comparison of Immunocytochemistry, ELISA, and Western Blot Methods in Alkaline phosphatase Measurement at Genistein-induced Osteoblast Cell

Osteoporosis is a bone disorder characterized by the decrease of bone mass along with bone micro-architecture damage and has a risk become a fracture. One of the causes of osteoporosis is estrogen deficiency. Genistein is a phytoestrogen compound in the isoflavone group containing a similar structure compared to 17β-estradiol, thus it can bind to estrogen receptors and produce an estrogenic effect. Genistein induction can stimulate bone formation and promote the increase of alkaline phosphate (ALP) activities in osteoblast cells which can be observed by immunocytochemistry or Enzyme-linked Immunosorbent Assay (ELISA) or Western blot method. Using the PRISMA guideline technique, choose and strategize article searches by reading the title, abstract, and then the whole text of the article. Articles with the keywords "genistein or osteoblast cells or alkaline phosphate or immunocytochemistry or immunofluorescence or ELISA or western blot" were retrieved from databases including Google Scholar, PubMed, Researchgate, and Sciencedirect. 24 relevant research articles were uncovered as a result of this systematic review. Comparison of immunocytochemistry and ELISA methods in order to analyze the activities of ALP in osteoblast induced by genistein includes selectivity, sensitivity, processing time, and cost efficiency parameters. The immunocytochemistry method has a higher level of sensitivity and a faster processing time, whereas the ELISA method has a higher level of selectivity and less cost efficiency. The western blot method has selectivity for detecting complex-level protein expression.

In vitro and in vivo antimicrobial activities of extracts and constituents derived from Desmodium styracifolium (Osb.) Merr. against various phytopathogenic fungi and bacteria

Phytopathogenic fungi and bacteria pose a threat to plant health and cause large losses in crop quality and production. Currently, green methods for controlling phytopathogenic fungi and bacteria have been paid attention to. In this study, in vitro and in vivo antimicrobial activities of Desmodium styracifolium and its metabolites against phytopathogenic fungi and bacteria were investigated to find a new solution for the green method. The result showed the crude extract of D. styracifolium exerts a potent suppression against fungal plant diseases in vivo. At 3000 µg/mL, n-hexane and dichloromethane-soluble extracts of D. styracifolium effectively controlled rice blast (84.6% and 53.8%) and tomato late blight (67.7% and 61.3%), respectively. Using in vitro antifungal bioassay-guided fractionation, sixteen compounds were isolated and identified. The occurrence of isoflavanones 5 and 7 in D. styracifolium, as well as pyrrole lactone alkaloid 14 in the genus Desmodium was firstly reported. Compound 9, a new isoflavone isolated from nature, displayed potent antifungal and antibacterial activities in vitro. The two remarkable bioactive groups of isoflavanones (5–7) and isoflavones (8–10) were determined as antifungal constituents from D. styracifolium with a wide-spectrum antifungal activity. Magnaporthe oryzae and Phytophthora species were susceptible to the isoflavonoid groups. Especially, in a range of 125–500 µg/mL, isoflavonoids 5 and 10 effectively inhibited M. oryzae in both in vitro and in vivo experiments. Compounds 5, 6, 8–11 significantly suppressed the bacterial growth of Acidovorax avenae subsp. cattlyae in vitro. Among them, 5 (IC50 = 33.1 µg/mL) and 9 (IC50 = 42.2 µg/mL) were the best inhibitors against A. avenae subsp. cattlyae. Our findings indicate that the isoflavanones and isoflavones of D. styracifolium are worthy of further consideration as lead molecules to develop a new class of inhibitors against phytopathogenic fungi and bacteria.

A CRITICAL REVIEW ON PHARMACOLOGICAL AND MECHANICAL PROPERTIES OF DAIDZEIN

Medicinal plants have proved to be of great importance since long back as they are traditionally used to make plant-derived medicines that are a good alternative to synthetic chemicals. Daidzein is one such chemical compound that belongs to the group of isoflavones and is obtained from leguminous plants, especially soy plants. Daidzein is structurally similar to human hormone estrogen due to which is also called a phytoestrogen. Daidzein is an isoflavone compound that is mostly found in glycosylated form in plants while in humans it is found in free form in the bloodstream. It is clinically used in treatment of variety of cancers. It has become quite successful in treating ovarian cancer, breast cancer, and thyroid cancer. Daidzein also possess some exquisite properties such as anti-inflammatory properties, anti-oxidant properties, and neuroprotective properties. In this paper mechanical properties of daidzein are also discussed in which daidzein has been proved as an excellent wood adhesive agent for industrial purpose. Also, daidzein is used as flame retardant and is doing good in dietary supplementations. Daidzein can be important for further pharmaceutical and industrial applications.

Effect of Soy Isoflavones Compared to Estradiol Valerate in Menopausal Women assessed by Menopause Quality of Life Questionnaire

BACKGROUND: There has recently been a global effort to develop preparations that aim for benefits of hormone replacement therapy with minimal discomfort or risk while isoflavones administration found to relieve complaints related to menopause and has been widely carried out. AIM: The aim of the study is to determine the effect of soy isoflavone compared to estradiol valerate administration in postmenopausal women assessed by the Menopause Quality of Life (MENQOL) questionnaire. METHODS: This is an experimental study with pre-post test non-randomized design using data from postmenopausal women who were divided into two groups, namely, group I Estradiol Valerate group which is 16 menopausal women were given Estradiol Valerate and group II Soy Isoflavone Supplements group which is 16 menopausal women were given Soy Isoflavone Supplements. RESULTS: It was found that in estradiol valerate group, total MENQOL value before estradiol valerate administration was 81.56 ± 19.77, and after administration was 74.55 ± 16.82 with p = 0.002, which indicates there is a significant total MENQOL score difference before and after administration estradiol valerate. In the soy isoflavone group, the total MENQOL scores before soy isoflavone administration were 91.0 ± 16.31, and after administration was 83.08 ± 13.85 with p = 0.001, which indicated that there was a significant total MENQOL score difference between before and after administration soy isoflavone. CONCLUSION: In comparison of menopausal complaints based on MENQOL scale in Estradiol Valerate and Soy Isoflavone groups after intervention, it was shown that there were significant differences in total MENQOL value after intervention.

Effects of isoflavone supplementation on endometrial thickness, endometrial hyperplasia, and cancer in ovariectomized cats.

Ovariectomy is identified as a standard treatment in different European countries. Isoflavones, as nonsteroidal compounds in plants, are common constituents of soy and soy products. Some available cat diets contain different concentrations of soy products. This study aimed to examine the effects of isoflavone supplementation on endometrial hyperplasia and endometrial thickness in ovariectomized cats. Fifteen neutered adult cats were divided into control, estradiol, and isoflavone groups (five cats per group). Subcutaneous injection of estradiol (0.5 μg) in sesame oil (100 μL) was done for 30 days in estradiol-treated cats. Isoflavone-treated cats ingested a single oral tablet of soy extract for 30 days, while the controls received subcutaneous injections of the vehicle and oral placebo for 30 days. Histopathological findings of hematoxylin and eosin-stained sections revealed a significant difference between the estradiol group and other groups in terms of hyperplastic epithelium and simple hyperplasia. Thickness of myometrium was greater in the estradiol group compared to the isoflavone and control groups. Higher concentrations of estrogen can affect the endometrium and myometrium, while 30-day ingestion of isoflavone didn't have any uterine effect.

Influence of genistein and diadizine on regularity of estrous cycle in cyclic female Wistar rat: interaction with estradiol receptors and vascular endothelial growth factor.

Isoflavones are estrogenic compounds that exist in soy, clover, and peanuts. They are selective estrogen receptor modulators. The study was planned to explain the interactions of isoflavones with estrogen receptors alpha (ERα), beta (ERβ), and vascular endothelial growth factor (VEGF) expressions in ovarian and uterine tissues during different stages of the estrous cycle of regular cyclic female Wistar rats. Thirty-two regular cyclic females were divided equally into control group: fed casein-based diet and isoflavones group: fed casein-based diet and gavaged 50 mg/kg/day soy isoflavones extract 40%. The regularity of estrus cycles was monitored. Final body weight (FBW), weight gain (BWG), and ovarian and uterine weights were estimated. Histopathology and immunohistochemistry for ERα, Erβ, and VEGF in ovarian and uterine tissues were performed. All females (100%, n = 16) in control group showed regularity in estrous cycle compared to 62.5% (n = 10) in isoflavones group. Estrus and diestrus phases revealed prolongation and shortening in isoflavones rats than control, respectively. Nonsignificant variation was noted in the duration of the whole cycle of both groups. FBW and BWG significantly decreased however, ovarian and uterine weights increased significantly in all estrous phases of isoflavones group than control. Histopathology demonstrated an increase in number of follicles/ovaries besides, hyperplasia and proliferation of luminal epithelium with hydropic degeneration in the isoflavones group. Also, uterine connective tissue stroma showed edema in the isoflavones group during all estrous phases. Immunostaining percentages of ERα, Erβ, and VEGF protein expression were significantly elevated in the isoflavones group during all estrous phases. Isoflavones induced irregularity of the estrous cycle that was encountered by increased and altered ERα, Erβ, and VEGF expressions in ovarian and uterine tissues.

Genistein: A Potential Natural Lead Molecule for New Drug Design and Development for Treating Memory Impairment.

Genistein is a naturally occurring polyphenolic molecule in the isoflavones group which is well known for its neuroprotection. In this review, we summarize the efficacy of genistein in attenuating the effects of memory impairment (MI) in animals. Scopus, PubMed, and Web of Science databases were used to find the relevant articles and discuss the effects of genistein in the brain, including its pharmacokinetics, bioavailability, behavioral effects, and some of the potential mechanisms of action on memory in several animal models. The results of the preclinical studies highly suggested that genistein is highly effective in enhancing the cognitive performance of the MI animal models, specifically in the memory domain, including spatial, recognition, retention, and reference memories, through its ability to reduce oxidative stress and attenuate neuroinflammation. This review also highlighted challenges and opportunities to improve the drug delivery of genistein for treating MI. Along with that, the possible structural modifications and derivatives of genistein to improve its physicochemical and drug-likeness properties are also discussed. The outcomes of the review proved that genistein can enhance the cognitive performance and ameliorate MI in different preclinical studies, thus indicating its potential as a natural lead for the design and development of a novel neuroprotective drug.

Erxian Decoction, a Famous Chinese Medicine Formula, Ameliorate Depression- Like Behavior in Perimenopausal Mice.

The present study was performed in order to find out the anti-depression effect of Erxian Decoction in perimenopausal mice. Erxian Decoction (EXD) has been used in folk medicine for the treatment of perimenopausal syndrome, but it has not been researched on perimenopausal depression. The present study aimed to evaluate the effect of extraction of Erxian Decoction on perimenopausal depressive mice. In this study, female ICR mice were randomly divided into 6 groups: Low, medium and high dose of EXD groups (0.5, 1.5, and 4.5 g/kg), soy isoflavones group (250 mg/kg) and Sham group. The mice in the Sham group received sham surgery (within ovaries), and the others were excised with bilateral ovaries and exerted by 28-day chronic mild unpredictable stimulation for the establishment of a perimenopausal depression model. Behavioral tests showed that EXD could relieve depression symptoms and improve spatial memory in mice. Western blotting showed that EXD significantly up-regulated the expression of brain-derived neurotrophic factor (BDNF) and Bcl-2 in hippocampus and estrogen receptors (ERs) in the uterus and adrenals, protecting hippocampal tissue and antagonizing the symptoms of estrogen deficiency in mice, which was further proved within a uterine morphology test. In addition, EXD reduced the serum levels of follicle-stimulating hormone, luteinizing hormone, and interleukin- 6. These results indicated that EXD can regulate hormone secretion and recover hippocampal damage in perimenopausal depressed mice. Besides, it can antagonize the symptoms of ovarian hormone deficiency as well as relieve perimenopausal syndrome.

Puerarin-an isoflavone with beneficial effects on bone health.

Puerarin is a compound from the group of isoflavones, naturally occurring in plants of the genus Pueraria, whose representatives include, among others, Pueraria lobata and Pueraria mirifica. Relatively many scientific studies on the biological activity of puerarin have been conducted so far. It seems that most attention was paid to the effect of puerarin on bone health. However, until now, no published studies have been collected and discussed in that regard. Based on the available data obtained from in vitro studies and on the animal model, it can be clearly shown that puerarin is an effective compound in inhibiting bone resorption and improving bone structure. Consumption of puerarin may be associated with the prevention of bone mass loss and thus can reduce the risk of developing osteoporosis. However, it is necessary to conduct human intervention studies to confirm the effectiveness of such action.

Intake of isoflavones reduces the risk of all-cause mortality in middle-aged Japanese.

To clarify the effects of intake of legumes and isoflavones on all-cause mortality in middle-aged and older Japanese. The subjects were 2136 randomly chosen community-dwelling Japanese men and women aged 40-79 years who participated in a first-wave survey (1997-2000; baseline). The subjects were followed from baseline to December 31, 2017 (mean period of 16.6 ± 4.2 years). Intake of legumes, soybeans, and isoflavones at baseline was assessed using a 3-day dietary record with photographs. The relationships of intake amounts of legumes and isoflavones to mortality were assessed using Cox proportional hazards regression controlling for age, sex, education, employment, body mass index, smoking habits, medical histories, drinking, and energy intake. There were 491 deaths during the follow-up period. We found inverse associations of the intake of total soy products and intake of each of the isoflavones with all-cause mortality (p for trend < 0.05) in subjects aged < 60 years: the multivariate-adjusted hazard ratios (95% confidence intervals) for all-cause mortality in the highest intake group (third tertile) of total soy products and total isoflavones were 0.32 (0.13-0.78) and 0.35 (0.17-0.73), respectively, compared with the reference group (first tertile). In contrast, there were no significant associations of intake amounts of legumes, soybeans, and isoflavones with all-cause mortality in subjects aged 60 years or older. The findings suggest that a higher intake of isoflavones might decrease the risk of all-cause mortality, especially in middle-aged Japanese.

Structure – Activity Relationship and Therapeutic Benefits of Flavonoids in the Management of Diabetes and Associated Disorders

Commonly flavonoids are the natural components found in vegetables, spices and colored fruits. Flavonoids include a large group of polyphenolic compounds, namely flavones, flavanols, flavonols, flavanones, isoflavones and anthocyanidins, which have been proposed as effective supplements for the management of diabetes and associated disorders. The aim of present review was to highlight various classes of flavonoids, their structure – activity relationships, bioavailability, and mechanisms involved in the management of diabetes and associated complications. The relevant research and review articles were collected from online (Pubmed, Sciencedirect, Scopus, Google, andWeb of science) and offline sources (books and journals from library). A total of 245 articles published between 1996 to 2018 were reviewed, and 232 articles were included in present review. Article being related with flavonoids and diabetes is the major criterion for inclusion in this compilation. Flavonoids regulate the redox status and prevent damage caused by oxidative stress and possess anti-oxidant activity. Flavonoids are a wide group of compounds including quercetin, kaempferol, luteolin, apigenin, genistein, glycitein, eriodictyol, hesperidin, catechin, gallocatechin, pelargonidin, and cyanidin. Type 2 diabetes mellitus is associated with insulin resistance, β-cell dysfunction, inflammation, altered lipid metabolism and increased oxidative stress. It can affect many metabolic processes may cause serious complications such as retinopathy, cardiovascular disease and nephropathy. Flavonoids produce antidiabetic effect through suppressing α-amylase activities, attenuating insulin resistance and promoting pancreatic β-cells proliferation. Several reports including in-vitro and in-vivo studies on flavonoids confirmed their major role in maintaining metabolic pathways during type 2 diabetes mellitus treatment.

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.

Effects of soy isoflavones extract on the lipid profile and uterus in ovariectomized rats

Aim Although soy isoflavones (ISO) have been shown to relief postmenopausal symptoms, it remains inconclusive whether ISO can improve lipid-profile without uterotrophic effects under estrogen-deficiency. Thus, we investigated the effects of ISO on lipid-profile and uterus of ovariectomized (Ovx) rats. Materials and methods Twenty-five adult rats were Ovx or Sham-operated (Sham) and assigned into five groups: Sham and Ovx groups, administered with vehicle solutions; Ovx-E, treated with 10 µg/kg of 17β-Estradiol; Ovx-ISO, treated with 200 mg/kg of ISO; Ovx-E + ISO, treated with estradiol + ISO combined. After fifty days of treatments, rats were euthanized and uterine horns were processed for histomorphometry or to collagen fibers and glycosaminoglycans evaluations. Blood samples were collected to evaluate levels of triglycerides, total cholesterol (TC) and its fractions (HDL/VLDL). Data were subjected to statistical analysis (p < .05). Results Uterus weight was lower in Ovx group than the Sham and Ovx-E groups, whereas it was similar between Ovx and Ovx-ISO groups. Histomorphometry showed atrophic uterus in Ovx and Ovx-ISO groups, whereas uterotrophic effects were noticed in Ovx-E and Ovx-E + ISO groups. Collagen fibers-birefringence was higher in Sham, Ovx, and Ovx-ISO groups than in Ovx-E and Ovx-E + ISO groups. Sulfated glycosaminoglycans content was similar among Sham, Ovx, and Ovx-ISO groups, while it was higher in estrogen-treated groups; total glycosaminoglycans content was similar among groups. TC and HDL was higher in Ovx-ISO group, whereas VLDL and triglycerides levels was higher in Ovx-E + ISO group and similar among other groups. Conclusion Soy isoflavones at 200 mg/kg have slight beneficial effects on lipid-profile without uterotrophic effects in Ovx rats.

Effects of isoflavones on bone turnover markers in peritoneal dialysis patients: a randomized controlled trial.

The aim of this study was to investigate the effects of soy isoflavones on serum markers of bone formation and resorption in peritoneal dialysis (PD) patients. In this randomized, double-blind, placebo-controlled trial, 40 PD patients were randomly assigned to either the soy isoflavone or the placebo group. The patients in the soy isoflavone group received 100mg soy isoflavones daily for 8weeks, whereas the placebo group received corresponding placebos. At baseline and the end of the 8th week, 7ml of blood was obtained from each patient after a 12- to 14-h fast and serum concentrations of bone formation markers (osteocalcin and bone alkaline phosphatase), bone resorption markers [N-telopeptide and receptor activator of nuclear factor kappa B ligand (RANKL)], and osteoprotegerin as an inhibitor of bone resorption were measured. Serum N-telopeptide concentration decreased significantly up to 27% in the soy isoflavone group at the end of week 8 compared to baseline (P = 0.003). Also, serum RANKL concentration reduced significantly up to 17% in the soy isoflavone group at the end of week 8 compared to baseline (P = 0.03). These bone resorption markers did not significantly change in the placebo group during the study. There were no significant differences between the two groups in mean changes of serum osteocalcin, bone alkaline phosphatase, and osteoprotegerin. This study indicates that daily administration of 100mg soy isoflavone supplement to PD patients reduces serum N-telopeptide and RANKL which are two bone resorption markers. CLINICALTRIALS.GOV: NCT03773029, 2018.