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Biomedicine & Pharmacotherapy =... Jul 2023Postmenopausal osteoporosis, an epidemic disorder is defined as a loss in bone mineral density and a greater possibility of fractures in older women. It is a... (Review)
Review
Postmenopausal osteoporosis, an epidemic disorder is defined as a loss in bone mineral density and a greater possibility of fractures in older women. It is a multifactorial disease under the control of various genetic, hormonal, and environmental factors. Insufficiency of estrogen hormone, leads to postmenopausal osteoporosis. Hormone replacement therapy (HRT), despite being the most effective treatment, it is associated with the risk of breast cancer and cardiovascular disorders. This review seeks to compile the most recent information on medicinal plants and natural compounds used to treat and prevent postmenopausal osteoporosis. Furthermore, the origin, chemical constituents and the molecular mechanisms responsible for this therapeutic and preventive effect are also discussed. Literature research was conducted using PubMed, Science direct, Scopus, Web of Science, and Google Scholar. Different plant extracts and pure compounds exerts their antiosteoporotic activity by inhibition of RANKL and upregulation of OPG. RANKL signaling regulates osteoclast formation, characterized by increased bone turnover and osteoprotegrin is a decoy receptor for RANKL thereby preventing bone loss from excessive resorption. In addition, this review also includes the chemical structure of bioactive compounds acting on NFκB, TNF α, RUNX2. In conclusion, we propose that postmenopausal osteoporosis could be prevented or treated with herbal products.
Topics: Female; Humans; Aged; Osteoporosis, Postmenopausal; Bone Density; Fractures, Bone; Estrogens; Phytochemicals
PubMed: 37172332
DOI: 10.1016/j.biopha.2023.114850 -
PeerJ 2023Postmenopausal osteoporosis and osteoporosis-related fractures are world-wide serious public health problem. Recent studies demonstrated that inhibiting caveolin-1 leads...
BACKGROUND
Postmenopausal osteoporosis and osteoporosis-related fractures are world-wide serious public health problem. Recent studies demonstrated that inhibiting caveolin-1 leads to osteoclastogenesis suppression and protection against OVX-induced osteoporosis. This study aimed to explore the mechanism of caveolin-1 mediating bone loss and the potential therapeutic target.
METHODS
Thirty C57BL/6 female mice were allocated randomly into three groups: sham or bilateral ovariectomy (OVX) surgeries were performed for mice and subsequently daidzein or vehicle was administrated to animals (control, OVX + vehicle and OVX + daidzein). After 8-week administration, femurs were harvested for Micro-CT scan, histological staining including H&E, immunohistochemistry, immunofluorescence, TRAP. Bone marrow endothelial cells (BMECs) were cultured and treated with inhibitors of caveolin-1 (daidzein) or EGFR (erlotinib) and then scratch wound healing and ki67 assays were performed. In addition, cells were harvested for western blot and PCR analysis.
RESULTS
Micro-CT showed inhibiting caveolin-1with daidzein alleviated OVX-induced osteoporosis and osteogenesis suppression. Further investigations revealed H-type vessels in cancellous bone were decreased in OVX-induced mice, which can be alleviated by daidzein. It was subsequently proved that daidzein improved migration and proliferation of BMECs hence improved H-type vessels formation through inhibiting caveolin-1, which suppressed EGFR/AKT/PI3K signaling in BMECs.
CONCLUSIONS
This study demonstrated that daidzein alleviates OVX-induced osteoporosis by promoting H-type vessels formation in cancellous bone, which then promotes bone formation. Activating EGFR/AKT/PI3K signaling could be the critical reason.
Topics: Female; Mice; Animals; Osteogenesis; Caveolin 1; Endothelial Cells; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Mice, Inbred C57BL; Osteoporosis; X-Ray Microtomography; ErbB Receptors
PubMed: 37868048
DOI: 10.7717/peerj.16121 -
Biomedicine & Pharmacotherapy =... Dec 2023Since inhaled glucocorticoids are the first-line treatment for asthma, asthma management becomes extremely difficult when asthma does not react well to glucocorticoids....
Since inhaled glucocorticoids are the first-line treatment for asthma, asthma management becomes extremely difficult when asthma does not react well to glucocorticoids. Formononetin, a bioactive isoflavone and typical phytoestrogen, has been shown to have an anti-inflammatory impact while alleviating epithelial barrier dysfunction, which plays a role in the pathogenesis of allergic illnesses like asthma. However, the biological mechanisms behind this impact are unknown. As a result, we set out to investigate the effects of formononetin on airway inflammation and epithelial barrier repair in house dust mite (HDM)-induced asthmatic mice. We further expanded on formononetin's putative mode of action in reducing airway inflammation by modifying epithelial barrier dysfunction. In the current study, researchers discovered that formononetin significantly lowered total IgE levels in serum and interleukin (IL)-4, IL-6, and IL-17A levels in bronchoalveolar lavage fluid (BALF) in HDM-challenged asthmatic mice. Experiments on cell proliferation, migration, and apoptosis were performed in vitro to determine the effect of formononetin on bronchial epithelial barrier repair. Furthermore, in lipopolysaccharide (LPS)-stimulated 16HBE cells, formononetin increased cell proliferation and migration while preventing apoptosis and lowering the Bax/Bcl-2 ratio. In vitro and in vivo, formononetin significantly inhibited toll-like receptor 4 (TLR4) and estrogen receptor (ESR1)/Nod-like receptor family pyrin domain-containing protein 3 (NLRP3)/Caspase-1 signaling. These findings show that formononetin can reduce airway inflammation in HDM-challenged asthmatic mice by promoting epithelial barrier repair and possibly by inhibiting ESR1/NLRP3/Caspase-1 signaling as the underlying mechanism; formononetin could be a promising alternative treatment for asthma.
Topics: Animals; Mice; NLR Family, Pyrin Domain-Containing 3 Protein; Caspase 1; Asthma; Isoflavones; Inflammation; Bronchi; Receptors, Estrogen; Disease Models, Animal; Lung
PubMed: 37922653
DOI: 10.1016/j.biopha.2023.115799 -
International Journal of Environmental... Aug 2023Polycystic ovarian syndrome (PCOS) is an endocrine condition that impacts nutritional status, metabolic, and hormonal function in females of reproductive age. This... (Review)
Review
Polycystic ovarian syndrome (PCOS) is an endocrine condition that impacts nutritional status, metabolic, and hormonal function in females of reproductive age. This condition is associated with increased androgen production (hyperandrogenism) and decreased insulin sensitivity, which often leads to insulin resistance and hyperinsulinemia. This increase in androgen production and insulin resistance is strongly associated with a high incidence of obesity, type-2 diabetes mellitus (T2DM), cardiovascular diseases (CVD), and certain types of gonad-related cancers among females who suffer from this condition. As research continues to grow, it has been demonstrated that PCOS is a complex condition, and some of its characteristics vary among the females that have this disorder. However, it has been suggested that oxidative stress and low-grade chronic inflammation could play an important role in the development of PCOS. Current evidence suggest that phytochemicals could potentially help with weight-loss by reducing oxidative stress and low-grade inflammation, as well as aid in metabolic and hormonal regulation due to their antioxidant properties. Some of the bioactive compounds found in plants that have shown positive effects in the attenuation of PCOS include flavonoids, polyphenols, phytoestrogen, and polyunsaturated fatty acids (PUFAs). Thus, a review of the current literature published on PCOS and phytochemicals was conducted in PubMed, Google Scholar, and the Academy of Nutrition and Dietetics databases for articles published between 2013 and 2023 with a study duration of 1 to 3 months and adequate sample sizes. The main purpose of this review of literature was to investigate the metabolic effects of phytochemical compounds and phytochemical-rich diets on females with PCOS by comparing the results of several randomized clinical trials.
Topics: Female; Humans; Polycystic Ovary Syndrome; Insulin Resistance; Androgens; Diet; Inflammation
PubMed: 37569074
DOI: 10.3390/ijerph20156534 -
Pharmaceuticals (Basel, Switzerland) Aug 2023Phytoestrogens (PEs) are plant-based compounds that can interact with estrogen receptors and are mainly used to treat menopausal complaints. However, the safety of...
Phytoestrogens (PEs) are plant-based compounds that can interact with estrogen receptors and are mainly used to treat menopausal complaints. However, the safety of products with assumed phytoestrogenic activity is not fully understood. This study aimed to identify plant species with assumed phytoestrogenic activity, review existing literature on their use and safety, and critically evaluate adverse reaction (AR) reports of single-herb, multi-herb, and mixed-multiple products, as submitted to the Netherlands Pharmacovigilance Centre Lareb and to VigiBase of the World Health Organization (WHO). In the Lareb database, the most commonly reported plant species to cause ARs (total of 67 reports) were L. (black cohosh) (47.8%), L. (hops) (32.8%), and (L.) Merr. (soybean) (22.4%). In the VigiBase database (total of 21,944 reports), the top three consisted of (L.) Merr. (71.4%), L. (11.6%), and L. (chaste tree) (6.4%). In the scoping review (total of 73 articles), L. (30.1%), (L.) Merr. (28.8%), and L. (13.7%) were the most frequently mentioned plant species. ARs were most frequently reported in the system organ classes "gastrointestinal disorders", "skin and subcutaneous tissue disorders", "reproductive system and breast disorders", and "general disorders and administration site conditions". Furthermore, from the scoping review, it appeared that the use of products with assumed phytoestrogenic activity was associated with postmenopausal bleeding. It was concluded that, while the potential benefits of products with assumed phytoestrogenic activity have been extensively pursued, the potential occurrence of ARs after using these products is less well understood. This study highlights the need for further investigation and careful monitoring of these products to better understand their effects and ensure the safety and well-being of individuals using them.
PubMed: 37631050
DOI: 10.3390/ph16081137 -
Scientific Reports Jul 2023Depression is a common mental disease, with some patients exhibiting ideas and behaviors such as self-harm and suicide. The drugs currently used to treat depression have...
Depression is a common mental disease, with some patients exhibiting ideas and behaviors such as self-harm and suicide. The drugs currently used to treat depression have not achieved good results. It has been reported that metabolites produced by intestinal microbiota affect the development of depression. In this study, core targets and core compounds were screened by specific algorithms in the database, and three-dimensional structures of these compounds and proteins were simulated by molecular docking and molecular dynamics software to further study the influence of intestinal microbiota metabolites on the pathogenesis of depression. By analyzing the RMSD gyration radius and RMSF, it was finally determined that NR1H4 had the best binding effect with genistein. Finally, according to Lipinski's five rules, equol, genistein, quercetin and glycocholic acid were identified as effective drugs for the treatment of depression. In conclusion, the intestinal microbiota can affect the development of depression through the metabolites equol, genistein and quercetin, which act on the critical targets of DPP4, CYP3A4, EP300, MGAM and NR1H4.
Topics: Humans; Systems Biology; Depression; Equol; Gastrointestinal Microbiome; Genistein; Molecular Docking Simulation; Quercetin
PubMed: 37433869
DOI: 10.1038/s41598-023-38444-8 -
Biomedicine & Pharmacotherapy =... Jul 2023Glucocorticoid-induced osteoporosis (GIO) complicates the clinical management of patients subjected to long-term glucocorticoid use. This study explored the effects of... (Randomized Controlled Trial)
Randomized Controlled Trial
Glucocorticoid-induced osteoporosis (GIO) complicates the clinical management of patients subjected to long-term glucocorticoid use. This study explored the effects of genistein on bone loss in a randomized double-blind alendronate-controlled trial in postmenopausal women with GIO. 200 postmenopausal women (taking at least 5 mg of prednisone equivalents) since 3 months, or more, and expected to continue for at least other 12 months, were randomized to receive genistein (54 mg/day daily) or alendronate (70 mg once a week) for 24 months. Both groups received also Calcium and Vitamin D3 supplementation. Median bone mineral density (BMD) at the antero-posterior lumbar spine significantly increased from 0.75 g/cm at baseline to 0.77 g/cm at 1 year and 0.79 g/cm at 2 years in alendronate-treated patients and from 0.77 g/cm at baseline to 0.79 g/cm at 12 months and to 0.80 g/cm at 24 months in genistein recipients. No difference was observed between the two treatments. Median BMD at the femoral neck increased from 0.67 g/cm at baseline to 0.68 g/cm at 1 year and 0.69 g/cm at 2 years in alendronate-treated patients and from 0.68 g/cm at baseline to 0.70 g/cm at 12 months and to 0.71 g/cm at 24 months in genistein recipients. No difference was observed between alendronate and genistein groups in BMD. Regarding bone markers genistein and alendronate statistically decreased c-terminal telopeptide, while osteocalcin, bone-ALP, and sclerostin showed greater changes in genistein treated patients. This randomized clinical trial suggests that genistein aglycone represents an additional therapeutic option for patients with GIO.
Topics: Humans; Female; Alendronate; Glucocorticoids; Genistein; Bone Density Conservation Agents; Osteoporosis; Bone Density; Osteoporosis, Postmenopausal; Double-Blind Method
PubMed: 37167726
DOI: 10.1016/j.biopha.2023.114821 -
Reproduction (Cambridge, England) Jul 2023Healthy development of the placenta is dependent on trophoblast cell migration and reduced oxidative stress presence. This article describes how a phytoestrogen found in...
IN BRIEF
Healthy development of the placenta is dependent on trophoblast cell migration and reduced oxidative stress presence. This article describes how a phytoestrogen found in spinach and soy causes impaired placental development during pregnancy.
ABSTRACT
Although vegetarianism has grown in popularity, especially among pregnant women, the effects of phytoestrogens in placentation lack understanding. Factors such as cellular oxidative stress and hypoxia and external factors including cigarette smoke, phytoestrogens, and dietary supplements can regulate placental development. The isoflavone phytoestrogen coumestrol was identified in spinach and soy and was found to not cross the fetal-placental barrier. Since coumestrol could be a valuable supplement or potent toxin during pregnancy, we sought to examine its role in trophoblast cell function and placentation in murine pregnancy. After treating trophoblast cells (HTR8/SVneo) with coumestrol and performing an RNA microarray, we determined 3079 genes were significantly changed with the top differentially changed pathways related to the oxidative stress response, cell cycle regulation, cell migration, and angiogenesis. Upon treatment with coumestrol, trophoblast cells exhibited reduced migration and proliferation. Additionally, we observed increased reactive oxygen species accumulation with coumestrol administration. We then examined the role of coumestrol within an in vivo pregnancy by treating wildtype pregnant mice with coumestrol or vehicle from day 0 to 12.5 of gestation. Upon euthanasia, fetal and placental weights were significantly decreased in coumestrol-treated animals with the placenta exhibiting a proportional decrease with no obvious changes in morphology. Therefore, we conclude that coumestrol impairs trophoblast cell migration and proliferation, causes accumulation of reactive oxygen species, and reduces fetal and placental weights in murine pregnancy.
Topics: Pregnancy; Female; Mice; Humans; Animals; Placenta; Coumestrol; Phytoestrogens; Reactive Oxygen Species; Cell Line; Placentation; Trophoblasts; Oxidative Stress
PubMed: 37078791
DOI: 10.1530/REP-23-0017 -
Molecules (Basel, Switzerland) Jul 2023Formononetin (FNT) is a plant-derived isoflavone natural product with anti-inflammatory, antioxidant, and anti-allergic properties. We showed previously that FNT...
Formononetin (FNT) is a plant-derived isoflavone natural product with anti-inflammatory, antioxidant, and anti-allergic properties. We showed previously that FNT inhibits immunoglobulin E (IgE)-dependent mast cell (MC) activation, but the effect of FNT on IgE-independent MC activation is yet unknown. Our aim was to investigate the effects and possible mechanisms of action of FNT on IgE-independent MC activation and pseudoallergic inflammation. We studied the effects of FNT on MC degranulation in vitro with a cell culture model using compound C48/80 to stimulate either mouse bone marrow-derived mast cells (BMMCs) or RBL-2H3 cells. We subsequently measured β-hexosaminase and histamine release, the expression of inflammatory factors, cell morphological changes, and changes in NF-κB signaling. We also studied the effects of FNT in several in vivo murine models of allergic reaction: C48/80-mediated passive cutaneous anaphylaxis (PCA), active systemic anaphylaxis (ASA), and 2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD). The results showed that FNT inhibited IgE-independent degranulation of MCs, evaluated by a decrease in the release of β-hexosaminase and histamine and a decreased expression of inflammatory factors. Additionally, FNT reduced cytomorphological elongation and F-actin reorganization and attenuated NF-κB p65 phosphorylation and NF-κB-dependent promoter activity. Moreover, the administration of FNT alleviated pseudoallergic responses in vivo in mouse models of C48/80-stimulated PCA and ASA, and DNCB-induced AD. In conclusion, we suggest that FNT may be a novel anti-allergic drug with great potential to alleviate pseudoallergic responses via the inhibition of IgE-independent MC degranulation and NF-κB signaling.
Topics: Mice; Animals; Mast Cells; p-Methoxy-N-methylphenethylamine; NF-kappa B; Cell Degranulation; Dinitrochlorobenzene; Anaphylaxis; Isoflavones; Immunoglobulin E; Anti-Allergic Agents
PubMed: 37446928
DOI: 10.3390/molecules28135271 -
Nutrients Apr 2024The aim of the study was to develop and evaluate a novel dietary index for gut microbiota (DI-GM) that captures dietary composition related to gut microbiota profiles.... (Review)
Review
The aim of the study was to develop and evaluate a novel dietary index for gut microbiota (DI-GM) that captures dietary composition related to gut microbiota profiles. We conducted a literature review of longitudinal studies on the association of diet with gut microbiota in adult populations and extracted those dietary components with evidence of beneficial or unfavorable effects. Dietary recall data from the National Health and Nutrition Examination Survey (NHANES, 2005-2010, = 3812) were used to compute the DI-GM, and associations with biomarkers of gut microbiota diversity (urinary enterodiol and enterolactone) were examined using linear regression. From a review of 106 articles, 14 foods or nutrients were identified as components of the DI-GM, including fermented dairy, chickpeas, soybean, whole grains, fiber, cranberries, avocados, broccoli, coffee, and green tea as beneficial components, and red meat, processed meat, refined grains, and high-fat diet (≥40% of energy from fat) as unfavorable components. Each component was scored 0 or 1 based on sex-specific median intakes, and scores were summed to develop the overall DI-GM score. In the NHANES, DI-GM scores ranged from 0-13 with a mean of 4.8 (SE = 0.04). Positive associations between DI-GM and urinary enterodiol and enterolactone were observed. The association of the novel DI-GM with markers of gut microbiota diversity demonstrates the potential utility of this index for gut health-related studies.
Topics: Adult; Female; Male; Humans; Gastrointestinal Microbiome; Nutrition Surveys; Diet, High-Fat; Meat; 4-Butyrolactone; Lignans
PubMed: 38613077
DOI: 10.3390/nu16071045