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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 -
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 -
Phytomedicine : International Journal... Jun 2024Psoriasis is a long-lasting, inflammatory, continuous illness caused through T cells and characterized mainly by abnormal growth and division of keratinocytes....
BACKGROUND
Psoriasis is a long-lasting, inflammatory, continuous illness caused through T cells and characterized mainly by abnormal growth and division of keratinocytes. Currently, corticosteroids are the preferred option. However, prolonged use of traditional topical medication can lead to adverse reactions and relapse, presenting a significant therapeutic obstacle. Improved alternative treatment options are urgently required. Formononetin (FMN) is a representative component of isoflavones in Huangqi (HQ) [Astragalus membranaceus (Fisch.) Bge.]. It possesses properties that reduce inflammation, combat oxidation, inhibit tumor growth, and mimic estrogen. Although FMN has been shown to ameliorate skin barrier devastation via regulating keratinocyte apoptosis and proliferation, there are no reports of its effectiveness in treating psoriasis.
OBJECTIVE
Through transcriptomics clues and experimental investigation, we aimed to elucidate the fundamental mechanisms underlying FMN's action on psoriasis.
MATERIALS AND METHODS
Cell viability was examined using CCK8 assay in this study. The results of analysis of differentially expressed genes (DEGs) between FMN-treated HaCaT cells and normal HaCaT cells using RNA-sequencing (RNA-seq) were presented on volcano plots and heatmap. Enrichment analysis was conducted on DEGs using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), and results were validated through RT-qPCR verification. After 12 days of FMN treatment in psoriasis mouse model, we gauged the PASI score and epidermis thickness. A variety of techniques were used to assess FMN's effectiveness on inhibiting inflammation and proliferation related to psoriasis, including RT-qPCR, HE staining, western blot, and immunohistochemistry (IHC).
RESULTS
The findings indicated that FMN could suppress the growth of HaCaT cells using CCK8 assay (with IC = 40.64 uM) and 20 uM FMN could reduce the level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) to the greatest extent. FMN-treated HaCaT cells exhibited 985 up-regulated and 855 down-regulated DEGs compared to normal HaCaT cells. GO analysis revealed that DEGs were linked to interferon (IFN) signaling pathway. Furthermore, FMN improved pathological features, which encompassed decreased erythema, scale, and thickness scores of skin lesions in psoriasis mouse model. In vivo experiments confirmed that FMN down-regulated expression of IFN-α, IFN-β, IFN-γ, decreased secretion of TNF-α and IL-17 inflammatory factors, inhibited expression of IFN-related chemokines included Cxcl9, Cxcl10, Cxcl11 and Cxcr3 and reduced expression of transcription factors p-STAT1, p-STAT3 and IFN regulatory factor 1 (IRF1) in the imiquimod (IMQ) group.
CONCLUSIONS
In summary, these results suggested that FMN played an anti-inflammatory and anti-proliferative role in alleviating psoriasis by inhibiting IFN signaling pathway, and FMN could be used as a potential therapeutic agent.
Topics: Isoflavones; Psoriasis; Animals; Signal Transduction; Humans; HaCaT Cells; Mice; Interferons; Cell Survival; Keratinocytes; Inflammation; Astragalus propinquus; Mice, Inbred BALB C; Male; Disease Models, Animal
PubMed: 38579666
DOI: 10.1016/j.phymed.2024.155412 -
Ageing Research Reviews Sep 2023With the increasing aging population worldwide, the incidence of senile cognitive impairment (CI) is increasing, posing a serious threat to the health of elderly... (Review)
Review
With the increasing aging population worldwide, the incidence of senile cognitive impairment (CI) is increasing, posing a serious threat to the health of elderly persons. Despite developing new drugs aimed at improving CI, progress in this regard has been insufficient. Natural preparations derived from plants have become an unparalleled resource for developing new drugs. Puerariae radix (PR) has a long history as Chinese herbal medicine. PR is rich in various chemical components such as isoflavones, triterpenes, and saponins. The isoflavones (puerarin, daidzein, formononetin, and genistein) exhibit potential therapeutic effects on CI through multiple mechanisms. Relevant literature was organized from major scientific databases such as PubMed, Elsevier, SpringerLink, ScienceDirect, and Web of Science. Using "Puerariae radix," "Pueraria lobata," "isoflavones," "puerarin," "antioxidant," "daidzein," "formononetin," "genistein," "Alzheimer"s disease," and "vascular cognitive impairment" as keywords, the relevant literature was extracted from the databases mentioned above. We found that isoflavones from PR have neuroprotective effects on multiple models of CI via multiple targets and mechanisms. These isoflavones prevent Aβ aggregation, inhibit tau hyperphosphorylation, increase cholinergic neurotransmitter levels, reduce neuroinflammation and oxidative stress, improve synaptic plasticity, promote nerve regeneration, and prevent apoptosis. PR has been used as traditional Chinese herbal medicine for a long time, and its constituent isoflavones exert significant therapeutic effects on CI through various neuroprotective mechanisms. This review will contribute to the future development of isoflavones present in PR as novel drug candidates for the clinical treatment of CI.
Topics: Aged; Humans; Genistein; Drugs, Chinese Herbal; Isoflavones; Cognitive Dysfunction
PubMed: 37619620
DOI: 10.1016/j.arr.2023.102040 -
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 -
The Journal of Nutritional Biochemistry Nov 2023A decrease in the NAD level in adipocytes causes adipose-tissue dysfunction, leading to systemic glucose, and lipid metabolism failure. Therefore, it is necessary to...
A decrease in the NAD level in adipocytes causes adipose-tissue dysfunction, leading to systemic glucose, and lipid metabolism failure. Therefore, it is necessary to develop small molecules and nutraceuticals that can increase NAD levels in adipocytes. Genistein, a nutraceutical derived from soybeans, has various physiological activities and improves glucose and lipid metabolism. In this study, we aimed to unravel the effects of genistein on the NAD level in adipocytes and the underlying molecular mechanisms. Genistein enhanced NAD biosynthesis by increasing the expression of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD biosynthesis. A pull-down assay using genistein-immobilized beads revealed prohibitin 1 (PHB1) as a target protein of genistein. The knockdown of Phb1 suppressed the genistein-induced increase in NAMPT expression and NAD level in adipocytes. Genistein-bound PHB1 contributed to the stabilization of the transcription factor CCAAT/enhancer-binding protein β through the activation of extracellular signal-regulated kinase, resulting in increased NAMPT expression at the transcriptional level. Genistein induced the dephosphorylation of peroxisome proliferator-activated receptor at serine 273 and increased the level of the insulin-sensitizing adipokine adiponectin in adipocytes, whereas the knockdown of Nampt and Phb1 abolished these genistein-mediated effects. Our results proved the potential efficacy of genistein in increasing the NAD level and restoring metabolic function in adipocytes. Furthermore, we identified PHB1, localized to the plasma membrane, as a novel candidate target protein for increased expression of NAMPT in adipocytes. Overall, these findings will assist in developing NAD-boosting nutraceuticals to alleviate metabolic dysfunctions in adipose tissues.
Topics: NAD; Genistein; Nicotinamide Phosphoribosyltransferase; Adipocytes; Cytokines; Glucose
PubMed: 37648097
DOI: 10.1016/j.jnutbio.2023.109433 -
The British Journal of Nutrition Sep 2023Phytoestrogens may have potential effects on hormone-related cancers (HRC) and cancer biomarkers, but the findings have been inconsistent so far. Participants from the...
Phytoestrogens may have potential effects on hormone-related cancers (HRC) and cancer biomarkers, but the findings have been inconsistent so far. Participants from the National Health and Nutrition Examination Survey 1999-2010 with information on the levels of urinary phytoestrogens, serum cancer biomarkers and cancer history were included. Sampling-weighted logistic regression models examined the association between urinary phytoestrogens concentrations (creatinine-standardised and log-transformed) and HRC, followed by stratified analyses by race/ethnicity, age and menopausal status for different gender. Correlation analyses between phytoestrogens and cancer biomarkers were performed. Of the total 8844 participants, there were 373 with HRC. We observed total isoflavone and enterodiol excretion were positively associated with HRC, especially in non-Hispanic white female subpopulations ( < 0·05). Similar association also existed in the total isoflavones and enterodiol levels with breast cancer. Whereas the highest concentration of total isoflavones was significantly linked to a reduced prevalence of HRC (OR = 0·40, 95 % CI: 0·19, 0·84) in white males and of prostate cancer (OR = 0·40, 95 % CI: 0·18, 0·86). Among twenty-four participants with HRC, urinary equol concentration was positively correlated with CA15.3. Also, an inverse correlation of total prostate-specific antigens (PSA) and positive correlation of the PSA ratio with urinary enterolactone were detected in thirteen prostate cancer patients. Our findings indicated that higher concentrations of total isoflavones and enterodiol were positively associated with HRC. Urinary certain phytoestrogen excretion may affect serum cancer biomarker levels in cancer patients. But further prospective studies are needed to provide stronger evidence.
Topics: Male; Humans; Phytoestrogens; Nutrition Surveys; Biomarkers, Tumor; Prostate-Specific Antigen; Lignans; Isoflavones; Prostatic Neoplasms
PubMed: 36474419
DOI: 10.1017/S0007114522003877 -
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 -
Molecular Nutrition & Food Research Mar 2024The human gut microbiota regulates estrogen metabolism through the "estrobolome," the collection of bacterial genes that encode enzymes like β-glucuronidases and... (Review)
Review
The human gut microbiota regulates estrogen metabolism through the "estrobolome," the collection of bacterial genes that encode enzymes like β-glucuronidases and β-glucosidases. These enzymes deconjugate and reactivate estrogen, influencing circulating levels. The estrobolome mediates the enterohepatic circulation and bioavailability of estrogen. Alterations in gut microbiota composition and estrobolome function have been associated with estrogen-related diseases like breast cancer, enometrial cancer, and polycystic ovarian syndrome (PCOS). This is likely due to dysregulated estrogen signaling partly contributed by the microbial impacts on estrogen metabolism. Dietary phytoestrogens also undergo bacterial metabolism into active metabolites like equol, which binds estrogen receptors and exhibits higher estrogenic potency than its precursor daidzein. However, the ability to produce equol varies across populations, depending on the presence of specific gut microbes. Characterizing the estrobolome and equol-producing genes across populations can provide microbiome-based biomarkers. Further research is needed to investigate specific components of the estrobolome, phytoestrogen-microbiota interactions, and mechanisms linking dysbiosis to estrogen-related pathology. However, current evidence suggests that the gut microbiota is an integral regulator of estrogen status with clinical relevance to women's health and hormonal disorders.
Topics: Female; Humans; Phytoestrogens; Gastrointestinal Microbiome; Equol; Estrogens; Breast Neoplasms
PubMed: 38342595
DOI: 10.1002/mnfr.202300688