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Nutrients Aug 2020Dietary phytoestrogens are bioactive compounds with estrogenic activity. With the growing popularity of plant-based diets, the intake of phytoestrogen-rich legumes... (Review)
Review
Dietary phytoestrogens are bioactive compounds with estrogenic activity. With the growing popularity of plant-based diets, the intake of phytoestrogen-rich legumes (especially soy) and legume-derived foods has increased. Evidence from preclinical studies suggests these compounds may have an effect on hormones and health, although the results of human trials are unclear. The effects of dietary phytoestrogens depend on the exposure (phytoestrogen type, matrix, concentration, and bioavailability), ethnicity, hormone levels (related to age, sex, and physiological condition), and health status of the consumer. In this review, we have summarized the results of human studies on dietary phytoestrogens with the aim of assessing the possible hormone-dependent outcomes and health effects of their consumption throughout a lifespan, focusing on pregnancy, childhood, adulthood, and the premenopausal and postmenopausal stages. In pregnant women, an improvement of insulin metabolism has been reported in only one study. Sex hormone alterations have been found in the late stages of childhood, and goitrogenic effects in children with hypothyroidism. In premenopausal and postmenopausal women, the reported impacts on hormones are inconsistent, although beneficial goitrogenic effects and improved glycemic control and cardiovascular risk markers have been described in postmenopausal individuals. In adult men, different authors report goitrogenic effects and a reduction of insulin in non-alcoholic fatty liver patients. Further carefully designed studies are warranted to better elucidate the impact of phytoestrogen consumption on the endocrine system at different life stages.
Topics: Adult; Child; Diet; Female; Gonadal Steroid Hormones; Heart Disease Risk Factors; Hormones; Humans; Hypothyroidism; Isoflavones; Lignans; Longevity; Male; Non-alcoholic Fatty Liver Disease; Phytoestrogens; Postmenopause; Pregnancy; Premenopause; Glycine max; Vegetables
PubMed: 32824177
DOI: 10.3390/nu12082456 -
International Journal of Molecular... Dec 2022Since chronic inflammation can be seen in severe, long-lasting diseases such as cancer, there is a high demand for effective methods to modulate inflammatory responses.... (Review)
Review
Since chronic inflammation can be seen in severe, long-lasting diseases such as cancer, there is a high demand for effective methods to modulate inflammatory responses. Among many therapeutic candidates, lignans, absorbed from various plant sources, represent a type of phytoestrogen classified into secoisolariciresionol (Seco), pinoresinol (Pino), matairesinol (Mat), medioresinol (Med), sesamin (Ses), syringaresinol (Syr), and lariciresinol (Lari). Lignans consumed by humans can be further modified into END or ENL by the activities of gut microbiota. Lignans are known to exert antioxidant and anti-inflammatory activities, together with activity in estrogen receptor-dependent pathways. Lignans may have therapeutic potential for postmenopausal symptoms, including cardiovascular disease, osteoporosis, and psychological disorders. Moreover, the antitumor efficacy of lignans has been demonstrated in various cancer cell lines, including hormone-dependent breast cancer and prostate cancer, as well as colorectal cancer. Interestingly, the molecular mechanisms of lignans in these diseases involve the inhibition of inflammatory signals, including the nuclear factor (NF)-κB pathway. Therefore, we summarize the recent in vitro and in vivo studies evaluating the biological effects of various lignans, focusing on their values as effective anti-inflammatory agents.
Topics: Humans; Anti-Inflammatory Agents; Antioxidants; Cardiovascular Diseases; Lignans; Neoplasms; NF-kappa B; Phytoestrogens
PubMed: 36555124
DOI: 10.3390/ijms232415482 -
Arthritis Research & Therapy May 2021To investigate the role and regulatory mechanisms of fargesin, one of the main components of Magnolia fargesii, in macrophage reprogramming and crosstalk across...
BACKGROUND
To investigate the role and regulatory mechanisms of fargesin, one of the main components of Magnolia fargesii, in macrophage reprogramming and crosstalk across cartilage and synovium during osteoarthritis (OA) development.
METHODS
Ten-week-old male C57BL/6 mice were randomized and assigned to vehicle, collagenase-induced OA (CIOA), or CIOA with intra-articular fargesin treatment groups. Articular cartilage degeneration was evaluated using the Osteoarthritis Research Society International (OARSI) score. Immunostaining and western blot analyses were conducted to detect relative protein. Raw264.7 cells were treated with LPS or IL-4 to investigate the role of polarized macrophages. ADTC5 cells were treated with IL-1β and conditioned medium was collected to investigate the crosstalk between chondrocytes and macrophages.
RESULTS
Fargesin attenuated articular cartilage degeneration and synovitis, resulting in substantially lower Osteoarthritis Research Society International (OARSI) and synovitis scores. In particular, significantly increased M2 polarization and decreased M1 polarization in synovial macrophages were found in fargesin-treated CIOA mice compared to controls. This was accompanied by downregulation of IL-6 and IL-1β and upregulation of IL-10 in serum. Conditioned medium (CM) from M1 macrophages treated with fargesin reduced the expression of matrix metalloproteinase-13, RUNX2, and type X collagen and increased Col2a1 and SOX9 in OA chondrocytes, but fargesin alone did not affect chondrocyte catabolic processes. Moreover, fargesin exerted protective effects by suppressing p38/ERK MAPK and p65/NF-κB signaling.
CONCLUSIONS
This study showed that fargesin switched the polarized phenotypes of macrophages from M1 to M2 subtypes and prevented cartilage degeneration partially by downregulating p38/ERK MAPK and p65/NF-κB signaling. Targeting macrophage reprogramming or blocking the crosstalk between macrophages and chondrocytes in early OA may be an effective preventive strategy.
Topics: Animals; Benzodioxoles; Cartilage, Articular; Chondrocytes; Interleukin-1beta; Lignans; Macrophages; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Osteoarthritis
PubMed: 33990219
DOI: 10.1186/s13075-021-02512-z -
Nature Communications Oct 2019Arctigenin (ATG) is a major component of Fructus Arctii, a traditional herbal remedy that reduced proteinuria in diabetic patients. However, whether ATG specifically...
Arctigenin (ATG) is a major component of Fructus Arctii, a traditional herbal remedy that reduced proteinuria in diabetic patients. However, whether ATG specifically provides renoprotection in DKD is not known. Here we report that ATG administration is sufficient to attenuate proteinuria and podocyte injury in mouse models of diabetes. Transcriptomic analysis of diabetic mouse glomeruli showed that cell adhesion and inflammation are two key pathways affected by ATG treatment, and mass spectrometry analysis identified protein phosphatase 2 A (PP2A) as one of the top ATG-interacting proteins in renal cells. Enhanced PP2A activity by ATG reduces p65 NF-κB-mediated inflammatory response and high glucose-induced migration in cultured podocytes via interaction with Drebrin-1. Importantly, podocyte-specific Pp2a deletion in mice exacerbates DKD injury and abrogates the ATG-mediated renoprotection. Collectively, our results demonstrate a renoprotective mechanism of ATG via PP2A activation and establish PP2A as a potential target for DKD progression.
Topics: Animals; Arctium; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Disease Progression; Furans; Humans; Lignans; Male; Mice; Mice, Knockout; Microscopy, Electron, Transmission; Nitric Oxide Synthase Type III; Podocytes; Protein Phosphatase 2; Streptozocin; Treatment Outcome
PubMed: 31586053
DOI: 10.1038/s41467-019-12433-w -
Nutrients Sep 2022Sesame ( L.), of the Pedaliaceae family, is one of the first oil crops used in humans. It is widely grown and has a mellow flavor and high nutritional value, making it... (Review)
Review
Sesame ( L.), of the Pedaliaceae family, is one of the first oil crops used in humans. It is widely grown and has a mellow flavor and high nutritional value, making it very popular in the diet. Sesame seeds are rich in protein and lipids and have many health benefits. A number of in vitro and in vivo studies and clinical trials have found sesame seeds to be rich in lignan-like active ingredients. They have antioxidant, cholesterol reduction, blood lipid regulation, liver and kidney protection, cardiovascular system protection, anti-inflammatory, anti-tumor, and other effects, which have great benefits to human health. In addition, the aqueous extract of sesame has been shown to be safe for animals. As an important medicinal and edible homologous food, sesame is used in various aspects of daily life such as food, feed, and cosmetics. The health food applications of sesame are increasing. This paper reviews the progress of research on the nutritional value, chemical composition, pharmacological effects, and processing uses of sesame to support the further development of more functionalities of sesame.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Humans; Lignans; Lipids; Nutritive Value; Phytochemicals; Seeds; Sesamum
PubMed: 36235731
DOI: 10.3390/nu14194079 -
European Journal of Medical Research Jul 2023Flaxseed (Linum usitatissimum L) is an ancient perennial plant species regarded as a multipurpose plant owing to its richness in omega-3 polyunsaturated fatty acids... (Review)
Review
Flaxseed (Linum usitatissimum L) is an ancient perennial plant species regarded as a multipurpose plant owing to its richness in omega-3 polyunsaturated fatty acids (PUFA) including α-linolenic acid (ALA). The extensive biochemical analysis of flaxseed resulted in the identification of its bioactive, i.e., lignans with potential application in the improvement of human health. Flaxseed oil, fibers, and lignans exert potential health benefits including reduction of cardiovascular disease, atherosclerosis, diabetes, cancer, arthritis, osteoporosis, and autoimmune and neurological disorders that have led to the diversification of flaxseed plant applications. This comprehensive review focuses on flaxseed oil as the major product of flaxseed with emphasis on the interrelationship between its chemical composition and biological effects. Effects reviewed include antioxidant, anti-inflammatory, antimicrobial, anticancer, antiulcer, anti-osteoporotic, cardioprotective, metabolic, and neuroprotective. This study provides an overview of flaxseed oil effects with the reported action mechanisms related to its phytochemical composition and in comparison, to other PUFA-rich oils. This study presents the most updated and comprehensive review summarizing flaxseed oil's health benefits for the treatment of various diseases.
Topics: Humans; Linseed Oil; Flax; Cardiovascular Diseases; Antioxidants; Lignans
PubMed: 37464425
DOI: 10.1186/s40001-023-01203-6 -
British Journal of Pharmacology Nov 2020Arctigenin, a major bioactive component of Fructus arctii, has been reported to have antidepressant-like effects. However, the mechanisms underlying these effects are...
BACKGROUND AND PURPOSE
Arctigenin, a major bioactive component of Fructus arctii, has been reported to have antidepressant-like effects. However, the mechanisms underlying these effects are still unclear. Neuroinflammation can be caused by excessive production of proinflammatory cytokines in microglia via high-mobility group box 1 (HMGB1)/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signalling pathways, leading to depression. In this study, we have investigated the antidepressant mechanism of arctigenin by conducting in vitro and in vivo studies.
EXPERIMENTAL APPROACH
The effects of chronic unpredictable mild stress (CUMS) on wild-type (WT) and TLR4 mice were examined. Antidepressant-like effects of arctigenin were tested using the CUMS-induced model of depression in WT mice. The effects of arctigenin were assessed on the HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signalling pathways in the prefrontal cortex (PFC) of mouse brain and HMGB1- or TNF-α-stimulated primary cultured microglia. The interaction between HMGB1 and TLR4 or TNF-α and TNFR1 with or without arctigenin was examined by localized surface plasmon resonance (LSPR) and co-immunoprecipitation assays.
KEY RESULTS
The immobility times in the tail suspension test (TST) and forced swimming test (FST) were reduced in TLR4 mice, compared with WT mice. Arctigenin exhibited antidepressant-like effects. Arctigenin also inhibited microglia activation and inflammatory responses in the PFC of mouse brain. Arctigenin inhibited HMGB1 and TLR4 or TNF-α and TNFR1 interactions, and suppressed both HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signalling pathways.
CONCLUSIONS AND IMPLICATIONS
Arctigenin has antidepressant-like effects by attenuating excessive microglial activation and neuroinflammation through the HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signalling pathways. This suggests that arctigenin has potential as a new drug candidate suitable for clinical trials to treat depression.
Topics: Animals; Depression; Furans; HMGB1 Protein; Lignans; Mice; Microglia; NF-kappa B; Receptors, Tumor Necrosis Factor, Type I; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha
PubMed: 32964428
DOI: 10.1111/bph.15261 -
European Journal of Nutrition Apr 2022Dietary lignans are phytoestrogens that are mostly found in plant-based foods, especially whole grains, seeds, nuts, legumes and vegetables. An accurate assessment of... (Review)
Review
Dietary lignans are phytoestrogens that are mostly found in plant-based foods, especially whole grains, seeds, nuts, legumes and vegetables. An accurate assessment of lignan exposure is crucial to evaluate their potential health benefits and to establish future recommendations and dietary guidelines. This narrative review aimed to (i) summarize the pros and the cons of the current main assessment methods for lignan exposure─i.e., dietary questionnaires, food composition tables and biomarkers, (ii) describe the individual lignans more consumed from a worldwide perspective, as well as their main food sources, (iii) determine the lignans concentrations in both urine and blood, and explore their heterogeneity among countries, and finally (iv) discuss the main determinants of lignan exposure.
Topics: Diet; Lignans; Nuts; Phytoestrogens; Vegetables
PubMed: 34799775
DOI: 10.1007/s00394-021-02736-4 -
International Journal of Molecular... Dec 2021Schizandrin A (SchA) can be extracted from the vine plant and has been reported to confer various biologically active properties. However, its potential biological...
Schizandrin A (SchA) can be extracted from the vine plant and has been reported to confer various biologically active properties. However, its potential biological effects on non‑small cell lung cancer (NSCLC) remain unknown. Therefore, the present study aims to address this issue. NSCLC and normal lung epithelial cell lines were first treated with SchA. Cell viability and proliferation were measured using CellTiter‑Glo Assay and colony formation assays, respectively. PI staining was used to measure cell cycle distribution. Cell cycle‑related proteins p53, p21, cyclin D1, CDK4, CDK6, cyclin E1, cyclin E2, CDK2 and DNA damage‑related protein SOX4 were detected by western blot analysis. Annexin V‑FITC/PI staining, DNA electrophoresis and Hoechst 33342/PI dual staining were used to detect apoptosis. JC‑1 and DCFH‑DA fluorescent dyes were used to measure the mitochondrial membrane potential and reactive oxygen species concentrations, respectively. Apoptosis‑related proteins caspase‑3, cleaved caspase‑3, poly(ADP‑ribose) polymerase (PARP), cleaved PARP, BimEL, BimL, BimS, Bcl2, Bax, caspase‑9 and cleaved caspas‑9 were measured by western blot analysis. Dansylcadaverine was used to detect the presence of the acidic lysosomal vesicles. The expression levels of the autophagy‑related proteins LC3‑I/II, p62/SQSTM and AMPKα activation were measured using western blot analysis. In addition, the autophagy inhibitor 3‑methyladenine was used to inhibit autophagy. SchA treatment was found to reduce NSCLC cell viability whilst inhibiting cell proliferation. Low concentrations of SchA (10‑20 µM) mainly induced G/S‑phase cell cycle arrest. By contrast, as the concentration of SchA used increases (20‑50 µM), cells underwent apoptosis and G/M‑phase cell cycle a13rrest. As the treatment concentration of SchA increased from 0 to 50 µM, the expression of p53 and SOX4 protein also concomitantly increased, but the expression of p21 protein was increased by 10 µM SchA and decreased by higher concentrations (20‑50 µM). In addition, the mRNA and protein expression levels of Bcl‑like 11 (Bim)EL, BimL and BimS increased following SchA application. SchA induced the accumulation of acidic vesicles and induced a marked increase in the expression of LC3‑II protein, suggsting that SchA activated the autophagy pathway. However, the expression of the p62 protein was found to be increased by SchA, suggesting that p62 was not degraded during the autophagic flux. The 3‑methyladenine exerted no notable effects on SchA‑induced apoptosis. Taken together, results from the present study suggest that SchA exerted inhibitory effects on NSCLC physiology by inducing cell cycle arrest and apoptosis. In addition, SchA partially induced autophagy, which did not result in any cytoprotective effects.
Topics: Adenosine Triphosphate; Antineoplastic Agents, Phytogenic; Apoptosis; Autophagy; Carcinoma, Non-Small-Cell Lung; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cyclooctanes; Humans; Lignans; Lung Neoplasms; Membrane Potential, Mitochondrial; Polycyclic Compounds; Proteins; Reactive Oxygen Species
PubMed: 34643254
DOI: 10.3892/ijmm.2021.5047 -
Journal of the American College of... Aug 2021
Topics: Cardiovascular Diseases; Humans; Lignans; Polyphenols
PubMed: 34384549
DOI: 10.1016/j.jacc.2021.06.014