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1.
NMR studies of daidzein and puerarin: active anti-oxidants in traditional Chinese medicine.
Yi, Y, Adrjan, B, Li, J, Hu, B, Roszak, S
Journal of molecular modeling. 2019;(7):202
Abstract
Radix puerariae-a popular traditional Chinese medicine-is used for the treatment of diarrhea, acute dysentery, deafness, and cardiovascular diseases. It can also be used as an effective antioxidant and has been tested as an anticancer drug. Daidzein and puerarin are its main active compounds. The present contribution was focused on experimental and theoretical studies of the 1H and 13C NMR chemical shifts and nuclear magnetic shielding parameters of daidzein and puerarin. Experimental data were gained by exploring standard one-dimensional spectra and a set of two-dimensional measurements: COSY, HSQC, and HMBC. The theoretical gauge independent atomic orbital density functional theory supporting studies, were performed to determine shielding constants and chemical shifts in vacuum and methanol-d4 solvent. The correlation between experimental and theoretical data was fairly good, especially when the DFT/PBE0 approach was used. The molecular properties of daidzein and puerine related to antiradical activity were studied in the context of a single-step hydrogen atom transfer mechanism and its correlation with 13C NMR chemical shifts. Graphical abstract Electron spin density distribution for daidzein radical.
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2.
Triggering of eryptosis, the suicidal erythrocyte death, by phenoxodiol.
Fink, M, Bhuyan, AAM, Nürnberg, B, Faggio, C, Lang, F
Naunyn-Schmiedeberg's archives of pharmacology. 2019;(10):1311-1318
Abstract
Phenoxodiol is used for the treatment of malignancy. The substance is effective by triggering suicidal tumor cell death or apoptosis. At least in theory, phenoxodiol could similarly stimulate suicidal erythrocyte death or eryptosis. Eryptosis is characterized by cell shrinkage and breakdown of cell membrane asymmetry with phosphatidylserine translocation to the erythrocyte surface. Signaling of eryptosis includes increase of cytosolic Ca2+ activity ([Ca2+]i), formation of reactive oxygen species (ROS), and increase of ceramide abundance at the cell surface. The present study explored whether phenoxodiol induces eryptosis and whether it modifies Ca2+ entry, ROS, and ceramide. Using flow cytometry, phosphatidylserine exposure at the cell surface was quantified from annexin V binding, cell volume from forward scatter, [Ca2+]i from Fluo3 fluorescence, ROS from DCFDA-dependent fluorescence, and ceramide abundance utilizing specific antibodies. A 48-h exposure of human erythrocytes to phenoxodiol (100 μg/ml [416 μM]) significantly increased the percentage of annexin V binding cells, significantly decreased average forward scatter and Fluo3 fluorescence and significantly increased ceramide abundance, but did not significantly modify DCFDA fluorescence. The effect of phenoxodiol on annexin V binding tended to decrease following removal of extracellular Ca2+, an effect, however, not reaching statistical significance. In conclusion, phenoxodiol triggers eryptosis, an effect paralleled by increase of ceramide abundance.
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3.
Polyphenols: A concise overview on the chemistry, occurrence, and human health.
Durazzo, A, Lucarini, M, Souto, EB, Cicala, C, Caiazzo, E, Izzo, AA, Novellino, E, Santini, A
Phytotherapy research : PTR. 2019;(9):2221-2243
Abstract
This review gives an updated picture of each class of phenolic compounds and their properties. The most common classification implies the subdivision of phenolics in two main groups: flavonoids (e.g., anthocyanins, flavanols, flavanones, flavonols, flavonones, and isoflavones) and non-flavonoids (e.g., phenolic acids, xanthones, stilbens, lignans, and tannins) polyphenols. The great interest in polyphenols is associated with their high potential application for food preservation and for therapeutic beneficial use. The relationship between polyphenol intake and human health has been exploited with special reference to cardiovascular diseases, hypertension, diabetes, metabolic syndrome, obesity, and cancer. The use of current existing databases of bioactive compounds including polyphenols is described as key tools for human health research.
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4.
Soy Isoflavone Supplementation Increases Long Interspersed Nucleotide Element-1 (LINE-1) Methylation in Head and Neck Squamous Cell Carcinoma.
Rozek, LS, Virani, S, Bellile, EL, Taylor, JMG, Sartor, MA, Zarins, KR, Virani, A, Cote, C, Worden, FP, Mark, MEP, et al
Nutrition and cancer. 2019;(5):772-780
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Abstract
AIM: Soy isoflavones have been suggested as epigenetic modulating agents with effects that could be important in carcinogenesis. Hypomethylation of LINE-1 has been associated with head and neck squamous cell carcinoma (HNSCC) development from oral premalignant lesions and with poor prognosis. To determine if neoadjuvant soy isoflavone supplementation could modulate LINE-1 methylation in HNSCC, we undertook a clinical trial. METHODS Thirty-nine patients received 2-3 weeks of soy isoflavone supplements (300 mg/day) orally prior to surgery. Methylation of LINE-1, and 6 other genes was measured by pyrosequencing in biopsy, resection, and whole blood (WB) specimens. Changes in methylation were tested using paired t tests and ANOVA. Median follow up was 45 months. RESULTS LINE-1 methylation increased significantly after soy isoflavone (P < 0.005). Amount of change correlated positively with days of isoflavone taken (P = 0.04). Similar changes were not seen in corresponding WB samples. No significant changes in tumor or blood methylation levels were seen in the other candidate genes. CONCLUSION This is the first demonstration of in vivo increases in tissue-specific global methylation associated with soy isoflavone intake in patients with HNSCC. Prior associations of LINE-1 hypomethylation with genetic instability, carcinogenesis, and prognosis suggest that soy isoflavones maybe potential chemopreventive agents in HNSCC.
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Soy, Soy Isoflavones, and Protein Intake in Relation to Mortality from All Causes, Cancers, and Cardiovascular Diseases: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.
Nachvak, SM, Moradi, S, Anjom-Shoae, J, Rahmani, J, Nasiri, M, Maleki, V, Sadeghi, O
Journal of the Academy of Nutrition and Dietetics. 2019;(9):1483-1500.e17
Abstract
OBJECTIVE We conducted a systematic review and dose-response meta-analysis of prospective studies to summarize findings on the associations between intakes of soy, soy isoflavones, and soy protein and risk of mortality from all causes, cancers, and cardiovascular diseases. METHODS Online databases were systematically searched to identify relevant articles published earlier than May 2018. We applied restricted cubic splines using random-effects analysis to assess dose-response associations. Between-study heterogeneity was assessed by I2 value and Cochrane Q test. Potential publication bias was assessed by visual inspection of funnel plots and Begg regression test. RESULTS In total, 23 prospective studies with an overall sample size of 330,826 participants were included in the current systematic review and the meta-analysis. Soy/soy products consumption was inversely associated with deaths from cancers (pooled relative risk 0.88, 95% CI 0.79 to 0.99; P=0.03; I2=47.1%, 95% CI 0.0% to 75.4%) and cardiovascular diseases (pooled effect size: 0.85, 95% CI 0.72 to 0.99; P=0.04; I2=50.0%, 95% CI 0.0% to 77.6%). Such significant associations were also observed for all-cause mortality in some subgroups of the included studies, particularly those with higher quality. In addition, higher intake of soy was associated with decreased risk of mortality from gastric, colorectal, and lung cancers as well as ischemic cardiovascular diseases. Participants in the highest category of dietary soy isoflavones intake had a 10% lower risk of all-cause mortality compared with those in the lowest category. We also found that a 10-mg/day increase in intake of soy isoflavones was associated with 7% and 9% decreased risk of mortality from all cancers and also breast cancer respectively. Furthermore, a 12% reduction in breast cancer death was indicated for each 5-g/day increase in consumption of soy protein. However, intake of soy protein was not significantly associated with all-cause and cardiovascular diseases mortality. CONCLUSIONS Soy and its isoflavones may favorably influence risk of mortality. In addition, soy protein intake was associated with a decreased risk in the mortality of breast cancer. Our findings may support the current recommendations to increase intake of soy for greater longevity.
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Isoflavone supplementation plus combined aerobic and resistance exercise do not change phase angle values in postmenopausal women: A randomized placebo-controlled clinical trial.
Barbosa, CD, Costa, JG, Giolo, JS, Rossato, LT, Nahas, PC, Mariano, IM, Batista, JP, Puga, GM, de Oliveira, EP
Experimental gerontology. 2019;:31-37
Abstract
OBJECTIVE The aim of this study was to evaluate the effect of isoflavone supplementation plus combined exercise protocol on phase angle (PhA) values in postmenopausal women. METHODS Thirty postmenopausal women were randomly assigned in a double blind, placebo-controlled clinical trial divided into two groups: 100 mg/day of isoflavone supplementation (n = 16) and 100 mg/day of starch (placebo; n = 14). In addition, both groups performed a combined aerobic and resistance exercise during 10 weeks. Body composition and PhA were evaluated by bioelectrical impedance. RESULTS PhA values did not change in the isoflavone group (PRE: 6.7 ± 0.7° to POST 6.7 ± 0.6°) and in the placebo group (PRE: 7.2 ± 1.0° to POST 6.8 ± 0.5°); p group = 0.304, p time = 0.227, p group x time interaction = 0.137. Additionally, delta values were not different (0.04 ± 0.5° vs. -0.40 ± 0.99°; p = 0.176) between isoflavone and placebo groups, respectively. CONCLUSION We conclude that isoflavone supplementation plus combined aerobic and resistance exercise did not change PhA in postmenopausal women. The patients were part of ClinicalTrials.gov: NCT03008785.
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Multiple docking analysis and In silico absorption, distribution, metabolism, excretion, and toxicity screening of anti-leprosy phytochemicals and dapsone against dihydropteroate synthase of Mycobacterium leprae.
Halder, ST, Dhorajiwala, TM, Samant, LR
International journal of mycobacteriology. 2019;(3):229-236
Abstract
BACKGROUND Leprosy is a neglected tropical disease affecting millions of people. The current treatment against leprosy includes various antibacterial drugs of which dapsone is known to bind to dihydropteroate synthase of Mycobacterium leprae. Dapsone is an expensive antibacterial drug with many side effects. A natural alternative for dapsone having less to no side effects and cheaper in production is needed. The three-dimensional protein structure of dihydropteroate synthase of M. leprae is not available. METHODS Protein homology modeling of target protein was carried out, and protein structure validation and energy minimization were performed. Phytochemicals mentioned in literature having anti-leprosy properties were studied for absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties and that which passed ADMET filters were further carried for comparative in silico docking analysis along with dapsone. Preliminary docking analysis was carried using AutoDock Vina, and results obtained were validated using AutoDock 4.2.6 and SwissDock. RESULTS Neobavaisoflavone was predicted to be ten times safer for administration than dapsone. On performing in silico docking, it was found that neobavaisoflavone has better binding affinity than dapsone and forms a stable protein-ligand complex. Residues GLY.50, THR.88, and VAL.107 play an important role as binding site residues. CONCLUSION Further, in vitro and in vivo experimental studies are required to confirm anti-leprosy properties of neobavaisoflavone over drug dapsone.
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Effect of S-equol and Soy Isoflavones on Heart and Brain.
Sekikawa, A, Ihara, M, Lopez, O, Kakuta, C, Lopresti, B, Higashiyama, A, Aizenstein, H, Chang, YF, Mathis, C, Miyamoto, Y, et al
Current cardiology reviews. 2019;(2):114-135
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Abstract
BACKGROUND Observational studies in Asia show that dietary intake of soy isoflavones had a significant inverse association with coronary heart disease (CHD). A recent randomized controlled trial (RCT) of soy isoflavones on atherosclerosis in the US, however, failed to show their benefit. The discrepancy may be due to the much lower prevalence of S-equol producers in Westerners: Only 20-30% of Westerners produce S-equol in contrast to 50-70% in Asians. S-equol is a metabolite of dietary soy isoflavone daidzein by gut microbiome and possesses the most antiatherogenic properties among all isoflavones. Several short-duration RCTs documented that soy isoflavones improves arterial stiffness. Accumulating evidence shows that both atherosclerosis and arterial stiffness are positively associated with cognitive decline/dementia. Therefore, potentially, soy isoflavones, especially S-equol, are protective against cognitive decline/dementia. METHODS/RESULTS This narrative review of clinical and epidemiological studies provides an overview of the health benefits of soy isoflavones and introduces S-equol. Second, we review recent evidence on the association of soy isoflavones and S-equol with CHD, atherosclerosis, and arterial stiffness as well as the association of atherosclerosis and arterial stiffness with cognitive decline/ dementia. Third, we highlight recent studies that report the association of soy isoflavones and S-equol with cognitive decline/dementia. Lastly, we discuss the future directions of clinical and epidemiological research on the relationship of S-equol and CHD and dementia. CONCLUSIONS Evidence from observational studies and short-term RCTs suggests that S-equol is anti-atherogenic and improves arterial stiffness and may prevent CHD and cognitive impairment/ dementia. Well-designed long-term (≥ 2years) RCTs should be pursued.
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Soy and isoflavones consumption and breast cancer survival and recurrence: a systematic review and meta-analysis.
Qiu, S, Jiang, C
European journal of nutrition. 2019;(8):3079-3090
Abstract
BACKGROUND Some studies have investigated the association between soy and isoflavones consumption and breast cancer survival, but the results are far from conclusive. Accordingly, we performed a systematic review and meta-analysis to explore this issue. METHODS We performed a comprehensive search of Web of Science, PubMed, and Embase from inception to January 2018. The summary hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a random effects model. RESULTS A total of 12 articles were included, which reported overall survival (OS), breast cancer specific survival (BCSS), and recurrence in 5770, 2386, and 1500 cases, respectively, among 37,275 women with breast cancer. The summary HR (95% CI) for the association (highest vs. lowest) of pre-diagnosis soy and isoflavones consumption with OS and BCSS was 0.84 (0.71-0.98) and 0.89 (0.74-1.07), respectively. Stratified analyses suggested that the reduced OS was more easily detected in studies that focused on post-menopausal patients. No significant association was found between post-diagnosis soy and isoflavones consumption with OS and BCSS, with summary HRs (95% CIs) of 0.80 (0.62-1.04) and 0.83 (0.64-1.07), respectively. Pre- and post-diagnosis soy isoflavones consumption were associated with reduced risk of recurrence. CONCLUSION This study provides limited evidence that pre-diagnosis soy and isoflavones intake is associated with a small reduction in post-menopausal breast cancer OS.
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Dietary soybean isoflavones in Alzheimer's disease prevention.
Lu, Y, An, Y, Lv, C, Ma, W, Xi, Y, Xiao, R
Asia Pacific journal of clinical nutrition. 2018;(5):946-954
Abstract
Soybean isoflavone (SIF) is a type of polyphenol present extensively in legumes. Because of its unique chemical construction and the physiological activity of the phenolic hydroxyl group, SIF exhibits strong antioxidant activity in antioxidant and nonantioxidant enzyme systems. Genistein is the major isoflavone in soy foods, accounting for more than 50% of the isoflavone content. The health effects of soybean dietary isoflavones on humans have gained increased attention. Recent studies have suggested that SIF may alleviate neurodegenerative diseases such as Alzheimer's disease (AD). Despite the comprehensive research on AD, effective treatments for AD are yet to be established. The early diagnosis and prevention of mild cognitive impairment (MCI) have become crucial for delaying AD development. Several dietary polyphenols have exerted cognitive effects on AD, and the appropriate intake of dietary SIF helps reduce the risk of AD. This study reviews the possible mechanisms of AD pathogenesis and their relationships with SIF intake; the results provide useful insights for AD prevention in the future.