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1.
Naturally Occurring Flavonoids and Isoflavonoids and Their Microbial Transformation: A Review.
Wang, JF, Liu, SS, Song, ZQ, Xu, TC, Liu, CS, Hou, YG, Huang, R, Wu, SH
Molecules (Basel, Switzerland). 2020;(21)
Abstract
Flavonoids and isoflavonoids are polyphenolic secondary metabolites usually produced by plants adapting to changing ecological environments over a long period of time. Therefore, their biosynthesis pathways are considered as the most distinctive natural product pathway in plants. Seemingly, the flavonoids and isoflavones from fungi and actinomycetes have been relatively overlooked. In this review, we summarized and classified the isoflavones and flavonoids derived from fungi and actinomycetes and described their biological activities. Increasing attention has been paid to bioactive substances derived from microorganism whole-cell biotransformation. Additionally, we described the utilization of isoflavones and flavonoids as substrates by fungi and actinomycetes for biotransformation through hydroxylation, methylation, halogenation, glycosylation, dehydrogenation, cyclisation, and hydrogenation reactions to obtain rare and highly active biofunctional derivatives. Overall, among all microorganisms, actinomycetes are the main producers of flavonoids. In our review, we also summarized the functional genes involved in flavonoid biosynthesis.
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2.
Scientific Evidence Supporting the Beneficial Effects of Isoflavones on Human Health.
Gómez-Zorita, S, González-Arceo, M, Fernández-Quintela, A, Eseberri, I, Trepiana, J, Portillo, MP
Nutrients. 2020;(12)
Abstract
Isoflavones are phenolic compounds with a chemical structure similar to that of estradiol. They are present in several vegetables, mainly in legumes such as soy, white and red clover, alfalfa and beans. The most significant food source of isoflavones in humans is soy-derived products. Isoflavones could be used as an alternative therapy for pathologies dependent on hormonal disorders such as breast and prostate cancer, cardiovascular diseases, as well as to minimize menopausal symptoms. According to the results gathered in the present review, it can be stated that there is scientific evidence showing the beneficial effect of isoflavones on bone health and thus in the prevention and treatment of osteoporosis on postmenopausal women, although the results do not seem entirely conclusive as there are discrepancies among the studies, probably related to their experimental designs. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. Regarding cancer, scientific evidence suggests that isoflavones could be useful in reducing the risk of suffering some types of cancer, such as breast and endometrial cancer, but further studies are needed to confirm these results. Finally, isoflavones could be useful in reducing hot flushes associated with menopause. However, a limitation in this field is that there is still a great heterogeneity among studies. Lastly, with regard to isoflavone consumption safety, it seems that they are safe and that the most common adverse effect is mild and occurs at the gastrointestinal level.
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3.
The potential health benefits of the isoflavone glycoside genistin.
Islam, A, Islam, MS, Uddin, MN, Hasan, MMI, Akanda, MR
Archives of pharmacal research. 2020;(4):395-408
Abstract
Genistin is a type of isoflavone glycoside and has a broad range of health benefits. It is found in a variety of dietary plants, such as soybean, kudzu (Japanese arrowroot), and other plant-based products. Genistin has been described to have several beneficial health impacts, such as decreasing the risk of osteoporosis and post-menopausal symptoms, as well as anti-cancer, anti-oxidative, cardioprotective, anti-apoptotic, neuroprotective, hepatoprotective, and anti-microbial activities. It may also assist individuals with metabolic syndrome. This review summarizes some of the molecular impacts and prospective roles of genistin in maintaining and treatment of health disorders. The review could help to develop novel genistin medicine with significant health benefits for application in the nutraceutical and pharmaceutical fields.
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4.
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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5.
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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6.
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.
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7.
Effect of soy isoflavone supplementation on plasma lipoprotein(a) concentrations: A meta-analysis.
Simental-Mendía, LE, Gotto, AM, Atkin, SL, Banach, M, Pirro, M, Sahebkar, A
Journal of clinical lipidology. 2018;(1):16-24
Abstract
BACKGROUND Soy supplementation has been shown to reduce total and low-density lipoprotein cholesterol, while increasing high-density lipoprotein cholesterol. However, contradictory effects of soy isoflavone supplementation on lipoprotein(a) [Lp(a)] have been reported suggesting the need for a meta-analysis to be undertaken. OBJECTIVE The aim of the study was to investigate the impact of supplementation with soy isoflavones on plasma Lp(a) levels through a systematic review and meta-analysis of eligible randomized placebo-controlled trials. METHODS The search included PubMed-Medline, Scopus, ISI Web of Knowledge, and Google Scholar databases (by March 26, 2017), and quality of studies was evaluated according to Cochrane criteria. Quantitative data synthesis was performed using a random-effects model, with standardized mean difference and 95% confidence interval as summary statistics. Meta-regression and leave-one-out sensitivity analysis were performed to assess the modifiers of treatment response. RESULTS Ten eligible studies comprising 11 treatment arms with 973 subjects were selected for the meta-analysis. Meta-analysis did not suggest any significant alteration of plasma Lp(a) levels after supplementation with soy isoflavones (standardized mean difference: 0.08, 95% confidence interval: -0.05, 0.20, P = .228). The effect size was robust in the leave-one-out sensitivity analysis. In meta-regression analysis, neither dose nor duration of supplementation with soy isoflavones was significantly associated with the effect size. CONCLUSION This meta-analysis of the 10 available randomized placebo-controlled trials revealed no significant effect of soy isoflavones treatment on plasma Lp(a) concentrations.
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8.
Effects of red clover on perimenopausal and postmenopausal women's blood lipid profile: A meta-analysis.
Luís, Â, Domingues, F, Pereira, L
Climacteric : the journal of the International Menopause Society. 2018;(5):446-453
Abstract
The study aimed to perform a systematic review with meta-analysis of randomized controlled trials (RCTs) to access the effects of red clover isoflavones on the blood lipid profile of both perimenopausal and postmenopausal women. PubMed, Web of Science, Scopus, SciELO, and Cochrane Library were searched for the terms 'red clover', 'Trifolium pratense', and 'randomized controlled trial' during November 2017. Summary measures were reported as weighted mean differences (WMD) with 95% confidence interval (CI). Fixed or random effects models were used for meta-analyses, according to heterogeneity. Risk of bias was measured with the Cochrane tool. Twelve RCTs (totalizing 1284 perimenopausal and postmenopausal women receiving red clover isoflavones for 4 weeks-18 months) resulted in a significant decrease in total cholesterol (WMD = -12.34 mg/dl; 95% CI: -18.21, -6.48), low-density lipoprotein cholesterol (WMD = -10.61 mg/dl; 95% CI: -15.51, -5.72), and triglycerides (WMD = -10.18 mg/dl; 95% CI: -16.23, -4.13) together with a significant increase in high-density lipoprotein cholesterol (WMD = 1.60 mg/dl; 95% CI: 0.17, 3.03). In conclusion, the results demonstrate that the ingestion of red clover may have a beneficial effect on the lipid profile of perimenopausal and postmenopausal women.
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9.
Isoflavones and bone health in perimenopausal and postmenopausal women.
Lambert, MNT, Jeppesen, PB
Current opinion in clinical nutrition and metabolic care. 2018;(6):475-480
Abstract
PURPOSE OF REVIEW Isoflavones exert estrogenic activity distinct from estrogen, they have the potential to treat diseases and symptoms related to estrogen deficiency with minimal side effects and risks. Isoflavone supplementation, in general, is shown to exert beneficial effects against estrogen-deficient bone loss in women, however, some clinical trials still produce conflicting findings. The purpose of this review is to highlight and summarize the most recent and up-to-date research in the field and to bring attention to factors that play a major role in the outcomes of clinical trials that investigate phytoestrogens. Here, we also discuss the latest and most relevant data regarding the clinical safety of these substances. RECENT FINDINGS Isoflavones are naturally occurring secondary metabolites found in the Fabacaea plant family. Clinical data from isoflavone interventions support that aglycones (abundant in fermented products) exert enhanced beneficial effects against estrogen-deficient bone loss in women compared with isoflavone glycosides. Studies that employ methods to determine isoflavone content and form of treatments are more likely detect beneficial effects on bone. EFSA have confirmed the safety of isoflavones for women in the most comprehensive report to date. SUMMARY Isoflavone aglycones exert greater effects against bone loss than glycosides. Isoflavones show promise as a first-line prophylactic/treatment for bone loss in women.
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10.
Effects of a standardised extract of Trifolium pratense (Promensil) at a dosage of 80mg in the treatment of menopausal hot flushes: A systematic review and meta-analysis.
Myers, SP, Vigar, V
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2017;:141-147
Abstract
OBJECTIVE To critically assess the evidence for a specific standardised extract of Trifolium pratense isoflavones (Promensil) at a dosage of 80mg/day in the treatment of menopausal hot flushes. DATA SOURCES Systematic literature searches were performed in Medline, Scopus, CINAHL Plus, Cochrane, AMED and InforRMIT and citations obtained from 1996 to March 2016. Reference lists were checked; corresponding authors contacted and the grey literature searched for additional publications. REVIEW METHODS Studies were selected according to predefined inclusion and exclusion criteria. All randomised clinical trials of a specific standardised extract of Trifolium pratense isoflavones (Promensil) used as a mono-component at 80mg/day and measuring vasomotor symptoms were included. The data extraction and quality assessment were performed independently by one reviewer and validated by a second with any disagreements being settled by discussion. Weighted mean differences and 95% confidence intervals were calculated for continuous data using the fixed-effects model. RESULTS Twenty potentially relevant papers were identified, with only five studies meeting the inclusion criteria. The meta-analysis demonstrated a statistical and clinically relevant reduction in hot flush frequency in the active treatment group compared to placebo. Weighted mean difference 3.63 hot flushes per day: [95% CI 2.70-4.56]; p˂0.00001). Due to a lack of homogeneity a priori defined sub-group analyses were performed demonstrating a substantive difference between cross-over and parallel-arm clinical trial designs. CONCLUSION There is evidence for a statistical and clinically significant benefit for using a specific standardised extract of red clover isoflavones (Promensil) at 80mg/day for treating hot flushes in menopausal women across the 3 studies included in the meta-analysis. The preparation was safe over the short-term duration of the studies (3 months).