Insect-induced daidzein, formononetin and their conjugates in soybean leaves.

In response to attack by bacterial pathogens, soybean (Gylcine max) leaves accumulate isoflavone aglucones, isoflavone glucosides, and glyceollins. In contrast to pathogens, the dynamics of related insect-inducible metabolites in soybean leaves remain poorly understood. In this study, we analyzed the biochemical responses of soybean leaves to Spodoptera litura (Lepidoptera: Noctuidae) herbivory and also S. litura gut contents, which contain oral secretion elicitors. Following S. litura herbivory, soybean leaves displayed an induced accumulation of the flavone and isoflavone aglycones 4',7-dihyroxyflavone, daidzein, and formononetin, and also the isoflavone glucoside daidzin. Interestingly, foliar application of S. litura oral secretions also elicited the accumulation of isoflavone aglycones (daidzein and formononetin), isoflavone 7-O-glucosides (daidzin, ononin), and isoflavone 7-O-(6'-O-malonyl-β-glucosides) (malonyldaidzin, malonylononin). Consistent with the up-regulation of the isoflavonoid biosynthetic pathway, folair phenylalanine levels also increased following oral secretion treatment. To establish that these metabolitic changes were the result of de novo biosynthesis, we demonstrated that labeled (13C9) phenylalanine was incorporated into the isoflavone aglucones. These results are consistent with the presence of soybean defense elicitors in S. litura oral secretions. We demonstrate that isoflavone aglycones and isoflavone conjugates are induced in soybean leaves, not only by pathogens as previously demonstrated, but also by foliar insect herbivory

PENGARUH SUPLEMENTASI ISOFLAVON KEDELAI TERHADAP WANITA PENDERITA AKNE VULGARIS : Kajian Jumlah Lesi, Dihydrotestosterone, Toll-Like Receptor-2, dan Interleukin-8

Latar belakang : Akne vulgaris (AV) merupakan penyakit inflamasi kulit yang paling sering dijumpai. Isoflavon kedelai telah terbukti sebagai antiandrogen dan antiinflamasi. Tujuan penelitian ini membuktikan pengaruh isoflavon kedelai terhadap lesi AV akibat penurunan kadar dihydrotestosterone (DHT), Toll-like receptor-2 (TLR-2), Interleukin-8 (IL-8) pada wanita penderita AV. Metoda : Randomized pre and post test control design. Penelitian pendahuluan dengan besar sampel 25 orang, dirandomisasi dalam kelompok plasebo, isoflavon 40 mg, 80 mg, 120 mg, 160 mg, lama penelitian 4 minggu. Penelitian lanjutan dengan 40 sampel, dirandomisasi dalam kelompok kontrol dan perlakuan, lama penelitian 12 minggu. Variabel bebas isoflavon kedelai, varibel terikat lesi AV dan variabel antara adalah DHT, TLR-2, dan IL-8. Hasil : Lesi AV pada awal penelitian pendahuluan 100,178,92 dan akhir penelitian 78,945,85 terdapat penurunan bermakna (t:2,525)(p:0,019). Delta kelompok isoflavon 160 mg lebih besar dari plasebo, isoflavon 40 mg, 80 mg, dan 120 mg (Z:-2,611)(p: 0,009). Lesi AV pada awal penelitian lanjutan 97,8547,614 dan akhir penelitian 59,3845,549, terdapat penurunan yang bermakna (Z:-4,300)(p:0,000). DHT awal penelitian 307,6150,38 pg/ml dan akhir penelitian 283,5253,13 pg/ml, terdapat penurunan yang bermakna (Z:-2,204)(p:0,027). TLR-2 awal penelitian 4539,82862 pg/ml dan akhir penelitian 3944,63592,42 pg/ml terdapat penurunan bermakna (Z:-3,624)(p:0,000). IL-8 awal penelitian 411,3167,137 pg/ml dan akhir penelitian 311,09103,917 pg/ml, terdapat penurunan bermakna (Z:-4,557) (p:0,000). Simpulan : Pemberian suplementasi isoflavon kedelai dengan variasi dosis selama 4 minggu, dapat menurunkan lesi AV dan diperoleh dosis yang paling baik yaitu dosis 160 mg serta pemberian selama 12 minggu menyebabkan penurunan bermakna terhadap lesi AV, DHT, TLR-2, dan IL-8 dibandingkan terapi standar. Kata kunci : Akne vulgaris, isoflavon kedelai, lesi AV, DHT, TLR-2, IL-8. Background. Acne vulgaris (AV) is the most common feature of skin inflammatory diseases. Soy isoflavone has proven as an anti-androgen and an anti-inflammation. The purpose of this research was to prove the effect of soy isoflavone in AV lesion that caused by the decreased level of dihydrotestoreone (DHT), Toll-like receptor-2 (TLR-2), Interleukin-8 (IL-8) in women with AV. Methods. This research used randomized pre and post test control design. The first research had 25 samples, randomized in 5 groups: placebo, isoflavone 40 mg, 80 mg, 120 mg, 160 mg group in 4 weeks length of research. The last research had 40 samples, randomized in controled and threated group in 12 weeks length of research. The independent variables was soy isoflavone, the dependent variables was AV, the confounding variables were DHT, TLR-2, and IL-8. Results. There was a significant degradation (t=2.525; p=0.019) of AV lesion in the early (100.1+78.92) and in the end of the first research (78.9+45.85). Delta of isoflavone 160 mg group more than other groups (Z=-2.61; p=0.009). There was a significant degradation (Z=-4.300; p=0.000) of AV lesion in the early (97.85+47.614) and in the end of the last research (59.38+45.5). DHT level had a signficant decrease (Z=-2.204; p=0.027) from the first research (307.6+150.38 pg/ml) to the last research (283.5+253.13 pg/ml). TLR-2 level had a signficant decrease (Z=-3.624; p=0.000) from the first research (4539.8+2862 pg/ml) to the last research (3944.6+3592.42 pg/ml). IL-8 level had a signficant decrease (Z=-4.557; p=0.000) from the first research (411.31+67.137 pg/ml) to the last research (311.09+103.917 pg/ml). Conclusion. The administration of soy isoflavone with variances of doses in 4 weeks can decrease AV lesion and the best dose was 160 mg, and the administration in 12 weeks can make significant degradation of AV lesion and significant decreased level of DHT, TLR-2, and IL-8 compared by standard therapy. Keywords: Acne vulgaris, soy isoflavone, AV lesion, DHT, TLR-2, IL-

Near Infrared Reflectance Spectroscopy (NIRS) Determination of Isoflavone Contents for Selected Soybean Accessions

Soybean isoflavones are of considerable interest in relation to their possible health effects in human diets. The rapid and economical determination of soybean isoflavone concentrations is essential for the investigation and development of soybean health foods as well as the selection of soybean seeds with optimal isoflavone levels for such foods. Fourier transforms near infrared reflectance spectroscopy (FT-NIRS) calibrations were developed for the rapid and cost-effective analysis of isoflavones in soybean seeds. FT-NIRS measurements were carried out in quadruplicate for 50 soybean lines selected from the USDA Soybean Germplasm Collection. The selected soybean seeds provided a wide range of isoflavone concentrations (from 0.3 to 6.0 mg/g) that is necessary for development of high-quality calibrations. Laboratory reference values of isoflavone composition were obtained by HPLC analysis of extracted soybean powders. Single soybean seeds were selected for each standard sample and were cut in half in order to avoid screening of the isoflavones NIR absorption bands by the seed coat. For comparison purposes, measurements were also made on soybean powders of the same samples. FT -NIR spectra were collected with a spectral range from 4000 to 12000 cm-1 at a resolution of 8 cm-1 on a Perkin-Elmer Spectrum one NTS spectrometer model. This spectrometer is optimized for high sensitivity analysis of single seed composition, being equipped with an NIRA, integrating sphere accessory and an extended range InGaAs detector

Synergistic inhibition of the Hedgehog pathway by newly designed Smo and Gli antagonists bearing the isoflavone scaffold

Aberrant activation of the Hedgehog (Hh) pathway is responsible for the onset and progression of several malignancies. Small molecules able to block the pathway at the upstream receptor Smoothened (Smo) or the downstream effector Gli1 have thus emerged recently as valuable anticancer agents. Here, we have designed, synthesized, and tested new Hh inhibitors taking advantage by the highly versatile and privileged isoflavone scaffold. The introduction of specific substitutions on the isoflavone's ring B allowed the identification of molecules targeting preferentially Smo or Gli1. Biological assays coupled with molecular modeling corroborated the design strategy, and provided new insights into the mechanism of action of these molecules. The combined administration of two different isoflavones behaving as Smo and Gli antagonists, respectively, in primary medulloblastoma (MB) cells highlighted the synergistic effects of these agents, thus paving the way to further and innovative strategies for the pharmacological inhibition of Hh signaling

Effect of soy in men with type 2 diabetes mellitus and subclinical hypogonadism: a randomised controlled study

Context: Isoflavones found in soy products have a chemical structure similar to estrogen, leading to concerns of an adverse estrogenic effect in men, particularly in those with type 2 diabetes mellitus (T2DM) who have low testosterone levels due to hypogonadism. Objective: The primary outcome was change in total testosterone levels. The secondary outcomes were the changes in glycaemia and cardiovascular risk markers. Design: Randomised double blind parallel study. Setting: Secondary care setting in UK. Participants: 200 men with T2DM with a total testosterone level≤12nmol/L Intervention: 15g soy protein with 66mg of isoflavones (SPI) or 15g soy protein alone without isoflavones (SP) daily as snack bars for three months. Results: There was no change in either total testosterone or in absolute free testosterone levels with either SPI or SP. There was an increase in TSH and reduction in fT4 (p<0.01) after SPI supplementation. Glycaemic control improved with a significant reduction in HbA1c (-4.19(7.29)mmol/mol,p<0.01) and HOMA-IR after SPI. Cardiovascular risk improved with a reduction in triglycerides, CRP and diastolic BP (p<0.05) with SPI versus SP supplementation. There was 6% improvement in 10-year coronary heart disease risk after three months of SPI supplementation. Endothelial function improved with both SPI and SP supplementation (p<0.01) with an increased reactive hyperemia index that was greater for the SPI group (p<0.05). Conclusions: Testosterone levels were unchanged and there was a significant improvement in glycaemia and cardiovascular risk markers with SPI compared to SP alone over three months. There was significant increase in TSH and a reduction in fT4

The role of Phytoestrogens in the management of menopausal symptoms

Menopause reflects a change in the woman’s physiological hormonal status and is regarded as a pivotal point in a woman’s life. The commonest symptoms experienced by women during the menopause are hot flushes and night sweats. Although HRT remains the gold standard for the treatment of menopausal symptoms, certain controversial studies have led to a shift against the regular use of HRT. Many physicians and women have turned to alternative ‘natural’ products, hoping that these can substitute the need for HRT. The evidence base for the efficacy and safety of phytoestrogens, in particular isoflavones, will be discussed.peer-reviewe

Soy protein improves cardiovascular risk in subclinical hypothyroidism : a randomized double-blinded crossover study

© 2017 Endocrine Society. Background: Soy protein with isoflavones appears to have an adverse effect on thyroid function, but it is not known whether it is the protein or isoflavone component that is deleterious. The effect of isoflavone-free soy on thyroid function was determined in patients with subclinical hypothyroidism, with a secondary aim of assessing its effect on cardiovascular risk indices. Methods: This was a randomized, double-blind, crossover study involving 80 patients with subclinical (compensated) hypothyroidism. Patients were randomly assigned to either isolated soy (isoflavone-free) protein (SP) or casein protein (CP) supplementation for 8 weeks, washed out for 8 weeks, and then crossed over for a further 8-week period. Results: Thyroid function was unaffected by either a SP or CP. There were significant decreases in fasting glucose (4.760.6 vs 5.561.4, P < 0.01), insulin resistance (3.3±3.0 vs 3.8±3.4, P = 0.05), total cholesterol (4.4 ± 0.9 vs 5.3 ± 1.2, P < 0.01), triglycerides (0.9 ± 0.5 vs 1.7 ± 0.9, P < 0.1), and highly sensitive C-reactive protein (hsCRP; 0.8 ± 0.7 vs 2.6 ± 2.8, P < 0.01) in the SP group compared with the CP group. Blood pressure, low-density lipoprotein, and high-density lipoprotein remained unchanged in both groups. Conclusion: SP alone had no effect on thyroid function in patients with subclinical hypothyroidism and resulted in a significant reduction in fasting glucose, insulin resistance, total cholesterol, triglycerides, and hsCRP compared with CP

Different Effects of Maternal Low-Isoflavone Soy Protein and Genistein Consumption on Hepatic Lipid Metabolism of 21-Day-Old Male Rat Offspring.

Amino acid composition and isoflavone are alleged contributors to the beneficial effects of soy protein isolate (SPI) on lipid metabolism. Therefore, we investigated the contributing component(s) of SPI in a maternal diet to the regulation of lipid metabolism in offspring. We also determined serum parameters in dams to investigate specific maternal cues that might be responsible for this regulation. Female rats were fed either a casein (CAS), a low-isoflavone SPI, or a casein plus genistein (GEN, 250 mg/kg) diet for two weeks before mating, as well as during pregnancy and lactation. Male offspring (CAS, SPI and GEN groups) were studied 21 days after birth. The SPI group had lower serum triglyceride levels than the other groups. Serum cholesterol was reduced in both the SPI and GEN groups compared with the CAS group. Expressions of target genes of peroxisome proliferator-activated receptor α were altered in the SPI group. Serum aromatic amino acid levels in dams were associated with serum triglyceride in offspring. In conclusion, the maternal consumption of a low-isoflavone SPI diet or a casein diet containing genistein has different effects on the lipid metabolism of their offspring; however, more profound effects were observed in the SPI group. Therefore, the altered lipid metabolism of offspring may be attributed to amino acid composition in maternal dietary protein sources

A Smo/Gli multitarget hedgehog pathway inhibitor impairs tumor growth

Pharmacological Hedgehog (Hh) pathway inhibition has emerged as a valuable anticancer strategy. A number of small molecules able to block the pathway at the upstream receptor Smoothened (Smo) or the downstream effector glioma-associated oncogene 1 (Gli1) has been designed and developed. In a recent study, we exploited the high versatility of the natural isoflavone scaffold for targeting the Hh signaling pathway at multiple levels showing that the simultaneous targeting of Smo and Gli1 provided synergistic Hh pathway inhibition stronger than single administration. This approach seems to effectively overcome the drug resistance, particularly at the level of Smo. Here, we combined the pharmacophores targeting Smo and Gli1 into a single and individual isoflavone, compound 22, which inhibits the Hh pathway at both upstream and downstream level. We demonstrate that this multitarget agent suppresses medulloblastoma growth in vitro and in vivo through antagonism of Smo and Gli1, which is a novel mechanism of action in Hh inhibition

The effect of soy phytoestrogen supplementation on thyroid status and cardiovascular risk markers in patients with subclinical hypothyroidism: A randomized, double-blind, crossover study

Context: There is concern whether soy phytoestrogens may affect thyroid function. If true, soy phytoestrogens may be expected to have a greater impact in subjects with subclinical hypothyroidism. Objective: The primary aim was to determine the effect of soy phytoestrogen supplementation on thyroid function, with a secondary aim of assessing the effects on cardiovascular risk indices in patients with subclinical hypothyroidism. Design and Setting: We conducted a randomized, double-blind, crossover study in a tertiary care setting. Participants: Sixty patients with subclinical hypothyroidism participated in the study. Intervention: Patients were randomly assigned to either low-dose phytoestrogen (30 g soy protein with 2 mg phytoestrogens, representative of a Western diet) or high-dose phytoestrogen (30 g soy protein with 16 mg phytoestrogens, representative of a vegetarian diet) supplementation for 8 wk, then crossed over after an 8-wk washout period. Main Outcome Measures: The primary outcome was progression to overt hypothyroidism, with secondary outcome measures of blood pressure, insulin resistance, lipids, and highly sensitive C-reactive protein (hsCRP). Results: Six female patients in the study progressed into overt hypothyroidism with a standardized rate ratio of 3.6 (95% confidence interval, 1.9, 6.2) after 16-mg phytoestrogen supplementation. Both systolic and diastolic blood pressure decreased with 16 mg phytoestrogens, whereas systolic pressure alone decreased with 2 mg phytoestrogens. Insulin resistance (homeostasis model assessment of insulin resistance, 3.5 ± 0.09 vs. 2.6 ± 0.08; P < 0.02) and hsCRP (4.9 ± 0.04 vs. 3.9 ± 0.03; P < 0.01) decreased with 16 mg phytoestrogens. Lipid profile remained unchanged. Conclusion: There is a 3-fold increased risk of developing overt hypothyroidism with dietary supplementation of 16 mg soy phytoestrogens with subclinical hypothyroidism. However, 16-mg soy phytoestrogen supplementation significantly reduces the insulin resistance, hsCRP, and blood pressure in these patients. Copyright © 2011 by The Endocrine Society