Development of Genistein Synthesis for Use as a Certified Reference Material

Introduction. The use of certified reference materials (CRMs) ensures metrological traceability and comparability of analysis results performed in different laboratories, by different analysts, at different times. Genistein is a promising substance with a wide spectrum of pharmacological action. genistein is widely used in dietary supplements. Development of regulatory documents for CRM of genistein will ensure the quality of drugs and dietary supplements.Aim. Aim of our study is to improve of the ways of synthesis and determination of spectrum characteristics of genistein for the certification of CRM.Materials and methods. We used synthetic genistein, (Ph.D. V. Yu. Kovtun SPC "Pharmzashchita") (sample № 1) and genistein synthesized and studied at the departments of pharmaceutical chemistry and chemical technology of medicinal substances SPCPU (sample № 2). Infrared spectra of genistein samples were collected on an FSM 1201 infrared Fourier spectrometer (OOO Infraspek, Russia) via KBr pellets technique. All the spectra were collected in the 4000–500 cm−1 range. The NMR (1H and 13C) measurements were performed with a BrukerAvance III NMR spectrometer (400 and 100 MHz) (Bruker, Germany) in DMSO-d6 solvent. Raman spectra were recorded by an ORTES-785TRS-2700 analytical Raman scattering system at a laser power of 100 mW (OPTEC JSC, Russia). Laser interaction time was 5, 10, 20 and 60 seconds. The results were processed using the software "BWSpec 4.10_4", USA. GC-MS was performed on an Agilent Technologies 7890A gas chromatograph (Agilent Technologies, USA) with a 7693 autoinjector and a Hewlett Packard 5975C mass selective detector.Results and discussion. The synthesis was carried out according to the developer's method. The stage "removal of the alkyl protection" has been improved. The spectra of the synthesis intermediate of genistein (biochanin A) correspond to the literature data. Samples of genistein were investigated by methods: MC and NMR 13С, 1Н. The structure of the investigated substance was confirmed; Raman and IR spectroscopy showed that the spectra of the samples do not differ from each other and there are no additional signals.Conclusion. The spectrum characteristics of samples of genistein were obtained by NMR, IR and Raman spectroscopy, which will be used in the regulatory documentation for CRM of genistein. All of this will make it possible to control the quality of medicines based on it and to identify substandard dietary supplements.

Hemp and buckwheat are valuable sources of dietary amino acids, beneficially modulating gastrointestinal hormones and promoting satiety in healthy volunteers

Purpose This study evaluated the postprandial effects following consumption of buckwheat, fava bean, pea, hemp and lupin compared to meat (beef); focussing on biomarkers of satiety, gut hormones, aminoacids and plant metabolites bioavailability and metabolism. Methods Ten subjects (n = 3 men; n = 7 women; 42 ± 11.8 years of age; BMI 26 ± 5.8 kg/m2) participated in six 1-day independent acute interventions, each meal containing 30 g of protein from buckwheat, fava bean, pea, hemp, lupin and meat (beef). Blood samples were collected during 24-h and VAS questionnaires over 5-h. Results Volunteers consumed significantly higher amounts of most amino acids from the meat meal, and with few exceptions, postprandial composition of plasma amino acids was not significantly different after consuming the plant-based meals. Buckwheat meal was the most satious (300 min hunger scores, p < 0.05).Significant increase in GLP-1 plasma (AUC, iAUC p = 0.01) found after hemp compared with the other plant-based meals. Decreased plasma ghrelin concentrations (iAUC p < 0.05) found on plant (hemp) vs. meat meal. Several plasma metabolites after hemp meal consumption were associated with hormone trends (partial least squares-discriminant analysis (PLS-DA): 4-hydroxyphenylpyruvic acid, indole 3-pyruvic acid, 5-hydoxytryptophan, genistein and biochanin A with GLP-1, PYY and insulin; 3-hydroxymandelic acid and luteolidin with GLP-1 and ghrelin and 4-hydroxymandelic acid, benzoic acid and secoisolariciresinol with insulin and ghrelin. Plasma branched-chain amino acids (BCAAs), (iAUC, p < 0.001); and phenylalanine and tyrosine (iAUC, p < 0.05) were lower after buckwheat comparison with meat meal. Conclusion Plants are valuable sources of amino acids which are promoting satiety. The impact of hemp and buckwheat on GLP-1 and, respectively, BCAAs should be explored further as could be relevant for aid and prevention of chronic diseases such as type 2 diabetes. Study registered with clinicaltrial.gov on 12th July 2013, study ID number: NCT01898351.

Microbial Polymers as Sustainable Agents for Mitigating Health Risks of Plant-Based Endocrine Disruptors in Surface Water

This study investigated the binding abilities of extracellular polymers produced by an environmentally isolated strain of Enterococcus hirae towards phytoestrogen endocrine disruptors—biochanin A, formonetin, genistein and daidzein. The extracellular biopolymer exhibited notable binding and removal for all four phytoestrogens, with a maximum removal of daidzein (87%) followed by genistein (72%) at a 1–1.5 mg/mL concentration. Adsorption proceeded rapidly at ambient temperature. The adsorption data fitted well with the Langmuir isotherm. Based on the adsorption energy, the biopolymer binding of phytoestrogens was inferred as daidzein > genistein > biochanin A > formononetin. Toxicity of the biopolymer (5–250 µg/mL) evaluated using RAW 264.7 cell lines indicated no significant (p < 0.05) changes in viability. In biopolymer-challenged Caenorhabditis elegans previously exposed to daidzein, complete protection to developmental toxicity, such as reduced egg-laying capacity, egg viability and progeny counts of the worm, was observed. The results of this study offer valuable insights into understanding the potential role of microbial extracellular biopolymers in binding and removal of phytoestrogens with sustainable technological implications in modulating the toxic effect of high levels of endocrine disruptors in the environment.

Biochanin A from Chinese Medicine: An Isoflavone with Diverse Pharmacological Properties

Biochanin A (BCA) is a dietary isoflavone, isolated from the leaves and stems of Trifolium pratense L and many other herbs of Chinese medicine. Recent findings indicated BCA as a promising drug candidate with diverse bioactive effects. On the purpose of evaluating the possibility of BCA in clinical application, this review is trying to provide a comprehensive summary of the pharmacological actions of BCA. The publications collected from PubMed, ScienceDirect, and Wiley databases were summarized for the last 10 years. Then, the potential therapeutic use of BCA on the treatment of various diseases was discussed according to its pharmacological properties, namely, anticancer, anti-inflammatory, anti-bacterial, anti-diabetic, and anti-obesity effects as well as neuroprotective, hepatoprotective, cardioprotective, and osteoprotective effects. BCA might mainly regulate the MAPK, PI3K, NRF2, and NF-kB pathways, respectively, to exert its bioactive effects. However, the limited definitive targets, poor biological availability, and insufficient safety evaluation might block the clinical application of BCA. This review may provide new insights for the development of BCA in the application of related diseases.

Phytoestrogens as Potential Antiandrogenic Agents against Prostate Cancer: An In Silico Analysis

Background: Prostate cancer is the second most common cancer worldwide. The androgen deprivation therapy or castration leads to the recurrence of castration-resistant prostate cancer after some time. Androgen receptor is one of the most promising targets for the treatment of prostate cancer. The health benefits of phytoestrogens led us to explore them for their androgen receptor inhibition potential that may lead to inhibition of initiation and progression of prostate cancer. Methods: Protein-ligand interaction plays a central role in structure-based drug design, so we screened 23 phytoestrogens for their binding affinity to the androgen receptor using the molecular docking approach. These phytoestrogens were also tested for their ADME and toxicity profiles using the software. Results: Based on binding affinity, interacting amino acid residues, pharmacokinetics and toxicity profile, four phytoestrogens, namely naringenin, luteolin, hesperetin, and biochanin A were shortlisted as lead molecules. Conclusion: Therefore, our study has shown that these four phytoestrogens could be promising candidates for further evaluation for prostate cancer treatment or management.