Remodeling the Epigenetic Landscape of Cancer—Application Potential of Flavonoids in the Prevention and Treatment of Cancer

Epigenetics, including DNA methylation, histone modification, and noncoding RNA regulation, are physiological regulatory changes that affect gene expression without modifying the DNA sequence. Although epigenetic disorders are considered a sign of cell carcinogenesis and malignant events that affect tumor progression and drug resistance, in view of the reversible nature of epigenetic modifications, clinicians believe that associated mechanisms can be a key target for cancer prevention and treatment. In contrast, epidemiological and preclinical studies indicated that the epigenome is constantly reprogrammed by intake of natural organic compounds and the environment, suggesting the possibility of utilizing natural compounds to influence epigenetics in cancer therapy. Flavonoids, although not synthesized in the human body, can be consumed daily and are common in medicinal plants, vegetables, fruits, and tea. Recently, numerous reports provided evidence for the regulation of cancer epigenetics by flavonoids. Considering their origin in natural and food sources, few side effects, and remarkable biological activity, the epigenetic antitumor effects of flavonoids warrant further investigation. In this article, we summarized and analyzed the multi-dimensional epigenetic effects of all 6 subtypes of flavonoids (including flavonols, flavones, isoflavones, flavanones, flavanols, and anthocyanidin) in different cancer types. Additionally, our report also provides new insights and a promising direction for future research and development of flavonoids in tumor prevention and treatment via epigenetic modification, in order to realize their potential as cancer therapeutic agents.

An Overview on Dietary Polyphenols and Their Biopharmaceutical Classification System (BCS)

Polyphenols are natural organic compounds produced by plants, acting as antioxidants by reacting with ROS. These compounds are widely consumed in daily diet and many studies report several benefits to human health thanks to their bioavailability in humans. However, the digestion process of phenolic compounds is still not completely clear. Moreover, bioavailability is dependent on the metabolic phase of these compounds. The LogP value can be managed as a simplified measure of the lipophilicity of a substance ingested within the human body, which affects resultant absorption. The biopharmaceutical classification system (BCS), a method used to classify drugs intended for gastrointestinal absorption, correlates the solubility and permeability of the drug with both the rate and extent of oral absorption. BCS may be helpful to measure the bioactive constituents of foods, such as polyphenols, in order to understand their nutraceutical potential. There are many literature studies that focus on permeability, absorption, and bioavailability of polyphenols and their resultant metabolic byproducts, but there is still confusion about their respective LogP values and BCS classification. This review will provide an overview of the information regarding 10 dietarypolyphenols (ferulic acid, chlorogenic acid, rutin, quercetin, apigenin, cirsimaritin, daidzein, resveratrol, ellagic acid, and curcumin) and their association with the BCS classification.

Treatment of AMD using a combination of saw dust, bentonite clay and phosphate in the removal of turbid materials and toxic metals

Acid mine drainage collected from the western decant in South Africa was treated in a series of small-scale laboratory experiments. 200 mL of the sample was poured into five 500 mL glass beakers using flocculants formed by mixing size-optimized 1.5 g of bentonite clay with 3.5 g saw dust and 1.0 g of Na3PO4 in triplicates (experiment A). Four similar sets of control experiments were conducted using the same amount of bentonite clay and saw dust with varying Na3PO4, contents in AMD treatment; the rationale being to determine the efficiency of Na3PO4 (experiments B, C and D). The results show that conductivity has an influence in the removal of the turbid materials. The removal efficiency of toxic metals using a flocculant containing 220 μm bentonite clay particle size and 0.012 or 0.25 M of Na3PO4 is higher than 96% when compared to that of the samples dosed with a flocculant containing 0.05 M Na3PO4, which is less than 91%. The flocculent also showed optimal removal efficiency of both turbid materials and toxic metals, i.e. removal efficiency within a range 96.5–99.3%. The flocculants containing 0.025 M Na3PO4 showed optimal removal efficiency of turbidity, colour, toxic metals and natural organic compounds.

The removal of pollutants and natural organic compounds from acid mine drainage using a combination of bentonite clay and MgSO4

200 mL of synthetic acid mine drainage (AMD) sample was poured into five 500 mL glass beakers and treated in a jar test and a shaker in sets of experiments, respectively. The samples were treated in small-scale laboratory experiments using synthetic AMD sample dosed with bentonite clay and MgSO4 respectively, and a flocculant consisting of the same reagents. The pH, EC, turbidity and oxidation reduction potential were measured. The removal of turbid materials in the samples dosed with a flocculant is higher compared to those of the samples dosed with each reagent alone. The samples with flocculant dosage show high removal efficiency of natural organic compounds and toxic metals, slightly higher compared to those with a dosage of a combination of bentonite clay and MgSO4. The removal efficiency of the samples treated in a shaker is better than those with rapid mixing. The SEM micrographs show sorption is a physico-chemical phenomenon.

Electrochemical Evaluation of Chrysin Flavonoid as Corrosion Inhibitor for Mild Steel in Sulphuric Acid Solution

Recently research is focused on natural organic compounds as metallic corrosion inhibitors demonstrating good corrosion protection and efficiencies. Steel corrosion behavior in acid media was evaluated in the presence of a pure natural flavonoid metabolite named Chrysin present in different plants. The evaluation of corrosion protection was studied using polarization curves, electrochemical impedance spectroscopy (EIS) and electrochemical current density under potentiostatic conditions. Polarization curves present active dissolution and at high overpotentials two passivation regions were found. Slight corrosion protection was obtained from EIS measurements and potentiostatic curves at three different anodic potentials: -370, +216 and +600 mV, revealed a more stable passive film in the presence of Chrysin at both passive regions. High corrosion protection was obtained on the film formed at +600 mV during the first 4 hours of immersion.

Results in Chemistry of Natural Organic Compounds. Synthesis of New Anticancer Vinca Alkaloids and Flavone Alkaloids

The antitumor indole–indoline alkaloids of the evergreen Catharanthus roseus—namely vinblastine and vincristine—are widely used in chemotherapy of cancer. Many efforts were made to synthesize more efficient derivatives with less side-effect. The 14,15-cyclopropane derivative of vinblastine was synthesized successfully by a five-step procedure starting from vindoline. Vincristine, vinorelbine and several derivatives condensed with a cyclopropane ring were synthesized. Various hybrid molecules were prepared by the coupling reaction of vindoline and methyl ester of tryptophan, which were conjugated by carrier peptides of octaarginine. Studying the halogenation reactions of vindoline and catharanthine some fluorine derivatives were obtained which showed promising antitumor activity on various tumor types. The synthesis of the Aspidospermane alkaloid bannucine and 5′-epibannucine were carried out using N-acyliminium intermediates. The same intermediate was also applied in the first synthesis of sessiline. The research group have synthesized of flavonoid alkaloids: dracocephins A and B. Further three flavonoid alkaloids, namely 8-(2”-pyrrolidinon-5′′-yl)quercetin, 6-(2′′-pyrrolidinon-5′′-yl)-(−)- and 8-(2′′-pyrrolidinon-5′′-yl)-(−)-epicatechin were prepared by acid-catalyzed regioselective Mannich reaction starting from the corresponding flavonoid precursor. Vindoline was also coupled to synthetic pharmacophores, such as triphenylphosphine and various N-heterocycles. Some of these hybrid molecules showed significant antitumor activity. Furthermore, 7-OH and 7-NH modified flavonoid derivatives were synthesized by a regioselective alkylation followed by Smiles rearrangement and hydrolysis.

Fulvic Acid: an Active Food Additive or Medication?

This review article is devoted to the fundamental task of pharmacology, i.e. the research and discovery of novel medications that render the maximal therapeutic effect at the minimal side consequences to health. Over recent years, the world has witnessed a growing interest towards natural organic compounds on the basis of humic substances (HS), which are broadly applied in animal husbandry, agriculture and veterinary medicine due to a wide spectrum of biologically active properties. The results of chemical and biological trials demonstrate that HS have a great potential for various fields of medicine.Numerous studies have demonstrated the cardioprotective, antioxidant, antitumour, antibacterial, antiviral, antifungal, antiallergic, membranotropic, hepatoprotective and anti-inflammatory properties of HS. In addition, these substances exhibit a stimulating effect on metabolism, thus enhancing specific and non-specific organismal resistance. Published evidence suggests no toxicity of HS and no inherent teratogenic, embryotoxic, mutagenic or carcinogenic properties.Fulvic acid (FA) belongs to humic acids, a family of HS. In the present study, we review its chemical properties and biological activity from the standpoint of traditional medicine. Understanding biological properties of FA and its usage in novel drug design is a perspective avenue of research in contemporary medicine.Published sources referenced in this review are indexed in Scopus, Web of Science, MedLine, the Cochrane Library, eLIBRARY, PubMed and other relevant databases.