Phytochemicals Involved in Mitigating Silent Toxicity Induced by Heavy Metals.

Heavy metals (HMs) are natural elements present in the Earth's crust, characterised by a high atomic mass and a density more than five times higher than water. Despite their origin from natural sources, extensive usage and processing of raw materials and their presence as silent poisons in our daily products and diets have drastically altered their biochemical balance, making them a threat to the environment and human health. Particularly, the food chain polluted with toxic metals represents a crucial route of human exposure. Therefore, the impact of HMs on human health has become a matter of concern because of the severe chronic effects induced by their excessive levels in the human body. Chelation therapy is an approved valid treatment for HM poisoning; however, despite the efficacy demonstrated by chelating agents, various dramatic side effects may occur. Numerous data demonstrate that dietary components and phytoantioxidants play a significant role in preventing or reducing the damage induced by HMs. This review summarises the role of various phytochemicals, plant and herbal extracts or probiotics in promoting human health by mitigating the toxic effects of different HMs.

Biological Activity of Selenium and Its Impact on Human Health.

Selenium (Se) is a naturally occurring metalloid element essential to human and animal health in trace amounts but it is harmful in excess. Se plays a substantial role in the functioning of the human organism. It is incorporated into selenoproteins, thus supporting antioxidant defense systems. Selenoproteins participate in the metabolism of thyroid hormones, control reproductive functions and exert neuroprotective effects. Among the elements, Se has one of the narrowest ranges between dietary deficiency and toxic levels. Its level of toxicity may depend on chemical form, as inorganic and organic species have distinct biological properties. Over the last decades, optimization of population Se intake for the prevention of diseases related to Se deficiency or excess has been recognized as a pressing issue in modern healthcare worldwide. Low selenium status has been associated with an increased risk of mortality, poor immune function, cognitive decline, and thyroid dysfunction. On the other hand, Se concentrations slightly above its nutritional levels have been shown to have adverse effects on a broad spectrum of neurological functions and to increase the risk of type-2 diabetes. Comprehension of the selenium biochemical pathways under normal physiological conditions is therefore an important issue to elucidate its effect on human diseases. This review gives an overview of the role of Se in human health highlighting the effects of its deficiency and excess in the body. The biological activity of Se, mainly performed through selenoproteins, and its epigenetic effect is discussed. Moreover, a brief overview of selenium phytoremediation and rhizofiltration approaches is reported.

Ancient Wheat as Promising Nutraceuticals for the Prevention of Chronic and Degenerative Diseases.

In the context of a balanced diet, wheat, mainly used as whole grains, is a good source of nutrients, including fibers and bioactive compounds. Cereals belong to the Poaceae family and are crucial for maintaining a healthy status, granted by their nutritional and chemical properties. Recent studies have demonstrated that the intake of whole grains and grain-based products may reduce the risk of oxidative stress, thus lowering chronic and age-related disorders, such as obesity, cardiovascular diseases, type II diabetes and cancer. Indeed, several studies report that regular whole grain consumption is associated with lower levels of total and LDL-cholesterol, triglycerides, fasting glucose, blood pressure and body mass index. Moreover, ancient wheat species have become increasingly interested in human health, containing several nutraceutical compounds, such as vitamins and minerals. The numerous phytochemicals present in ancient wheat (polyphenols, carotenoids, phytosterols and phenolic compounds) provide, in fact, antioxidant properties, which are essential in the prevention of various chronic and degenerative diseases. This review aims to report information on ancient wheat species, discussing their composition and nutraceutical properties compared with modern varieties and highlighting the beneficial impact on human health.

Are Nutraceuticals Effective in COVID-19 and Post-COVID Prevention and Treatment?

The beginning of the end or the end of the beginning? After two years mastered by coronavirus disease 19 (COVID-19) pandemic, we are now witnessing a turnaround. The reduction of severe cases and deaths from COVID-19 led to increasing importance of a new disease called post-COVID syndrome. The term post-COVID is used to indicate permanency of symptoms in patients who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Immune, antiviral, antimicrobial therapies, as well as ozone therapy have been used to treat COVID-19 disease. Vaccines have then become available and administered worldwide to prevent the insurgence of the disease. However, the pandemic is not over yet at all given the emergence of new omicron variants. New therapeutic strategies are urgently needed. In this view, great interest was found in nutraceutical products, including vitamins (C, D, and E), minerals (zinc), melatonin, probiotics, flavonoids (quercetin), and curcumin. This review summarizes the role of nutraceuticals in the prevention and/or treatment of COVID-19 disease and post-COVID syndrome.

Opuntia ficus indica (L.) Mill. An Ancient Plant Source of Nutraceuticals.

Opuntia ficus-indica (L.) Mill. (OFI) is a plant with numerous beneficial properties known in traditional medicine. It has been a domesticated plant in Latin America, Africa, Mediterranean countries, the Middle East, India and Australia. Nowadays, the research concentrates on natural compounds to lower costs and the possible side effects of synthetic compounds. The use of nutraceuticals, bioactive compounds of vegetable origin with important nutritional values, is encouraged. OFI has shown numerous activities due to its high content of antioxidants, including flavonoids and ascorbate, pigments, carotenoids and betalains, phenolic acids and other phytochemical components, such as biopeptides and soluble fibers. The most important effects of OFI are represented by the activity against acne, arthrosis, dermatosis, diabetes, diarrhea, fever, high blood pressure, prostatitis, rheumatism, stomachache, tumor, wart, allergy, wound, colitis and some viral diseases. Moreover, a promising role has been suggested in inflammatory bowel disease, colitis and metabolic syndrome. The most recent studies addressed the role of OFI in preventing and treating COVID-19 disease. In light of the above, this review summarizes the biological activities and health benefits that this plant may exert.

Exploring the anticancer and antioxidant properties of Vicia faba L. pods extracts, a promising source of nutraceuticals.

Background: Pulse crops are considered the major sources of proteins, dietary fiber, micronutrients, and bioactive phytochemicals. Among the numerous pulse crops, broad beans (Vicia faba L.) have received particular attention due to their nutraceutical, functional and economic importance. Our attention was mainly focused on the broad bean pods (VFs), which are the primary by-product of the domestic and industrial processing of broad beans and an attractive source of valuable ingredients. Methods: In order to investigate the VFs properties, the flours from broad beans of three different harvest periods were extracted with acetone, methanol and 70% aqueous ethanol and the dried extracts were analyzed, qualitatively and quantitatively, and tested for their antioxidant through DPPH and ABTS assay and anticancer activities using the MTT assay and immunofluorescence analysis. Results: The VF extracts demonstrated a good in vitro radical scavenging activity from the first stage of collection of all the V. faba L. extracts. Additionally, the extracts were tested for their cytotoxicity against a panel of cancer and normal cells and the outcomes indicated the ethanol extract as the most active against the melanoma cell line Sk-Mel-28, without affecting the viability of the normal cells. Finally, we found out that the ethanol extract interfered with the microtubules organization, leading to the cancer cells death by apoptosis.

The Significant Role of Nutraceutical Compounds in Ulcerative Colitis Treatment.

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) mainly affecting the colon and the rectum. Its main characteristics include relapsing and remitting mucosal inflammation, starting in the rectum and typically extending continuously proximally through part of or the entire colon. UC pathogenesis depends on multiple factors, such as genetic predisposition, defects in the epithelial barrier, dysregulated immune responses, and environmental causes. The most frequent symptoms are abdominal pain, weight loss, mucus discharge, bloody diarrhoea, incontinence, nocturnal defecations, fever, and anemia. Existing therapies for UC include 5-aminosalicylic acid (5-ASA) and its derivatives, steroids, immunosuppressants, and biological drugs. However, limited efficacy and unwanted adverse effects hardly limit these strategies of treatment. In the last decades, research studies have been driven towards complementary and alternative medicines for the treatment of UC. Various nutraceuticals have exhibited promising results in modulating intestinal inflammation while improving symptoms. These compounds possess a wide spectrum of positive health effects evidenced by in vitro studies, characterized by their involvement in antioxidant defenses, cell proliferation, and gene expression. The present review analyzes the available data about the different types of nutraceuticals and their potential effectiveness as adjuvant therapy of IBD, with particular emphasis to UC.

The Discovery of Highly Potent THP Derivatives as OCTN2 Inhibitors: From Structure-Based Virtual Screening to In Vivo Biological Activity.

A mismatch between ß-oxidation and the tricarboxylic acid cycle (TCA) cycle flux in mitochondria produces an accumulation of lipid metabolic intermediates, resulting in both blunted metabolic flexibility and decreased glucose utilization in the affected cells. The ability of the cell to switch to glucose as an energy substrate can be restored by reducing the reliance of the cell on fatty acid oxidation. The inhibition of the carnitine system, limiting the carnitine shuttle to the oxidation of lipids in the mitochondria, allows cells to develop a high plasticity to metabolic rewiring with a decrease in fatty acid oxidation and a parallel increase in glucose oxidation. We found that 3-(2,2,2-trimethylhydrazine)propionate (THP), which is able to reduce cellular carnitine levels by blocking both carnitine biosynthesis and the cell membrane carnitine/organic cation transporter (OCTN2), was reported to improve mitochondrial dysfunction in several diseases, such as Huntington's disease (HD). Here, new THP-derived carnitine-lowering agents (TCL), characterized by a high affinity for the OCTN2 with a minimal effect on carnitine synthesis, were developed, and their biological activities were evaluated in both in vitro and in vivo HD models. Certain compounds showed promising biological activities: reducing protein aggregates in HD cells, ameliorating motility defects, and increasing the lifespan of HD Drosophila melanogaster.

Anchusa azurea Mill. (Boraginaceae) aerial parts methanol extract interfering with cytoskeleton organization induces programmed cancer cells death.

The present study aimed to determine the chemical composition, antioxidant effects and antitumor properties of a methanol extract of Anchusa azurea Mill. (Boraginaceae) aerial parts against four tumour cell lines (MCF-7, MDA-MB-231, RKO, and R2C). The antioxidant effects were assessed by using ß-carotene bleaching, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing ability power (FRAP) tests. HPLC analyses revealed chlorogenic acid, catechin, caffeic acid, and astragalin as the most abundant compounds. Interesting results were obtained in the ß-carotene bleaching test with IC50 values of 7.6 and 27.5 µg mL-1 after 30 and 60 min of incubation, respectively. Furthermore, the A. azurea extract protects 3T3-L1 mouse cells from oxidative stress induced by menadione and exhibits good antitumor activity, with very low toxicity. Our data indicate that the antitumor properties are due to the ability to induce programmed cancer cell death through caspase 3/7 and 9 activation and interference with the cytoskeleton dynamics.

Finding solutions for agricultural wastes: antioxidant and antitumor properties of pomegranate Akko peel extracts and ß-glucan recovery.

Pomegranate peels are the major by-products of the processing of pomegranate juice. Scientific research studies have shown that pomegranate peels are an extraordinary source of bioactive compounds, most of which can be converted into value added products. From this point of view, the present study was carried out with the aim of providing a solid basis for the use of whole pomegranate peels (Akko variety) as a source of nutraceutical compounds, such as ß-glucans. Moreover, acetone (S1) and methanolic (S2) extracts, obtained in the preliminary stage of the ß-glucan isolation procedure, have been tested for their antioxidant and antitumor activities. The total phenolic content and phenolic profile of S1 and S2 were determined. S1 and S2 exhibited a significant DPPH scavenging activity, with an IC50 value for S1 1.5-fold lower than that for the standard Trolox. Both S1 and S2 extracts possess in vitro ROS scavenging activity toward 3T3-L1 murine fibroblasts and Hek-293 human embryonic kidney epithelial cells and antiproliferative activity towards human breast MCF-7 and uterine HeLa cancer cells.

N-alkyl carbazole derivatives as new tools for Alzheimer's disease: preliminary studies.

Alzheimer's disease (AD) is a progressive and age-related neurodegenerative disorder affecting brain cells and is the most common form of "dementia", because of the cognitive detriment which takes place. Neuronal disruption represents its major feature, due to the cytosolic accumulation of amyloid ß-peptide (Aß) which leads to senile plaques formation and intracellular neurofibrillary tangles. Many studies have focused on the design and therapeutic use of new molecules able to inhibit Aß aggregation. In this context, we evaluated the ability of two recently synthesized series of N-alkyl carbazole derivatives to increase the Aß soluble forms, through molecular docking simulations and in vitro experiments. Our data evidenced that two carbazole derivatives, the most active, adopt distinct binding modes involving key residues for Aß fibrillization. They exhibit a good interfering activity on Aß aggregation in mouse (N2a) cells, stably expressing wild-type human amyloid precursor protein (APP) 695. These preliminary results are promising and we are confident that the N-alkyl carbazole derivatives may encourage next future studies needed for enlarging the knowledge about the AD disease approach.

Mercury toxicity and neurodegenerative effects.

Mercury is among the most toxic heavy metals and has no known physiological role in humans. Three forms of mercury exist: elemental, inorganic and organic. Mercury has been used by man since ancient times. Among the earliest were the Chinese and Romans, who employed cinnabar (mercury sulfide) as a red dye in ink (Clarkson et al. 2007). Mercury has also been used to purify gold and silver minerals by forming amalgams. This is a hazardous practice, but is still widespread in Brazil's Amazon basin, in Laos and in Venezuela, where tens of thousands of miners are engaged in local mining activities to find and purify gold or silver. Mercury compounds were long used to treat syphilis and the element is still used as an antiseptic,as a medicinal preservative and as a fungicide. Dental amalgams, which contain about 50% mercury, have been used to repair dental caries in the U.S. since 1856.Mercury still exists in many common household products around the world.Examples are: thermometers, barometers, batteries, and light bulbs (Swain et al.2007). In small amounts, some organo mercury-compounds (e.g., ethylmercury tiosalicylate(thimerosal) and phenylmercury nitrate) are used as preservatives in some medicines and vaccines (Ballet al. 2001).Each mercury form has its own toxicity profile. Exposure to Hg0 vapor and MeHg produce symptoms in CNS, whereas, the kidney is the target organ when exposures to the mono- and di-valent salts of mercury (Hg+ and Hg++, respectively)occur. Chronic exposure to inorganic mercury produces stomatitis, erethism and tremors. Chronic MeHg exposure induced symptoms similar to those observed in ALS, such as the early onset of hind limb weakness (Johnson and Atchison 2009).Among the organic mercury compounds, MeHg is the most biologically available and toxic (Scheuhammer et a!. 2007). MeHg is neurotoxic, reaching high levels of accumulation in the CNS; it can impair physiological function by disrupting endocrine glands (Tan et a!. 2009).The most important mechanism by which mercury causes toxicity appears to bemitochondrial damage via depletion of GSH (Nicole et a!. 1998), coupled with binding to thiol groups ( -SH), which generates free radicals. Mercury has a high affinity for thiol groups ( -SH) and seleno groups ( -SeH) that are present in amino acids as cysteine and N-acetyl cysteine, lipoic acid, proteins, and enzymes. N-acetylcysteine and cysteine are precursors for the biosynthesis of GSH, which is among the most powerful intracellular antioxidants available to protect against oxidative stress and inflammation.Mercury and methylmercury induce mitochondrial dysfunction, which reduces ATP synthesis and increases lipid, protein and DNA peroxidation. The content of metallothioneines, GSH, selenium and fish high in omega-3 fatty acids appear to be strongly related with degree of inorganic and organic mercury toxicity, and with the protective detoxifying mechanisms in humans. In conclusion, depletion of GSH,breakage of mitochondria, increased lipid peroxidation, and oxidation of proteins and DNA in the brain, induced by mercury and his salts, appear to be important factors in conditions such as ALS and AD (Bains and Shaw 1997; Nicole eta!. 1998;Spencer eta!. 1998; Alberti et a!. 1999).

Synthesis and evaluation of cytotoxic activities of new guanidines derived from carbazoles.

Several new alkylguanidines derived from carbazole have been synthesized in a simple one-pot reaction starting from 3-aminocarbazole derivatives. The aminocarbazoles were reacted with ethoxycarbonylisothiocyanate, to give thiourea intermediates, followed by the addition of an alkylamine and HgCl2 to give ethoxycarbonylguanidine intermediates. The reaction mixture was then heated at 160 °C to give the N-(1,4-dimethyl-9H-carbazol-3-yl)-N'-alkylguanidines. The cytotoxic activity of all the synthesized guanidines was evaluated against different cell lines.