Elena Maria Varoni

Melatonin in traditional Mediterranean diets.

Abstract:  Compared with other industrialized countries, the lower incidence of chronic‐degenerative disorders in Mediterranean populations has been emphasized in recent decades. The health‐promoting effects arising from Mediterranean dietary habits have been attributed to the large intake of plant foodstuffs rich in bioactive phytochemicals, such as melatonin. Recently, it has been suggested that melatonin present in edible plants may improve human health, by virtue of its biological activities and its good bioavailability. Plant melatonin, besides contributing to optimize the physiological functions regulated, in humans, by endogenous melatonin, may be involved in nutritional therapy to reduce the risk of cancer, cardiovascular and neurodegenerative diseases in western populations. In this view, the presence of melatonin in some Mediterranean foods and beverages adds a new element to the hypothesis of health benefits associated to Mediterranean dietary patterns, although the available data are still preliminary and incomplete.

Anticancer Molecular Mechanisms of Resveratrol

Resveratrol is a pleiotropic phytochemical belonging to the stilbene family. Though it is only significantly present in grape products, a huge amount of preclinical studies investigated its anticancer properties in a plethora of cellular and animal models. Molecular mechanisms of resveratrol involved signaling pathways related to extracellular growth factors and receptor tyrosine kinases; formation of multiprotein complexes and cell metabolism; cell proliferation and genome instability; cytoplasmic tyrosine kinase signaling (cytokine, integrin, and developmental pathways); signal transduction by the transforming growth factor-β super-family; apoptosis and inflammation; and immune surveillance and hormone signaling. Resveratrol also showed a promising role to counteract multidrug resistance: in adjuvant therapy, associated with 5-fluoruracyl and cisplatin, resveratrol had additive and/or synergistic effects increasing the chemosensitization of cancer cells. Resveratrol, by acting on diverse mechanisms simultaneously, has been emphasized as a promising, multi-target, anticancer agent, relevant in both cancer prevention and treatment.

Plant Polyphenols and Oral Health: Old Phytochemicals for New Fields

Despite the protective role of diets rich in fruit plant polyphenols against some cancers and chronic degenerative and inflammatory diseases, insufficient emphasis has been placed on oral health. Numerous studies have aimed to ascertain the role of polyphenols in the prevention and treatment of oral diseases; however, even when in vitro evidence appears convincing, the same is not true for in vivo studies, and thus there is a general paucity of solid evidence based on animal and clinical trials. To the best of our knowledge, only two reviews of polyphenols and oral health have been published; however, neither considered the potential role of whole plant extracts, which contain mixtures of many polyphenols that are often not completely identified. In the present study, our main aim was to review the current state of knowledge (search period: January 1965 to March 2011) on the effects of plant extracts/polyphenols on oral health. We found data on grapes, berries, tea, cocoa, coffee, myrtle, chamomile, honey/propolis, aloe extracts and the three main groups of polyphenols (stilbenes, flavonoids and proanthocyanidins). Their effects on caries, gingivitis, periodontal disease, candidiasis, oral aphtae, oral mucositis, oral lichen planus, leukoplakia and oral cancer were investigated. The data suggest that there is a lack of strong evidence, in particular regarding randomized clinical trials. However, a fascinating starting point has been provided by pre-clinical studies that have shown interesting activities of polyphenols against the most common oral diseases (caries, periodontitis and candidiasis), as well as in oral cancer prevention.

Cell Surface Receptor Targeted Biomimetic Apatite Nanocrystals for Cancer Therapy

Nanosized drug carriers functionalized with moieties specifically targeting tumor cells are promising tools in cancer therapy, due to their ability to circulate in the bloodstream for longer periods and their selectivity for tumor cells, enabling the sparing of healthy tissues. Because of its biocompatibility, high bioresorbability, and responsiveness to pH changes, synthetic biomimetic nanocrystalline apatites are used as nanocarriers to produce multifunctional nanoparticles, by coupling them with the chemotherapeutic drug doxorubicin (DOXO) and the DO-24 monoclonal antibody (mAb) directed against the Met/Hepatocyte Growth Factor receptor (Met/HGFR), which is over-expressed on different types of carcinomas and thus represents a useful tumor target. The chemical-physical features of the nanoparticles are fully investigated and their interaction with cells expressing (GTL-16 gastric carcinoma line) or not expressing (NIH-3T3 fibroblasts) the Met/HGFR is analyzed. Functionalized nanoparticles specifically bind to and are internalized in cells expressing the receptor (GTL-16) but not in the ones that do not express it (NIH-3T3). Moreover they discharge DOXO in the targeted GTL-16 cells that reach the nucleus and display cytotoxicity as assessed in an MTT assay. Two different types of ternary nanoparticles are prepared, differing for the sequence of the functionalization steps (adsorption of DOXO first and then mAb or vice versa), and it is found that the ones in which mAb is adsorbed first are more efficient under all the examined aspects (binding, internalization, cytotoxicity), possibly because of a better mAb orientation on the nanoparticle surface. These multifunctional nanoparticles could thus be useful instruments for targeted local or systemic drug delivery, allowing a reduction in the therapeutic dose of the drug and thus adverse side effects. Moreover, this work opens new perspectives in the use of nanocrystalline apatites as a new platform for theranostic applications in nanomedicine.

Conjugation of hydroxyapatite nanocrystals with human immunoglobulin G for nanomedical applications.

Inorganic nanosized drug carriers are a promising field in nanomedicine applied to cancer. Their conjugation with antibodies combines the properties of the nanoparticles themselves with the specific and selective recognition ability of the antibodies to antigens. Biomimetic carbonate-hydroxyapatite (HA) nanoparticles were synthesized and fully characterized; human IgGs, used as model antibodies, were coupled to these nanocrystals. The maximum loading amount, the interaction modelling, the preferential orientation and the secondary structure modifications were evaluated using theoretical models (Langmuir, Freundlich and Langmuir-Freundlich) spectroscopic (UV-Vis, Raman), calorimetric (TGA), and immunochemical techniques (ELISA, Western Blot). HA nanoparticles of about 30 nm adsorbed human IgGs, in a dose-dependent, saturable and stable manner with micromolar affinity and adsorption capability around 2.3 mg/m(2). Adsorption isotherm could be described by Langmuir-Freundlich model, and was due to both energetically homogeneous and heterogeneous binding sites on HA surface, mainly of electrostatic nature. Binding did not induce secondary structure modification of IgGs. A preferential IgG end-on orientation with the involvement of IgG Fc moiety in the adsorption seems most probable due to the steric hindrance of their Fab domains. Biomimetic HA nanocrystals are suitable substrates to produce nanoparticles which can be functionalized with antibodies for efficient targeted drug delivery to tumours.

Chemopreventive Potential of Flavonoids in Oral Squamous Cell Carcinoma in Human Studies

Evidence available from nutritional epidemiology has indicated an inverse association between regular consumption of fruits and vegetables and the risk of developing certain types of cancer. In turn, preclinical studies have attributed the health-promoting effects of plant foods to some groups of phytochemicals, by virtue of their many biological activities. In this survey, we briefly examine the chemopreventive potential of flavonoids and flavonoid-rich foods in human oral carcinogenesis. Despite the paucity of data from clinical trials and epidemiological studies, in comparison to in vitro/in vivo investigations, a high level of evidence has been reported for epigallocatechin gallate (EGCG) and anthocyanins. These flavonoids, abundant in green tea and black raspberries, respectively, represent promising chemopreventive agents in human oral cancer.

Tissue-engineered skin substitutes: an overview

Extensive skin loss and chronic wounds are still a significant challenge to clinicians: even if injured epidermis is normally able to self-renew, deep injuries can cause negative regulation of the wound healing cascade, leading to chronic wound formation. Skin-autografting surgical procedures are often limited by the poor availability of healthy tissue, whereas the use of non-self-tissues for allografts presents some severe risks. Tissue-engineered skin substitutes have recently become viable as a suitable alternative to auto- and allografts. However, biologists, biochemists, and technical engineers are still struggling to produce complex skin substitutes that can readily be transplanted in large quantities. The ambitious goal is now to construct a dermoepidermal substitute that rapidly vascularizes and optimally supports a stratifying epidermal graft on a biodegradable matrix. This review analyzes these aspects in light of the available literature and the authors’ experience.

Agarose Gel as Biomaterial or Scaffold for Implantation Surgery: Characterization, Histological and Histomorphometric Study on Soft Tissue Response

Maxillofacial, orthopedic, oral, and plastic surgery require materials for tissue augmentation, guided regeneration, and tissue engineering approaches. In this study, the aim was to develop and characterize a new extrudable hydrogel, based on agarose gel (AG; 1.5% wt) and to evaluate the local effects after subcutaneous implantation in comparison with collagen and hyaluronic acid. AG chemical–physical properties were ascertained through Fourier transform infrared (FT-IR) spectroscopy and rheological analysis. In vivo subcutaneous implants were performed, and histological and histomorphometric evaluations were done at 1, 4, 12, and 16 weeks. FT-IR confirmed that spectroscopic properties were the same for the baseline agarose and rheological characterization established that AG is a weak hydrogel. Subcutaneous AG implants induced new vessels and fibrous tissue formation rich in neutrophils; the capsule thickness around AG increased until the 12th week but remained thinner than those around hyaluronic acid and collagen. At 16 weeks, the thickness of the capsule significantly decreased around all materials. This study confirmed that 1.5% wt AG possesses some of the most important features of the ideal biocompatible material: safety, effectiveness, costless, and easily obtained with specific chemical and geometrical characters; the AG can represent a finely controllable and biodegradable polymeric system for cells and drug delivery applications.

Plants of the Genus Zingiber as a Source of Bioactive Phytochemicals: From Tradition to Pharmacy

Plants of the genus Zingiber (Family Zingiberaceae) are widely used throughout the world as food and medicinal plants. They represent very popular herbal remedies in various traditional healing systems; in particular, rhizome of Zingiber spp. plants has a long history of ethnobotanical uses because of a plethora of curative properties. Antimicrobial activity of rhizome essential oil has been extensively confirmed in vitro and attributed to its chemical components, mainly consisting of monoterpene and sesquiterpene hydrocarbons such as α-zingiberene, ar-curcumene, β-bisabolene and β-sesquiphellandrene. In addition, gingerols have been identified as the major active components in the fresh rhizome, whereas shogaols, dehydrated gingerol derivatives, are the predominant pungent constituents in dried rhizome. Zingiber spp. may thus represent a promising and innovative source of natural alternatives to chemical food preservatives. This approach would meet the increasing concern of consumers aware of the potential health risks associated with the conventional antimicrobial agents in food. This narrative review aims at providing a literature overview on Zingiber spp. plants, their cultivation, traditional uses, phytochemical constituents and biological activities.

Melatonin in Mediterranean diet, a new perspective

The health-promoting properties of the Mediterranean diet have been attributed, at least in part, to the chemical diversity of plant foods. Among phytochemicals, polyphenols represent the paradigm of the relationship between healthy foods and reduced risk of chronic-degenerative diseases, although, in the past few years, a new element has enriched this scenario. Melatonin, and possibly other indoleamines recently discovered in some relevant Mediterranean foods, may represent a new factor contributing to the elucidation of the protective effects of diets rich in plant products. Therefore, in synergy with polyphenols and other bioactive phytochemicals (e.g. carotenoids and glucosinolates), melatonin may contribute to maximizing the benefits of healthy dietary styles. This brief survey deals with the occurrence of melatonin in the Mediterranean diet, with an emphasis on grape products, and focuses on the biological significance of dietary melatonin, an emerging and exciting topic in the field of nutritional sciences.