Current Drug Targets - Volume 18, Issue 2, 2017

For decades polyphenols have been considered to be sound, naturally occurring therapeutic compounds. While there are several polyphenols with special applications used in the treatment of cancer and other diseases, they need a specific carrier in order to reach the cells targeted for treatment. Recently, a number of new technologies have been developed on a nanoscale, such as nanoparticles, nanocapsules and nanofibers that can provide targeted delivery of polyphenols for medical purposes. This work summarizes the current trends in nanoscale delivery technology for polyphenols in cancer treatment and outlines its capabilities and the significant improvements that have been made. Special emphasis is given to the materials and to the manufacturing processes used to produce these kinds of drug delivery system nanostructures.

Polyphenols are a structural class of natural and synthetic organic chemicals which contain phenol units. Numerous epidemiological, preclinical and clinical studies have strongly supported their benefical effects for human health. Polyphenols group include molecules of utterly different complexity grades, ranging from simple molecules to highly polymerized structures. They are classified into: Phenolic acids, Flavonoids, Lignans and the less common Stilbenes. This work first intends to review the current studies on classification, chemical composition and metabolism of polyphenols. Then, we have reported cancer preventive and treatment effects of polyphenols, especially focused in the green tea polyphenol (GTP) (-)-Epigallocatechin-3-gallate (EGCG). Polyphenols such as EGCG and their synthetic analogs interfere in carcinogenesis by modulating and regulating multiple signaling pathways and transcription factors, membrane-associated receptor tyrosine kinases (RTKs), fatty acid metabolism and lipid rafts or methylation together with other emerging targets such as proteasome, telomerase and cancer stem cells. Here, we have reviewed several potential molecular targets of polyphenols (mainly EGCG and EGCG analogs) and their anticancer effects in cellular and animal models of different human carcinomas and we have also listed Phases I and II clinical trials conducted to study the antitumor properties of GTPs.

Polyphenols constitute a group of a paramount importance within the natural products in the plant kingdom, with an approximate amount of 8000 phenolic structures currently known. Fruits, vegetables, whole grains and several other foods and beverages (as tea, chocolate and wine, for instance) are rich and important sources of polyphenols. The scientific literature provides pre-clinical experimental evidence on the antinociceptive effects of polyphenolic compounds, found in plant extracts, in animal models of neuropathic pain. But not only neuropathic pain is attenuated: in fact, nociceptive pain, caused by stimulation of nerve fibers (either somatic or visceral) responding only to stimuli approaching or exceeding harmful intensity thresholds (nociceptors), and also inflammatory pain, which is associated with tissue damage and infiltration of immune cells, are both reduced and alleviated by polyphenols. In the present work, the antinociceptive effects of polyphenols are reviewed.

Medical advances in the last decades have increased the average life expectancy, but also the incidence and prevalence of age-associated neurodegenerative diseases. Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases and the most prevalent type of dementia. A plethora of different mechanisms contribute to AD, among which oxidative stress plays a key role in its development and progression. So far, there are no pharmacological treatments available and the current medications are mainly symptomatic. In the last years, dietary polyphenols have gained research attention due to their interesting biological activities, and more specifically their antioxidant properties. (-)- Epigallocatechin-3-gallate (EGCG) is a natural flavanol that has been extensively studied regarding its potential effects in AD. In this review we present the current in vitro and in vivo experimentation regarding the use of EGCG in AD. We also review the complex mechanisms of action of EGCG, not only limited to its antioxidant activity, which may explain its beneficial health effects.

Due to potential health benefits and the general assumption that natural products are safe, there is an increasing trend in the general population – including pregnant women – to supplement their diet with flavonoid-based food supplements. In addition, preclinical studies aim to prevent developmental adverse effects induced by toxic substances, infections, maternal or genetic diseases of the unborn child by administration of flavonoids at doses far above those reached by normal diets. Because these substances do not undergo classical risk assessment processes, our aim was to review the available literature on the potential adverse effects of maternal diet supplementation with flavonoid-based products for the developing child. A systematic literature search was performed in three databases and screened following four exclusion criteria. Selected studies were classified into two groups: 1. Studies on the developmental toxicity of single flavonoids in vitro or in animals in vivo, and 2. Studies on the developmental toxicity of single flavonoids or on flavonoid-mixtures in humans. The data collected indicate that there is a concern for the safety of some flavonoids within realistic human exposure scenarios. This concern is accompanied by a tremendous lack of studies on safety of these compounds during development making definite safety decisions impossible. Besides studies of survival, especially the more specific developmental processes like nervous system development need to be addressed experimentally. Before new high-dose, flavonoid-based therapeutic strategies are developed for pregnant women further research on the safety of these compounds is clearly needed.

Despite the consistent and significant advancements made in the treatment of head and neck cancer (HNSCC), it remains one of the most devastating cancers globally killing approximately 350,000 people every year. Both clinical and basic research revealed that the transcription factor NF-ΚB, is constitutively expressed in HNSCC and this persistent expression of NF-ΚB is the root cause of this disease resulting in cancer cell proliferation, survival, invasion, metastases and poor survival of patients. Activation of NF-ΚB is pragmatic in most of the premalignant dysplastic lesions indicating it as an early episode in malignant transformation of this disease. Therefore, therapies designed to inhibit or block the activity of NF-ΚB, would result in downregulation of key cellular processes involved in tumor growth and its dissemination to metastatic sites. In addition, substantial evidences have revealed that NF-ΚB plays an indispensable role in the development of both chemo and radiation resistance in HNSCC which is identified to be a primary cause for the failure of therapies. This shows the potential of targeting NF- ΚB in developing therapies against this disease. This review summarises the role of NF-ΚB in the development of HNSCC and the potential of using NF-ΚB as a target to develop novel highly effective therapies for this disease.