Current Pharmaceutical Biotechnology - Volume 15, Issue 4, 2014

In the last decades epidemiological studies and associated meta-analyses have strongly suggested that long term consumption of plant foods (fruits, vegetables, cereals, dry legumes, and beverages like wine, coffee and tea) offers protection against development of oxidative stress related pathologies, such as cancers, cardiovascular diseases, diabetes, osteoporosis and neurodegenerative diseases [1, 2]. These results have prompted research to study polyphenols, following the discovery of their antioxidant and radical scavenger activities [3]. So, the antioxidant properties of polyphenols have been widely studied from the mid- 1990s, but the latest research indicates that the mechanisms of action of polyphenols go beyond the modulation of oxidative stress [3]. Polyphenols protective activity can be ascribed to their capacity of interact with cellular functions at different levels, such as affecting gene expression, protein synthesis and enzyme activities, binding to membrane or nuclear receptors as either an elective ligand or a ligand mimic. Recently, it has been also demonstrated the antibacterial activity of some polyphenols against multidrug-resistant bacteria [4]. The goal of this special issue is to present novel results about dietary polyphenols healthy properties, with particular attention to their mechanisms of action. On behalf of all authors, we hope that this issue of Current Pharmaceutical Biotechnology will promote novel ideas and provide prospects for theirs scientific activity. Finally, we would like to thanks all the contributors and reviewer for their precious and valuable contribution in this issue.

Stroke is an important cerebrovascular disease which causes chronic disability and death in patients. Despite of its high morbidity and mortality, there are limited available effective neuroprotective agents for stroke. In recent years, the research aimed at finding novel neuroprotective agents from natural origins has been intensified. Camellia sinensis L. (tea) is the second most consumed beverage worldwide, after water. It is classified into green and white, oolong, black and red, and Pu-erh tea based on the manufacturing process. Catechins are the main phytochemical constituents of Camellia sinensis which are known for their high antioxidant capacity. On other hand, it is well known that oxidative stress plays an important role in the initiation and progression of different cardiovascular diseases such as stroke. Therefore, the present article is aimed to review scientific studies that show the protective effects of tea consumption against ischemic stroke.

Polyphenols are a structural class of natural and synthetic, organic chemicals characterized mainly by the presence of phenol structural units. Numerous epidemiological and experimental studies have strongly suggested their beneficial effects for human health. This view is supported by their biological activities, which are associated with chemical and biochemical properties, including the ability to act as antioxidants, their antineoplastic effect and the regulation of gene expression in chronic degenerative diseases. These mechanisms of action could account for their preventive and therapeutic uses in human subjects. Moreover, in some therapeutic uses, such as antineoplastic effect, a prooxidant therapeutic action has been suggested. In the diet, numerous compounds could participate in the beneficial properties, and this likely could result in synergistic effects because the whole effect is better than the separately action of each compound. However, the pharmacokinetic and pharmacodynamic properties of these bioactive micronutrients are yet to be further characterized. More research is required to fully establish the therapeutic use of polyphenols against human disease. Based on biological and pharmacological properties of polyphenols both as diet components and supplements, the objective of this work is to show an updated version about the role that polyphenols could play in several chronic diseases such as hypertension, diabetes mellitus, cancer and neurodegenerative disorders.

Under normal conditions, most of the central nervous system (CNS) is protected by the blood brain barrier (BBB) from systemic inflammation progression and from the infiltration of immune cells. As a consequence, the CNS developed an original way to provide surveillance, defense and repair, which relies on the complex process of neuroinflammation. Despite tight regulation, neuroinflammation is frequently the cause of irreversible nerve cell loss but it is also where the solution lies. Specific immune crosstalk taking place in the CNS needs to be decoded in order to identify the best therapeutic strategies aimed at helping the CNS restore homeostasis in difficult conditions such as in neurodegenerative disorders. This review deals with the double-edged sword nature of neuroinflammation and the use of resveratrol in various models as one of the most promising therapeutic molecules for preventing the consequences of nerve cell autodestruction.

Polyphenols are the most abundant components of our daily food, occupying the major portion of naturally occurring phytochemicals in plants. Currently, polyphenols have received a special attention from the scientific community against health risk because of their antioxidant capacity and the ability to scavenge the free radicals formed during the pathological process like cancer, cardiovascular diseases and neurodegenerative disorders. Alzheimer’s disease, one of the common forms of dementia is an intricate, multifactorial mental illness which is characterized by age-dependent memory loss ultimately leading to a steady decline of cognitive function. Extracellular amyloid beta deposition and intracellular tau hyperphosphorylation are the two main alterations occurring in the cells reported to cause neuronal dysfunction during AD. Dietary intake of polyphenols is known to attenuate the progression of the disease by showing strong potential to tackle the alterations and reduce the risk of AD by reversing the cognitive deficits. A large number of polyphenolic compounds showing promising results against AD pathologies have been identified and described in the past decade. Many efforts have been made to unravel the molecular mechanisms and the specific interactions of polyphenols with their targets in the pathway. This review focuses on the therapeutic potential and promising role of dietary polyphenols as nutraceuticals to combat AD.

In the lasts years it has become evident that polyphenols modify cell functionality through epigenetic mechanisms, such as modulating microRNA (miRNA) levels. miRNAs are small non-coding RNAs of about 22 nucleotides in length, that modulate gene expression at the post-transcriptional level. miRNAs are involved in almost all biological processes, affect most metabolic pathways and recent evidence suggests their dysregulation in a number of metabolic disorders and diseases. In this sense, miRNAs are emerging as potential biomarkers of numerous pathologies and therefore as new therapeutic targets. Polyphenolic modulation of miRNAs is very attractive as a strategy to target numerous cell processes and potentially reduce the risk of chronic diseases.

Flavonoids are one of the most abundant secondary metabolites having a polyphenolic structure in plant and animal species with various desired pharmacological effects towards human health. Many flavonoid derivatives have been reported to possess neuroprotective activity through different mechanisms of action and, among them, cholinesterase (ChE) inhibition constitutes an important clinically applied treatment strategy of Alzheimer’s disease (AD). Some flavonoid derivatives have been demonstrated to inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) to varying extent, which are called the sister enzymes linked to the pathogenesis of AD. On the other hand, diverse bioproduction techniques such as plant tissue culture, microbial transformation, etc. are applicable for flavonoids and, among them, production of flavonoids through metabolic engineering using special bacteria or yeast species has recently become popular. In the current review, some common flavonoids with ChE inhibitory effect as well as the examples of flavonoids obtained from metabolic engineering methods will be discussed.

Gallic acid (3,4,5-trihydroxybenzoic acid) is a phenolic acid widely distributed in many different families of higher plants, both in free state, and as a part of more complex molecules, such as ester derivatives or polymers. In nature, gallic acid and its derivatives are present in nearly every part of the plant, such as bark, wood, leaf, fruit, root and seed. They are present in different concentrations in common foodstuffs such as blueberry, blackberry, strawberry, plums, grapes, mango, cashew nut, hazelnut, walnut, tea, wine and so on. After consumption, about 70% of gallic acid is adsorbed and then excreted in the urine as 4-O-methylgallic acid. Differently, the ester derivatives of gallic acid, such as catechin gallate ester or gallotannins, are hydrolyzed to gallic acid before being metabolized to methylated derivatives. Gallic acid is a well known antioxidant compounds which has neuroprotective actions in different models of neurodegeneration, neurotoxicity and oxidative stress. In this review, we discuss about the neuroprotective actions of gallic acid and derivatives and their potential mechanisms of action.

Moderate physical exercise leads the organism to adapt to this stressful situation. However, when exercise is exhaustive, it is also known to induce an overproduction of reactive species which can result in oxidative damage to macromolecules and tissues. Many studies have been carried out to evaluate the validity of dietary strategies or micronutrients in order to attenuate exercise-induced oxidative stress. Polyphenols are a large group of compounds widely distributed throughout the plant kingdom. This review summarizes recent evidence in relation to the effects of polyphenols as antioxidant and anti-inflammatory agents, using exercise as a model of study.

Polyphenols are a widely distributed group of natural products found in fruits, vegetables, nuts, seeds, stems and flowers. Such compounds, especially dietary flavonoids and tannins, have been shown to exert antioxidant, antiinflammatory, anti-cancer and antibacterial effects and may have beneficial effects on human health. The antimicrobial activity of polyphenols has been widely studied and hundreds of publications reporting the antimicrobial activity of polyphenols have been recently published. In an era of increasing antibiotic resistance, the development of new strategies to fight bacteria is welcome. Further studies are needed to evaluate the therapeutic potential of polyphenols alone or in combination with currently available antibiotics.

Type-2 diabetes (T2D) is a complex metabolic syndrome that is characterized by persistent hyperglycemia due to either lack of insulin secretion and/or insulin resistance. The prevalence of T2D along with its major risk factor, obesity, has been increasing with an epidemic proportion in recent years. To date, there is no drug of cure for diabetes and the existing therapeutic approaches have serious drawbacks including side effects and loss of efficacy during prolonged use. Dietary polyphenols are one group of natural products that have shown promise as potential antidiabetic agents. In this review, their molecular mechanisms of action including, antioxidant, anti-inflammatory, receptor agonist/antagonist effect and modulation of key signal transduction cascades, glucose transport, enzyme activity, receptor agonistic/antagonist effect, etc. in major insulin-sensitive cells are discussed.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) possesses multiple protective properties in the vasculature, including anti-oxidative and anti-inflammatory effects and improvement of endothelial function. A substantial part of these effects is attributable to gene expression changes induced by the compound. Resveratrol can activate the NAD-dependent deacetylase sirtuin 1 (SIRT1), leading to deacetylation of SIRT1 target molecules such as NF-kB and forkhead box O (FOXO) transcription factors. The inhibition of NF-kB by resveratrol reduces the expression of inflammation mediators. FOXO factors are implicated in the upregulation of antioxidant enzymes and the endothelial-type nitric oxide synthase. In addition, resveratrol upregulates a number of antioxidant enzymes by activating nuclear factor-E2-related factor-2 (Nrf2) and downregulates NADPH oxidases through yet known mechanisms.

Natural phenolic compounds have been considered as one of the interesting secondary metabolites for their chemopreventive and chemotherapeutic effects in cancer for a long time. These are a large and diverse family of phytochemicals classified into several subgroups such as simple phenols, lignans, phenylpropanoids, flavonoids, coumarins, etc. The antioxidant potential of phenolic compounds is almost bolded in the treatment and prevention of cancer. Due to the concerns on the diverse effects of antioxidants in cancer, differentiation and clarification of their anti-neoplastic mechanisms are necessary. An important mechanism for phenolic compounds is related to their direct effect on the cell cycle progression, which has not been discussed in detail so far. This study aims to criticize the evidence on regulatory mechanisms of phenolic compounds in the cell cycle. Recent studies indicate that phenolic compounds from several subgroups significantly inhibit the proliferation of different cancer cells. The structural diversity of these compounds influences various components involved in cell cycle regulation. Forming active metabolites and sensitizing cancerous cells to chemotherapeutic medicines are additional values of these compounds. In the recent years, many studies on neoplastic cell cultures have been carried out to investigate the mechanisms of action of these compounds but dissimilarity of in vitro systems in comparison with human body in terms of metabolism and bioavailability is a major concern. Therefore, further studies are still needed.

Seven indigenously isolated fungal strains (Aspergillus niger, Aspergillus flavus, Aspergillus terreus, Penicillium citrinum, Penicillium notatum, Pleurotus ostreatus and Trichoderma viradae) were tested for their potential to produce cholesterol lowering drug lovastatin by using different agro-industrial wastes (Corn cobs, corn stover, banana stalk, wheat straw, wheat bran, bagasse) in submerged as well as solid state fermentation. Aspergillus terreus showed maximum production of 18.74 mg/100mL by wheat bran in solid state fermentation. The fermentation parameters (pH, temperature, Inoculum size, moisture contents and fermentation time) were also optimized for optimum production of lovastatin. It was found that Aspergillus terreus could produce 27.14 mg/100mL lovastatin under optimum condition of pH (6), temperature (30oC), Inoculum size (2mL), moisture contents (60%) and fermentation time (120hrs) in solid state fermentation. The optimized lovastatin was extracted from fermented broth and orally administered to rats. The hypocholesterolemic effect of fermented lovastatin was evaluated on serum ALT, AST, HDL-C, LDL-C, TG and TC level of rats. It was concluded from the study, fermented lovastatin effectively lower the cholesterol level of rats.