Current Pharmaceutical Design - Volume 22, Issue 2, 2016

Exposure to environmental toxicants is a well-documented predisposing factor for cancer. Although genetic alterations have long been known to occur through exposure to some environmental carcinogens, there is another layer of genome regulatory system named epigenetic system. Epigenetics is defined as any reversible and heritable change in cellular patterns of gene expression that does not alter DNA sequence. This layer of gene control plays a key role in early stages of carcinogenesis by reprogramming cells to what is known as cancer stem cells, a process with great similarities to somatic cell reprogramming into “induced pluripotent stem cell”. Environmental toxicants could directly promote carcinogenesis through disturbing promoter CpG island hypermethylation, and silencing of tumor suppressor genes, hypomethylation of transposable elements and genomic instability induced by environmental toxicants. Environmental toxicants could also indirectly affect epigenetic programming of nucleus through inducing inflammatory signaling pathways that converge on NF-κB or STAT3 activation. Considering the reversibility of epigenetic alterations and their pivotal role in early carcinogenesis, reversion of these alterations could be a promising approach for chemoprevention. Selected phytochemicals have shown desirable effects through regulation of the most important epigenetic mechanisms including DNA methylation, histone modifications and microRNA expression, as well as modulation of SIRT-1 and STAT-3 signaling pathways. The present review aims to outline the epigenetic mechanisms underlying carcinogenic effects of environmental toxicants, and the protective effects of phytochemicals in reversing epigenetic aberrations in the regulatory pathways steering normal cell homeostasis.

Flaxseed contains 32% to 45% of its mass as oil of which 51% to 55% is α-linolenic acid. Flax lignan complex and secoisolariciresinol diglucoside (SDG) have been isolated from flaxseed. Flaxseed and its components have antioxidant, hypolipidemic and hypoglycemic effects. These are mostly due to the SDG content. Oxidative stress has been implicated in both type 1 and type 2 diabetes. Flaxseed, flaxseed oil and flax lignan complex have not been investigated as to whether they reduce the incidence of diabetes and/or delay the development of diabetes. However, their effects on serum glucose have been studied. Flaxseed and flax lignan complex improve glycemic control. Animal models of type I diabetes involving streptozotocin administration or utilizing Bio-Breed diabetic (BBdp) prone rats are associated with oxidative stress. SDG treatment reduced the incidence of diabetes using serum glucose levels by 75% in the streptozotocin model of diabetes and by 72% in the BBdp rat model of diabetes. These reductions in development of diabetes were associated with decreases in oxidative stress measured by serum and pancreatic malondialdehyde (MDA). SDG delays the development of diabetes in Zucker diabetic fatty (ZDF) rat model of type 2 diabetes and this effect was associated with a reduction in serum MDA and glycated haemoglobin A1C. The data suggest that SDG may have a great potential for reducing the incidence of type 1 diabetes and delaying the development of type 2 diabetes in humans.

Cognitive decline and dementia are major public health social problems, suggesting the specific need to provide research into risk factors for cognitive decline as priority topic. Increasing evidence supports the hypothesis that oxidative stress and neuroinflammation might play a crucial role in the pathophysiology of cognitive decline. Further, cognitive dysfunction and dementia in Alzheimer’s disease as well as in vascular dementia seem to be also the consequence of cerebral blood flow decrease and deregulation, also suggesting a putative pathophysiological convergence of mechanisms between atherosclerosis and Alzheimer's disease. In keeping with this, a growing interest has been addressed to flavonoids as potential nutraceuticals with neuroprotective effects. Of interest, cocoa beans have been described as a fundamental source of anti-oxidant flavonoids with the flavan-3-ols and their derivatives being present in high concentrations. Therefore, recent studies specifically focused on the favorable effects of flavonoid-rich cocoa and chocolate on cerebrovascular risk factors and cognitive function. Aim of this review is to summarize new findings concerning the cocoa effects on cognitive function, particularly focusing on some putative mechanisms of vascular and antioxidant action involved in preventing dementia.

Cardiovascular diseases remain the leading cause of morbidity and mortality among postmenopausal women in western societies. There are still no specific and highly efficient methods of preservation of women's vascular health in modern preventive medicine. For many years physicians have assumed that hormone replacement therapy prevents the development of atherosclerosis in menopausal women. However, the results of the largest international trials involving thousands of women have completely destroyed this hope. The modern perspective for the development of effective and safe drugs to enhance the quality of life and to prevent atherosclerosis progression in postmenopausal women may be the use of phytoestrogens, the substances of plant origin possessing estrogen- like effects, and possibly providing anti-atherosclerotic and anti-climacteric action. Phytoestrogens are often considered as a possible alternative to hormone replacement therapy, since they are believed to alleviate some symptoms of menopause. However, until now there is no exact evidence to consider phytoestrogens as the substances that protect women from atherosclerosis. It should be noted that the data from clinical studies with inconsistent results are mainly inconsistent per se, as most of the studies have serious limitations due to the study design and the participants’ compliance. Nevertheless, there is a substantial evidence that phytoestrogens have the potential to address several conditions and diseases associated with the menopausal transition. Phytoestrogens, at least, can potentially reduce atherosclerosis and atherosclerosis-related diseases through multiple mechanisms, by regulating serum lipid metabolism, arterial vessels, cytokine levels, and coagulation/fibrinolysis system. However, a skepticism exists concerning the true potential of phytoestrogens to beneficially modify these processes. An analysis of findings from supplementing the diet with phytoestrogens has failed, in general, to confirm them as the agents responsible for beneficial cardiovascular effects. Fortunalely, now there is a growing interest to the use of phytoestrogens for primary prevention of cardiovascular disease in postmenopausal women. Clinical and epidemiologic data indicate that phytoestrogens possess anti-atherosclerotic effects and may be used to prevent and treat cardiovascular diseases, and that adding phytoestrogens to the diet can contribute to the health of postmenopausal women. This review discusses the effects of phytoestrogens possibly beneficial for cardiovascular health, and how these effects could retard the progression of atherosclerosis, as well as the areas that need further investigation.

Chlorella vulgaris is a green unicellular microalgae with biological and pharmacological properties important for human health. C. vulgaris has a long history of use as a food source and contains a unique and diverse composition of functional macro- and micro-nutrients including proteinsChlorella vulgaris is a green unicellular microalgae with biological and pharmacological properties important for human health. C. vulgaris has a long history of use as a food source and contains a unique and diverse composition of functional macro- and micro-nutrients including proteins, omega-3 polyunsaturated fatty acids, polysaccharides, vitamins and minerals. Clinical trials have suggested that supplementation with C. vulgaris can ameliorate amelioration hyperlipidemia and hyperglycemia, and protect against oxidative stress, cancer and chronic obstructive pulmonary disease. In this review, we summarize the findings on the health benefits of Chlorella supplementation and the molecular mechanisms underlying these effects., omega-3 polyunsaturated fatty acids, polysaccharides, vitamins and minerals. Clinical trials have suggested that supplementation with C. vulgaris can ameliorate amelioration hyperlipidemia and hyperglycemia, and protect against oxidative stress, cancer and chronic obstructive pulmonary disease. In this review, we summarize the findings on the health benefits of Chlorella supplementation and the molecular mechanisms underlying these effects.

The role of polyphenols in the cardiovascular diseases prevention is still a matter of scientific discussion. However, recent clinical studies indicate that intake of anthocyanins and in a lesser extent procyanidins can participate in prevention of hypertension and type 2 diabetes. Fruits of Aronia melanocarpa (chokeberry) are known to be a reach source of these polyphenols. Moreover, its extracts were shown to express strong antioxidant, antiinflammatory, vasorelaxant and antithrombotic properties. The aim of the review is to summarize the results of the hitherto research regarding the biological effects at the molecular and clinical level.

Inflammatory bowel disease (IBD) including ulcerative colitis and Crohn’s disease are chronic relapsing and remitting chronic diseases for which there is no cure. The treatment of IBD frequently requires immunosuppressive and biologic therapies which carry an increased risk of infections and possible malignancy. There is a continued search for safer and more natural therapies in the treatment of IBD. This review aims to summarize the most current literature on the use of dietary supplements for the treatment of IBD. Specifically, the efficacy and adverse effects of vitamin D, fish oil, probiotics, prebiotics, curcumin, Boswellia serrata, aloe vera and cannabis sativa are reviewed.

Antioxidant-rich foods scavenge free radicals and other reactive species, decreasing the risk of different non-communicable chronic diseases. The objective of this study was to review the content of total antioxidant capacity of commonly foods comparing with experimental data and to explore the health benefits due to foods with moderate to high TAC. The TAC was analytically measured using the "Total Antioxidant Capacity" (NX2332) test from Randox® (UK) by spectrometry at 600 nm. Brazil nut (Bertholletia excelsa), “guaraná” (Paullinia cupana Kunth) powder, ready to drink boiled coffee (Coffea arabica L.), and milk chocolate (made from seeds of Theobroma cacao) had the highest TAC values, followed by collard greens (Brassica oleracea L.), beets (Beta vulgaris L.), apples (Malus domestica Borkh.), bananas (Musa paradisiaca), common beans (Phaseolus vulgaris), oranges (Citrus sinensis (L.) Osbeck), onions (Allium cepa L.), and lettuce (Lactuca sativa L.). Other foods also showed antioxidant capacity. The binomial antioxidant capacity of foods and health was extensively discussed according to science literature. Based on the high TAC content of Brazil nuts, guaraná, coffee, chocolate, collard greens, apples, beets, beans, oranges, onions and other foods, their regular dietary intake is strongly recommended to reduce the risk of chronic non-communicable diseases.

Garlic is believed to produce beneficial changes in different cardiovascular risk factors, thus possessing antiatherosclerotic properties. The hypotensive and cholesterol-lowering effects were investigated in two studies in men with mild arterial hypertension and in men with mild hypercholesterolemia. Eight-week treatment resulted in the reduction of both systolic and diastolic blood pressure by 5.2% (P=0.008) and 4.0% (P=0.014), respectively. In hypolipidemic study, the 12-week treatment resulted in a decrease in LDL cholesterol by 11.8% (P=0.002), while HDL cholesterol increased by 11.5% (P=0.013). In men with cerebral atherosclerosis it has been demonstrated that 14-days treatment inhibited ADP-induced platelet aggregation by 25.4% (P<0.05) and increased plasma fibrinolytic activity by 22.4% (P<0.05). One more study was performed in high-risk patients to evaluate the changes of prognostic cardiovascular risk that was calculated using algorithms derived from Framingham and Muenster Studies. Twelve-months treatment lowered 10-years prognostic risk of CHD by 13.2% in men (P=0.005), and by 7.1% in women (P=0.040). Ten-year prognostic risk of acute myocardial infarction and sudden coronary death was lowered by 26.1% in men (P=0.025). The Atherosclerosis Monitoring and Atherogenicity Reduction Study (AMAR) was designed to estimate the effect of two-year treatment with garlic powder pills on the progression of carotid atherosclerosis in asymptomatic men. A significant correlation has been revealed between the changes in blood serum atherogenicity and the changes in carotid intima-media thickness (r=0.144, P=0.045). Evidence obtained from these studies as well as series of double-blinded placebo-controlled clinical trials indicates that garlic powder pills are effective for prevention of cardiovascular disorders.

Atherosclerosis is the primary cause of coronary artery disease, heart attack, strokes, and peripheral vascular disease. Alternative/complimentary medicines, although are unacceptable by medical community, may be of great help in suppression, slowing of progression and regression of atherosclerosis. Numerous natural products are in use for therapy in spite of lack of evidence. This paper discusses the basic mechanism of atherosclerosis, risk factors for atherosclerosis, and prevention, slowing of progression and regression of atherosclerosis with flaxseed-derived secoisolariciresinol diglucoside (SDG). SDG content of flaxseed varies from 6mg/g to 18 mg/g. Flaxseed is the richest source of SDG. SDG possesses antioxidant, antihypertensive, antidiabetic, hypolipidemic, anti-inflammatory and antiatherogenic activities. SDG content of some commonly used food has been described. SDG in very low dose (15 mg/ kg) suppressed the development of hypercholesterolemic atherosclerosis by 73 % and this effect was associated with reduction in serum total cholesterol, LDL-C, and oxidative stress, and an increase in the levels HDL-C. A summary of the effects of flaxseed and its components on hypercholesterolemic atherosclerosis has been provided. Reduction in hypercholesterolemic atherosclerosis by flaxseed, CDC-flaxseed, flaxseed oil, flax lignan complex and SDG are 46 %, 69 %, 0 %, 34 % and 73 % respectively in dietary cholesterol -induced rabbit model of atherosclerosis. SDG slows the progression of atherosclerosis in animal model. Long-term use of SDG regresses hypercholesterolemic atherosclerosis. It is interesting that regular diet following high cholesterol diet accelerates in this animal model of atherosclerosis. In conclusion SDG suppresses, slow the progression and regresses the atherosclerosis. It could serve as an alternative medicine for the prevention, slowing of progression and regression of atherosclerosis and hence for the treatment of coronary artery disease, stroke and peripheral arterial vascular diseases.

Atherosclerotic cardiovascular disease (CVD) leading to coronary heart disease is the leading cause of morbidity and mortality in the world. Nutrition is one of the key factors in the etiology of atherosclerosis. Micronutrient supplements are widely used to prevent many chronic diseases including atherosclerosis. However, scientific evidence regarding this issue is still insufficient and current data on the association of dietary micronutrients and CVD risk is contradictory. Most of the randomized studies have failed to demonstrate beneficial effects of micronutrient supplementation on markers of subclinical atherosclerosis. In this review, role of each micronutrient on subclinical atherosclerosis will be evaluated thoroughly.

Oral microbiota of the mouth is the most diverse microbial community in the human body and plays a decisive role in the emergence and evolution of gingival pathology, contributing as well to the host general health condition, based on complex interactions established between the microbial community members and the host. A specific shift in the quantity and diversity of the microbial community developed on dental and mucosal surfaces, could lead to the occurrence of chronic inflammation mediated by the overproduction of pro-inflammatory cytokines. The mechanical treatment and current medication efficiency for the periodontal disease is limited in time due to the rapid plaque forming. Also, the antimicrobial treatment is limited by the sessile growth of the microorganisms, resulting in a poor biofilm penetration by biocides or antibiotics. In line with that, the attention of the scientific community shifted to ethnopharmacology as a complementary, or alternative therapeutic option for fighting infections with resistant bacteria. The vegetal and bee products are an important source of bioactive compounds, acting as harmless antimicrobials and periodontal inflammation suppressors. Vegetable bioproducts have been proven to exhibit multiple antipathogenic effects, such as microbicidal activity, virulence attenuation, and synergistic effects between the components found in the complex vegetal matrixes, or with conventional biocides, as well as immunomodulatory effects. The purpose of this review is to highlight the importance of vegetable products as a possible complementary treatment for periodontitis and their potential for the development of innovative therapeutic strategies.

Parkinson's disease (PD) is a neurodegenerative disorder due to dopamine deficit in substatia nigra. PD is mainly a sporadic disease with unestablished etiology. However, exposure to environmental toxins, head trauma, inflammation, and free radicals are potential reasons. Recently, the role of oxidative stress in neurological abnormalities, including PD, has been particularly addressed. Antioxidant remedies, particularly herbal antioxidants, have revealed new perspectives of research and therapy as possible preventive and therapeutic approaches for PD. In this paper, we reviewed the recently published papers on the effects of herbal medicines on PD alongside the pathogenesis of PD with regard to oxidative stress.

Diseases associated with chronic inflammatory pathology claim a major share of worldwide deaths each year. A principal reason behind the huge number of casualties is associated with mild or unnoticed symptoms for long period of time since the outset, and that specific treatment options for these diseases have not yet emerged. Current anti-inflammatory drugs essentially have become ineffective for long term protection from these diseases as they also interfere with essential cellular pathways and associated toxicities. Notably, recent studies with a number of phytochemicals have shown promising results. These compounds isolated from various medicinal plants express their anti-inflammatory activities by down regulating expression of several crucial pro-inflammatory mediators. These are mostly antioxidants; inhibit induction of key transcription factors like nuclear factor kappa B (NF-κB) that are responsible for expression of proinflammatory mediators, and other growth regulators. Definitely, some of these compounds have the potential to be developed into new therapeutic agents to better control inflammation associated diseases in near future. This review summarizes recent findings on the molecular mechanisms through which various inflammatory activities are linked to disease progression and a group of natural products that have shown promise in controlling these processes.