Chemical Compounds of Berry-Derived Polyphenols and Their Effects on Gut Microbiota, Inflammation, and Cancer

Berry-derived polyphenols are bioactive compounds synthesized and secreted by several berry fruits. These polyphenols feature a diversity of chemical compounds, including phenolic acids and flavonoids. Here, we report the beneficial health effects of berry-derived polyphenols and their therapeutical application on gut-microbiota-related diseases, including inflammation and cancer. Pharmacokinetic investigations have confirmed the absorption, availability, and metabolism of berry-derived polyphenols. In vitro and in vivo tests, as well as clinical trials, showed that berry-derived polyphenols can positively modulate the gut microbiota, inhibiting inflammation and cancer development. Indeed, these compounds inhibit the growth of pathogenic bacteria and also promote beneficial bacteria. Moreover, berry-derived polyphenols exhibit therapeutic effects against different gut-microbiota-related disorders such as inflammation, cancer, and metabolic disorders. Moreover, these polyphenols can manage the inflammation via various mechanisms, in particular the inhibition of the transcriptional factor Nf-κB. Berry-derived polyphenols have also shown remarkable effects on different types of cancer, including colorectal, breast, esophageal, and prostate cancer. Moreover, certain metabolic disorders such as diabetes and atherosclerosis were also managed by berry-derived polyphenols through different mechanisms. These data showed that polyphenols from berries are a promising source of bioactive compounds capable of modulating the intestinal microbiota, and therefore managing cancer and associated metabolic diseases. However, further investigations should be carried out to determine the mechanisms of action of berry-derived polyphenol bioactive compounds to validate their safety and examinate their clinical uses

Natural bioactive compounds targeting DNA methyltransferase enzymes in cancer: Mechanisms insights and efficiencies

The regulation of gene expression is fundamental to health and life and is essentially carried out at the promoter region of the DNA of each gene. Depending on the molecular context, this region may be accessible or non-accessible (possibility of integration of RNA polymerase or not at this region). Among enzymes that control this process, DNA methyltransferase enzymes (DNMTs), are responsible for DNA demethylation at the CpG islands, particularly at the promoter regions, to regulate transcription. The aberrant activity of these enzymes, i.e. their abnormal expression or activity, can result in the repression or overactivation of gene expression. Consequently, this can generate cellular dysregulation leading to instability and tumor development. Several reports highlighted the involvement of DNMTs in human cancers. The inhibition or activation of DNMTs is a promising therapeutic approach in many human cancers. In the present work, we provide a comprehensive and critical summary of natural bioactive molecules as primary inhibitors of DNMTs in human cancers. The active compounds hold the potential to be developed as anti-cancer epidrugs targeting DNMTs

Establishment of the hematology reference intervals in a healthy population of adults in the Northwest of Morocco (Tangier-Tetouan region)

Introduction: Among the most useful biological examinations in common medical practice, blood count is the most prescribed. The reference intervals of the hematological parameters of this examination are of major importance for clinical orientations and therapeutic decisions. In Morocco, the reference values used by the laboratories of medical biology and used by doctors are ones collected from Caucasian and European individuals. These values could be different in the Moroccan population. Besides, reference intervals of the blood count specific to the various Moroccan regions are missing. We decided to determine the reference intervals from a population of healthy adults of the Tangier-Tetouan region by following the procedures recommended by the IFCC-CLSI guidelines in 2008 and comparing them to those of the literature. Methods: Blood samples were taken from 15840 adult volunteers (8402 men from 18 to 55 years old and 7438 women from 18 to 50 years old) from the regional transfusion center of Tangier and Tetouan during a period between November 2014 and May 2016. The complete blood count was measured by the Sysmex KX21N® analyzer. For each sample a systematic blood smear was done to determine the leukocyte differential. The data analysis was made by the software SPSS 20.0 by using percentiles 2.5th and 97.5th. Results: A significant difference between both sexes was noted (p<0,001) for all the hematological parameters (red blood cells, hematocrit, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, leukocytes, neutrophils, basophils, eosinophils, monocytes, platelets and mean platelet volume) except for the numeration of lymphocytes (p = 0.552). The values of this study were compared with those reported in Arabic, Caucasian and African populations. Said comparisons showed the existence of significant differences. Conclusion: This study tries to accentuate the necessity of proceeding with the establishment of reference intervals specific to the blood count of the Moroccan population to avoid errors of diagnosis, allow clinicians to interpret with greater specificity the hematological examinations and to improve the quality of medical care distributed to patients

Dietary phenolic compounds as anticancer natural drugs:Recent update on molecular mechanisms and clinical trials

Given the stochastic complexity of cancer diseases, the development of chemotherapeutic drugs is almost limited by problems of selectivity and side effects. Furthermore, an increasing number of protective approaches have been recently considered as the main way to limit these pathologies. Natural bioactive compounds, and particularly dietary phenolic compounds, showed major protective and therapeutic effects against different types of human cancers. Indeed, phenolic substances have functional groups that allow them to exert several anti-cancer mechanisms, such as the induction of apoptosis, autophagy, cell cycle arrest at different stages, and the inhibition of telomerase. In addition, in vivo studies show that these phenolic compounds also have anti-angiogenic effects via the inhibition of invasion and angiogenesis. Moreover, clinical studies have already highlighted certain phenolic compounds producing clinical effects alone, or in combination with drugs used in chemotherapy. In the present work, we present a major advance in research concerning the mechanisms of action of the different phenolic compounds that are contained in food medicinal plants, as well as evidence from the clinical trials that focus on them

Advances in Dietary Phenolic Compounds to Improve Chemosensitivity of Anticancer Drugs

Despite the significant advances and mechanistic understanding of tumor processes, therapeutic agents against different types of cancer still have a high rate of recurrence associated with the development of resistance by tumor cells. This chemoresistance involves several mechanisms, including the programming of glucose metabolism, mitochondrial damage, and lysosome dysfunction. However, combining several anticancer agents can decrease resistance and increase therapeutic efficacy. Furthermore, this treatment can improve the effectiveness of chemotherapy. This work focuses on the recent advances in using natural bioactive molecules derived from phenolic compounds isolated from medicinal plants to sensitize cancer cells towards chemotherapeutic agents and their application in combination with conventional anticancer drugs. Dietary phenolic compounds such as resveratrol, gallic acid, caffeic acid, rosmarinic acid, sinapic acid, and curcumin exhibit remarkable anticancer activities through sub-cellular, cellular, and molecular mechanisms. These compounds have recently revealed their capacity to increase the sensitivity of different human cancers to the used chemotherapeutic drugs. Moreover, they can increase the effectiveness and improve the therapeutic index of some used chemotherapeutic agents. The involved mechanisms are complex and stochastic, and involve different signaling pathways in cancer checkpoints, including reactive oxygen species signaling pathways in mitochondria, autophagy-related pathways, proteasome oncogene degradation, and epigenetic perturbations

Anticancer clinical efficiency and stochastic mechanisms of belinostat

Cancer progression is strongly affected by epigenetic events in addition to genetic modifications. One of the key elements in the epigenetic control of gene expression is histone modification through acetylation, which is regulated by the synergy between histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs are thought to offer considerable potential for the development of anticancer medications, particularly when used in conjunction with other anticancer medications and/or radiotherapy. Belinostat (Beleodaq, PXD101) is a pan-HDAC unsaturated hydroxamate inhibitor with a sulfonamide group that has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of refractory or relapsed peripheral T-cell lymphoma (PTCL) and solid malignancies or and other hematological tissues. This drug modifies histones and epigenetic pathways. Because HDAC and HAT imbalance can lead to downregulation of regulatory genes, resulting in tumorigenesis. Inhibition of HDACs by belinostat indirectly promotes anti-cancer therapeutic effect by provoking acetylated histone accumulation, re-establishing normal gene expressions in cancer cells and stimulating other routes such as the immune response, p27 signaling cascades, caspase 3 activation, nuclear protein poly (ADP-ribose) polymerase-1 (PARP-1) degradation, cyclin A (G2/M phase), cyclin E1 (G1/S phase) and other events. In addition, belinostat has already been discovered to increase p21WAF1 in a number of cell lines (melanoma, prostate, breast, lung, colon, and ovary). This cyclin-dependent kinase inhibitor actually has a role in processes that cause cell cycle arrest and apoptosis. Belinostat's clinical effectiveness, comprising Phase I and II studies within the areas of solid and hematological cancers, has been evidenced through several investigative trials that have supported its potential to be a valuable anti-cancer drug. The purpose of this research was to provide insight on the specific molecular processes through which belinostat inhibits HDAC. The ability to investigate new therapeutic options employing targeted therapy and acquire a deeper understanding of cancer cell abnormalities may result from a better understanding of these particular routes

Natural Bioactive Compounds Targeting Epigenetic Pathways in Cancer: A Review on Alkaloids, Terpenoids, Quinones, and Isothiocyanates

Cancer is one of the most complex and systemic diseases affecting the health of mankind, causing major deaths with a significant increase. This pathology is caused by several risk factors, of which genetic disturbances constitute the major elements, which not only initiate tumor transformation but also epigenetic disturbances which are linked to it and which can induce transcriptional instability. Indeed, the involvement of epigenetic disturbances in cancer has been the subject of correlations today, in addition to the use of drugs that operate specifically on different epigenetic pathways. Natural molecules, especially those isolated from medicinal plants, have shown anticancer effects linked to mechanisms of action. The objective of this review is to explore the anticancer effects of alkaloids, terpenoids, quinones, and isothiocyanates

Phytochemical Compounds and Nanoparticles as Phytochemical Delivery Systems for Alzheimer’s Disease Management

Alzheimer’s disease remains one of the most widespread neurodegenerative reasons for dementia worldwide and is associated with considerable mortality and morbidity. Therefore, it has been considered a priority for research. Indeed, several risk factors are involved in the complexity of the therapeutic ways of this pathology, including age, traumatic brain injury, genetics, exposure to aluminum, infections, diabetes, vascular diseases, hypertension, dyslipidemia, and obesity. The pathophysiology of Alzheimer’s disease is mostly associated with hyperphosphorylated protein in the neuronal cytoplasm and extracellular plaques of the insoluble β-amyloid peptide. Therefore, the management of this pathology needs the screening of drugs targeting different pathological levels, such as acetylcholinesterase (AchE), amyloid β formation, and lipoxygenase inhibitors. Among the pharmacological strategies used for the management of Alzheimer’s disease, natural drugs are considered a promising therapeutic strategy. Indeed, bioactive compounds isolated from different natural sources exhibit important anti-Alzheimer effects by their effectiveness in promoting neuroplasticity and protecting against neurodegeneration as well as neuroinflammation and oxidative stress in the brain. These effects involve different sub-cellular, cellular, and/or molecular mechanisms, such as the inhibition of acetylcholinesterase (AchE), the modulation of signaling pathways, and the inhibition of oxidative stress. Moreover, some nanoparticles were recently used as phytochemical delivery systems to improve the effects of phytochemical compounds against Alzheimer’s disease. Therefore, the present work aims to provide a comprehensive overview of the key advances concerning nano-drug delivery applications of phytochemicals for Alzheimer’s disease management