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Special Issue "Role of Polyphenols and Other Phytochemicals in Prevention and Therapy of Civilization Diseases"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: 15 August 2021.

Special Issue Editors

Dr. Robert Kubina
E-Mail Website
Guest Editor
Department of Pathology, Faculty of Pharmaceutical Sciences in Sosnowiec Medical University of Silesia in Katowice, ul. Ostrogórska 30 41-200 Sosnowiec, Poland
Interests: Immunohistochemistry; Immunofluorescence microscopy; Apoptosis; Cell biology; Flow cytometry; cancer biology; cancer biomarkers; flavonoids; head and neck cancer; immunology; immunopathology; cytopathology
Dr. Agata Kabała-Dzik
E-Mail Website
Guest Editor
Department of Pathology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, ul. Ostrogórska 30 41-200 Sosnowiec, Poland
Interests: natural bioactive compounds; honeybee products; flavonoids; polyphenols; chemoprevention; cell cycle; cancer biology; apoptosis; cytopathology
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Never has so much attention been paid by scientific world to civilization diseases as it is at present. Even nowadays, during COVID-19 pandemic, we are observing numerous reports of comorbidities. One of them are civilization diseases, including cancer, chronic obstructive pulmonary disease, asthma, Alzheimer's, arthritis, stroke, heart disease, hypertensive disease, atherosclerosis, chronic liver disease or cirrhosis, type 2 diabetes, metabolic syndrome, chronic renal failure, osteoporosis, depression, gastric ulcer, obesity and overweight. On the other hand, scientists are constantly looking for new drugs, and they pay special attention to the use of natural products, especially phytochemicals and polyphenols.

Phytochemical is a broad term meaning plant chemical referring to a wide variety of compounds that occur naturally in plants. Polyphenols are secondary metabolites of plants. They are abundant micronutrients in our diet, and evidence for their role in the prevention of degenerative diseases is emerging. The health effects of polyphenols and other phytochemicals depend on the amount consumed and on their bioavailability. There are many reports of positive effects of these natural agents on cells in vitro, in vivo, such as anti-inflammatory, antibacterial, anti-cancer, antioxidant and others. Moreover, there are promising strategies implemented already in use natural compounds to treat metabolic disorders. Multiple research show mechanisms of activity of phytochemicals and polyphenols. There are (but not limited to) potential modulation of cancer initiation and growth, cellular differentiation, apoptosis and autophagy, angiogenesis, and metastatic dissemination, migration inhibition.

In this special issue, we would like to focus on polyphenols and other phytochemicals, as prospect agents in treat of diseases of civilization and lifestyle.

Potential topics (not limited to):

  • Effects of natural products and derivatives (focus on phytochemicals and polyphenols) on nutrition and diet on lifestyle diseases
  • New research of influence polyphenols and mechanism of their activity in order to treat obesity, cancer, diabetes, asthma and others
  • New derivatives of phytochemicals with potential bioactive, their extraction and synthesis and bioactivity
  • Molecular mechanism of polyphenols activity in civilization diseases
  • Potential effect of phytochemicals in cancer

Dr. Robert Kubina
Dr. Agata Kabała-Dzik
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Natural products
  • Natural compounds
  • New compounds
  • Phytochemicals
  • Diseases of civilization and lifestyle
  • Prevention and therapy of civilization diseases
  • Bioavailability of phytochemicals
  • Role of phytochemical in inflammatory process
  • The health benefits of phytochemicals
  • Mechanisms of action
  • Functional foods and nutraceuticals
  • Bioactivity
  • New methodologies and procedures

Published Papers (8 papers)

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Research

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Open AccessArticle
Evaluation of Dimer of Epicatechin from an Endophytic Fungus Curvularia australiensis FC2AP on Acute Toxicity Levels, Anti-Inflammatory and Anti-Cervical Cancer Activity in Animal Models
Molecules 2021, 26(3), 654; https://doi.org/10.3390/molecules26030654 - 27 Jan 2021
Viewed by 430
Abstract
Cervical cancer, as the most frequent cancer in women globally and accounts almost 14% in India. It can be prevented or treated with vaccines, radiation, chemotherapy, and brachytherapy. The chemotherapeutic agents cause adverse post effects by the destruction of the neighboring normal cells [...] Read more.
Cervical cancer, as the most frequent cancer in women globally and accounts almost 14% in India. It can be prevented or treated with vaccines, radiation, chemotherapy, and brachytherapy. The chemotherapeutic agents cause adverse post effects by the destruction of the neighboring normal cells or altering the properties of the cells. In order to reduce the severity of the side effects caused by the chemically synthesized therapeutic agents, the current research developed an anti-cancer agent dimer of epicatechin (DoE), a natural bioactive secondary metabolite (BSM) mediated from an endophytic fungus Curvularia australiensis FC2AP. The investigation has initiated with the evaluation of inhibiting the angiogenesis which is a main activity in metastasis, and it was assessed through Hen’s Egg Test on Chorio Allantoic Membrane (HET-CAM) test; the BSM inhibited the growth of blood vessels in the developing chick embryo. Further the DoE was evaluated for its acute toxicity levels in albino mice, whereas the survival dose was found to be 1250 mg/kg and the lethal dose was 1500 mg/kg body weight of albino mice; hematological, biochemical, and histopathological analyses were assessed. The anti-inflammatory responses of the DoE were evaluated in carrageenan induced Wistar rats and the reduction of inflammation occurred in a dose-dependent manner. By fixing the effective dose for anti-inflammation analysis, the DoE was taken for the anti-cervical cancer analysis in benzo (a) pyrene induced female Sprague-Dawley rats for 60 days trial. After the stipulated days, the rats were taken for hematological antioxidants, lipid peroxidation (LPO), member bound enzymes, cervical histopathological and carcinogenic markers analyses. The results specified that the DoE has the capability of reducing the tumor in an efficient way. This is the first report of flavonoid-DoE production from an endophytic fungus C. australiensis has the anticancer potentiality and it can be stated as anti-cancer drug. Full article
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Open AccessFeature PaperArticle
Anticancer Activity of the Acetylenic Derivative of Betulin Phosphate Involves Induction of Necrotic-Like Death in Breast Cancer Cells In Vitro
Molecules 2021, 26(3), 615; https://doi.org/10.3390/molecules26030615 - 25 Jan 2021
Viewed by 519
Abstract
Betulin (BT) is a natural pentacyclic lupane-type triterpene exhibiting anticancer activity. Betulin derivatives bearing propynoyloxy and phosphate groups were prepared in an effort to improve the availability and efficacy of the drug. In this study, a comparative assessment of the in vitro anticancer [...] Read more.
Betulin (BT) is a natural pentacyclic lupane-type triterpene exhibiting anticancer activity. Betulin derivatives bearing propynoyloxy and phosphate groups were prepared in an effort to improve the availability and efficacy of the drug. In this study, a comparative assessment of the in vitro anticancer activity of betulin and its four derivatives was carried out using two human breast cancer cell lines: SK-BR-3 and MCF-7. In both studied cell lines, 30-diethoxyphosphoryl-28-propynoylbetulin (compound 4) turned out to be the most powerful inhibitor of growth and inducer of cellular death. Detailed examination of that derivative pertained to the mechanisms underlying its anticancer action. Treatment with compound 4 decreased DNA synthesis and up-regulated p21WAF1/Cip1 mRNA and protein levels in both cell lines. On the other hand, that derivative caused a significant increase in cell death, as evidenced by increased lactate dehydrogenase (LDH) release and ethidium homodimer uptake. Shortly after the compound addition, an increased generation of reactive oxygen species and loss of mitochondrial membrane potential were detected. The activation of caspase-3 and fragmentation of genomic DNA suggested an apoptotic type of cell death. However, analysis of cellular morphology did not reveal any nuclear features typical of apoptosis. Despite necrosis-like morphology, dead cells exhibited activation of the cascade of caspases. These observations have led to the conclusion that compound 4 pushed cells to undergo a form of necrotic-like regulated cell demise. Full article
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Open AccessArticle
Cicer arietinum L. Sprouts’ Influence on Mineralization of Saos-2 and Migration of MCF-7 Cells
Molecules 2020, 25(19), 4490; https://doi.org/10.3390/molecules25194490 - 30 Sep 2020
Viewed by 696
Abstract
In the present study, we investigated the biological activity of four extracts obtained from Cicer arietinum L. sprouts. The fermentation of the sprouts with Lactobacillus casei and their incubation with β-glucosidase elevated the concentrations of isoflavonoids, especially coumestrol, formononetin and biochanin A. To [...] Read more.
In the present study, we investigated the biological activity of four extracts obtained from Cicer arietinum L. sprouts. The fermentation of the sprouts with Lactobacillus casei and their incubation with β-glucosidase elevated the concentrations of isoflavonoids, especially coumestrol, formononetin and biochanin A. To study the biological activity of C. arietinum, the human osteosarcoma Saos-2 and human breast cancer MCF-7 cell lines were used. The extracts obtained from fermented sprouts exhibited the strongest ability to decrease intracellular oxidative stress in both types of cells. They augmented mineralization and alkaline phosphatase activity in Saos-2 cells, as well as diminished the secretion of interleukin-6 and tumor necrosis factor α. Simultaneously, the extracts, at the same doses, inhibited the migration of MCF-7 cells. On the other hand, elevated concentrations of C. arietinum induced apoptosis in estrogen-dependent MCF-7 cells, while lower doses stimulated cell proliferation. These results are important for carefully considering the use of fermented C. arietinum sprouts as a dietary supplement component for the prevention of osteoporosis. Full article
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Open AccessArticle
Caffeic Acid Phenethyl Ester (CAPE) Induced Apoptosis in Serous Ovarian Cancer OV7 Cells by Deregulation of BCL2/BAX Genes
Molecules 2020, 25(15), 3514; https://doi.org/10.3390/molecules25153514 - 31 Jul 2020
Cited by 2 | Viewed by 973
Abstract
Ovarian cancer has the worst prognosis among all gynecological cancers. Therefore, it seems reasonable to seek new drugs that may improve the effectiveness of treatment or mitigate the adverse effects of chemotherapy. Caffeic acid phenethyl ester (CAPE) has many beneficial biological properties. The [...] Read more.
Ovarian cancer has the worst prognosis among all gynecological cancers. Therefore, it seems reasonable to seek new drugs that may improve the effectiveness of treatment or mitigate the adverse effects of chemotherapy. Caffeic acid phenethyl ester (CAPE) has many beneficial biological properties. The aim of the study was to assess the anticancer properties of CAPE against serum ovarian carcinoma cells. The morphology of the cells was evaluated in H-E staining and in transmission electron microscopy. The cytotoxic and proapoptotic activity of CAPE was investigated by using the XTT-NR-SRB assay, qRT-PCR analysis of BAX/BCL2 expression, and by cytometric evaluation. CAPE causes constriction in OV7 cells, numerous granulomas were observed in the cytoplasm, the cell nuclei were pyknotic. Autophagosomal vacuoles could suggest the occurrence of aponecrosis. CAPE significantly decreased the lysosomal activity and the total synthesis of cellular proteins. CAPE exhibited, dose and time dependent, cytotoxic activity against OV7 serum ovarian cancer cells. In OV7 cells CAPE induced apoptosis via dysregulation of BAX/BCL2 balance, while activated proapoptotic BAX gene expression level was 10 times higher than BCL2. Full article
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Open AccessFeature PaperArticle
Regulation of the Mitochondrial BKCa Channel by the Citrus Flavonoid Naringenin as a Potential Means of Preventing Cell Damage
Molecules 2020, 25(13), 3010; https://doi.org/10.3390/molecules25133010 - 30 Jun 2020
Cited by 4 | Viewed by 1037
Abstract
Naringenin, a flavanone obtained from citrus fruits and present in many traditional Chinese herbal medicines, has been shown to have various beneficial effects on cells both in vitro and in vivo. Although the antioxidant activity of naringenin has long been believed to be [...] Read more.
Naringenin, a flavanone obtained from citrus fruits and present in many traditional Chinese herbal medicines, has been shown to have various beneficial effects on cells both in vitro and in vivo. Although the antioxidant activity of naringenin has long been believed to be crucial for its effects on cells, mitochondrial pathways (including mitochondrial ion channels) are emerging as potential targets for the specific pharmacological action of naringenin in cardioprotective strategies. In the present study, we describe interactions between the mitochondrial large-conductance calcium-regulated potassium channel (mitoBKCa channel) and naringenin. Using the patch-clamp method, we showed that 10 µM naringenin activated the mitoBKCa channel present in endothelial cells. In the presence of 30 µM Ca2+, the increase in the mitoBKCa channel probability of opening from approximately 0.25 to 0.50 at −40 mV was observed. In addition, regulation of the mitoBKCa channel by naringenin was dependent on the concentration of calcium ions. To confirm our data, physiological studies on the mitochondria were performed. An increase in oxygen consumption and a decrease in membrane potential was observed after naringenin treatment. In addition, contributions of the mitoBKCa channel to apoptosis and necrosis were investigated. Naringenin protected cells against damage induced by tumor necrosis factor α (TNF-α) in combination with cycloheximide. In this study, we demonstrated that the flavonoid naringenin can activate the mitoBKCa channel present in the inner mitochondrial membrane of endothelial cells. Our studies describing the regulation of the mitoBKCa channel by this natural, plant-derived substance may help to elucidate flavonoid-induced cytoprotective mechanisms. Full article
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Review

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Open AccessReview
Nanoformulations for Delivery of Pentacyclic Triterpenoids in Anticancer Therapies
Molecules 2021, 26(6), 1764; https://doi.org/10.3390/molecules26061764 - 21 Mar 2021
Viewed by 318
Abstract
The search for safe and effective anticancer therapies is one of the major challenges of the 21st century. The ineffective treatment of cancers, classified as civilization diseases, contributes to a decreased quality of life, health loss, and premature mortality in oncological patients. Many [...] Read more.
The search for safe and effective anticancer therapies is one of the major challenges of the 21st century. The ineffective treatment of cancers, classified as civilization diseases, contributes to a decreased quality of life, health loss, and premature mortality in oncological patients. Many natural phytochemicals have anticancer potential. Pentacyclic triterpenoids, characterized by six- and five-membered ring structures, are one of the largest class of natural metabolites sourced from the plant kingdom. Among the known natural triterpenoids, we can distinguish lupane-, oleanane-, and ursane-types. Pentacyclic triterpenoids are known to have many biological activities, e.g., anti-inflammatory, antibacterial, hepatoprotective, immunomodulatory, antioxidant, and anticancer properties. Unfortunately, they are also characterized by poor water solubility and, hence, low bioavailability. These pharmacological properties may be improved by both introducing some modifications to their native structures and developing novel delivery systems based on the latest nanotechnological achievements. The development of nanocarrier-delivery systems is aimed at increasing the transport capacity of bioactive compounds by enhancing their solubility, bioavailability, stability in vivo and ensuring tumor-targeting while their toxicity and risk of side effects are significantly reduced. Nanocarriers may vary in sizes, constituents, shapes, and surface properties, all of which affect the ultimate efficacy and safety of a given anticancer therapy, as presented in this review. The presented results demonstrate the high antitumor potential of systems for delivery of pentacyclic triterpenoids. Full article
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Open AccessReview
Anti-Cancer Properties of Theaflavins
Molecules 2021, 26(4), 987; https://doi.org/10.3390/molecules26040987 - 13 Feb 2021
Viewed by 565
Abstract
Cancer is a disease characterized by aberrant proliferative and apoptotic signaling pathways, leading to uncontrolled proliferation of cancer cells combined with enhanced survival and evasion of cell death. Current treatment strategies are sometimes ineffective in eradicating more aggressive, metastatic forms of cancer, indicating [...] Read more.
Cancer is a disease characterized by aberrant proliferative and apoptotic signaling pathways, leading to uncontrolled proliferation of cancer cells combined with enhanced survival and evasion of cell death. Current treatment strategies are sometimes ineffective in eradicating more aggressive, metastatic forms of cancer, indicating the need to develop novel therapeutics targeting signaling pathways which are essential for cancer progression. Historically, plant-derived compounds have been utilized in the production of pharmaceuticals and chemotherapeutic compounds for the treatment of cancer, including paclitaxel and docetaxel. Theaflavins, phenolic components present in black tea, have demonstrated anti-cancer potential in cell cultures in vitro and in animal studies in vivo. Theaflavins have been shown to inhibit proliferation, survival, and migration of many cancer cellswhile promoting apoptosis. Treatment with theaflavins has been associated with increased levels of cleaved poly (ADP-ribose) polymerase (PARP) and cleaved caspases-3, -7, -8, and -9, all markers of apoptosis, and increased expression of the proapoptotic marker Bcl-2-associated X protein (Bax) and concomitant reduction in the antiapoptotic marker B-cell lymphoma 2 (Bcl-2). Additionally, theaflavin treatment reduced phosphorylated Akt, phosphorylated mechanistic target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K), and c-Myc levels with increased expression of the tumour suppressor p53. This review summarizes the current in vitro and in vivo evidence available investigating the anti-cancer effects of theaflavins across various cancer cell lines and animal models. Full article
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Open AccessReview
Cardioprotective Activity of Selected Polyphenols Based on Epithelial and Aortic Cell Lines. A Review
Molecules 2020, 25(22), 5343; https://doi.org/10.3390/molecules25225343 - 16 Nov 2020
Cited by 1 | Viewed by 520
Abstract
Polyphenols have recently gained popularity among the general public as products and diets classified as healthy and containing naturally occurring phenols. Many polyphenolic extracts are available on the market as dietary supplements, functional foods, or cosmetics, taking advantage of clients’ desire to live [...] Read more.
Polyphenols have recently gained popularity among the general public as products and diets classified as healthy and containing naturally occurring phenols. Many polyphenolic extracts are available on the market as dietary supplements, functional foods, or cosmetics, taking advantage of clients’ desire to live a healthier and longer life. However, due to the difficulty of discovering the in vivo functions of polyphenols, most of the research focuses on in vitro studies. In this review, we focused on the cardioprotective activity of different polyphenols as possible candidates for use in cardiovascular disease therapy and for improving the quality of life of patients. Thus, the studies, which were mainly based on endothelial cells, aortic cells, and some in vivo studies, were analyzed. Based on the reviewed articles, polyphenols have a few points of action, including inhibition of acetylcholinesterase, decrease in reactive oxygen species production and endothelial tube formation, stimulation of acetylcholine-induced endothelium-derived mediator release, and others, which lead to their cardio- and/or vasoprotective effects on endothelial cells. The obtained results suggest positive effects of polyphenols, but more long-term in vivo studies demonstrating effects on mechanism of action, sensitivity, and specificity or efficacy are needed before legal health claims can be made. Full article
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