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Role of Polyphenols and Other Phytochemicals in Prevention and Therapy of Civilization Diseases

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

Deadline for manuscript submissions: closed (15 August 2021) | Viewed by 31841

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Dr. Robert Kubina

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1. Department of Pathology, Medical University of Silesia, Katowice, Poland
2. Silesia LabMed: Centre for Research and Implementation, Katowice, Poland
Interests: use of natural product in the treatment in neoplastic diseases; mechanism of biological activity of natural compounds
Special Issues, Collections and Topics in MDPI journals

Dr. Agata Kabała-Dzik

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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, Collections and Topics in MDPI journals

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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

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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

Related Special Issue

Role of Polyphenols and Other Phytochemicals in Prevention and Therapy of Civilization Diseases II in Molecules (1 article)

Published Papers (10 papers)

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Research

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12 pages, 2311 KiB

Open AccessArticle

An Analysis of Variability in the Content of Phenolic Acids and Flavonoids in Camelina Seeds Depending on Weather Conditions, Functional Form, and Genotypes

by Danuta Kurasiak-Popowska, Małgorzata Graczyk, Anna Przybylska-Balcerek, Kinga Stuper-Szablewska and Lidia Szwajkowska-Michałek

Molecules 2022, 27(11), 3364; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27113364 - 24 May 2022

Cited by 5 | Viewed by 1177

Abstract

Camelina oil obtained from the seeds of Camelina sativa exhibits strong antioxidative properties. This study was based on four years of field experiments conducted on 63 genotypes of spring and 11 genotypes of winter camelina. The aim of the study was to determine the variability in the content of the selected bioactive compounds, depending on the weather conditions during the cultivation, the functional form, and genotype. The cultivation form of the genotypes analysed in our study did not exhibit significant differences in the quantitative profiles of the tested phenolic acids and flavonoids. Sinapic acid was the most abundant of all phenolic acids under analysis (617–668 mg/kg), while quercetin was the main flavonoid (91–161 mg/kg). Camelina has great potential not only for the food industry but also for researchers attempting to breed an oil plant with the stable biosynthesis of bioactive compounds to ensure oxidative protection of obtained fat. Full article

(This article belongs to the Special Issue Role of Polyphenols and Other Phytochemicals in Prevention and Therapy of Civilization Diseases II)

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19 pages, 5878 KiB

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

by Vellingiri Manon Mani, Arockiam Jeyasundar Parimala Gnana Soundari, Balamuralikrishnan Balasubramanian, Sungkwon Park, Utthapon Issara, Kathirvel Preethi and Wen-Chao Liu

Molecules 2021, 26(3), 654; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26030654 - 27 Jan 2021

Cited by 8 | Viewed by 2642

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 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

(This article belongs to the Special Issue Role of Polyphenols and Other Phytochemicals in Prevention and Therapy of Civilization Diseases)

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23 pages, 13229 KiB

Open AccessFeature PaperArticle

Anticancer Activity of the Acetylenic Derivative of Betulin Phosphate Involves Induction of Necrotic-Like Death in Breast Cancer Cells In Vitro

by Arkadiusz Orchel, Ewa Chodurek, Marzena Jaworska-Kik, Piotr Paduszyński, Anna Kaps, Elwira Chrobak, Ewa Bębenek, Stanisław Boryczka, Paulina Borkowska and Janusz Kasperczyk

Molecules 2021, 26(3), 615; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26030615 - 25 Jan 2021

Cited by 11 | Viewed by 2849

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 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 p21^WAF1/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

(This article belongs to the Special Issue Role of Polyphenols and Other Phytochemicals in Prevention and Therapy of Civilization Diseases)

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23 pages, 5208 KiB

Open AccessArticle

Cicer arietinum L. Sprouts’ Influence on Mineralization of Saos-2 and Migration of MCF-7 Cells

by Małgorzata Zakłos-Szyda, Ilona Gałązka-Czarnecka, Joanna Grzelczyk and Grażyna Budryn

Molecules 2020, 25(19), 4490; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25194490 - 30 Sep 2020

Cited by 4 | Viewed by 2429

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 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

(This article belongs to the Special Issue Role of Polyphenols and Other Phytochemicals in Prevention and Therapy of Civilization Diseases)

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21 pages, 8029 KiB

Open AccessArticle

Caffeic Acid Phenethyl Ester (CAPE) Induced Apoptosis in Serous Ovarian Cancer OV7 Cells by Deregulation of BCL2/BAX Genes

by Anna Kleczka, Robert Kubina, Radosław Dzik, Krzysztof Jasik, Jerzy Stojko, Krzysztof Cholewa and Agata Kabała-Dzik

Molecules 2020, 25(15), 3514; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25153514 - 31 Jul 2020

Cited by 19 | Viewed by 3002

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 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

(This article belongs to the Special Issue Role of Polyphenols and Other Phytochemicals in Prevention and Therapy of Civilization Diseases)

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16 pages, 3259 KiB

Open AccessFeature PaperArticle

Regulation of the Mitochondrial BK_Ca Channel by the Citrus Flavonoid Naringenin as a Potential Means of Preventing Cell Damage

by Anna Kicinska, Rafał P. Kampa, Jan Daniluk, Aleksandra Sek, Wieslawa Jarmuszkiewicz, Adam Szewczyk and Piotr Bednarczyk

Molecules 2020, 25(13), 3010; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25133010 - 30 Jun 2020

Cited by 30 | Viewed by 3695

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 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 (mitoBK_Ca channel) and naringenin. Using the patch-clamp method, we showed that 10 µM naringenin activated the mitoBK_Ca channel present in endothelial cells. In the presence of 30 µM Ca²⁺, the increase in the mitoBK_Ca channel probability of opening from approximately 0.25 to 0.50 at −40 mV was observed. In addition, regulation of the mitoBK_Ca 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 mitoBK_Ca 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 mitoBK_Ca channel present in the inner mitochondrial membrane of endothelial cells. Our studies describing the regulation of the mitoBK_Ca channel by this natural, plant-derived substance may help to elucidate flavonoid-induced cytoprotective mechanisms. Full article

(This article belongs to the Special Issue Role of Polyphenols and Other Phytochemicals in Prevention and Therapy of Civilization Diseases)

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Review

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21 pages, 5012 KiB

Open AccessReview

Revisiting Therapeutic Strategies for H. pylori Treatment in the Context of Antibiotic Resistance: Focus on Alternative and Complementary Therapies

by Ioana Alexandra Cardos, Dana Carmen Zaha, Rakesh K. Sindhu and Simona Cavalu

Molecules 2021, 26(19), 6078; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26196078 - 08 Oct 2021

Cited by 26 | Viewed by 5571

Abstract

The prevalence of Helicobacter pylori infection remains significant worldwide and it depends on many factors: gender, age, socio-economic status, geographic area, diet, and lifestyle. All successful infectious diseases treatments use antibiotic-susceptibility testing, but this strategy is not currently practical for H. pylori and the usual cure rates of H. pylori are lower than other bacterial infections. Actually, there is no treatment that ensures complete eradication of this pathogen. In the context of an alarming increase in resistance to antibiotics (especially to clarithromycin and metronidazole), alternative and complementary options and strategies are taken into consideration. As the success of antibacterial therapy depends not only on the susceptibility to given drugs, but also on the specific doses, formulations, use of adjuvants, treatment duration, and reinfection rates, this review discusses the current therapies for H. pylori treatment along with their advantages and limitations. As an alternative option, this work offers an extensively referenced approach on natural medicines against H. pylori, including the significance of nanotechnology in developing new strategies for treatment of H. pylori infection. Full article

(This article belongs to the Special Issue Role of Polyphenols and Other Phytochemicals in Prevention and Therapy of Civilization Diseases)

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19 pages, 2098 KiB

Open AccessReview

Nanoformulations for Delivery of Pentacyclic Triterpenoids in Anticancer Therapies

by Anna Kaps, Paweł Gwiazdoń and Ewa Chodurek

Molecules 2021, 26(6), 1764; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26061764 - 21 Mar 2021

Cited by 21 | Viewed by 2855

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 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

(This article belongs to the Special Issue Role of Polyphenols and Other Phytochemicals in Prevention and Therapy of Civilization Diseases)

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26 pages, 883 KiB

Open AccessReview

Anti-Cancer Properties of Theaflavins

by Eric J. O’Neill, Deborah Termini, Alexandria Albano and Evangelia Tsiani

Molecules 2021, 26(4), 987; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26040987 - 13 Feb 2021

Cited by 36 | Viewed by 5221

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 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

(This article belongs to the Special Issue Role of Polyphenols and Other Phytochemicals in Prevention and Therapy of Civilization Diseases)

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15 pages, 683 KiB

Open AccessReview

Cardioprotective Activity of Selected Polyphenols Based on Epithelial and Aortic Cell Lines. A Review

by Michał Otręba, Leon Kośmider, Jerzy Stojko and Anna Rzepecka-Stojko

Molecules 2020, 25(22), 5343; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25225343 - 16 Nov 2020

Cited by 7 | Viewed by 2359

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 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

(This article belongs to the Special Issue Role of Polyphenols and Other Phytochemicals in Prevention and Therapy of Civilization Diseases)

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