Dear Colleagues,

Chronic diseases are the leading causes of death and disability worldwide. However, the quality of treatment, treatment options, and management of chronic diseases remain low in many aspects. The existing therapies for most chronic conditions sometimes have more debilitating effects than the disease itself. The question is, can we slow down or prevent the onset of chronic diseases using cost-effective therapeutic alternatives, such as readily available, less toxic, antioxidant-rich foods? Numerous scientific data indicate that foods rich in flavonoids can prevent the development of chronic diseases and maintain homeostasis and genetic stability of an organism in both health and disease. Almost 25 centuries ago, Hippocrates, the father of medicine, stated that foods rich in antioxidants could have beneficial effects on human health. He proclaimed: “Let food be thy medicine and medicine be thy food.” Flavonoids, as a sub-class of plant polyphenols, possess a 15-carbon skeleton usually abbreviated as C6-C3-C6. They are composed of two benzene rings (A and B) linked via a heterocyclic pyran ring (C) and are usually classified into flavones, flavonols, flavanones, flavanonols, flavans, flavanols, isoflavones, and chalcones.

Flavonoids, as bioactive compounds with powerful antioxidant and anti-inflammatory properties, could be useful for reducing the risk of oxidative stress and chronic inflammation-mediated pathogenesis of human diseases such as cancer, diabetes, obesity, ischemic heart disease, cardiovascular disorders, cerebrovascular diseases, Alzheimer’s disease and other dementias, osteoarthritis, osteoporosis, chronic obstructive pulmonary disease (COPD), neck pain, chronic kidney disease, cirrhosis of the liver, allergy, autoimmune diseases, atherosclerosis, inflammatory bowel diseases, and neurodegenerative and other disorders which emerge as a result of tissue injury and genomic changes induced by ongoing low-grade inflammation in and around the affected tissue or organ. The antioxidative, anti-inflammatory, antimutagenic, and anticarcinogenic effects of flavonoids are mediated by modulatory actions on multifaceted cell signaling pathways related to inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that generally promote inflammation. Flavonoids reduce the symptoms of various chronic diseases due to multiple biological mechanisms of action, including their effects on the activation of survival genes and signaling pathways, epigenetic regulations, gut microbiota and microbial metabolites, regulation of mitochondrial functions and bioenergetics, and modulation of inflammatory response. Dietary supplementation with flavonoids may offer additional protection against oxidative stress and prevention of DNA damage caused by ionizing and UV radiations, carcinogenic agents, and various chemicals and toxins. Flavonoids, through their free radical scavenging properties, inhibition of prooxidative enzymes, metal chelation, inhibition of CYP enzymes, enhanced synthesis of antioxidant enzymes, activation of Nrf2, and inhibition of NF-κB pathways, may participate in the DNA repair mechanism or DNA damage tolerance and in the process of detoxification of toxins and carcinogens. Furthermore, flavonoids play important roles in the prevention of metabolic abnormalities such as dyslipidemia, insulin resistance, hypertension, and glucose intolerance. However, they also show pro-oxidant activity and can induce DNA damage and mutagenic effects. Pro-oxidative and mutagenic properties of flavonoids are dependent on their structure, concentration, and environmental conditions. However, the pro-oxidant activity of flavonoids can contribute to their health-promoting activity by inducing important detoxifying enzymes, suggesting potential beneficial effects of a chemical reaction presumed to be toxic.

Currently, many studies are directed toward better understanding of the pharmacological properties of flavonoids and their potential as health-promoting products capable of exerting physiological benefits, reducing chronic disease risk or otherwise optimizing health. Unfortunately, due to their poor bioavailability, the risk of some chronic diseases may be reduced only at high intake of dietary flavonoids. This problem could be overcome by structural modifications and application of nanotechnology, such as encapsulation. Nanotechnology could be a promising approach for applying flavonoids with greater therapeutic efficacy and with fewer side effects in comparison with commercially available anti-inflammatory drugs.

This Special Issue aims to bring comprehensive insight into the most recent discoveries and benefits of dietary flavonoids and their derivatives in the prevention and treatment of chronic disease. Our goal is to highlight the structural diversity of flavonoids, modulatory effects on intracellular signaling cascades, target molecules and mechanisms of action of flavonoids, current trends in the research and development of flavonoids, function and application of flavonoids as potential drugs in the prevention of chronic disease, as well as future research directions and challenges.

We cordially invite authors to contribute original articles as well as review papers that bring new insights into scientific progress and the exact mechanisms of flavonoid action, and which will hopefully contribute to potential clinical application of flavonoids in the prevention and therapy of numerous chronic diseases.

Prof. Dr. Nada Orsolic
Dr. Maja Jazvinšćak Jembrek
Guest Editors

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• flavonoids and oxidative stress-related diseases
• chronic diseases
• metabolic syndrome
• natural bioactive compounds
• chronic inflammation-mediated pathogenesis of human diseases
• biological and pharmacological activity
• health benefits of flavonoids
• side effects of flavonoids