Encapsulation of Flavonoids in Nanocarriers: A Novel Strategy to Enhance Their Bioefficacy and Oral Bioavailability

Introduction

Plants are main sources of majority of foods, drugs, and dietary supplements. All the plant chemicals known as phytochemicals can be classified as primary and secondary metabolites. Primary metabolites are central to sustain plant life as they are main players of the functions like cell division, growth, reproduction, respiration, metabolism, and storage. Secondary metabolites are not merely the plant waste products of primary metabolism but have profound effects on plant defensive mechanisms, ecology, and evolution (Udomsuk et al., 2011, Corradini et al., 2011). Among the major plant secondary metabolites are flavonoids. Flavonoid is the name given to class of more than 6000 compounds having fifteen- carbon skeleton with the core structure of 2- phenyl- benzopyrone with three-carbon bridge cyclized with oxygen. Such structure makes them important variable phenolic compounds with marked antioxidant activities (Morales et al., 2012). Flavonoids are abundantly found in vegetables and fruits that are regularly eaten by humans. Such compounds occur as secondary metabolites in plants (fruits, vegetables, roots, stems, flowers, bark, leaves) and are reported to have propitious effects on human health for the reason of which they are incorporated in the constituents of various nutraceuticals, medicines, cosmetic products (Winkel et al., 2011). Flavonoids have been reported to have anti-viral, anti-allergic, anti-mutagenic, anti-tumor, anti-inflammatory, anti-oxidative, anti- carcinogenic and anti-ageing capacities along with the ability to modulate cellular enzyme functions, induce apoptosis, and inhibit cell proliferation, among others. (Fig. 1). They have been reported to be efficient singlet oxygen quenchers and thus could reduce the lode of ROS in systems under stress by acting as antioxidants (Panche et al., 2016). Investigations are focusing mainly on the antioxidant activities, particularly their role in cancer control. Almost all plant parts including fruits and vegetables pack a big flavonoid punch. Compounds like procyanidin, catechin, epicatechin, chlorogenic acid, Phloridzin and quercetin are main flavonoids occurring in edible plant parts. They are actively incorporated in the plant life processes like UV filtration, symbiotic nitrogen fixation and play an important role as chemical messengers, regulators of physiology, and inhibitors of pathogens that are involved in plant diseases. Data from literature have also revealed that flavonoids get incorporated in the response against pathogens, both when they are enhanced following infection of plants tissues, as well as when they are applied externally. A plethora of evidence supports that after a plant is challenged by a pathogen or other abiotic stressors like physical, chemical, or biological stressors, various biochemical changes in the plant tissue take place inwardly which trigger down- or upregulation of specific phenolic compounds. Such alterations which mainly lead to the over expression of phytoalexins in turn may play a cardinal role in resistance/susceptibility of that plant to that invader. An added impulse on the process of research on flavonoids is gained since the discovery of French paradox in which low mortality rate was observed in populations because of consumption of red wine which is considered as richest source of flavonoids. Current trends of research on Flavonoids and other phenolic compounds relate to their identification, isolation, characterization, and particularly in the prevention of degenerative conditions including cancers, cardiovascular and neurodegenerative diseases. Knowledge of bioinformatics and molecular docking is being employed to predict potential application of flavonoids related to human health and disease. Current trends of research relate to their identification, isolation, characterization, and disease modulating capabilities as well as their impact on defending the growth and proliferation of plant pathogenic microorganisms by acting as phytoalexins (Kumar et al., 2013, Kay et al., 2012).