Flavonoids, a group of natural substances with variable phenolic structures, are found in fruits, vegetables, grains, bark, roots, stems, flowers, tea and wine. These natural products are well known for their beneficial effects on health and efforts are being made to isolate the ingredients so called flavonoids. Flavonoids are now considered as an indispensable component in a variety of nutraceutical, pharmaceutical, medicinal and cosmetic applications. This is attributed to their anti-oxidative, anti-inflammatory, anti-mutagenic and anti-carcinogenic properties coupled with their capacity to modulate key cellular enzyme function. Research on flavonoids received an added impulse with the discovery of the low cardiovascular mortality rate and also prevention of CHD. Information on the working mechanisms of flavonoids is still not understood properly. However, it has widely been known for centuries that derivatives of plant origin possess a broad spectrum of biological activity. Current trends of research and development activities on flavonoids relate to isolation, identification, characterisation and functions of flavonoids and finally their applications on health benefits. Molecular docking and knowledge of bioinformatics are also being used to predict potential applications and manufacturing by industry. In the present review, attempts have been made to discuss the current trends of research and development on flavonoids, working mechanisms of flavonoids, flavonoid functions and applications, prediction of flavonoids as potential drugs in preventing chronic diseases and future research directions.
Flavonoids are an important class of natural products; particularly, they belong to a class of plant secondary metabolites having a polyphenolic structure, widely found in fruits, vegetables and certain beverages. They have miscellaneous favourable biochemical and antioxidant effects associated with various diseases such as cancer, Alzheimer's disease (AD), atherosclerosis, etc.. Flavonoids are associated with a broad spectrum of health-promoting effects and are an indispensable component in a variety of nutraceutical, pharmaceutical, medicinal and cosmetic applications. This is because of their antioxidative, anti-inflammatory, anti-mutagenic and anti-carcinogenic properties coupled with their capacity to modulate key cellular enzyme functions. They are also known to be potent inhibitors for several enzymes, such as xanthine oxidase (XO), cyclo-oxygenase (COX), lipoxygenase and phosphoinositide 3-kinase.
In nature, flavonoid compounds are products extracted from plants and they are found in several parts of the plant. Flavonoids are used by vegetables for their growth and defence against plaques. They belong to a class of low-molecular-weight phenolic compounds that are widely distributed in the plant kingdom. They constitute one of the most characteristic classes of compounds in higher plants. Many flavonoids are easily recognised as flower pigments in most angiosperm families. However, their occurrence is not restricted to flowers but are found in all parts of plants. Flavonoids are also abundantly found in foods and beverages of plant origin, such as fruits, vegetables, tea, cocoa and wine; hence they are termed as dietary flavonoids. Flavonoids have several subgroups, which include chalcones, flavones, flavonols and isoflavones. These subgroups have unique major sources. For example, onions and tea are major dietary sources of flavonols and flavones.
Flavonoids play a variety of biological activities in plants, animals and bacteria. In plants, flavonoids have long been known to be synthesised in particular sites and are responsible for the colour and aroma of flowers, and in fruits to attract pollinators and consequently fruit dispersion to help in seed and spore germination, and the growth and development of seedlings. Flavonoids protect plants from different biotic and abiotic stresses and act as unique UV filters, function as signal molecules, allopathic compounds, phytoalexins, detoxifying agents and antimicrobial defensive compounds. Flavonoids have roles against frost hardiness, drought resistance and may play a functional role in plant heat acclimatisation and freezing tolerance. Jorgensen has mentioned that the early advances in floral genetics were primarily due to mutation techniques making an impact on flavonoid-derived flower colours, and demonstrated that functional gene silencing in plants was associated with flavonoid biosynthesis. Flavonoids have been ascribed positive effects on human and animal health and the current interest is for disease therapy and chemoprevention. Currently there are about 6000 flavonoids that contribute to the colourful pigments of fruits, herbs, vegetables and medicinal plants. Dixon & Pasinetti reviewed plant flavonoids and isoflavonoids in detail and discussed their applications to agriculture and neurosciences in human beings. Kumar & Pandey reviewed the protective roles of flavonoids against human diseases as well as their functions in plants. Recently Panche et al.while reviewing AD and current therapeutic methods, discussed in detail uses of flavonoids as plant secondary metabolites for the treatment of AD and the mechanisms involved. In the present review, attempts have been made to discuss the current trends of research and development on flavonoids, their applications as dietary and health benefits along with broad classification and future research directions.
Flavonoids can be subdivided into different subgroups depending on the carbon of the C ring on which the B ring is attached and the degree of unsaturation and oxidation of the C ring . Flavonoids in which the B ring is linked in position 3 of the C ring are called isoflavones. Those in which the B ring is linked in position 4 are called neoflavonoids, while those in which the B ring is linked in position 2 can be further subdivided into several subgroups on the basis of the structural features of the C ring. These subgroups are: flavones, flavonols, flavanones, flavanonols, flavanols or catechins, anthocyanins and chalcones .
Flavones are one of the important subgroups of flavonoids. Flavones are widely present in leaves, flowers and fruits as glucosides. Celery, parsley, red peppers, chamomile, mint and ginkgo biloba are among the major sources of flavones. Luteolin, apigenin and tangeritin belong to this subclass of flavonoids . The peels of citrus fruits are rich in the polymethoxylated flavones, tageretin, nobiletin and sinensetin. They have a double bond between positions 2 and 3 and a ketone in position 4 of the C ring. Most flavones of vegetables and fruits have a hydroxyl group in position 5 of the A ring, while hydroxylation in other positions, for the most part in position 7 of the A ring or 3′ and 4′ of the B ring, may vary according to the taxonomic classification of the particular vegetable or fruit.
Flavonols are flavonoids with a ketone group. They are building blocks of proanthocyanins. Flavonols occur abundantly in a variety of fruits and vegetables. The most studied flavonols are kaempferol, quercetin, myricetin and fisetin . Onions, kale, lettuce, tomatoes, apples, grapes and berries are rich sources of flavonols. Apart from fruits and vegetables, tea and red wine are also sources of flavonols. Intake of flavonols is found to be associated with a wide range of health benefits which includes antioxidant potential and reduced risk of vascular disease.
Compared with flavones, flavonols have a hydroxyl group in position 3 of the C ring, which may also be glycosylated. Like flavones, flavonols are very diverse in methylation and hydroxylation patterns as well and, considering the different glycosylation patterns, they are perhaps the most common and largest subgroup of flavonoids in fruits and vegetables. For example, quercetin is present in many plant foods.
Flavanones are another important class which is generally present in all citrus fruits such as oranges, lemons and grapes. Hesperitin, naringenin and eriodictyol are examples of this class of flavonoids . Flavonones are associated with a number of health benefits because of their free radical-scavenging properties. These compounds are responsible for the bitter taste of the juice and peel of citrus fruits. Citrus flavonoids exert interesting pharmacological effects as antioxidant, anti-inflammatory, blood lipid-lowering and cholesterol-lowering agents. Flavanones, also called dihydroflavones, have the C ring saturated; therefore, unlike flavones, the double bond between positions 2 and 3 is saturated and this is the only structural difference between the two subgroups of flavonoids. Over the past 15 years, the number of flavanones has significantly increased.
Isoflavonoids are a large and very distinctive subgroup of flavonoids. Isoflavonoids enjoy only a limited distribution in the plant kingdom and are predominantly found in soyabeans and other leguminous plants. Some isoflavonoids have also been reported to be present in microbes(,18). They are also found to play an important role as precursors for the development of phytoalexins during plant microbe interactions(,19,20). Isoflavonoids exhibit tremendous potential to fight a number of diseases. Isoflavones such as genistein and daidzein are commonly regarded to be phyto-oestrogens because of their oestrogenic activity in certain animal models (Fig. 2). Szkudelska & Nogowski reviewed the effect of genistein inducing hormonal and metabolic changes, by virtue of which they can influence various disease pathways(,21).
Neoflavonoids are a class of polyphenolic compounds. While flavonoids have a 2-phenylchromen-4-one backbone, neoflavonoids have a 4-phenylchromen backbone with no hydroxyl group substitution at position 2. The first neoflavone isolated from natural sources in 1951 was calophyllolide from Calophyllum inophyllum seeds. It is also found in the bark and timber of the Sri Lankan endemic plant Mesua thwaitesii.
Flavanonols, also called dihydroflavonols or catechins, are the 3-hydroxy derivatives of flavanones. They are a highly diversified and multisubstituted subgroup. Flavanols are also referred to flavan-3-ols as the hydroxyl group is always bound to position 3 of the C ring. Unlike many flavonoids, there is no double bond between positions 2 and 3. Flavanols are found abundantly in bananas, apples, blueberries, peaches and pears.
Anthocyanins are pigments responsible for colours in plants, flowers and fruits. Cyanidin, delphinidin, malvidin, pelargonidin and peonidin are the most commonly studied anthocyanins . They occur predominantly in the outer cell layers of various fruits such as cranberries, black currants, red grapes, merlot grapes, raspberries, strawberries, blueberries, bilberries and blackberries. Stability coupled with health benefits of these compounds facilitate them to be used in the food industry in a variety of applications. The colour of the anthocyanin depends on the pH and also by methylation or acylation at the hydroxyl groups on the A and B rings(.
Chalcones are a subclass of flavonoids. They are characterised by the absence of ‘ring C’ of the basic flavonoid . Hence, they can also be referred to as open-chain flavonoids. Major examples of chalcones include phloridzin, arbutin, phloretin and chalconaringenin. Chalcones occur in significant amounts in tomatoes, pears, strawberries, bearberries and certain wheat products. Chalcones and their derivatives have garnered considerable attention because of numerous nutritional and biological benefits.. The intake of flavonoids through food sources could be the simplest and safest way to combat diseases as well as modulate activities.
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