Chemistry and Role of Flavonoids in Agriculture: A Recent Update

Abstract

Flavonoids are a remarkable group of plant secondary metabolites, and are of importance and interest to a wide variety of physical and biological scientists. Continuing works on their chemistry, occurrence, natural distribution and biological function have already resulted a lot and have created a stir in the field of chemical and biological sciences due to their immense biological and pharmacological/therapeutic potential. Also flavonoids play an important role in the biological activities of plant system. They can be responsible for the color of flowers and fruits and for the attraction of pollinators. The plant flavonoids are used naturally to improve their adaptation to environmental stress, to improve food quality, and to increase crop yield. The present book chapter deals with chemistry and significance role of reported novel natural flavonoids along with a variety of activities in agriculture.

1. Introduction

Nature is an extremely rich source of highly diverse and innovative chemical structures with a variety of structural arrangement and interesting biological activities, which have played a significant role in the process of drug discovery and design. Chemistry of Natural Products has lately undergone explosive growth; natural products are of much interest and of promise in the present day research directed particularly toward drug-design and drug-discovery. Much research works were already carried out and also intensive works are now going on world-wide in the perspective of academic as well as pharmacological/therapeutic scenario. Statistically, only less than ~10–15% of the plants have been investigated so far; a major portion of them is still being left. To gather more knowledge on the natural availability of chemical compounds, their structural variety, properties, and the isolated compounds for detailed studies in regards to biological and pharmacological potentials, more and more research is demanded for the exploration of chemical nature of plants, particularly those ones which have been used as traditional medicines all over the world. Hence, the present investigator has been motivated to undertake this work on some plants traditionally used as medicine in India.

Research into secondary metabolism has long centered on flavonoids. Scientists from a wide variety of fields are interested and intrigued by flavonoids, which are widely found throughout the plant kingdom. Over the past few years, it has been revealed that plant flavonoids play a vital role in our lives and in the health of our plants. As a result of ongoing research on chemistry, occurrence, natural distribution and biological function of flavonoids, a number of reviews have already been published time to time [1, 2, 3, 4, 5, 6, 7, 8, 9, 10]. A PubMed search incorporating the term “flavonoid” returns more than 58,180 articles from last 5 years. The role of flavonoids in plants has received considerable attention in recent decades [11].

Human culture is facing the greatest threat because of global climate change. Increasing global food prices and global warming put the future of humanity at risk. Scientists from NASA’s Goddard Institute for Space Studies (GISS) estimate that global temperatures have risen by around 1°C since 1880 [12]. Every 2°C increase in global temperature could annihilate up to a hundred million people and wipe out up to a million species [13]. In addition to using fossil fuels to generate energy, agricultural activities are among the biggest contributors to climate change through the emission of greenhouse gases [14]. In spite of the convenience, ease of use, and rapid soil nutrient recharge, commercial fertilizers have become viewed as a source of toxic and residual soil issues. Using less mineral fertilizer may lower GHG emissions by 20% [15]. Global warming has made it necessary to rethink outdated and ineffective policies. Eco-friendly farming practices and a more sustainable agricultural system are urgently needed. Bio-based products, for example, might usher in organic farming, bio-fertilizers, and bio-control, all of which would be significant steps toward assuring global food security in the long run. Flavonoids are one type of biostimulant discussed in this chapter, and their role in sustainable agriculture. The flavonoids are an important class of polyphenolic secondary metabolites involved in plant physiological function, and show protection against biotic and abiotic stresses, including ultraviolet radiation, salt stress, and drought [16, 17, 18], at least in part by detoxifying the reactive oxygen species (ROS) produced when plants are under stress conditions [19]. Flavonoids may help protect Mediterranean endemic species from UV radiation and drought stress, as evidenced by recent studies that show polyphenol concentrations fluctuate monthly with the maximum values occurring at midday during the summer when drought, temperature, and UV radiation are high [20, 21]. The flavonoids in some plants play a critical role in plant defense and growth. There are several flavonoids that comprise plant pigments, including anthocyanins (red, orange, blue, and purple pigments); chalcones and aurones (yellow pigments); and flavonols and flavones (white and pale yellow pigments), which contribute to a diverse range of plant colors [22]. The flavonoids are also crucial in symbiotic associations between plants and microbes, such as rhizobial and arbuscular mycorrhizal symbioses [23]. As a signaling compound, certain flavonoids trigger the induction of nodule induction in rhizobia, which is the first step in legume-rhizobia symbiotic relationships [24]. In addition to preventing pests and pathogens, some flavonoids have antimicrobial properties [25]. The color pigments contained in some classes of flavonoids make leaf and flower petals distinctive, aiding plants in attracting pollinators [26]. Further, flavonoids have indirect effects on nutrient availability and supply since they enhance mycorrhizal symbiosis and enhance rhizosphere colonization by beneficial microbes [27].

2. Flavonoids: classification and biosynthesis network in plant

Flavonoids are the most diverse group of natural products; they are found in plants in over 10,000 different compounds [28]. In contrast to stilbenes (a class of flavonoids) which has a C6-C2-C6 structure (Figure 1), flavonoids have a C6-C3-C6 basic structure composed of three phenolic rings, A (6 carbons) and B (6 carbons), linked by a 3-carbon heterocyclic ring (ring C). This structure, in turn, can give rise to several derivatives and sub-classes of compounds with distinct substituents [11, 29]. According to the degree of oxidation of the heterocyclic ring and the number of hydroxyl or methyl groups on the benzene ring, flavonoids can be divided into 12 subgroups: anthocyanins, aurones, chalcones, dihydroflavonols, flavanones, flavones, flavanols, isoflavones, leucoanthocyanidins, phlobaphenes, proanthocyanidins and stilbenes (Figure 1) [9, 30, 31]. However, in terms of attachment of the B ring to the C ring, flavonoids are into three main groups: Flavonoids (2-phenylbenzopyrans): the B ring is attached at the 2-position of the C ring, Isoflavonoids (3-phenylbenzopyrans): the B ring is attached at the 3-position of the C ring, and Neoflavonoids (4-phenylbenzopyrans): the B ring is attached at position 4 of the ring C [11, 32].

Figure 1.

Basic structure of flavonoids subclasses.

The phenylpropanoid pathway produces flavonoids from phenylalanine, whereas the shikimate pathway produces phenylalanine [33]. It is generally recognized that the first three steps of the phenylpropanoid pathway are known as the general phenylpropanoid pathway [28]. Using this pathway, aromatic amino acid phenylalanine is transformed to top-coumaroyl-CoA via phenylalanine ammonia lyase (PAL), cinnamic acid 4-hydroxylase (C4H), and 4-coumarate: CoA ligase (4CL). A primary catalytic function of PAL is to catalyze deamination of phenylalanine to trans-cinnamic acid, the first in a general phenylpropanoid pathway [34]. Further, PAL is essential for the regulation of carbon flux from primary to secondary metabolism in plants [35]. StlA, which encodes PAL in Photorhabdus luminescens, has been shown to play a role in generating a stilbene antibiotic [34]. PAL activity has also been linked to anthocyanins and other phenolic compounds in strawberry fruit [36]. In the general phenylpropanoid pathway, the second step involves C4H, a monooxygenase found in cytochrome P450 and responsible for hydroxylating trans-cinnamic acid to generate p-coumaric acid. The flavonoid synthesis pathway involves this first oxidation reaction as well [37]. It has been found that the expression of C4H in Populus trichocarpa and Arabidopsis thaliana can be correlated with lignin content, an important phenylpropanoid metabolite [28]. The enzyme 4CL catalyzes the synthesis of p-coumaroyl-CoA by coupling with a co-enzyme A (CoA) unit to p-coumaric acid at the third step of the general phenylpropanoid pathway. A chalcone synthesizing enzyme, chalcone synthase (CHS), contributes to the biosynthesis of specific flavonoid-based compounds by combining one molecule of 4-coumaroyl-CoA (6-carbon) with three molecules of malonyl-CoA. As a result of two different pathways of cell metabolism, ring A and ring B are generated via the acetate pathway and shikimate pathway, respectively, with chain linkages delivering ring C. During the acetate pathway, malonyl-CoA is converted to ring A by carboxylation of acetyl-CoA, whereas ring B and the linking chain (ring C) are generated via the shikimate pathway (Figure 2) from coumaroyl-CoA. In the phenylpropanoid pathway, coumaryl-CoA is directly generated by three enzymatic reactions from phenylalanine [29]. Following the condensation of these aromatic rings, these pathways lead to the synthesis of chalcone, which will then undergo isomerase-catalyzed cyclization to form flavanone (Figure 2). In addition to hydroxylation, glycosylation, and methylation, the latter compounds undergo additional modifications, resulting in an enormous variety of colors (Figure 2).

Figure 2.

Biosynthesis network of flavonoids in plant.

3. The production of flavonoids by microorganisms

Since plants and chemical synthesis produce low levels of flavonoids, researchers have turned to open fermentation and metabolic engineering to produce flavonoids in microorganisms [38]. Toxic chemicals and extreme reaction conditions are necessary for the chemical synthesis of flavonoids [39]. Combinatorial biosynthesis offers an advantage in the production of rare and expensive natural products, thanks to the rapid development of molecular biology tools and genome information flooding from a wide variety of organisms. Unlike the tedious blocking and de-blocking steps common to organic synthesis, it also allows for simple and complex transformations [40]. In addition to Escherichia coli, Phellinus igniarius, Saccharomyces cerevisiae and Streptomyces venezuelae, and, a medicinal mushroom, flavonoids can also be produced by additional prokaryotes and eukaryotes [41], a variety of other cultures have been used to produce flavonoids.

3.1 Phenylpropanoid pathway

Several flavonoids are synthesized in plants using the phenylpropanoid pathway from naringenin chalcone. A recently established biosynthesis pathway was established in a heterologous microorganism by fermentation of E. coli carrying an artificially assembled phenylpropanoid pathway to produce flavanones from amino acids such as phenylalanine and tyrosine [42]. Plants use phenylalanine ammonia lyase (PAL) to deaminate phenylalanine to produce cinnamic acid as the first step in the phenylpropanoid pathway. As a result of the action of cinnamate-4-hydroxylase (C4H), cinnamate-4-hydroxylase (C4H) converts cinnamate to p-coumaric acid, which is then converted to p-coumaroyl-CoA by 4-coumarate: CoA ligase, cinnamic acid becomes p-coumaric acid. The naringenin chalcone is synthesized by three acetate units from malonyl-CoA with p-coumaroyl-CoA using Chalcone Synthesis (CHS). In vitro, naringenin is converted to naringenin using chalcone isomerase (CHI) or nonenzymatically without activating enzymes [43].

3.2 Enhancement of flavonoid synthesis

For heterologous flavonoids production, many molecular biology technologies are used, including choosing promoter and target genes, knocking out related genes, over expressing malonyl-CoA, and creating artificial P450 enzymes. Genes from the phenylpropanoid pathway are cloned in the host under the control of the promoter, due to which secondary metabolites are often expressed heterologously. In an effort to promote flavonoids production, several promoters have been used depending on host requirements, including T7, ermE, and GAL1 promoters [41]. One of the limitations of microbiological flavonoids production was the extremely low concentration of malonyl-CoA. An increased production of flavonoids was achieved by co-expressing acetyl-CoA carboxylase genes from Photorhabdus luminescens [44]. Also essential for flavonoid biosynthesis is the presence of UDP-glucose. Using the udg gene, researchers knocked out the endogenous system for consuming UDP-glucose resulting in an increase in intracellular UDP-glucose concentrations and subsequently increased flavanones and anthocyanins production [45].

Scientists were able to generate a wider range of natural and unnatural products when combining bacteria and eukaryotic cells in a pot. Using a modified S. cerevisiae strain, de novo generation of the important flavonoid intermediate naringenin from glucose was achieved for the first time, leading to four times higher concentrations than those seen in previous de novo biosynthesis experiments [46, 47].

4. Chemistry of flavonoids

At the present scenario of scientific research, bioflavonoids are being considered as promising drug candidates, and extensive researches directed toward structural studies and biological efficacies of such class of compounds are in progress, which would eventually boost the on-going efforts leading to the discovery of new efficacious lead molecules. This remarkable class of natural compounds draws the attention of the scientists for their immense biological and pharmacological potentiality. Presently, over 10,000 individual flavonoid compounds are known, which are based on very few core structural skeletons (viz. flavone, flavanol, isoflavone, flavan, flavanone, chalcone, anthocyanin, coumarin etc. see in Figure 1) [9, 10, 30, 31].

Flavonoids are a group of natural compounds with low molecular weight polyphenolic substances based on the flavan nucleus are found mostly in plants. A novel chemical was extracted from oranges in 1930. It was given the name vitamin P at that time because it was thought to belong to a novel class of vitamins. Later, it was discovered that this material was a flavonoid (rutin), and as of now, more than 10,000 different flavonoid species have been found [48]. According to their chemical structure, flavonoids contain a 15-carbon skeleton. This skeleton consists of two benzene rings (A and B) linked by a heterocyclic pyrane ring (C) (Figure 1). These include flavones (such as luteolin apigenin and Itoside N), flavanols (such as kaempferol, myricetin and quercetin), flavanones (such as hesperetin, naringenin and abyssinoflavanone VI), and others. Table 1 shows their general structures and other related information. Individual compounds within a class differ in the pattern of substitution of the A and B rings, whereas the many classes of flavonoids differ in the level of oxidation and pattern of substitution of the C ring [48]. Among the many forms of flavonoids, there are aglycones, glycosides, and methylated derivatives. Flavonoids contain aglycones as their basic structure (Figure 1). The α-pyrone (flavonols and flavanones) or its dihydro derivative (flavanols and flavanones) is a six-member ring that is condensed with the benzene ring (flavonols and flavanones) is a six-member ring that is condensed with the benzene ring. Based on the position of the benzenoid substituent, flavonoids are classified as flavonoids with a 2-position and isoflavonoids with a 3-position. Unlike flavanones, flavanols contain a hydroxyl group at the 3-position and a double bond between C2 and C3 [49, 50, 51]. The most common positions of hydroxylation for flavonoids are 3, 5, 7, 2, 3′, 4′, and 5′. There is evidence to suggest that alcohol group methyl ethers and acetyl esters occur in nature. It is normally found that glycosides form when the glycosidic linkage appears in positions 3 or 7, and the carbohydrate is usually L-rhamnose, D-glucose, glucorhamnose, galactose, or arabinose [49, 50, 52].

Table 1.

Structure of some selective known flavonoids [9, 10, 49].

Name of flavonoids	No. of hydroxyl (-OH) groups	Position of OH groups	Other substitutions on the basic structure	Position of the substitutions
Myricetin	6	3, 5, 7, 3′, 4′, 5′	—	—
Gossypetin	6	3, 5, 7, 8, 3′, 4′	—	—
Quercetagen	6	3, 5, 6, 7, 3′, 4″	—	—
Hypolactin	5	5, 7, 8, 3′, 4′	—	—
Quercetin	5	3, 5, 7, 3′, 4′	—	—
Myricetrin	5	5, 7, 3′, 4′, 5′	O-Rha	3
Rutin	4	5, 7, 3′, 4′	O-Rut	3
Kaempferol	4	3, 5, 7, 4′	—	—
Quercetrin	4	5, 7, 3′, 4′	O-Rha	3
Fisetin	4	3, 7, 3′, 4′	—	—
Rhamnetin	4	3, 5, 3′, 4′	O-Me	7
Orientin	4	5, 7, 3′, 4′	Glc	8
Apigenin	3	5, 7, 4′	—	—
Galangin	3	3, 5, 7	—	—
Kaempferide	3	3, 5, 7	O-Me	4′
Luteolin-7-glucoside	3	5, 3′, 4′	O-Glc	7
Vicenin-2	3	5, 7, 4′	Glc	6, 8
Sideritoflavone	3	5, 3′, 4′	O-Me	6, 7, 8
Pinocembrin	2	5, 7
Gardenin-D	2	5, 3′	O-Me	6, 7, 8, 4′
Diosrnin	2	3, 3′	O-Rut, O-Me	5, 4′
Robinin	2	5, 4′	O-Galc-Rha, Rha	3, 7′
Cirsimaritin	2	5, 4′	O-Me	6, 7
Xanthomicrol	2	5, 4′	O-Me	6, 7, 8
8-Methoxycirisilincol	2	5, 4′	O-Me	6, 7, 8, 3′
3-OH-Flavone	1	3		—
Techtochyrsin	1	5	O-Me	7
Troxerutin	1	5	O-Rut, O-He, O-He, O-He	3, 7, 3′, 4′

Table 2.

Some example of substitution pattern of flavonoids [9, 49, 59].

4.1 Spectral characteristics of flavonoids

UV spectroscopic analysis of flavonoids identified two major absorption bands: Band I (320–385 nm) representing the absorption of the B ring, and Band II (250–285 nm) representing the absorption of the A ring. A shift in absorption can occur due to functional groups attached to flavonoid skeletons, such as 367 nm for kaempferol (3,5,7,4′-hydroxyl groups) and 371 nm for quercetin (3,5,7,3′,4′-hydroxyl groups) and 374 nm for myricetin (3,5,7,3′,4′,5′-hydroxyl groups) [53]. An absence of a 3-hydroxyl group distinguishes flavones from flavanols. According to their UV spectral properties, flavanones have a saturated heterocyclic C ring with no conjugation between the A and B rings [54]. Flavanones show only a shoulder for Band I at 326 and 327 nm and a very significant Band II absorption maximum between 270 and 295 nm, namely 288 nm for naringenin and 285 nm for taxifolin. In compounds with a monosubstituted B ring, Band II shows one peak (270 nm), but when a di-, tri-, or o-substituted B ring is present, it shows two peaks or one peak (258 nm) with a shoulder (272 nm). The color of anthocyanins varies with the quantity and position of the hydroxyl groups because they exhibit discrete Band I peaks in the 450–560 nm area due to the hydroxyl cinnamoyl system of the B ring and Band II peaks in the 240–280 nm region due to the benzoyl system of the A ring [55].

Nuclear magnetic resonance (NMR) spectroscopy has proven essential in the structural elucidation of natural products; it is one of the most effective methods available to natural product chemists [10].

In ¹H NMR investigations, the chemical shifts (δ) and the coupling constants (J), also known as and spin–spin couplings, are a good indicator. By comparing the recorded chemical shifts with the gathered data, this parameter provides important information on the relative number and kind of hydrogens. The number and anomeric configuration of the glycoside moieties connected to the aglycone, as well as the aglycone and acyl type groups associated to it, may all be determined using this [10]. The molecular architecture of flavone (Itoside N) can be learned a lot from the analysis of its 1H NMR spectrum data. The presence of an aromatic proton at C-3 in ring-C is shown by the one-proton singlet that appears at δ 6.86. The presence of two aromatic protons at C-6 and C-8, respectively, in ring-A is indicated by the signals that occurred as doublets (d) at δ 6.46 (1H, d, J = 2.0 Hz) and 6.80 (1H, d, J = 2.0 Hz). Four aromatic protons of the B-ring in the flavone skeleton may be the cause of the doublet (d) signals that emerged at δ 7.97 (2H, dd, J = 8.0 Hz) for two protons and δ 6.97 (2H, dd, J = 8.0 Hz) for another pair of protons. Ring B is definitely para-disubstituted, according to the chemical shifts and coupling constant values for its four protons. Moreover, the ¹H NMR spectrum of Itoside N (Table 1) indicates that a partial structure similar in structure to p,p′-dihydroxy-μ-truxinic acid in Itoside N is formed by two p-dihydroxy benzenoid groups that combination with a cyclobutane [δ 42.9 (C-2′′′), 43.5 (C-3′′′), 45.5 (C-2′′′′), 42.9 (C-3′′′′)] moiety [9, 10].

When combined with ¹H NMR data, ¹³C NMR data can be used to determine the types of groups that are present in molecules. It should be noted, however, that ¹³C NMR is not as responsive as ¹H NMR because ¹³C is less abundant (1.1%) than ¹H (99.9%) [10]. The C-2/C-II-2 and C-3/C-II-3 sp2-hybridized carbons can be found, respectively, at δ_C 152.5–165.5 and 103–132.1 in ¹³C-NMR spectra. According to ¹³C NMR data of flavonoid compounds, C-4/C-II-4 appear between δ_C 176.2 and δ_C 182.9 when C-2-C-3 is unsaturated (sp2), but when C-2/C-3 is sp3 hybridized, a down-field shift of C-4/C-I-4 is typically observed between δ_C 196.2 to δ_C 197.9. The typical range of δ_C 159.6–164.7 includes the aromatic C-5, C-6, C-7, C-8, C-9/C-4a, and C-10/C-8a. Generally CMR of glucopyranosyl moiety appeared in the range of δ_C 60.6–102.11; rhamnopyranosyl (Rha) also appeared in the range of δ_C 17.23–101.0; and glucuronopyranoside showed the value in δ_C 98.4–171.6. The value of glucuronopyranoside is nearly identical to that of the glucopyranosyl moiety, however the carboxylic group is what gives the compound its high value (δ_C 171.6). The flavone, Itoside N is found to appear around a range δ_C of 42.9–172.2 for the 4′′/6′′-p-hydroxy-μ-truxinyl group [10].

4.2 Substitution pattern of flavonoids

The main flavonoid classes and some of their discovered structural variants are shown in Table 2. Within the primary classes, flavonoids’ structures differ significantly by substitutions such as hydroxylation, glycosylation, hydrogenation, methylation, malonylation, and sulphation etc. Many flavonoids are found in nature as flavonoid glycosides, and D-glucose, L-rhamnose, glucorhamnose, galactose, lignin, and arabinose are some examples of carbohydrate substitutes [9, 49, 50]. The most prevalent flavonoid glycosides in the diet are quercitrin, rutin, and robinin. Intestinal flora hydrolyzes them to create the physiologically active aglycone (sugar-free flavonoid). Due to its prominence as the primary flavonoid present in foods, quercetin has been the focus of numerous studies examining the biological impacts of flavonoids [9, 49, 50].

4.3 Polymerization of flavonoids

In term of units of flavonoids molecules there are three types of flavonoids namely monomers, dimers, and oligomers. There are huge differences between the molecular weights of different monomers. Polymers of flavonoids make up condensed tannins. Epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate are the four primary catechin components found in tea tannins. The main catechin in tea, epigallocatechin gallate, accounts for more than half of the total catechin content. The dimeric theaflavins and polymeric thearubigins of black Indian tea, which generate brightness and astringency, respectively, are produced by enzymatic oxidation of tea catechins during fermentation of macerated tea leaves [56, 57]. Thearubigins come in a wide variety of sizes, from molecules with up to 100 flavonoid units to oligomers of four or five units [56]. Green “Chinese” tea does not undergo fermentation during processing, in contrast to black tea, hence its flavonoids largely exist as monomers. The anthocyanins and other flavonoids in red wine polymerize to create tannins, which give the wine its distinctive hues, tastes, and astringency [58, 59].

5. Role of flavonoids in plants

Plants are the key source of natural products and plants had already yielded a vast number of phytochemicals and still continue to a major source of biologically active molecules. Numerous plants have already established their potentiality as a source of naturally occurring insecticides, pesticides, fungicides and agro-chemicals as an alternative to toxic and hazardous synthetic chemicals. Owing to ever-increasing awareness to the hazardous side effects of synthetic chemicals, more and more emphasis is being given on the use of products obtained from natural sources so that ecological balance is well-maintained. The WHO has already called for an immediate ban on the use of many synthetic chemicals viz. endosulfan is a dangerous synthetic pesticide that causes severe damage to the eyes, kidneys, and liver. The Government of India had already banned the use of 12 highly toxic and hazardous pesticides and imposed restriction on the use of many others to prevent environmental pollution. To minimize the hazardous effects and to control environmental pollution, attempts are now being made to develop naturally occurring plant-based pesticides. Many phytochemicals such as phytoecdysones, and azadirachtin (from Indian neem) have been reported to possess pesticidal and insecticidal properties and are being widely used in protecting the loss of crop from the attack of insects and parasites in place of their synthetic analogues because of their non-toxic, non-pollutant, readily bio-degradable character and harmless nature of their residues.

As a result of changes in plant growth, conditions, and maturity, there are more than 10,000 types of flavonoid compounds found in vascular plants, which vary in type and quantity according to a variety of factors. There is still a lack of systematic analysis of the flavonoid content of many plant species, which makes it difficult to identify and quantify all the flavonoids humans consume [57]. In order to defend themselves against herbivores, pathogens, oxidative cell damage, and fungal parasites, plants have evolved to synthesize flavonoids [58]. On the other hand, flavonoids act as a stimulant that aids in pollination and guides insects on their way to food sources. For example, flavonoid compounds anthocyanins are responsible for the pink, blue red, light purple and violet colors in flowers, fruits, and vegetables [56, 59].

5.1 Combating oxidative stress of flavonoids

It has long been reported that flavonoids have a variety of functions in plants [60]. Both abiotic and biotic factors contribute to oxidative stress in plants as a result of ROS being generated in plants. A high level of oxidative stress commonly enhances the synthesis of flavonoids in plants. The pigments are capable of absorbing the most energetic rays of the sun (i.e., UV-B and UV-A), inhibiting ROS production, and quenching ROS once they have been generated [61]. When plants moved from water to soil, flavonoids were primarily responsible for screening UV-B. Different flavonoids have different antioxidant capacities and UV-wavelength-absorbing capabilities based on their substitutions. There is an increase in antioxidant capacity in flavonoids with dihydroxy B rings substituted for these rings, whereas flavonoids with monohydroxy B rings have a greater ability to absorb UV wave lengths. Glycosylation is generally the hallmark of the most reactive hydroxyl groups of flavonoids (7-OH in flavones or 3-OH in flavanols). Flavonoids can be transported from the endoplasmic reticulum to various cellular compartments and secreted from their plasma membrane and cell wall through glycosylation, thereby increasing their solubility in the aqueous cellular environment, protecting the reactive hydroxyl groups from auto-oxidation [62]. Studies have shown that antioxidant flavonoids are found in cells of the mesophyll and in chloroplasts, which generate ROS. Using this method, they are able to easily quench H₂O₂, hydroxyl radicals, and singlet oxygen [61, 63]. Conditions that restrict CO₂ diffusion to carboxylation sites and carboxylation efficiency may exacerbate oxidative stress caused by an excessive amount of excitation energy in chloroplasts [61, 64]. A number of environmental factors can restrict CO₂ assimilation, including drought/salinity, temperature fluctuations, and nutrient scarcity. This can decrease the activity of ROS detoxifying enzymes in the chloroplast [65], which increases the production of antioxidant flavonoids. Flavonoids are highly important for plants under severe stress conditions because of their reducing properties. In addition to their functional roles, dihydroxy B ring substitutes are also highly concentrated [66]. It has been suggested that flavonoids represent a secondary antioxidant defense system in plants under stress [61]. In response to oxidative stress, lipid peroxidation occurs, causing cell membrane degradation. It has been suggested that quercetin-3-O-rutinoside (Rutin) interacts with phospholipids polar head at the water lipid interface, increasing membrane inflexibility and thereby protecting membranes from oxidative damage [67].

5.2 Role of flavonoids as growth regulator

Role of Flavonoids as Growth Regulator: in plant-environment interactions, flavonoids play an essential role. There is evidence that flavonoids control auxin catabolism and movement by using in nanomolar range. When flavonoids produce auxin gradients, they produce phenotypes with different morphoanatomical characteristics [68]. Stress-induced morphogenic responses of plants are controlled largely by flavonoids, which may have a direct relevance to flight strategies of sessile organisms exposed to unfavorable environments [69]. A species that produces dihydroxy flavonoids exhibits phenotypic characteristics that are strikingly different from a species that produces monohydroxy flavonoids [70]. In sunny situations, dwarf bushy phenotypes with few, tiny, and thick leaves are typically prevalent, shielding leaves deep in the canopy from light-induced severe cellular homeostasis disruptions. Alternatively, shaded plants, which contain kaempferol and/or apigenin derivatives, have long internodes and large leaf lamina, along with reduced leaf thickness [69]. PIN/MDR glycoproteins that facilitate cell-to-cell movement of auxin are inhibited by flavonoids at the plasma membrane. In flavonoids, the catechol group is present at the B ring of the flavonoid skeleton that is responsible for inhibiting the activity of the efflux facilitator PIN and MDR proteins. The chemical structure of flavonoids also influences their action on IAA-oxidase significantly [71]. In recent years, it has been found that flavonoids can influence the activity of proteins involved in cell growth due to a nuclear location of flavonoids as well as the actions of enzymes that produce flavonoids [72]. This suggests that flavonoids may be able to regulate transcription [73]. In Table 3 showed some flavonoids and their rich dietary sources [74].

Class of flavonoids	Name of flavonoids	Dietary sources
Anthocyanidin	Peonidin	Cranberries, blueberries, plums, grapes, cherries, sweet potatoes
Catechin	Theaflavin	Tea leaves, black tea, oolong tea
Coumarin	Scopoletin	Vinegar, dandelion coffee
Flavan	Epicatechin	Milk, chocolate, commercial, reduced fat
Flavanol	Taxifolin	Vinegar, citrus fruits
Flavanone	Abyssinones	French bean seeds
	Eriodictyol	Lemons, rosehips
	Hesperidin	Bitter orange, petit grain, orange, orange juice, lemon, lime
	Naringenin	Grapes
Flavone	Diosmetin	Vetch
	Apigenin	Milk, chocolate, commercial, reduced fat
	Luteolin	Celery, broccoli, green pepper, parsley, thyme, dandelion, perilla, chamomile tea, carrots, olive oil, peppermint, rosemary, navel oranges, oregano
	Tricin	Rice bran
Flavanol	Fisetin	Strawberries, apples, persimmons, onions, cucumbers
	Kaempferol	Apples, grapes, tomatoes, green tea, potatoes, onions, broccoli, Brussels sprouts, squash, cucumbers, lettuce, green beans, peaches, blackberries, raspberries, spinach
	Myricetin	Vegetables, fruits, nuts, berries, tea, red wine
	Rutin	Green tea, grape seeds, red pepper, apple, citrus fruits, berries, peaches
	Quercetin	Vegetables, fruits and beverages, spices, soups, fruit juices
Isoflavone	Biochanin	Red clover, soya, alfalfa sprouts, peanuts, chickpeas (Cicer arietinum), other legumes
	Daidzein	Soyabeans, tofu
	Genistein	Fats, oils, beef, red clover, soyabeans, psoralea, lupin, fava beans, kudzu, psoralea

Table 3.

Example of some flavonoids and their rich dietary sources [74].

6. Role of flavonoids in pest control

There is an ever-growing demand for natural pesticides from plants. As an alternative to synthetic pesticides, flavonoids are being used to develop new pesticides. A variety of insect larvae can be prevented from growing if they are inhibited by these compounds [75]. It is known that some flavonoids inhibit the production of juvenile hormone which is involved in molting and reproduction in several insects [76]. A number of flavonoids have been shown to suppress agricultural pest activity, such as oviposition, fecundity, mortality, weight reduction, and the emergence of adults [77, 78]. In their article, Lena Schnarr et al. [79] reported 281 different pesticidal active flavonoids that were investigated in either pure form or as extracts containing flavonoid, with the most studied compounds being quercetin, kaempferol, apigenin, luteolin and their glycosides [79]. In another study, Quercetin, rutin, and naringin were all effective in controlling Eriosoma lanigerum Hausmann nymphs and adults. An integrated management program for this aphid can use these products as an insecticide [80]. Flavonoids may have an insecticidal effect depending on their concentration; if too low, they are ineffective [81]; as a result, it is crucial to determine the minimum concentration for flavonoids to be effective [79, 81].

7. Patent information

About 40 patent information on agriculture related matter including all necessary agenda are presented in Table 4, which deal with, synthesis of various flavonoids in plant and their analogs, method for increasing the flavonoids content, pest control and pesticidal activity of plant and plant protection.

Patent number	Filing date	Issue date	Original assignee	Title	Inventors	Refs
US2465854A	26-08-44	29-03-49	Shell Dev	Insecticidal composition containing an aromatic unsaturated carbonyl compound	S.C. Dorman, S.A. Ballard	[82]
US4193984A	09-04-76	18-03-80	Herculite Protective Fabrics Corporation	Method and compositions for controlling flying insects	A.F. Kydonieus	[83]
JPS57120501A	19-01-81	27-07-82	Kiyoshi Saotome	Protecting method of field crop	K. Saotome	[84]
FR2529755A1	06-07-82	13-01-84	Kiyoshi Saotome	Crop protection method by means of Cinnamaldehyde	K. Saotome	[85]
JPH01261303A	13-04-88	18-10-89	Taiyo Koryo Kk	Insect pest repellent	H. Miyawaki, K. Saotome	[86]
US5149715A	09-02-89	22-09-92	Monterey Mushroom, Inc.	Control of fungal diseases in the production of mushrooms	G.L. Armstrong, N.S. Dunn-Coleman, M. Wach	[87]
WO1996020594A1	29-12-95	11-07-96	Proguard Inc. (US)	Use of flavonoid aldehydes as insecticides	R.W. Emerson, B.G. Crandall, Jr	[88]
US6548085B1	30-03-99	15-04-03	Woodstream Corp	Insecticidal compositions and method of controlling insect pests using same	K.A. Zobitne, M.J. Gehret	[89]
US6593299B1	02-08-99	15-07-03	University of Florida Research Foundation Inc. Insect Biotechnology Inc	Compositions and methods for controlling pests	J. Bennett, A. Brandt, D. Borovsky	[90]
US6841577B2	18-12-01	11-01-05	GIBRALTAR BUSINESS CAPITAL LLC Kittrich	Pesticidal activity of plant essential oils and their constituents	S.M. Bessette, M.A. Beigler	[91]
US20050031761A1	07-05-04	10-02-05	SUNRISE COFFEE CO	Methods of producing a functionalized coffee	D. Brucker, M. Sweeney, T. Breen	[92]
US20050208643A1; US7604968B2	01-03-05	22-09-05; 20-10-09	University of Minnesota	Microorganisms for the recombinant production of resveratrol and other flavonoids	C. Schmidt-Dannert, K. Watts	[93]
US20070232495A1	23-03-07	04-10-07	Nappa Alvaro O, Lorenzini Felipe C, Sanhueza Andres L	Compositions and methods to add value to plant products, increasing the commercial quality, resistance to external factors and polyphenol content thereof	A. Nappa, F. Lorenzini, A. Sanhueza	[94]
US20060019334A1	11-07-05	04-03-08	Research Foundation of State University of New York	Production of flavonoids by recombinant microorganisms	M. Koffas, E. Leonard, Y. Yan, J. Chemler	[95]
US20080274519A1	07-07-08	06-11-08	BIORES HEALTH Ltd	Flavonoid concentrates	R.G. Wallace	[96]
US7750211B2	10-09-03	06-07-10	Noble Research Institute LLC	Methods and compositions for production of flavonoid and isoflavonoid nutraceuticals	R.A. Dixon, C.-J. Liu, B. Deavours	[97]
NZ580217A	23-04-08	29-07-11	Samuel Roberts Noble Found Inc	Production of proanthocyanidins to improve forage quality	R.A. Dixon, L.V. Modolo, G. Peel	[98]
US8142801B2	02-02-10	27-03-12	HOMS LLC	Pesticidal compositions and methods of use thereof	A. Jones	[99]
AU2010306410A1; AU2010306410B2	15-10-10	03-05-12; 13-08-15	Agriculture Victoria Services Pty Ltd	Manipulation of flavonoid biosynthetic pathway	A. Mouradov, G. Spangenberg	[100]
JP5002848B2	13-04-10	15-08-12	Suntory Holdings Ltd	Flavonoid 3′,5′ hydroxylase gene sequence and method of use thereof	P. B. Yoshikazu, T. J. Mason	[101]
MX2011010032A	23-09-11	25-03-13	M.S. Aguilar, Y.M. H. Romero, C.M.R. Narvaez	Pesticide made of isoquinoline alkaloids, flavonoids and vegetable and/or essential oils.	M.S. Aguilar, Y.M. H. Romero, C.M.R. Narvaez	[102]
US20130340118A1; US9567600B2	26-08-13	19-12-13; 14-02-17	Agriculture Victoria Services Pty Ltd	Modification of flavonoid biosynthesis in plants	A. Mouradov, G. Spangenberg	[103]
WO2014122446A1	05-02-14	14-08-14	Phyto Innovative Product Ltd.,	Plant protection composition and method	I. Ripley	[104]
US8877219B2	31-01-13	04-11-14	Kittrich Corp	Pesticidal compositions containing rosemary oil and wintergreen oil	S.M. Bessette, A. D. Lindsay	[105]
US 2014/0335210A1	13-05-13	13-11-14	FLAVITPURE, INC., Cheyenne	Method and agrochemical composition for using larch wood extracts in agriculture	S.V. Philippov, I. M. Bogorodov	[106]
AU2013338110A1; AU2013338110B2	29-10-13	30-04-15; 01-12-16	Novozymes BioAg AS	Compositions and methods for enhancing plant growth	L. Blankenshi, A. Habib, Y. Kang, S. Semones	[107]
CN104640461A; CN104640461B	06-08-13	20-05-15; 19-12-17	Nestec SA	Anthocyanin colored composition	N. Gallifer, M. Meeker, S. Carwin, K. Boltlick, P. Choisy	[108]
US 2015/0216181A1	21-03-12	06-08-15	PROMOTORATECNICA INDUSTRIAL, S.A. DE C.V., Jiutepec, Estado de Mexico	Pesticide having an insecticide, acarcide and nematicde action based on isoquinoline alkaloids and flavonoids	Y.M.H. Romero, C.M.R. Narvaez, M.S. Aguilar	[109]
CN104823979A	18-05-15	12-08-15	South China Agricultural University	Application of flavonoid compound theaflavanoside II to prevention and treatment of plant nematode diseases	W. Yanhua, S.Y. Liao, J. X. Hui	[110]
EP2906055A1; EP2906055B1	08-10-13	19-08-15; 16-12-20	RJ Reynolds Tobacco Co	Method of extracting tobacco-derived o-methylated flavonoid and use thereof	A. R. Gerardi	[111]
ES2464642B1	21-03-12	20-11-15	PROMOTORA TECNICA INDUSTRIAL	Pesticide with insecticide, acaricide and nematiciated action based on isoquinolinic alcaloids and flavonoids	H. Romero, R. Narvaez, S. Aguilar	[112]
US9439886B2	27-04-15	13-09-16	Agency for Science Technology and Research Singapore	Methods for producing crosslinked flavonoid hydrogels	M. Kurisawa, F. Lee, J. E. Chung, P.Y. P. Chan	[113]
US9523089B2	13-09-13	20-12-16	Agriculture Victoria Services Pty Ltd	Manipulation of flavonoid biosynthesis in plants	G. Spangenberg, T.I. Sawbridge, E.-K. Ong, M. Emmerling	[114]
US9580725B2	26-06-14	28-02-17	Norfolk Plant Sciences Ltd	Methods and compositions for modifying plant flavonoid composition and disease resistance	J. Luo, E. Butelli, J. Jones, L. Tomlinson, C.R. Martin	[115]
KR101802249B1	03-08-15	29-11-17	Sunjin Industry Co., Ltd. Eco Farm	Natural composition and method for manufacturing the composition avoiding and/or controlling the Hemiptera	K. In-Gyu, K. Chang-Gil, K. Yeol, L. Mok-Hyeong, Y. Hae, G. Jeong, H.Y. Choi, C. Han-Jeung, J. Jae-Doo, Y. Hwan-Sang	[116]
US9949490B2	02-07-14	24-04-18	Ralco Nutrition, Inc.	Agricultural compositions and applications utilizing essential oils	R.D. Lamb, M.D. Johnson	[117]
WO2019016806A1	19-07-17	24-01-19	Future Tense Technological Development and Entrepreneurship Ltd	Pesticide containing antioxidants	Y. Tsivion	[118]
US10285393B2	24-10-14	14-04-19	Red Band Traps, Llc	Arthropod pest trapping device, system and method	T.V. Bailey	[119]
RU2729743C1	27-02-20	11-08-20	Federal State Budgetary Scientific Institution	Method for increasing content of flavonoids in buckwheat fruits	A.G. Klykov, G.A. Murugova, O.A. Timoshinova, S.A. Borovaya, E.L. Chaikina	[120]
EP3912470A1	16-01-20	24-11-21	SDS Biotech Corp Idemitsu Kosan Co Ltd	Plant growth regulating agent	S. Ishida, K. Inai, M. Tanaka, T. Nomoto	[121]

Table 4.

Some patent information on agriculture related matter.

8. Concluding remarks

Naturally occurring flavonoids are of much interest to the scientific community at a large due to their multidirectional therapeutic applications. Besides, knowledge about natural distribution of flavonoids of varying structural skeletons is also very much essential to the taxonomists for classifying plants in the light of chemotaxonomy. Thus, flavonoids are of much interest to the workers of interdisciplinary fields.

The use of plant flavonoids could provide eco-friendly and sustainable approaches to improving food quality and crop yield as well as improving their adaptation to environmental stress. When applied in practice, flavonoids could be very effective in the field, as a result of their phytotoxic and pesticidal properties. Also natural herbicides made from bioflavonoids are being investigated more and more in integrated weed control.

Further research and investigations are required to understand the full range of activity of flavonoids produced naturally and/or applied artificially for batter benefit in the field of agriculture.

Acknowledgments

SKJ is grateful to the Department of Chemistry, Krishna Chandra College, Hetampur for providing necessary infrastructural facilities to carry out this work.

Conflict of interest

The authors declare no conflict of interest.