Open access peer-reviewed chapter
Abstract
Flavonoids are polyhydroxylated natural chemicals that have been shown to improve human health. These are a type of bioactive molecules that can be found in abundance in plants. These polyphenolic chemicals are naturally generated from plant metabolites. Before entering the intestine, flavonoid glycosides are deglycosylated, while aglycones can readily pass-through cell membranes. They are absorbed and transferred to the liver, where they undergo substantial metabolism, resulting in glucuronides, sulfates, and methylation compounds. These conjugates are responsible for the health-promoting possessions of flavonoids. The flavonol subclass was the first to be researched, with quercetin as the most common dietary flavonol, and information on other flavonoid subclasses is still developing. Cellular signaling pathways mediate the antidiabetic benefits of dietary flavonoids in the pancreas, liver, and skeletal muscle. Flavonoids modulate distinct signaling pathways in pancreatic cells, hepatocytes, adipocytes, and skeletal myofibers via acting on various molecular targets. Flavonoids may help people with diabetes firstly by improving hyperglycemia through glucose metabolism regulation in hepatocytes and secondly by reducing insulin resistance, inflammation, and oxidative stress in muscle and fat and by increasing glucose uptake in skeletal muscle and white adipose tissue. A greater understanding of the flavonoid pathway’s regulatory mechanisms would likely favor the progress of novel bioprocessing techniques for the production of value-added plants with optimal flavonoid content.
Keywords
- deglycosylated
- hyperglycemia
- molecular targets
- plant metabolites
- polyhydroxylated natural chemicals
1. Introduction
Flavonoids are secondary metabolites found in high concentrations in vascular florae and minor amounts in lichens. They get to build up in all structures and matters at various periods of expansion and in response to conservational factors. These compounds are of prodigious significance to social nourishment and wellbeing, and their many characteristics in plant progress and variation in the atmosphere. They do help in the organoleptic eminence of plant-derived goods, as well as being helpful to social wellbeing and cell aging anticipation. Increased consumption of vegetables and fruits has been known to protect against cancer and cardiovascular disease. These are a major class of natural antioxidants found in a plant-based diet and may have a role in this protective effect. Fruits (cherry, grapes, and apple), vegetables (onion, broccoli, and spinach), beverages (coffee and tea), soy products, and basils are all good sources of flavonoids [1]. They can be found inside the cells of all plant tissues as well as on the exteriors of many plant tissues. The phenylpropanoid unit, C6C3, is a common building component in the carbon skeleton of these phenols. This route creates a wide range of plant phenols during biosynthesis. The molecular structure of this class of composites is created on a diphenyl propane (C6-C3-C6) skeleton with 2 aromatic rings joined by a 3-carbon “bridge” to form a 6-member heterocyclic ring. Flavonoids are classified into 3 groups based on the aromatic ring’s link to the heterocyclic ring: flavonoids (2-phenylbenzopyrans), isoflavonoids (3-phenylbenzopyrans), and neoflavonoids (4-phenylbenzopyrans) [2]. They can be separated into numerous sets based on the degree of oxidation and saturation in the heterocyclic C-ring, as shown in Figure 1. Hydroxylation occurs in positions 3, 5, 7, 3′, 4′, and/or 5′ in flavonoids. Methylated, acylated, prenylated, or sulfated hydroxyl groups are frequently found. Flavonoids are commonly found in plants as O- or C-glycosides. Sugar substituents are destined to a hydroxyl group of the aglycone, commonly at site 3 or 7, in O-glycosides, whereas saccharide groups are connected to a carbon of the aglycone typically at site C6 or C8 in C-glycosides. Rhamnose, glucose, galactose, and arabinose are the most common saccharides. Plant metabolism, defense, signaling, disease, and symbiosis all benefit from flavonoids [3, 4]. These chemicals are accountable for floral color and are implicated in stress retort mechanisms, such as UV-B radiation [5, 6], microbial infection [7], and herbivore attacks by animals and insects [8].
Figure 1.
Subclasses of flavonoids.
2. Role of flavonoids in plant development
Polyphenols are a wide class of phenolic chemicals that includes flavonoids. Phenolic chemicals were important during evolution because they helped plants for the adaptation to life on land. At least 6000 molecules make up the flavonoid family, which could be split into, aurones, phlobaphenes, isoflavonoids, flavonols, flavones, anthocyanins, and flavonols [9]. The general phenylpropanoid route is utilized to produce these compounds from the starting compound phenylalanine. Several divisions of the general phenylpropanoid pathway supply precursors for synthesizing hundreds of chemicals. Lignins are structural polymers that give the secondary cell wall strength and stiffness and are necessary for waterproofing vascular cells [10]. Anthocyanin pigments are generated from the flavylium cation (2-phenyl benzo pyrylium) and are glycosylated anthocyanidin precursors, as shown below in Figure 2.
Figure 2.
Biosynthetic route for phenolic compounds.
This subgroup contains at least 400 molecules that range in hue dependent on pH, co-pigmentation, obtainable positive metallic ion, and backbone alterations. The color ranges from orange-red to purple. They are synthesized in the ground plasm and subsequently stored in the follicle. They are also present in cell membranes, chloroplasts, centers, and even the extracellular space, depending on the plant types, material, or phase of progress. Flavonoids, and phenolic chemicals, play a role in biotic stress resistance [11]. Since most of these chemicals have antibacterial and pesticide capabilities, serving as a vile and preventing pest progress and change, they may be constitutively produced or gather in retort to the bacterial incursion. In addition to their many activities in plants, Flavonoids have a wide range of medical, pharmacological, and nutritional qualities, earning them the moniker “nutraceutical” chemicals [12]. These metabolites provide promise for the prevention of a variety of illnesses, including cancer. They cause cancer cells to die, stimulate DNA repair, protect them from oxidative stress, and prevent cancer cells from multiplying [13].
3. Metabolism of flavonoids
In the uptake of flavonoids, two major compartments must be considered. The first compartment contains tissues such as the small intestine, liver, and kidneys. The colon is the body’s second compartment (Figure 3). Flavonoids that have been consumed and then released with bile will make their way to the colon. Although around 40% of the absorbed ()-catechin was released in rats, the role of biliary secretion in humans is unclear in the small intestine with bile [14]. Metabolism of flavonoids in tissues and in the colon is discussed below in detail.
Figure 3.
Compartments involved in the metabolism of plant phenols.
3.1 Metabolism in tissues
Biotransformation enzymes operate on flavonoids in the first compartment, including the small intestine and liver. Flavonol biotransformation enzymes can also be found in the kidney. Flavonoids and their colonic metabolites have been found to have polar hydroxyl groups conjugated with sulfate, glucuronic acid, or glycine [15]. Furthermore, O-methylation of flavonoids and their colonic metabolites by the enzyme catechol-O-methyltransferase is significant in the inactivation of the catechol moiety, that is, the two contiguous (ortho) aromatic hydroxyl groups. The conjugation reactions are exceedingly efficient in humans, as indicated by the fact that flavonoids primarily appear as conjugates in plasma and urine and that flavonoid aglycones in plasma are difficult to detect since they are mainly below the analytical methods’ detection limits. Differential (HPLC) tests demonstrate the existence of flavonoid conjugates in humans, including O-methylated couples, with and deprived of hydrolysis of the model with a combination of b-glucuronidases and sulfatases: flavonols, flavones, catechins, flavanones, and anthocyanins. Anthocyanins, on the other hand, take a diverse approach. The indication is mounting that anthocyanidin glycosides can tolerate deglycosylation events in humans, at least in part. LC-MS [16] has revealed the presence of peonidin-3-glucoside, as well as peonidin-3-sambubioside [17] and pelargonidin-3-glucoside in urine.
3.2 Metabolism in the colon
Microbes break down the flavonoid fragment, splitting the flavonoid core, i.e., heterocyclic oxygen-containing ring, and the breakdown products are detected in urine and plasma. Several hydroxylated phenyl carboxylic acids are among them. Flavonols are broken down into phenylacetic acids and phenyl propionic acids. However, the effects of these phenyl propionic acids have yet to be proven in humans [18, 19]. In bodily tissues, these phenyl carboxylic acids are extra degraded by bacteria and transformed by enzymes. The phenyl propionic acids will be oxidized to benzoic acids as a result. Although roughly 60 possible phenolic acid metabolites were recognized and measured, only a small amount of phenolic acids were discovered. Hippuric acid, the glycine ester of benzoic acid, was an actual significant metabolite in people who had subsequent tea consumption [19, 20]. Microorganisms in the colon have been found to show an imperative role in the conversion of flavonoids to phenolic acids. Colonic bacteria generate glucuronidases, glycosidases, and sulfatases, which can shred flavonoid conjugates of their sugar moieties, glucuronic acids, and sulfates, in addition to the destruction of the flavonoid ring structure O-glycosides and C-glycosides that could be hydrolyzed by human gut bacteria [21].
3.3 The extent of metabolism of flavonoids
Flavonols were the initial to be examined, and human urine excretion was found to be quite modest. Only 0.1 percent to 3.6% of quercetin in the diet was eliminated in urine as quercetin conjugates. The sum of complete quercetin in blood plasma will be correlated with urinary excretion. Because the fascination of quercetin glucosides is high (up to 50%), while the evacuation of whole quercetin in urine is low, this indicates that quercetin undergoes substantial metabolism. Additional subclasses were investigated with helpers, and urine evacuation of metabolites with intact flavonoid structures was measured. Isoflavones have the highest rate of excretion of all flavonoids. Although isoflavones have a high bioavailability, flavonols glucosides have a higher bioavailability but a lower urine elimination. This would suggest that with isoflavones, the ring arrangement’s metabolic modification level is less than through flavonols.
4. Recent advances in the role of flavonoids
Plant metabolites containing one oxygenated ring and two aromatic rings are known as flavonoids. Flavonoids are categorized depending on the degree of oxidation of their carbon rings; they can then undergo glycosylations, hydroxylations, acylations, methylations, or prenylations to modify their properties. As a result of these modifications, a new emergence of a huge number of different chemicals with varied functions in plants has occurred. UV wavelengths absorb all flavonoids, which are mostly present in the epidermis of plant cells and are produced in response to UV exposure. As a result, it has been proposed that they shield plants from this type of radiation. Anthocyanins, which absorb light in the visible range, are an example of flavonoids that absorb light at various wavelengths. Furthermore, certain flavonoids have antioxidant properties, which implies they serve as reactive oxygen species scavengers. However, most findings to date have remained based on in vitro studies, with little indication of how their functions are carried out in real life. In this assessment, we discuss recent advances in the study of the role of flavonols, flavones, and anthocyanins, three of the most prevalent flavonoids, in protecting plants from UV and high light exposure [22].
4.1 Advances in topical drug delivery
Topical delivery is one of the greatest popular methods for overcoming the disadvantages of other methods such as parenteral, oral, and so on. Oral distribution of phytochemicals is undesired due to the drug’s distinctive flavor and odor, as well as the possibility of gastrointestinal (GI) breakdown until absorption [23].
4.1.1 Flavonols
Flavonols are O-glycosidic, ketonic chemicals with a 3-position sugar fraction. Flavonols are antioxidants that prevent the development of ROS. Due to UV, ozone radiation, and other damaging substances, the skin is the most prevalent target for oxidative stress. The combination of conjugated double bonds in the C-ring and adjacent hydroxyl groups in the B-ring gives flavonols their antioxidant properties [24]. Quercetin, kaempferol, myricetin, and other compounds are included in this class.
4.1.2 Quercetin
Quercetin is a flavonol in various foods, including leafy greens, citrus fruits, berries, and other fruits and vegetables. Quercetin inhibits edema, leukocyte production, and irritation. It helps reconstruct the skin’s structure by endorsing the synthesis of new collagen fibers and generating ground substances [25]. Inflammatory mediators such as interleukins (IL) and prostaglandins (PGs), which are generated by COX, LOX, and LPS, are likewise suppressed by quercetin. The enzyme nitric oxide synthase, which also creates reactive nitrogen species like peroxynitrite, produces nitric oxide (NO), an inflammatory mediator. Quercetin is an antioxidant that prevents oxidative stress by inhibiting all of the mediators that cause it [26]. It avoids cell death by inhibiting the caspase-3 pathway and lowers mast cell development by inhibiting mast cell synthesis has an anti-allergic impact on histidine decarboxylase, IL-6, and monocyte chemoattractant protein (MCP-1).
4.1.3 Kaempferol
Kaempferol is primarily present in berries and plants of the allium and brassica family. It has antineoplastic, anti-inflammatory, and anti-allergic properties. It works as an anti-inflammatory drug by inhibiting NO synthase, which produces NO, a pro-inflammatory mediator. With the help of nuclear factor-inducing kinase (NIK) and mitogen-activated protein kinase (MAPKs), it also suppresses (NF-kappa B) [27]. It also inhibits COX-2 via decreasing nitric oxide synthase and TNF-, resulting in anti-inflammatory action. However, because kaempferol suffers significant first-pass metabolism and has a bioavailability of about 2%, topical application is preferable. UVB-induced cancer and photo-inflammation are treated with kaempferol, a new drug. It has been tested in skin cancer patients who have high levels of COX 2 enzymes. JB6 P+ mouse epidermal cells reduce AP-1 (Activator protein) activity via reducing COX-2. To test for AP-1 transactivation, JB6 P+ mouse epidermal cells were transfected with a luciferase reporter plasmid containing AP-1, and it was discovered that kaempferol reduces COX and AP-1 activities in a dose-dependent way, assisting in anticancer activity. The protooncogene tyrosine protein-kinase Src (Src) is a protooncogene that plays a key role in cell propagation, differentiation, and survival. Src activity is inhibited by kaempferol, which strives with ATP for the Src requisite position.
4.2 Flavanones
Consequent to the flavones origin, these fragrant ketones in citrus fruits like oranges and lemons. As a byproduct of citrus farming, a substantial quantity of hesperidin is produced. They are cytotoxic and inhibit tumor development; therefore, they might be used as anticancer drugs. Flavanones also serve as an anti-inflammatory and constrain protein tyrosine kinase, affecting cell development, distinction, mitosis, and death [28].
4.2.1 Hesperetin and hesperidin
Hesperidin has anti-inflammatory, antidiabetic, neuroprotective, and other properties. The aglycone component of hesperidin has antioxidant and anti-inflammatory properties by intruding with arachidonic acid, inhibiting COX and LOX enzymes, and limiting inflammatory mediator production [29]. It can whiten skin by reducing hyperpigmentation caused by UV radiation. Hesperetin and hesperidin generate anti-allergic action by constraining the issue of histamine from mast cells. They can also lower HMG CoA reductase and acyl CoA levels, resulting in a hypolipidemic effect. Hesperetin has a log P value ranging from 1.7 to 2.20, making it lipophilic and hard to absorb orally.
4.2.2 Naringenin
Naringenin has numerous properties, including antioxidant, antidiabetic, anti-inflammatory, and antineoplastic properties. It demonstrates antioxidants. MC1R: Melanocortin 1 receptor, MSH: Melanocyte stimulating hormone, MiTF: Microphthalmia associated transcription factor, Type-1: Tyrosinase related protein 1, Type-2: Tyrosinase related protein 2, ASIP: Agouti signaling protein] [− MSH: Melanocyte stimulating hormone, MC1R: Melanocortin 1 receptor, MiTF: Microphthalmia associated transcription factor, Type-2: Tyrosina Journal of Controlled Release 296 (2019) 190–201 R.L. Nagula, S. Wairkar 195 acts via chelating metal ions and constraining xanthine oxidase, averting oxygen radical generation and lipid peroxidation. It can also scavenge ROS through the ∙OH substitution. Because naringenin is hydrophobic and has low solubility and bioavailability, it can be used topically to create an effective formulation [30].
4.3 Flavanols
They are not to be mistaken with flavonol since they lack the ketone group. Epigallocatechin-3-gallate, proanthocyanidins, and other members of this class are included. Tea, chocolate, and a variety of vegetables and fruits contain them naturally [31]. The FDA, for use in a variety of medicinal formulations, has approved catechins and their derivatives.
4.3.1 Catechins
Catechins have antioxidant, photoprotective, anti-aging, anti-inflammatory, anticancer, neuroprotective, cardioprotective, antiviral, and antibacterial properties, among others. Epigallocatechin and epicatechin are abundant in grape seed extract and tea polyphenols. By scavenging free radicals, it has an antioxidant action [32]. Anti-inflammatory action is induced via inhibiting the COX enzyme, NO, PGs, and H2O2 production. Catechins help wounds heal faster by foraging free radicals at the wound site.
4.3.2 Anthocyanins
Anthocyanins are colorful glycosylated, water-soluble pigments that give fruits and vegetables their blue, red, and purple hues. They have been revealed to have antioxidant, anti-inflammatory, and depigmentation qualities in numerous scientific research.
Delphinidin contains anti-inflammatory, antioxidant, antitumorigenic, and antiangiogenic effects and is identified to suppress osteoclastogenesis in osteoporosis. Delphinidin inhibits the production of seditious intermediaries such as iNOS, NO, IL-6, MCP-1, and TNF-, which are produced when LPS inhibits the NF-B pathway and MEK1/2-ERK1/2 signaling [33]. It was tested for psoriasis on flaky skin mice and shown to reduce epidermal thickness. Infiltrating macrophages and caspase 14 downregulation were also seen. Keratin-14, which induces hyperproliferation, was also reduced. By inhibiting keratin-14, delphinidin serves as an antiproliferative. The level of pathological indicators of psoriasis lesions is reduced when delphinidin is applied to flaky mouse skin.
4.3.3 Role of anthocyanins in promoting human health
Anthocyanins may play a beneficial role in human health, according to numerous research. They function as neuroprotective agents and have antidiabetic and antiobesity properties. These substances could be helpful in lowering inflammation and protecting the heart [34]. Additionally, they appear to be effective in halting and preventing the spread of cancer. The biological activity of anthocyanins in rats was recently confirmed by a study by Vanzo and colleagues [35], where the ability of anthocyanins to influence mammalian metabolism was shown in an investigation of metabolomic changes in the brain and plasma of adult rats after intravenously administering cy-3- glc [36]. In the blood, kidneys, and liver of rats, it was demonstrated that cy-3-glc changes a number of significant cellular metabolites, including bile acids, glutathione, oxidized glutathione, and certain lipids [35]. Due to the high anthocyanin concentration in blueberries, this fruit may be a food that improves or promotes health. Routray and Orsat [37] provided evidence for this in a study that analyzed a number of factors related to the potential health effects of anthocyanins, emphasizing understanding [35].
Prebiotics present in brown rice, such as arabinoxylan and -glucan, are advantageous for the Bifidobacterium and Lactobacillus that make up the human gut microbiota. They are thought to play a part in creating an anti-obesity impact. Additionally, brown rice was employed as a preventative measure for type 2 diabetes due to its antidiabetic benefits. This is probably because one of their constituents, −oryzanol, is crucial in regulating the ER stress brought on by a high-fat diet in the hypothalamus, which aids in lowering the desire for fatty foods. Additionally, brown rice’s oryzanol has been shown to lower blood cholesterol levels and stop pancreatic cells from dying. Through their antioxidant action, dietary rice brans, which give brown rice its brown color, also demonstrate powerful anticancer properties [37, 38].
5. Biotechnological applications of flavonoids
Accepting the complex control of flavonoid production has apparent implications, such as the generation of distinct flower colors and fruit types with appealing esthetic and/or agronomic traits, thereby increasing natural selection that has happened from the beginning of time. Petunia an1 (bHLH) or an2 (MYB) variations, morning glory Ipivs (bHLH), c (InMYB1), and ca (InWDR1) mutants, and gentian GtMYB3 mutants have all been characterized as having flowers with a diversity of coloration produced by mutations in the encrypting arrangement of one or more components of the MBW composite. An alteration produces the lack of coloration in fruits in the coding arrangement of the MYB genetic factor VvMYBA2 and MrMYB1, as well as a jumping gene pullout in the promoter of the MYBA1 gene. Grape berry and Chinese bayberry are two examples. Manipulation of flavonoid production to produce fruit and vegetables high in antioxidants and nutritious components, befitting the moniker “superfruit. Nutraceuticals,” would be of prodigious importance to human wellbeing than ever [39]. Anthocyanin accumulation was caused by the ectopic appearance of the MYB-encoding gene LeANT1 in tomato skin and subepidermal cell layers. Likewise, co-expression of the bHLH Delila and MYB Rosea 1 genes below the regulator of the fruit-specific promoter E8 resulted in a significant upsurge in anthocyanin pigments in the flesh and skin resulting in dark purple fruits. Their lifespan was significantly increased when cancer-prone p53 knockout mice were given these transgenic tomatoes. This study is the first step in developing fruits that are high in flavonoid bioactive components and might be part of a healthy daily diet. MdMYB10 and IbMYB1 are two genes that control anthocyanin accumulation in apples [40]. This flavonoid is found by modifying the expression of these commonly eaten foods. The content of these foods might be raised. In tomatoes, constitutive expression of ZmLc, Delila, and MYC-RP/GP led to anthocyanin accumulation in aerial tissues and roots, suggesting that plant transformation with bHLH transcription factors may be investigated. Finally, increasing PA content in forage crops (mainly alfalfa and clover) may assist in preventing pasture bloat in ruminant animals by delaying fermentation in the rumen. PA accumulation may arise from overexpression of ZmLc in alfalfa leaves. Overexpression of ZmSn in the bird’s foot trefoil increased PA biogenesis and anthocyanin accumulation in certain leaf areas. However, constitutive expression of a transgene in many circumstances under Ecological pressure, such as cold and bright light, is necessary since a heterologous system is insufficient to stimulate flavonoid accumulation automatically. In Arabidopsis 35S::PAP1 plants, for example, poor growth circumstances led to the downregulation of positive regulators and the overexpression of putative transcriptional repressors AtMYB6, AtMYB3, and AtMYBL2 [41].
6. Utilizing modern technology to research the flavonoid pathway
We currently have extraordinary knowledge about how different chemical components in plants are controlled in abundance, thanks to the recent rapid development of metabolomics and the use of varied populations for genetic mapping [42]. In a population of rice Zhenshan 97 and Minghui 63 recombinant inbred lines (RILs), metabolic QTL were discovered using high-throughput genotyping and metabolomics data, and some of the candidate genes for flavonoid content were further validated by looking at over-expression transgenic rice lines [43]. Flavonol 3-O-gentiobioside 7-O-rhamnoside (F3GG7R) synthesis in an Arabidopsis RIL population has recently been linked to a novel gene (BETA GLUCOSIDASE 6; BGLU6) [44, 45]. Following genome wide association studies (GWAS) on a diverse maize population that revealed the genetic effects underpinning metabolic heterogeneity, hundreds of loci related with metabolites from numerous pathways, including flavonoid metabolism, were found in maize [46]. The co-expression and direct target genes of the R2R3-MYB transcription factor P1 were also studied using near isogenic lines (NILs) carrying P1-rr and P1-ww. This discovery marked a significant advancement in our understanding of P1’s gene regulation circuitry because targeted molecular tests showed that P1 regulates some well-known genes involved in flavonoid biosynthesis, such as FLS1 and A1 [47]. The corn earworm (
7. Conclusion
Over the last 5 years, our understanding of the metabolism of entire subclasses of flavonoids has progressively improved. Flavonoids are probable nutraceuticals abundantly distributed in vegetables and fruits, given the special focus on wellbeing and illness anticipation over stable nourishment incorporating ordinary goods. This information is crucial for fully assessing their possible health implications, and it still needs to be expanded. We still need to explore information on the quantities and metabolic forms of flavonoids that tissues and cells get exposed to after their consumption. The next stage is investigating possible biological impacts at the tissue and cellular levels. New genomic approaches will open up a world of possibilities in this discipline. Knowing which metabolites will reach tissues and cells, at what concentrations, and to what extent they will be taken up and changed in cells after a flavonoid-rich diet is crucial. The high-throughput genomics technologies will then help us better understand how flavonoids influence metabolic paths and, as a result, improve social health.
Acknowledgments
The authors are thankful to the Institute of the Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam.
Conflict of interest
The authors declare that they have no competing interests to declare.
Abbreviations
| DNA | deoxyribonucleic acid |
| HPLC | High Performance Liquid Chromatography |
| LC-MS | Liquid Chromatography-Mass Spectrometry |
| UV | ultra violet |
| GI | gastro intestinal |
| ROS | reactive oxygen species |
| IL | interleukins |
| PGs | prostaglandins |
| COX | cyclooxygenase |
| LOX | lipoxygenase |
| LPS | lipopolysaccharide |
| NO | nitric oxide |
| MCP | monocyte chemoattractant protein |
| NIK | nuclear factor-inducing kinase |
| MAPK | mitogen-activated protein kinase |
| PAs | proanthocyanidins |
| TNF | tumor necrosis factor |
| AP | activator protein |
| Src proto | oncogene tyrosine-protein kinase |
| ATP | adenosine tri phosphate |
| HMG-CoA β | hydroxy β-methylglutaryl-CoA |
| MC1R | melanocortin 1 receptor |
| MSH | melanocyte stimulating hormone |
| MiTF | microphthalmia associated transcription factor |
| ASIP | agouti signaling protein |
| MiTF | microphthalmia associated transcription factor |
| FDA | Food and Drug Administration |
| MEK | mitogen-activated protein kinase |
| ERK | extracellular signal-regulated kinase |
| TFs | transcription factors |
| BGLU6 | beta glucosidase 6 |
| F3G | flavonol 3-O-glucoside |
| FLS1 | flavonoid 7-O-glucoside; FLS1 |
| BGLU6 | beta glucosidase |
| F3GG7R | flavonol 3-O-gentiobioside 7-O-rhamnoside |
| NILs | near isogenic lines |
| sm1 | Salmon silks 1 |
| sm2 | Salmon silks 2 |
| GWAS | genome wide association studies |
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