What are Anthocyanins?
French Bordeaux University's Dr. Jacques Mascoule discovered a bitter-tasting substance in peanut skins and later named it anthocyanin, a general term for a large class of polyphenolic compounds that can be converted to anthocyanins under acidic conditions. Subsequently, anthocyanins were found to exist in many plants, such as cranberries, purple sweet potatoes, grapes, eggplant skins, cherries, strawberries, mulberries, hawthorn peels, perilla leaves, apples, black (red) rice, and tea leaves, among others. Under natural conditions, anthocyanins are generally not found in their monomeric form; the majority of them exist as stable anthocyanin glycosides, forming glycosidic bonds with monosaccharides or polysaccharides. Currently, 23 types of anthocyanins are known to exist in nature, with common ones found in plants including pelargonidin, cyanidin, delphinidin, peonidin, petunidin, and malvidin. Anthocyanins belong to a class of polyhydroxy phenolic substances and have a 2-phenylbenzopyran cation structure. Generally, the stability of substances with this structure decreases as the number of hydroxyl groups increases.
Biosynthesis of Anthocyanins
The biosynthetic pathway of anthocyanins is well characterized in model plants such as Arabidopsis and tobacco, as well as various crops, and it is generally highly conserved. This pathway is an important branch of the phenylpropanoid pathway, starting from phenylalanine and ultimately leading to the production of different types of anthocyanins. Phenylalanine is converted to cinnamic acid by phenylalanine ammonia-lyase (PAL). Cinnamic acid is then transformed into p-coumaric acid by cinnamate-4-hydroxylase (C4H), followed by the conversion to 4-coumaroyl-CoA by 4-coumarate-CoA ligase (4CL). Under the action of chalcone synthase (CHS), one molecule of 4-coumaroyl-CoA (I) condenses with three molecules of malonyl-CoA (II) to form naringenin chalcone (III). Naringenin chalcone is then isomerized to dihydroflavonol (IV), also known as leucocyanidin, by chalcone isomerase (CHI). Dihydroflavonol is further hydroxylated on the C-ring by flavanone 3-hydroxylase (F3H) to generate various flavonoid compounds, serving as the central pivot for the synthesis of dihydrokaempferol (VII), dihydroquercetin (VIII), and dihydromyricetin (IX). F3'H and F3'5'H catalyze the hydroxylation of the B-ring of dihydroflavonols, producing eriodictyol (V) and dihydroquercetin-3'-glucoside (VI), respectively.
The next step in anthocyanin biosynthesis is catalyzed by dihydroflavonol 4-reductase (DFR), which acts on one of the three dihydroflavonols, namely, dihydrokaempferol (VII), dihydroquercetin (VIII), or dihydromyricetin (IX), to produce the corresponding colorless anthocyanidins, namely, colorless pelargonidin (X), colorless cyanidin (XI), and colorless delphinidin (XII). These colorless anthocyanidins are then converted into the corresponding anthocyanins, such as red cyanidin (XIII), purple delphinidin (XIV), and blue petunidin (XV), through the action of leucoanthocyanidin dioxygenase/anthocyanidin synthase (LDOX/ANS).
The final step in anthocyanin biosynthesis is O-glycosylation. In contrast to the conserved major flavonoid pathway, glycosylation for anthocyanin modification is diverse, with family and species dependencies. Enzymes driving these modifications are specific to the position and donor substrates of the modification. Cytoplasmic glycosyltransferases facilitate glycosylation. Glycosylation occurs immediately after stabilization of anthocyanins by ANS. The most extensively studied glycosylation involves the addition of glucose by UDP-glucose:flavonoid 3-O-glucosyltransferase (UFGT/3GT).
The synthesis of anthocyanins is controlled by regulatory genes. At the transcriptional level, the expression of anthocyanin biosynthesis genes is regulated by R2R3-MYB transcription factors and the tri-complex (MBW complex) formed by R2R4-MYB, bHLH, and WD40 factors. MYB75, a member of the R2R3-MYB family of transcription factors, has been shown to regulate anthocyanin synthesis in various plants. For example, Arabidopsis plants overexpressing the MYB75 gene exhibit increased accumulation of anthocyanins in roots, stems, leaves, and flowers, while MYB75 mutants show lower accumulation of these molecules. The importance of MYB75 in regulating anthocyanin accumulation has also been demonstrated in crops such as kiwifruit, tomato, danshen, and turnip. Current studies have identified the WD40 repeat gene OsTTG1 as a regulator of rice anthocyanin biosynthesis, with most research focusing on crops such as lettuce, cabbage, wheat, and rapeseed.
Different genes are expressed at different levels in different tissues as a function of developmental stages and environmental conditions. Genomic regulation in specific tissues highlights their specificity by influencing the target genes of receptors, thereby affecting the expression of specific anthocyanin biosynthesis genes and regulating the differential accumulation of flavonoids in that tissue. Therefore, the correct distribution of anthocyanins in plant tissues requires accurate spatiotemporal regulation of the flavonoid biosynthetic pathway and reflects the tissue-specific combinations of transcription factors.
The pathway of anthocyanin biosynthesis in plants (Zha et al., 2017).
Physiological Functions and Mechanisms of Action of Anthocyanins
Antioxidant Properties
Anthocyanins have strong antioxidant characteristics that are essential for defending plants against oxidative stress brought on by outside causes. These substances neutralize free radicals and reactive oxygen species (ROS), protecting plant tissues from cellular deterioration. Anthocyanins have been widely examined for their antioxidant potential, and it has been suggested that humans may benefit from their capability to scavenge toxic compounds.
Anti-inflammatory Effects
The immune system's natural response to damage or infection is inflammation. Chronic inflammation, however, has been linked to a number of illnesses, including as cancer, diabetes, and cardiovascular problems. It has been shown that anthocyanins have anti-inflammatory properties via blocking pro-inflammatory enzymes including cyclooxygenase (COX) and lipoxygenase (LOX). Additionally, these substances have the ability to control the production of inflammatory cytokines including tumor necrosis factor-alpha (TNF-) and interleukin-6 (IL-6), which reduces the inflammatory response.
Cardiovascular Health
Due to their enormous impact on mortality rates globally, cardiovascular diseases (CVDs) are a serious global health problem. Anthocyanins have drawn interest due to their ability to ward against CVDs. These substances have been proven in studies to enhance endothelial function, lower blood pressure, prevent platelet aggregation, and prevent the development of atherosclerotic plaques. Additionally, anthocyanins have anti-thrombotic qualities that can help prevent blood clots from forming and lower the risk of heart attacks and strokes.
Anti-Cancer Potential
Cancer is a complex disease characterized by uncontrolled cell growth and the ability to invade surrounding tissues. Anthocyanins have shown promise in inhibiting tumor initiation, progression, and metastasis through multiple mechanisms. These mechanisms include the modulation of cell signaling pathways, induction of apoptosis (programmed cell death), inhibition of angiogenesis (formation of new blood vessels), and suppression of inflammation. Although further research is needed, the anti-cancer potential of anthocyanins holds great promise for future therapeutic interventions.
Neuroprotective Effects
Progressive neuronal death and brain function impairment are hallmarks of neurodegenerative illnesses including Alzheimer's and Parkinson's. By lowering oxidative stress, controlling neuroinflammation, and preventing the development of amyloid-beta plaques, which are linked to Alzheimer's disease, anthocyanins have shown to have neuroprotective properties. Additionally, these substances improve neural communication and encourage the synthesis of neurotrophic factors, which are crucial for the survival and expansion of neurons. Anthocyanins may be able to prevent or postpone the onset of neurodegenerative disorders due to their neuroprotective characteristics.
Metabolic Health and Diabetes Management
Anthocyanin compounds have been shown to improve insulin sensitivity, reduce insulin resistance, and regulate glucose metabolism. In addition, anthocyanins can inhibit the enzymes responsible for carbohydrate digestion and absorption, thereby reducing postprandial glucose levels.
Skin Health and Cosmetics
The potential advantages of anthocyanins for the health and appearance of skin have been acknowledged by the cosmetics industry. These substances have anti-inflammatory and antioxidant effects that can decrease inflammation brought on by skin aging and damage and protect the skin from oxidative stress. Additionally, anthocyanins encourage collagen production, improve skin suppleness, and stop certain enzymes from degrading collagen. Anthocyanins have been added to several skincare items, including creams, serums, and masks, as a consequence, to revitalize the skin and enhance its general look.
Overview of major human protective effects associated to ACNs consumption reported in the literature (Câmara et al., 2022).
References
- Zha, Jian, and Mattheos AG Koffas. "Production of anthocyanins in metabolically engineered microorganisms: Current status and perspectives." Synthetic and Systems Biotechnology 2.4 (2017): 259-266.
- Câmara, José S., et al. "Behind the Scenes of Anthocyanins—From the Health Benefits to Potential Applications in Food, Pharmaceutical and Cosmetic Fields." Nutrients 14.23 (2022): 5133.
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