Anthocyanins are glucosides of anthocyanidins, a type of water-soluble pigment synthesized via the phenylpropanoid pathway (Mattioli et al., 2020). Structurally, anthocyanins are formed by 2-phenylchromenylium (a flavylium cation), which links methoxyl (−OCH₃) and/or hydroxyl (−OH) groups, along with one or more sugars (Al-Khayri et al., 2022). Anthocyanins are extensively found in the fruits, flowers, and vegetables of many plants, including fig (Ficus carica L.), juçara (Euterpe edulis Mart.), blackberry (Rubus fruticosus L.), grumixama (Eugenia brasiliensis Lam.), grapes (Vitis vinifera L.), blueberry (Vaccinium myrtillus L.), and petals of saffron (Crocus sativus L.) (Cerezo et al., 2020). These metabolites exhibit various colors such as blue, purple, and red, depending on their concentration and the complementary light absorption of chlorophyll (Bendokas et al., 2019).

Anthocyanins are commonly utilized as natural colorants (Enaru et al., 2021). Nevertheless, pH, temperature, light, and structure all affect the color and stability of these metabolites (Khoo et al., 2017). For example, these pigments change from red at an acidic pH to blue at a basic pH. Additionally, the stability of anthocyanins is influenced by the presence of methoxyl or hydroxyl groups (Kang et al., 2021). Delphinidin, cyanidin, malvidin, pelargonidin, petunidin, and peonidin are the main anthocyanidins found in foods (Figure 1) (Enaru et al., 2021).

The total anthocyanin content in blueberries ranges from 85 to 270 mg/100 g fresh weight (FW). In blackberries, the primary anthocyanins are 3-glycoside derivatives of several flavonoids, including cyanidin, delphinidin, malvidin, petunidin, and peonidin. In contrast, cranberries have a lower total anthocyanin concentration, ranging from 25 to 100 mg/100 g FW. The dominant anthocyanins in cranberries are the 3-O-galactoside and 3-O-arabinoside forms of cyanidin and peonidin (Padmanabhan et al., 2016).

Carotenoids (a type of fat-soluble pigment) are naturally found in algae, plants, animals, photosynthetic bacteria, and some species of fungi and archaea (Bhatt and Patel, 2020). These metabolites are tetraterpene pigments, which impart orange, purple, yellow, and red colors (Maoka, 2020). The intensity of their color is typically correlated with the quantity of carotenoids. Carotenoids are most abundant in fruits and vegetables. Their basic structures commonly consist of a 40-carbon backbone with eight isoprene units (Sun et al., 2022).

Structurally, carotenoids can be classified into two groups: carotenes and xanthophylls (Figure 1). Carotenes are hydrocarbons, including compounds like lycopene and β-carotene. In contrast, xanthophylls are derived from carotenes through the introduction of oxygen-containing functional groups such as hydroxyl, methoxy, carboxyl, keto, and epoxy. Prominent xanthophylls include lutein, β-cryptoxanthin, zeaxanthin, and fucoxanthin (Maoka, 2020; Nisar et al., 2015). Additionally, carotenoids can exist in an acyclic form, as in the case of lycopene, or exhibit various cyclic structures at one or both ends, similar to β-carotene. Due to the numerous double bonds in their molecular chains, carotenoids can adopt several cis/trans isomeric forms, although the all-trans isomer is the most stable and is predominantly found in nature (Molina et al., 2023). Martí et al. (2016) reported that tomatoes are a source of carotenoids, including lycopene, phytoene, phytofluene, β-carotene, γ-carotene, and δ-carotene, with concentrations ranging from 7.8 to 18.1 mg/100 g FW, 1.0–2.9 mg/100 g FW, 0.2–1.6 mg/100 g FW, 0.1–1.2 mg/100 g FW, 0.05–0.3 mg/100 g FW, and 0–0.2 mg/100 g FW, respectively.

Chlorophylls are naturally occurring green pigments found in algae, cyanobacteria, and several plants (Tanaka and Tanaka, 2019). Structurally, chlorophylls are complex molecules classified as porphyrins. They consist of four pyrrole rings and an additional isocyclic ring adjacent to the third pyrrole ring. These rings are connected by methylene bridges, with a magnesium atom at the center of the molecule. Additionally, in the fourth pyrrole ring, the propionic acid is esterified with a long-chain acyclic alcohol, typically phytol, which imparts a hydrophobic property to chlorophyll a (Molina et al., 2023; Vaňková et al., 2018). Chlorophylls are commonly found in two major forms: chlorophyll a and chlorophyll b (Figure 1), which differ at the 7-carbon position (Yilmaz and Gökmen, 2016). Chlorophyll a contains a methyl (–CH₃) group, while chlorophyll b contains an aldehyde (–CHO) group. These structural differences result in different colors; chlorophyll a appears green-blue, while chlorophyll b appears green-yellow. The ratio of chlorophyll a to chlorophyll b in plants is typically 3:1 (Carillo et al., 2022).

Chlorophylls have relatively low stability due to their structural susceptibility to various factors that can alter their color characteristics. One of the most common reactions affecting chlorophyll stability is the replacement of the central magnesium ion with two hydrogen ions. This substitution causes a significant color change, as magnesium-containing derivatives appear green, whereas those lacking magnesium, such as pheophytins and pheophorbides, exhibit a brown coloration (Molina et al., 2023).

He et al. (2018) found that the concentrations of chlorophyll a and chlorophyll b in the green alga Ulva prolifera at 28°C were 3.2 ± 0.04 μg/mL and 1.90 ± 0.06 μg/mL, respectively. Furthermore, Šamec et al. (2021) examined the chlorophyll content in Brassica leafy vegetables. Their results showed that kale had chlorophyll a and chlorophyll b concentrations of 7.21 ± 0.19 μg/g dry weight (DW) and 3.50 ± 0.48 μg/g DW, respectively. White cabbage exhibited chlorophyll a and chlorophyll b concentrations of 4.69 ± 0.40 μg/g DW and 2.17 ± 0.87 μg/g DW, respectively, while Chinese cabbage contained chlorophyll a and chlorophyll b at concentrations of 4.67 ± 0.46 μg/g DW and 4.30 ± 0.53 μg/g DW, respectively.

Betalains, water-soluble nitrogenous pigments, are composed of betalamic acid (4-(2-oxoethylidene)-1,2,3,4-tetrahydropyridine-2,6-dicarboxylic acid) as their basic structure (Madadi et al., 2020). These pigments are classified into two groups: betaxanthins (yellow pigments) and betacyanins (violet pigments) (Figure 1) (Calva-Estrada et al., 2022). Cyclo-L-3,4-dihydroxyphenylalanine (cyclo-DOPA) or its glucosyl derivatives condense with betalamic acid to form betacyanins (Silva et al., 2020). Additionally, betalamic acid and amino metabolites condense to form betaxanthins (Figure 2) (Silva et al., 2020). Betalains are widespread in vegetables and fruits, with concentrations ranging from 13.81 to 2,252 mg/100 g in red dragon fruit (Selenicereus monacanthus (Lem.) D.R. Hunt), prickly pear (Opuntia spp.), and xoconostle (Opuntia joconostle F.A.C. Weber ex Diguet) (Kumar et al., 2020; Jiménez-Alvarado et al., 2015).

Selectivity is another essential aspect in extracting natural pigment to improve the purity of the metabolite, increase the concentration of targeted metabolites, or avoid undesired metabolites. These objectives can be achieved using Supercritical Fluid Extraction (SFE) (Lefebvre et al., 2021). Supercritical fluid has low viscosity and relatively high diffusivity. By altering the pressure and temperature, these characteristics are easily modified to the desired solubility therefore allowing the extraction process to aim for a specific metabolite. The high diffusivity of supercritical fluid increases the mass transport of the metabolite to the solvent (Al Jitan et al., 2018).

Carbon dioxide (CO₂) is the prevalent extraction supercritical fluid. Another advantage of SFE is that this fluid is easily mixed with other solvents to obtain a modifier that allows selective extraction. For instance, the extraction of pigment from Rosemary using SFE reported that rich carotenoid extract could be obtained using pure CO₂ at 25°C and the pressure of 20 MPa. In contrast, extraction of chlorophylls reached the optimum condition by using 30% ethanol as a modifier (Lefebvre et al., 2021). Extraction of carotenoid and chlorophylls from Nannochloropsis salina D.J.Hibberd. microalgae also reported similar conditions where CO₂ would result in better carotenoid retention. At the same time, ethanol co-solvent increased both recoveries of chlorophylls and carotenoids by 67.6% and 12%, respectively (Mouahid et al., 2020).

Pressure plays a significant role in the optimization of the SFE method. The extraction of pigments from microalgae species, Nannochloropsis maritima D.J.Hibberd., showed that the effect of pressure during SFE treatment varies among pigments. Under 200 bar, pressure significantly affects total carotenoids’ recovery but is insignificant to chlorophylls. Meanwhile, above 200 bar, a linear correlation between pressure and both pigment’s recovery was observed (Mouahid et al., 2020). In addition, pressure could also affect the retention time needed to extract polyphenols. Lefebvre et al. (2021) reported that the extraction time of rosmarinic acid was reduced to 5.1 min from the initial time of 7.5 min by increasing the pressure from 10 to 20 MPa. In this case, increasing the pressure resulted in increased solubility of the modifier (10% EtOH:Water), allowing faster extraction.

The anticancer potentials of natural pigments have been reported extensively in recent years (Table 2). Lu et al. (2024) studied the effect of zeaxanthin on the adhesion, proliferation, invasion, and migration of human glioblastoma (GBM) cell lines. They found that zeaxanthin may prevent GBM angiogenesis and tumor growth by downregulating a series of oncogenic signaling pathways. Zeaxanthin inhibited the activation of the VEGFR2 kinase pathway produced by VEGF and reduced the expression of p-AKT, p-ERK, p-STAT3, and FAK in U251 cells (Lu et al., 2024). Similarly, Shin et al. (2020) studied the ability of astaxanthin (AXT) as a novel anticancer agent. They reported that low doses (4–8 μM) of AXT decreased the expression of the tumor protein p53 and increased the levels of cyclin-dependent kinase (CDK) 2 and p-Cdk2/3 in the astroglioma cell lines U251-MG (Shin et al., 2020).

Furthermore, it has been reported by Kim et al. (2016) that delphinidin exhibits anticancer activity against A549 lung cancer cells. When 80 µM delphinidin was administered, EGF-induced angiogenesis was almost entirely inhibited and significantly decreased. Additionally, the EGF-induced rise in hemoglobin content was dose-dependently decreased by delphinidin (Kim et al., 2016).

Some natural pigments besides having anticancer activity can also function as co-treatments that can increase the effectiveness of anticancer drugs and/or reduce their side effects. For example, astaxanthin at a concentration of 5 μg/mL can increase MCF-7 breast cancer cell proliferation by 14%, while concentrations of 10 and 15 μg/mL can inhibit cell proliferation by 1% and 19%, respectively. However, when astaxanthin 5 μg/mL was combined with carbendazim at doses of 15 and 30 μM, the antiproliferative effect was increased by 8% and 16%, respectively (Atalay et al., 2019). The search for new anticancer metabolites also targets mortalin, a protein that can bind to p53 and prevent p53 from entering the nucleus. This causes inhibition of cell cycle arrest and apoptosis in cancer cells. Fucoxanthin has been reported to suppress mortalin transcription. In addition, fucoxanthin causes a decrease in cell proliferation, cell metastasis, and survival of cancer cells but is safe for normal cells (Garg et al., 2019). Fucoxanthin can also be an adjuvant therapy with doxorubicin in breast cancer. The combination of 1 µM of doxorubicin and 10 µM of fucoxanthin against MDA-MB-231 cells could significantly increase the number of apoptotic cells and decrease cell proliferation (Malhão et al., 2021). Bacterially produced bio-pigments mostly have medicinal properties. Astaxanthin from Pontibacter kolensis sp. nov. inhibits the growth of the MCF-7 cell line (Pachaiyappan et al., 2021).

Anthocyanins can trigger apoptosis and inhibit the proliferation of HT29 cells in human colon cancer. In a mouse colon tumor model, anthocyanins can reduce PI3K protein expression, increasing Bcl-2/Bax- and caspase-dependent apoptotic pathways and decreasing colorectal cancer growth (Zhao X. et al., 2019).

BIU87 cell growth in bladder cancer can be inhibited at a rate of 36.28% with anthocyanins obtained from purple sweet potato at a concentration of 800 μg/mL through an apoptotic mechanism. Apoptosis increases with increasing concentration, which indicates that the anticancer activity of purple sweet potato anthocyanins is dose-dependent (Li et al., 2018). The substituent on B-rings of anthocyanins affects their anticancer activity. Orto-dihydroxy phenyl on B-rings of anthocyanins can inhibit the growth and metastasis of cancer cells starting with the inhibition of inflammation by suppression of COX-2 and iNOS and expression via the PI3K/Akt andNF-κB pathway at the initial stage. Anthocyanins with orto-dihydroxyphenyl on B-rings also can regulate the expression of cancer-associated genes, thereby triggering cell cycle arrest and DNA repair by inhibiting RTK activity and playing a role in MAPK and AP-1 pathways. This mechanism occurs at the formation stage. Anthocyanins mediated by ROS and JNK/p38-MAPK can activate caspases resulting in cancer cell apoptosis at the development stage (Lin et al., 2017).

Some cancer proteins such as IGF-1R kinase proteins, CDK-2, and CDK-6 bind to anthocyanidins, namely petunidin, peonidin, malvidin, pelargonidin, delphinidin, and cyanidin, thus anthocyanidins are promising metabolites for the development of cancer drugs (Sravani et al., 2021).

Crocin and crocetin, carotenoids from Iranian saffron, inhibit SOD activity by scavenging superoxide radicals and affecting the copper-binding site, respectively. This inhibition was observed in breast cancer cells using docking analysis (Hashemi et al., 2020). Crocin and crocetin also have antimetastatic effects on 4T1 cells, triple negative metastatic breast cancer cells, through inhibition of cell mobility, migration, and invasion, also reduce adhesion to the extracellular matrix (Arzi et al., 2018).

Recent decades have demonstrated that natural pigments possess significant antioxidant properties (Lu et al., 2021). Chlorophyllin, is a water-soluble salt containing copper and sodium that is a homologue of the common green pigment chlorophyll and has been reported to exert an antioxidant effect. Chlorophyllin boosted the activities of antioxidant enzymes (glutathione reductase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase) (Ozcan et al., 2021). Moreover, it has been reported by Yu et al. (2020) that cyanidin-3-glucoside (C3G) has been shown to have a hepatoprotective impact for liver damage caused by oxidative stress because of its antioxidant effect. C3G increases the activity of antioxidant enzymes and upregulating the Nrf2-antioxidant pathway (Yu et al., 2020).

The role of carotenoids in disease cannot be separated from their antioxidant abilities (Rodriguez-Amaya, 2019). Lycopene is a carotenoid that has the highest antioxidant activity compared to other carotenoids (Costa-Rodrigues et al., 2018). Astaxanthin which is a C-C double chain conjugated with olefins can bind ROS and free radicals (Zhao T. et al., 2019) with a mechanism of action to form epoxides, the same as -Carotene and Zeaxanthin (Nishino et al., 2017). Fucoxanthin from Phaeodactylum tricornutum Bohlin, in a dose-dependent manner, can increase the ratio of reduced to oxidized glutathione in HeLa cells by up to 3.3 times (Neumann et al., 2019).

Anthocyanins have potential for treating neurodegenerative diseases because they can modulate various aspects of the disease, particularly the antioxidant pathway (Winter and Bickford, 2019). Chlorogenic acid and cyanidin are the most common anthocyanins found in mahonia fruit extracts, which exhibit antioxidant activity that is twofold higher than that of the phenolic fraction (Coklar and Akbulut, 2017). The ethanol extract of blueberry contains delphinidin, petunidin, cyanidin, peonidin, and malvidin, which are believed to contribute to the antioxidant activity of the extract (Zhou et al., 2019). The anthocyanin content of black chokeberry is 930 mg/g dry weight and consists of four primary anthocyanins: cyanidin-3-O-galactoside, cyanidin-3-O-xyloside, cyanidin-3-O-glucoside, and cyanidin-3-O-arabinoside (Meng et al., 2019). Summarized in vivo studies on the antioxidant activity of natural pigments are presented in Table 3.

The anti-inflammatory activity of anthocyanins was obtained through inhibiting the activation of NF-κB signalling pathway (Duarte et al., 2018; Mirza et al., 2019; Nguyen et al., 2018), decreased serum levels of IFN-γ (Ouyang & O’Garra, 2019), NO (Duarte et al., 2018; Winter et al., 2017), TNF-α, the expression of TLR4 (Cui et al., 2018), and iNOS (Duarte et al., 2018), inhibited MAPKs signaling pathway (Zhang et al., 2020) and reduce the production of ROS (González-Ponce et al., 2018).

The anti-inflammatory of anthocyanins from Dioscorea alata L. tubers was investigated using a mouse model with inflammatory bowel disease. The disease activity index reduces significantly compared to negative control with 80 μg/kg body weight of anthocyanins fraction. The responses, such as body weight, fecal consistency, and fecal occult blood, were similar to the positive control, 5-aminosalicylic acid. The anthocyanins fraction can downregulate the pro-inflammatory cytokines such as TNF-α, IFN-γ, MPO, and iNOS (Chen T. et al., 2017). The main anthocyanin in strawberry fruit, namely pelargonidin-3-O-glucoside, can modulate IL-10 production at a dose of 0.08 mol/L (Amini et al., 2017). Anthocyanins extract from sour cherry fruit (Prunus cerasus L.) at a dose of 50 μM can decrease IL-6 and IL-8 in the inflammation model using the Caco-2 cell line (Nguyen et al., 2018). In addition, anthocyanins from red clover (Trifolium pratense L.) in a dose-dependent manner can inhibit macrophage cells from secreting TNF-α to RAW 264.7 cells (Lee et al., 2020).

Lycopene not only has the highest antioxidant activity among other carotenoids, but it also has anti-inflammatory activity (Thies et al., 2017) through production inhibition of pro-inflammatory cytokines (IL-6β, TNF-α, and IL-1β) (Liu et al., 2018). Bixin, a derivative carotenoid, from Bixa orellana L. seeds, can reduce edema and increase heat resistance on the paw of rats induced by 30 mg/kg of carrageenan orally. The anti-inflammatory mechanism of bixin is related to decreased migration of neutrophils (Pacheco et al., 2019). Combining carotenoids and other compounds can increase their antioxidant and anti-inflammatory activity. For example, 5 µM of fucoxanthin and rosmarinic can decrease apoptosis and ROS production, and downregulate the production of interleukin (IL)-1β, NLRP3, Caspase-1, and ASC. In addition, the pre-treated with the combination can increase the expression of antioxidant genes (HO-1 and Nrf2) in HaCat cells exposed to UV-B (Rodriguez-Luna et al., 2019). Table 4 illustrates the anti-inflammatory activity of natural pigments through in vivo evaluation.

There has been a significant increase in interest in discovering new antibacterial substances, particularly those derived from natural sources, such as plants and marine ecosystems (seaweeds, microalgae, and crustaceans) (Gomes et al., 2022). Seaweeds contain a wide array of pigment compositions that provide several secondary metabolites, including carotenoids, chlorophylls, and phycobiliproteins (PBPs). Additionally, the pigments in seaweeds also include phenolic metabolites, which are responsible for antibacterial activity. A metabolite consisting of phlorotannins, which have a low molecular weight and are extracted from the brown seaweed Sargassum thunbergii, caused Vibrio parahaemolyticus to lose the integrity of its cell walls and membrane (Besednova et al., 2020). By altering and destroying the cell membrane, Fucus vesiculosus L. [Fucaceae, Fucus], a brown seaweed, produced oligomeric phlorotannins (phloroglucinol) that had bacteriostatic effects on pathogenic Streptococcus aureus and S. pneumoniae (Bogolitsyn et al., 2019; Gomes et al., 2022). Research has indicated that carotenoids, particularly fucoxanthin, a pigment found in seaweeds, are effective against both Gram-negative and Gram-positive bacteria. The findings showed that carotenoids hindered various bacteria’s ability to thrive under aerobic conditions. Fucoxanthin was effective in this study against some Gram-positive bacteria, such as S. aureus, S. agalactiae, and S. epidermidis, but ineffective against Gram-negative bacteria, such as Klebsiella oxytoca, Escherichia coli, and K. pneumoniae (Karpiński and Adamczak, 2019).

Anthocyanins, another group of natural pigments, also exhibit antibacterial effects. An earlier study found that anthocyanins had an antibacterial effect on S. aureus, E. coli, Pseudomonas aeruginosa, and Enterococcus faecalis, which are resistant to vancomycin, with minimum inhibitory concentration (MIC) and maximum tolerated concentration (MTC) of 31.07 and 7.76 mg phenol/well, respectively (Côté et al., 2011). Moreover, anthocyanins demonstrated the strongest sensitivity to both Listeria innocua and Aeromonas hydrophilia, with MIC values of 50 and 40 mg/mL, respectively (Genskowsky et al., 2016).

Fucoxanthin, a natural xanthophyll pigment belonging to the carotenoid family, frequently acts against aerobic bacteria at low concentrations (10–250 μg/mL) (Karpiński et al., 2021). Rajauria and Abu-Ghannam (2013) reported that fucoxanthin also acts against Listeria monocytogenes (inhibition zone: 10.27 mm) at a concentration of 25 µg compound/disc. In a different study, Peraman and Nachimuthu (2019) found that the MIC values of fucoxanthin against fungi (Aspergillus brasiliensis, A. fumigatus, and Candida albicans) as well as bacteria were between 1,000 and 4,000 μg/mL. Furthermore, Šudomová et al. (2019) demonstrated that fucoxanthin showed very low MIC values against Mycobacterium tuberculosis (2.8–4.1 µM, or 1.85–2.7 μg/mL).

Similarly Contreras-Ortiz et al. (2017), evaluated the antimicrobial effect of astaxanthin. They found that the viability of Trypanosoma cruzi was reduced in an in vitro study with astaxanthin dosages of 200–300 μg/mL. In another study, Shanmugapriya et al. (2018) demonstrated that astaxanthin can act against a variety of bacteria when formulated as a nanoemulsion. The minimum inhibitory concentration (MIC) values for both Gram-positive and Gram-negative species ranged from 500 to 4,000 μg/mL.

Raspberry, blueberry, strawberry, and blackcurrant extracts are examples of anthocyanin-rich extracts that have shown efficacy against Gram-negative bacteria, but not Gram-positive bacteria. This finding could be explained by the differences in cell wall structure between Gram-positive and Gram-negative bacteria. The outer membranes of Gram-negative bacteria protect them from hydrophobic chemicals but not from hydrophilic ones (Mayasari et al., 2021a). The antimicrobial properties of extracts containing anthocyanins may result from a variety of processes and synergistic interactions between the phytochemicals present, including anthocyanins, phenolic acids, weak organic acids, and a mixture of different chemical forms that interact differently with Gram-positive and Gram-negative bacteria (Tarozzi et al., 2007).

Similar to how blackcurrant extract affects Saccharomyces cerevisiae and E. coli (benefiting their growth), but slows the growth of S. aureus and E. faecium (Werlein et al., 2005). Another study found that the anthocyanin metabolite carboxypyranocyanidin-3-O-glucoside prevents P. aeruginosa and S. aureus strains from producing biofilms in persistent wounds (Correia et al., 2021).

Anthocyanins found in red, purple, and blue vegetables and fruits are key biological compounds that help prevent microbial infections through various mechanisms (Gawai et al., 2017). They exhibit antibacterial activity through several processes, such as damaging the morphology of bacterial cells and compromising the integrity of the cell membrane, including the structure of the intracellular matrix and cell wall. Additionally, anthocyanins cause instability in the cytoplasmic membrane, inhibit extracellular microbial enzymes, and lead to the permeabilization of the plasma membrane (Burdulis et al., 2009). The antimicrobial effects of natural pigments from various sources are summarized in Table 5.

Anthocyanins are phenolic pigments that are both colored and water-soluble. These pigments are found in glycosylated forms and are responsible for the purple, red, and blue colors in fruits and vegetables. Scientific research has shown that anthocyanins possess antibacterial and neuroprotective properties, promote neurological health, support vision, and guard against some non-communicable diseases (Gawai et al., 2017). The therapeutic effects of anthocyanins in treating neurodegenerative conditions, such as Parkinson’s disease, include their anti-apoptotic, anti-neuroinflammatory, and antioxidant capabilities (Patek-Mohd et al., 2018).

Both in vivo and in vitro studies have been conducted to assess the neuroprotective effects of anthocyanin metabolites. An in vitro study demonstrated that cyanidin-3-glucoside and cyanidin have neuroprotective properties against oxidative stress induced by hydrogen peroxide in a human neuronal cell line (SH-SY5Y). The results showed that pre-treatment with cyanidin-3-glucoside and 100 µM cyanidin significantly enhanced antioxidant activity in both the cytosolic fraction and membrane of SH-SY5Y cells. Moreover, cyanidin dramatically increased the proportion of active mitochondria and prevented DNA fragmentation caused by hydrogen peroxide (Tarozzi et al., 2007).

Research suggests that anthocyanins may be effective in treating neurodegenerative diseases, such as ischemia, Alzheimer’s disease, Parkinson’s disease, and other forms of nerve damage (Airoldi et al., 2018; Jung and Kim, 2018). Anthocyanins in their glycosylated forms can cross the blood-brain barrier and enter the central nervous system (CNS), where they exert their biological effects. The neuroprotective activity of anthocyanins is linked to the transporter bili translocase, which primarily targets the vascular endothelium and subsequently the brain network (Aqil et al., 2014). Furthermore, the polyphenolic cationic structure of anthocyanins enables them to scavenge free radicals, reduce ROS production, and suggest their potential efficacy in disorders associated with neurodegenerative processes. Anthocyanins support the PI3K/Akt/HO-1 pathway in Alzheimer’s disease and regulate the endogenous antioxidant Nrf2/HO-1 pathway (Ali et al., 2018).

In APP/PS1 transgenic AD mice, anthocyanin (12 mg/kg i. p. over 30 days) significantly improved memory performance. Cyanidin-3-O-glucoside may also inhibit the formation of soluble amyloid-β 25–35 oligomers and associated neurotoxicity in the human nerve cell line SH-SY5Y (Tarozzi et al., 2007). Additionally, when microglial cells are exposed to a blueberry anthocyanin-rich extract, the expression of the inflammatory genes iNOX and COX is reduced (Bensalem et al., 2016). The neuroprotective effects of the natural pigment anthocyanin are summarized in Table 6.

Age-related macular degeneration (AMD) is a vision impairment linked to aging, causing damage to the macula and central retina, resulting in symptoms like dark spots, distortion, visual field defects, and vision loss (Machida et al., 2020). The retinal macular area contains high levels of xanthophyll carotenoids, including lutein, zeaxanthin, and meso-zeaxanthin (a zeaxanthin isomer). These carotenoids, known as macular pigment, are believed to protect the retina and vision by acting as antioxidants and filtering blue light (Johnson et al., 2020).

However, studies have shown that the levels of carotenoids in the macula decline with age. Additionally, analysis of macular pigment optical density (MPOD) indicates that MPOD also decreases with age, highlighting the importance of increasing carotenoid levels in the macular region for maintaining eye health (Wilson et al., 2021). MPOD measures the concentrations of lutein and zeaxanthin in the macula, expressed in optical density units ranging from 0 to 1 (Kijlstra et al., 2012). To date, several clinical studies have examined the effects of lutein and zeaxanthin supplementation on MPOD (Table 7).

Hammond et al. (2017) investigated the impact of lutein and zeaxanthin supplementation on MPOD. Sixty-two older adults were randomized into two groups: one receiving 10 mg of lutein and 2 mg of zeaxanthin (n = 42), and the other receiving a visually identical placebo (n = 20). Data from 51 participants (average age 73.7 years) were analyzed, revealing a significant increase in MPOD from baseline to the 12-month mark (M = 0.58, SD = 0.23; p < 0.03) in the active supplement group, while the placebo group showed no significant change over the year (Hammond et al., 2017).

In a separate study, Renzi-Hammond et al. (2017) investigated the impact of lutein and zeaxanthin supplementation on cognitive function in younger, healthy adults. They conducted a randomized, double-blind, placebo-controlled trial involving 51 participants aged 18 to 30, who were part of a larger research project on xanthophylls and cognitive performance. The subjects were divided into an active supplement group (n = 37) and a placebo group (n = 14). The findings showed that the supplement, which contained 10 mg of lutein and 2 mg of zeaxanthin, significantly increased MPOD over the year compared to the placebo (p < 0.001). Daily intake of lutein and zeaxanthin, along with the rise in MPOD, was linked to notable improvements in spatial memory (p < 0.04) (Renzi-Hammond et al., 2017).