**Abstract**

The objectives of this chapter are to summarize and discuss (i) the anthocyanins structure and content in foodstuffs and their dietary intake (ii) the anthocyanins bioavailability and human metabolic pathways and (iii) the *in vitro* and *in vivo* potent anti-neuroinflammatory effects of anthocyanins and their metabolites. Indeed, anthocyanins are polyphenolic compounds belonging to the group of flavonoids, and are one of the most commonly consumed polyphenols in a normal diet. They are responsible of red, blue and purple color of several fruits and vegetables and their intake has been related with several human health benefits. The anthocyanins structures diversities as well as their content in various fruits, vegetables and cereals is addressed. Moreover, despite the growing evidence for the protective effects of anthocyanins, it is important to highlight that the *in vivo* bioavailability of these compounds is relatively low in comparison to their more stable metabolites. Indeed, after consumption, these bioactives are subjected to substantial transformations in human body. Phase I and II metabolites generated by intestinal and hepatic enzymatic reactions, and phenolic acids produced by gut microbiota and their metabolized forms, are the most important metabolic anthocyanins forms. For this reason, the study of the biological properties of these circulating metabolites represents a more *in vivo* realistic situation. Although the anthocyanin bioavailability researches in humans are limited, they will be discussed together with a global metabolic pathway for the main anthocyanins. Moreover, several works have demonstrated that anthocyanins can cross the blood brain barrier, and accumulate in brain endothelial cells, brain parenchymal tissue, striatum, hippocampus, cerebellum and cortex. Consequently, the study of anthocyanins as potent therapeutic agents in neurodegenerative diseases has gained relevance and the principal and the most recent studies are also discussed in the book chapter.

**Keywords:** anthocyanin, metabolites, neuroinflammation, phenolic acids, bioactives

### **1. Introduction**

Anthocyanins (deriving from the Greek *anthos* means flower, and *kyanos* means blue) are one of the most important pigments in the plant kingdom after chlorophyll. Anthocyanins belong to the widespread family of flavonoid polyphenolic compounds and are responsible of red, purple and blue colors of a great numbers of vegetables and fruits [1]. Although several hundred of natural anthocyanins has been identified (more than 600), they all derived from 31 naturally known anthocyanidins (anthocyanins aglycone) [2, 3]. When looking at the human diet (fruits, vegetables and cereals), the number of anthocyanidins can be reduce to only six different anthocyanidins which are: pelargonidin, cyanidin, peonidin, delphinidin, petunidin, and malvidin. Among these, cyanidin represents the most widespread anthocyanidin in plants (50%). Cyanidin, delphinidin and pelargonidin are the non-methylated anthocyanidins whereas peonidin, malvidin and peonidin possess *O*-methylation. However, as free aglycones are considerable unstable, anthocyanins (the glycosylated forms) are more usually present in natural sources [1, 4].

Apart of being responsible for the color of many foods and beverages, anthocyanins also have numerous health benefits resulting of their antioxidant and antiinflammatory activities, among others. Although the dietary intake of anthocyanins depends on the nutritional habits [5], they have received less attention than other flavonoids compounds. This may be due to the fact that anthocyanins are poorly absorbed, highly metabolized, and rapidly excreted in the urine [6]. In addition, their bioavailability and the metabolites formed by intestinal, hepatic enzymatic reactions, and gut microbiota depend on the chemical structure of anthocyanin.

This book chapter will summarize and discuss (i) the anthocyanins structure and content found in fruits, vegetables and cereals as well as the global dietary intake (ii) the anthocyanin bioavailability and human metabolic pathways and (iii) the *in vitro* and *in vivo* anti-neuroinflammatory effects of anthocyanins and their metabolites.

### **2. Anthocyanins: chemistry, intake and dietary sources**

From a structural point of view, anthocyanins are glycosylated, polyhydroxy or polymethoxy derivatives of 2-phenylbenzopyrylium (or flavylium cation) containing two benzoyl rings (A and B) separated by a heterocyclic (C). The number of hydroxyl groups and their degree of methylation, the nature and number of the sugar and the position of the attachment, as well as the nature and number of aliphatic or aromatic acids attached to the sugars, determine their different structural variations [3, 7].

Regarding sugars, they can be attached at different positions: 3-monoglycosides, 3-diglycosides, or 3-triglycosides, 3,5-diglycosides and to a lesser extent 3,7-diglycosides. Glucose is the most common sugar moiety but other monosaccharides as rutinoside, rhamnose, galactose, arabinose, xylose are found. Furthermore, the disaccharides as sambubioside or sophoroside and as well as trisaccharides like as xylosilrutinoside or glucosylrutinoside can also be present [8, 9]. The linking of acyl substituents to sugars make possible a further degree of complexity of anthocyanins. Among them, aliphatic (acetic, malonic, succinic, malic) and cinnamic acids (*p*-coumaric, ferulic, sinapic) are the most predominant [10]. Both glycosylation and acylation affects the chemical and physical properties of anthocyanins. Thus, glycosylation improves water solubility whereas acylation have the contrary effect [11].

Anthocyanins are sensible to different factors such as temperature, light, oxygen or enzymes but pH represent one of the most important factors affecting them.

#### *Anthocyanins: Dietary Sources, Bioavailability, Human Metabolic Pathways, and Potential… DOI: http://dx.doi.org/10.5772/intechopen.99927*

Four different equilibrium species can co-exist, the flavylium cation (red; pH 1), the quinonoidal base (bleu, pH 4), the carbinol pseudobase (colorless or pale yellow, pH 5) and the chalcone (*−cis* and *-trans*) (colorless; pH 6). At pH values higher than 7, anthocyanis are degraded. Generally, anthocyanins are more stable and more soluble at low pH [12]. Among anthocyanidins, pelargonidin is the most stable compounds because of its B ring substituents and the presence of hydroxyl or methoxyl groups decrease the stability. However, the glycosylation confers to the molecules a higher stability at neutral pH, since the presence of sugar avoid the degradation into phenolic acid and aldehyde compounds [13].

The determination of the dietary intake of flavonoids, and among them, the mean consumption of anthocyanins has been the subject of several studies over the last two decades. In United States the daily consumption of these compounds in adults has been estimated in 12.5 mg/day, representing cyanidin anthocyanins the 44.7% of the total intake followed by delphinidin, malvidin, petunidin, peonidin and pelargonidin anthocyanidins [14]. Another study in adults (17900 individuals) showed a lower anthocyanidin intake, 9.20 ± 0.79 mg/day. In addition, they stated differences among anthocyanin consumption according to gender (women's consume higher anthocyanins than men's) and sociodemographic and lifestyle factors such as education, alcohol consumption and activity levels [15]. Concerning European data, the European Prospective Investigation into Cancer and Nutrition (EPIC) study estimated a mean of anthocyanin intake of 31 mg/day. At the same time, they also observed that these values vary according to the country, age, sex, body mass index (BMI), level of education, smoking status and physical activity level [5]. Between European countries, significant differences were reported. Indeed, Italy, France and Germany displays the greater mean values, from 35.1 to 42.3 mg/day, whereas Netherlands and Sweeden are the countries with a lower anthocyanin consumption (22.6 and 20.9 mg/day, respectively). More recently, after the study of the dietary habits of 30000 subjects in 14 European countries the mean intake of anthocyanins was estimated to be 19 mg/ day [16]. In other continents and countries such as Australia (12153 subjects) or China (1393 subjects) the estimated anthocyanin mean intake was calculated at 24.2 mg/day and 27.6 mg/day, respectively, which are very closed values to European levels [17, 18].

Apart of being present in many colored fruits and vegetables they appeared also in beverages as red wine or juices and in processed foods as jams. Both, the type and the concentrations of anthocyanins are influenced by genetics (cultivar, species), cultivation, climate, soil, and processing [19]. However, one of the best sources of anthocyanins are berries. Among them, bilberries, blueberries and blackcurrants can be reach values greater than 1000 mg/100 g of fresh weight (FW) (**Table 1**). Among vegetables and cereals, red cabbage, cauliflower and colored corn and rice represent good sources of anthocyanins. The most common anthocyanins are cyanidin glucosides, but some fruits contain other predominant anthocyanin (**Table 1**). For example, pelargonidin-3-*O*-glucoside is the principal anthocyanin of strawberries, whereas malvidin-3-*O*glucoside predominates in grapes and cyanidin-3,5-diglucoside is the major one in pomegranates [29–31]. Generally, the main anthocyanins in vegetables and cereals are chemically more complex in comparison with fruits. In fact, acylated and diglucosylated anthocyanins such as cyanidin-3-(*p*-coumaroyl)-diglucoside-5-glucoside can be found [33]. In addition, others less conventional sugars like sophoroside (cauliflower and radish) or laminiaribioside (red onions) can be present [35, 36, 39]. Interestingly, the most common anthocyanin type in sorghum, are the 3-deoxyanthocyanidins luteolinidin and apigeninidin (characterized by the lack of hydroxyl group at C3 position) and their derivatives, which are not commonly found in higher plants [44].


*Anthocyanins: Dietary Sources, Bioavailability, Human Metabolic Pathways, and Potential… DOI: http://dx.doi.org/10.5772/intechopen.99927*


*Cy: cyanidin; Delp: delphinidin; Mv: malvidin; Peo: peonidin; Pel: pelargonidin; Pet: petunidin; gluc: glucoside; digluc: diglucoside; sam: sambubioside; gal: galactoside; ara: arabinoside; rut: rutinoside; soph: sophoroside; DW: dry weight; FW: fresh weight.*

#### **Table 1.**

*Content and main anthocyanins in foodstuffs.*
