**2. Flavonoids structure and brain bioavailability**

Flavonoids are a large group of naturally occurring plant-based compounds that are commonly consumed through a diet rich in fruit, vegetables, tea, wine, and soybased foods, being of considerable scientific and therapeutic interest. Flavonoids are responsible for numerous functions in plants. Among them, we can mention protection against ultraviolet rays, against insects, fungi, viruses, and bacteria, and the ability to provide the attraction of pollinating animals. In addition to these characteristics, many of these compounds also possess important pharmacological properties, such as antiviral, antitumor, anti-inflammatory, antioxidant, antiinflammatory activity, and neuroprotective actions.

Flavonoids consist of two aromatic carbon rings, benzopyran (A and C rings) and benzene (B ring) (**Figure 1**). Flavonoids can be subdivided into different subclasses depending on the carbon of the C ring on which the B ring is attached and the degree of unsaturation and oxidation of the C ring on which the B ring is attached and the degree of unsaturation and oxidation of C ring. Thus, they may be divided in seven subclasses as: (1) flavones (e.g. apigenin, luteolin); (2) flavonols (e.g. kaempferol, quercetin); (3) isoflavones (e.g. daidzein, genistein); (4) chalcones (e.g. phloretin, chalconaringenin); (5) flavanones (e.g. naringenin, hesperetin); (6) anthocyanidins (e.g. delphinidin, cyanidin) and, (7) flavanols [e.g. catechin, epicatechin,

*Flavonoids as Modulators of Synaptic Plasticity: Implications for the Development of Novel… DOI: http://dx.doi.org/10.5772/intechopen.84164*

**Figure 1.**

*Basic skeleton structure of flavonoids, subclasses, and their natural sources.*

epigallocatechin, epigallocatechin gallate (EGCG)] [8]. For further information regarding the structure and classes of flavonoids, you can see references Andersen and Markhan [8].

Although flavonoids display directly modulate brain function, during absorption; they are extensive metabolized, resulting in a wide variety of metabolic derivatives. Do flavonoids access the brain?

In order to understand whether flavonoids are capable of modulating brain function, it is important to understand the bioavailability. Bioavailability is a crucial factor determining their biological activity *in vivo*. Therefore, information on the absorption and metabolism of dietary flavonoids in the digestive tract is important for determining their physiological functions, and what if flavonoids and their metabolic derivatives cross the Blood-Brain Barrier (BBB) [9–11]. This point is still a matter of debate, despite a number of studies shows the presence of flavonoids and their metabolites in brain tissue following oral administration of flavonol, e.g. (−) epicatechin [10], flavanones, e.g. hesperetin [11] and flavone, e. g. baicalein [12, 13]. The capacity of flavonoids and their metabolites to cross BBB is dependent on the degree of lipophilicity of each compound, i.e., less polar O-methylated metabolites may be capable of greater brain uptake than the more polar flavonoid glucuronides [14].

Bioavailability studies using flavonoids labeled with radioactive were found in various brain tissues such as hypothalamus, superior colliculus, cerebellum, striatum, and in limbic system structures as cortex and hippocampus [9, 11, 15], both important for memory formation, and are also adversely affected by aging and neurodegenerative diseases. It is a necessary work to discuss bioavailability of flavonoids in brain; however, some studies showed the direct and protective effects of flavonoids in modulating brain function, which will be discussed below.
