Anthocyanins: A Comprehensive Review of Their Chemical Properties and Health Effects on Cardiovascular and Neurodegenerative Diseases

Abstract

Anthocyanins are a class of water-soluble flavonoids widely present in fruits and vegetables. Dietary sources of anthocyanins include red and purple berries, grapes, apples, plums, cabbage, or foods containing high levels of natural colorants. Cyanidin, delphinidin, malvidin, peonidin, petunidin, and pelargonidin are the six common anthocyanidins. Following consumption, anthocyanin, absorption occurs along the gastrointestinal tract, the distal lower bowel being the place where most of the absorption and metabolism occurs. In the intestine, anthocyanins first undergo extensive microbial catabolism followed by absorption and human phase II metabolism. This produces hybrid microbial-human metabolites which are absorbed and subsequently increase the bioavailability of anthocyanins. Health benefits of anthocyanins have been widely described, especially in the prevention of diseases associated with oxidative stress, such as cardiovascular and neurodegenerative diseases. Furthermore, recent evidence suggests that health-promoting effects attributed to anthocyanins may also be related to modulation of gut microbiota. In this paper we attempt to provide a comprehensive view of the state-of-the-art literature on anthocyanins, summarizing recent findings on their chemistry, biosynthesis, nutritional value and on their effects on human health.

Keywords: anthocyanidins; anthocyanins; antioxidants; bioavailability; biological activity; biosynthesis; colorants.

Figure 1

Chemical structure of the flavylium cation on the left and of anthocyanidin backbone on the right with atom numbering and ring label (R = H, OH).

Figure 2

Cyanidin (anthocyanidin, left) and its 3-O-glycosyl product chrysanthemin (anthocyanin, right) derived from the enzymatic activity of glucosyltransferase.

Figure 3

Chemical structure of some naturally occurring anthocyanidins (left) and corresponding mono- or di-glycosylated anthocyanins (right).

Figure 4

Molecular states and electronic delocalization of cyanidin at different pH values.

Figure 5

Cyanidin antioxidant scavenging mechanisms against a generic radical oxidant (RO•). Radical attack on position 3 (left) and 4´ (right) are shown with the respective electron delocalization and resonance structures.

Figure 6

DPPH• hydrogen atom abstraction (HAT) and ABTS+• single electron transfer (SET) reactions with a generic antioxidants species (AH).

Figure 7

Stable colored and colorless forms of cyanidin at different pH values.

Figure 8

UV-visible absorption spectra of cyanidin-3-O-β-glucoside at pH 1.0 (red line) and pH 4.5 (black line).

Figure 9

Flavylium cation form (left) and colorless cyanidin–sulfonic acid adduct after bleaching reaction with bisulfite (right).

Figure 10

Schematic representation of anthocyanin biosynthetic pathway. PAL, phenylalanine ammonia-lyase; C4H, cinnamate-4-hydroxylase; 4CL, 4-coumaroil CoA ligase; CHS, chalcone synthase; CHI, chalcone isomerase; F3H, flavanone 3-hydroxylase; F3′H, flavonoid 3′-hydroxylase; DFR, dihydroflavonol reductase; ANS, anthocyanidin synthase; UFGT, UDP-glucose:flavonoid-3-O-glycosyltransferase.

Figure 11

Anthocyanins’ protective effects against atherosclerosis. Anthocyanins’ (ANT) protection occurs in all atherosclerotic stages. ANT decrease plasma low-density lipoprotein (LDL), leading to a reduction in their accumulation in the walls of medium and large arteries. Therefore, ANT indirectly inhibit endothelial cell dysfunction/activation promoted by LDL. Endothelium damage impairs the release of nitric oxide (NO), which together with a local enhanced degradation of NO by increased generation of reactive oxygen species (ROS), decreases NO availability. ANT can increase NO availability by several mechanisms. After activation, endothelia start to express cell adhesion molecules on their surface (ICAM-1, intercellular adhesion molecule-1 and VCAM-1, vascular cell adhesion molecule-1) in order to recruit circulating monocytes to the site of oxidized LDL (oxLDL) accumulation. The expression of these adhesion molecules is downregulated by ANT. In the luminal side, ANT decrease chemokines (CK), which also results in a decline in myeloid cell recruitment. ANT counteract ROS in both the luminal and intimal side, reducing LDL oxidation in vessel wall. During atherogenesis progression, neutrophil-derived granule proteins stimulate macrophage activation to a proinflammatory state which can be inhibited by ANT. Both antioxidant and anti-inflammatory effects of ANT decrease foam cell formation. Moreover, ANT decrease cholesterol by reducing their accumulation in the lipid-rich necrotic core. During the late stages of atherosclerosis, ANT reduce the expression of Toll-like receptor 2 (TLR2) signaling in endothelial cells that regulate neutrophil stimulation of endothelial cell stress and apoptosis. The arrowhead denotes the routes of atherosclerosis progression, whereas the hammerhead represents the effects of ANT.