**1. Introduction**

Anthocyanins belong to polyphenols, which are one kind of secondary metabolite with polyphenolic structure widely occurring in plants. They serve as key antioxidants and pigments that contribute to the coloration of flowers and fruits. Although anthocyanins vary in di fferent plants, six anthocyanidins, including pelargonidins, cyanidins, delphinidins, peonidins, petunidins, and malvidins, are considered as the major natural anthocyanidins. Berries, such as red raspberry (*Rubus idaeus* L.), blue honeysuckle (*Lonicera caerulea* L.), and mulberry are used as folk medicine traditionally, and their extracts have been used in the treatment of disorders such as cardiovascular disease [1], obesity [2], neurodegeneration [3], liver diseases [4], and cancer [5], in recent years. Cyanidin-3-glucoside (C3G) is one of the most common anthocyanins naturally found in black rice, black bean, purple potato, and many colorful berries. C3G possesses strong antioxidant activity potentially due to the two hydroxyls on the B ring [6], as shown in Figure 1. Recent studies have suggested that C3G potentially exerts functions primarily through C3G metabolites (C3G-Ms) [7], and more than 20 kinds of C3G-Ms have been identified in serum by a pharmacokinetics study in humans [8]. Although the function and mechanism of C3G-Ms are still not clear, protocatechuic acid (PCA) [9–12], phloroglucinaldehyde (PGA) [1], vanillic acid (VA) [13–15], ferulic acid (FA) [16–19], and their derivates represent the main bioactive metabolites of C3G due to their antioxidant and anti-inflammatory properties.

**Figure 1.** The catabolism process of cyanidin-3-glucoside (C3G) in an organism. C3G can be hydrolyzed to its aglycone by enzymes in the small intestine, and further degraded to phenolic compounds by gu<sup>t</sup> microbiota. Microbial catabolism of C3G in the distal small intestine and large intestine is performed by the cleavage of the heterocyclic flavylium ring (C-ring), followed by dehydroxylation or decarboxylation to form multistage metabolites, which enter the liver and kidney by circulation. C3G, cyanidin-3-glucoside; FA, ferulic acid; PCA, protocatechuic acid; PGA, phloroglucinaldehyde; VA, vanillic acid.

#### **2. Absorption and Catabolism of C3G in the Gastrointestine**

Most of the anthocyanins remain stable in the stomach and upper intestine [20,21]. The stomach is considered as one of the predominant sites for anthocyanin and C3G absorption [22,23], although high concentration (85%) of anthocyanins has been found in the distal intestine [24]. There is potential for the first-pass metabolism of C3G in the stomach, that is, C3G can be effectively absorbed from the gastrointestinal tract and undergoes extensive first-pass metabolism, which can enter the systemic circulation as metabolites [25].

Anthocyanins are stable under acidic conditions but extremely unstable under alkaline conditions. The higher the pH is, the more colorless and substituent forms of anthocyanin are predominant [26]. The catabolism of C3G is mainly completed in the distal small intestine, such as ileum [22], and in the upper large intestine, such as the colon [27], with the decomposition by microbiota [28]. C3G can be hydrolyzed to their aglycones by enzymes in the small intestine, and further degraded to phenolic compounds by gu<sup>t</sup> microbiota, in which microbial catabolism of C3G is performed by the cleavage of the heterocyclic flavylium ring (C-ring), followed by dehydroxylation or decarboxylation [29]. Subsequently, phase II metabolites and multistage metabolites (including bacterial metabolites) can enter the liver and kidney to form more methylate, gluronide, and sulfate conjugated metabolites by enterohepatic circulation and blood circulation (Figure 1).
