By-products of agro-industrial provenance and food waste are severe global concerns, particularly in many developed countries [1]. Food consumption has increased as a consequence of urbanization, population expansion, and economic growth, and it remains a consistent issue worldwide in the long run ^[2][3][2,3]. The most bothersome sectors are the wheat flour production, apple juice production, and tomato-processing industries, which generate massive amounts of residues, as a result of the extensive yearly processed tonnage. On the other hand, the low cost and straightforward availability of this residual biomass shelter the economic prospects of its potentially valuable components [4].

2. Polyphenols in Apple-Processing By-Products

Apples are one of the most consumed fruits worldwide, both in industry and at the individual population level ^[5][31]. Approximately 11 million metric tons of apples is produced and used annually in the apple-processing industry and alcoholic beverage production in Europe ^[6][32]. Apple pomace is one of the most widely produced agrifood wastes, with an annual production rate of about 4 million tons worldwide ^[7][33]. The recovery rate for this by-product, however, is modest. Pomace is frequently discarded and dumped in landfills as waste, which causes environmental issues and presents a potential risk to public health ^[3][8][3,34]. The amount of pomace resulting after apple processing can be reused in biotechnological routs as a substrate for the production of different compounds, such as flavoring compounds, pigments, fuel, and citric acid, or as raw materials for the extraction of fibers and phenolic compounds ^{[9][10][11][12]}[35,36,37,38]. From a nutritional point of view, apple pomace is a by-product rich in fibers, vitamins, minerals, phenolic compounds, and pigments ^[13][19]. All these macronutrients have a significant role in the human organism through their effects on metabolism. Therefore, apple pomace has attracted researchers’ consideration, as well as stakeholders’ attention, by virtue of its valuable composition and by presenting suitable properties for further sustainable use ^[14][39]. The nutritional profile of apple pomace is mainly represented by phenolic compounds, carbohydrates, and fibers, as presented in table Table 1. These constituents can help treat gastrointestinal disorders, decrease serum triglycerides and LDL-cholesterol, and regulate glycemia ^[15][16][40,41]. All these effects in the human organism can be explained through their high concentration of the beneficial compounds mentioned above, primarily exerting anti-inflammatory and antioxidant roles ^[17][42]. In addition to the benefits, the consumption of apple pomace may raise questions associated with toxicity when it comes to its applicability in the food industry ^[19][44], with seeds representing 4–5% of the apple pomace ^[20][45]. Apple seeds contain a plant toxin called cyanogenic glycoside amygdalin, which can interact with digestive enzymes, resulting in the release of hydrogen cyanide. This toxin can cause different symptoms, from mild symptoms such as dizziness to severe symptoms such as paralysis and coma ^[21][46]. However, to reach poisoning levels, the ingested quantity must be significantly high; more exactly, between 83–500 apple seeds are needed to reach the poisoning level, or the person must consume more than 800 g of apple pomace ^[7][22][33,47]. Studies on apple seed oil have confirmed the safety of its use, as the limit was found to be below the toxicity level ^[23][48]. Phenolic compounds are concentrated mainly in the core, seeds, peel, calyx, and stem, as well as in smaller amounts in the pulp, highlighting how apple pomace can be valorized through its high amount of antioxidant compounds. As shown in Figure 1, the total phenolic content of seeds has a higher value compared with the pulp, followed by the peel, both being part of apple pomace. The predominant phenolic compound families in apple pomace are dihydrochalcones, procyanidins, flavan-3-ol monomers, flavonols, anthocyanidins, and hydroxycinnamic acids. The most representative compounds are phlorizin from the dihydrochalcones family, chlorogenic acid from the hydroxycinnamic acids family, and epicatechin from the flavan-3-ol monomer family ^[25][50]. One of the representative phenolic compounds in apples and, remarkably, apple pomace, is phlorizin (Figure 2A). As the main compound from the dihydrochalcone family, the amount of phlorizin in apple pomace is approximately 1.6 mg/g dry weight, highlighted in a study by Lavelli et al. on the stability of phenolic compounds in apple pomace ^[26][51]. Phlorizin is used as a marker of apple varieties and is mainly concentrated in apple seeds. This polyphenol is also used as a reliable marker for spotting the presence of apples, a less expensive alternative compared with the reported fruits ^[27][52]. Nevertheless, it also acts as a strong antioxidant, anti-inflammatory, and antimicrobial compound ^[28][29][53,54]. Regarding its benefits, phlorizin exerts several health benefits, mainly in diabetes, due to its ability to alter the glucose absorbed and excreted. A recent study illustrated that the intestine and kidney’s sodium/glucose cotransporters are specifically and competitively inhibited by phlorizin. In addition, postprandial hyperglycemia therapy in diabetes and other associated illnesses, such as obesity, may benefit from this characteristic ^[30][55]. A study conducted on streptozotocin-induced diabetic mice showed that a diet containing 0.5% phlorizin significantly improves the exacerbated elevations in blood glucose levels ^[31][32][56,57]. Another health benefit can be seen in colitis, where it acts as a protective compound for the intestinal brush border ^[33][58]. Chlorogenic acid (Figure 2B) is representative in the peel and flesh of apples compared with their seeds. Chlorogenic acid is a powerful antioxidant known for counteracting pathologies caused by oxidative processes ^[34][35][59,60]. A study conducted on the improvement of mood and cognition in the elderly showed enhanced results after the administration of enriched decaffeinated coffee with chlorogenic acid, displaying that the consumption of products containing chlorogenic acid can help in the treatment of neuro-cognitive diseases ^[36][61]. Besides the benefits mentioned previously, chlorogenic acid can also confer positive effects by lowering blood pressure, confirmed in a randomized trial involving healthy volunteers after the administration of 400 mg chlorogenic acid in 400 mL low-nitrate water. This effect can be explained by the ability of phenolic compounds to increase nitric oxide, which improves cardiovascular health ^[37][62]. The third phenolic compound found in apple pomace in smaller amounts is epicatechin (Figure 2C). Besides all its fulfilled roles (e.g., antioxidation, anti-inflammation), epicatechin can exert its role in diabetes, cancer, and cardiovascular disease, acting as a neuroprotective compound, and it improves muscle performance ^[38][63]. Cilleros et al. showed, in an in vitro study, the effect of epicatechin in regulating glucose uptake and bolstering the insulin signaling pathway ^[39][64]. A study conducted on human monocytic cells (THP1 cells) showed similar results regarding the beneficial effects of epicatechin in diabetes through the attenuation of high-glucose-induced inflammation ^[40][65].