Martínez-Las Heras et al. ^[1][24] analyzed the content of EP and the antioxidant capacity of the fruit, leaves, and fiber extracted from Rojo Brillante persimmon during its in vitro digestion. The results showed that the oral phase and the presence of α-amylase were the factors that most affected the reduction in the recovery index of the EP, especially in the leaves of persimmon. An increase in the recovery index of EP was observed in persimmon fruit and fibers during the small intestine phase. This could be because of the extended period of this phase (>2 h) and the effect of intestinal enzymes and bile salts, which could facilitate the release of polyphenols from the persimmon matrix. However, antioxidant capacity during digestion resulted in total losses at the end of digestion in leaves, persimmon fruit, and fibers. The bioaccessibility of the EP in the persimmon fiber was higher than in the fruit and persimmon leaves. Moreover, the bioaccessibility of the total antioxidant capacity was lower than those of EP and never exceeded 40%. They concluded that the EP and total antioxidant capacity of the aqueous extract of persimmon leaf were more sensitive to the gastrointestinal environment than those derived from persimmon fruits or fibers. Although the bioaccessibility of the total antioxidant compounds in the persimmon fruit and the fiber was greater than in the aqueous extract of persimmon leaves, an infusion with persimmon leaf (1.5 g in 110 mL of water) and persimmon fruit (200 g) would provide similar bioaccessible antioxidants at the end of digestion.

Zhu et al. ^[2][25] analyzed the inhibitory effect of tannins extracted from persimmon Niuxin on pancreatic lipase. This critical enzyme is associated with hyperlipidemia and obesity. The results showed the tannins extracted from persimmon had a high affinity for pancreatic lipase and inhibited the activity of this enzyme; the interaction was spontaneous through non-covalent bonds. Therefore, the binding and inhibition capacity of persimmon tannins on lipid digestive enzymes may have effectiveness for the treatment and prevention of obesity.

Li et al. ^[3][26] showed the effect of the tannins extracted from the fresh GongChengYueShi persimmon on the digestibility of corn starch and on the activity of α-amylase and α-glucosidase; two of the main digestive enzymes involved in the hydrolysis of the starch. The digestibility of starch decreased with the addition of tannins from persimmon; the higher the concentration of added persimmon tannins, the greater the inhibition of starch digestibility. Moreover, the results showed persimmon tannins interacted with the starch, interacting with amylose more than amylopectin. However, tannins exerted a great inhibitory effect on α-amylase and α-glucosidase. Generally, data suggest that tannins in persimmon may help reduce postprandial hyperglycemia, regulating glucose levels in the human body.

Lee et al. ^[4][27] evaluated the polymers and oligomers of proanthocyanidins from persimmon peel against diabetes. The oligomeric proanthocyanidins exerted a higher interaction with α-glucosidase and the polymeric proanthocyanidins had greater interaction with α-amylase. This suggests that the inhibition of both enzymes depends on the degree of polymerization of the phenols. Therefore, persimmon peel could have an antidiabetic action.

In a study conducted by Zhou et al. ^[5][8], the total content of EP and NEP present in Mopan persimmon was evaluated. The action against α-glucosidase of EP and NEP and their antioxidant capacity were also compared. In addition, the release of EP from NEP was studied throughout in vitro digestion, considering the oral, gastric, and small intestinal phases. The results showed the NEP content in fresh persimmon was higher than EP. The EP had a greater inhibition capacity of α-glucosidase than the NEP. This could be because EP comprised low molecular weight molecules, which can be more easily attached and have a greater ability to interact with the enzyme. Both had a higher α-glucosidase inhibition capacity than acarbose—an oligosaccharide used as a drug reducing the speed of carbohydrate digestion. After in vitro digestion of NEP, the polyphenols content and the antioxidant capacity were lower in the oral phase and significantly increased in the gastric and intestinal phases. The acidic conditions of the stomach environment can enhance the release of NEP. Therefore, NEP was released after simulated gastrointestinal digestion, and the gastric phase played a key role in their release. Thus, NEP was the most effective antioxidant in persimmon fruit after digestion. Nevertheless, Zhou et al. ^[5][8] suggested further investigations to explain the composition and structure of EP and NEP to clarify their differences in biological activities.

Several authors have studied the in vitro digestibility of polyphenols in products such as persimmon flour, spaghetti, and pork liver pâté enriched with persimmon flour, persimmon peels, and dehydrated persimmon. Lucas-González et al. ^[6][28] evaluated the recovery index, bioaccessibility of EP, and total soluble flavonoids during the in vitro digestion of persimmon flour derived from the Rojo Brillante and Triumph varieties. The recovery index of the EP in both varieties was similar, except in the oral phase, where Triumph showed lower values, and the recovery index of total soluble flavonoids was higher in the Rojo Brillante variety. These could be related to the different compositions of the persimmon varieties (total dietary fiber is higher in the Triumph variety) and the interaction of phenolic compounds with α-amylase. The highest recovery index was obtained after the gastric phase and the lowest after the small intestine phase in both varieties. This could be explained by the different pH in the digestion phases. At the acidic pH present in the stomach, phenols are often found in a very stable chemical form—the Flavylium cation. Therefore, the bioaccessibility in the stomach could be higher. However, this bioaccessibility drastically decreases in the intestine because of interactions with dietary compounds such as fiber, chemical reactions of oxidation, and polymerization, or molecular changes because of enzyme action. Regarding the bioaccessibility of EP, the results indicated both flours presented similar values. Triumph presented greater bioaccessibility of soluble flavonoids than the Rojo Brillante variety, probably because of the different flavonoid profiles of the persimmon flours. Therefore, the different fiber content, the interaction of α-amylase with polyphenols, the pH during the gastric and intestinal phase, and the total content of polyphenols and flavonoids in the persimmon samples are the main factors affecting the behavior of these bioactive compounds during digestion ^[6][28].

In another study, Lucas-González et al. ^[7][12] formulated spaghetti with 3% and 6% of the persimmon flours obtained from the Rojo Brillante and Triumph varieties. The profile of EP and NEP and their bioaccessibility and antioxidant capacity after simulated in vitro digestion were determined. Spaghetti enriched with persimmon flours modified the polyphenolic profile with the appearance of two new compounds, gallic acid and p-coumaric-o-hexoside, increasing the antioxidant capacity. After in vitro digestion, numerous polyphenols remained bound to the cell wall or to indigestible polysaccharides. The EP bioaccessibility determined in the small intestine phase was poor and did not improve with the addition of persimmon flours; many EP could become part of the NEP. The authors concluded that although most NEP did not release from the food matrix during gastrointestinal digestion, they may still have a health-promoting effect as they could be available in the colon ^[7][12].

Furthermore, Lucas-González et al. ^[8][29] enriched pork liver pâté with 3% and 6% of Rojo Brillante persimmon flour. In both samples of enriched pâté, 2 EP and 21 NEP were detected, provided by the persimmon flour. After in vitro digestion of the pâté samples, EP and NEP were evaluated. The in vitro digestion consisted of the oral, gastric, and two small intestine phases; one with pancreatin high lipase activity (C1) and the other with pancreatine low lipase activity (C2). More NEP than EP was detected in all digestion stages. In addition, it was observed that the intestinal phase C1 was more suitable to recover NEP after digestion than the intestinal phase C2. This could be associated with a greater release of fatty acids in the digestive environment, which could have a protective effect on polyphenols by interacting with them. However, the observed polyphenols were NEP, which were not released. Therefore, they probably reached the colon intact, and some could be metabolized by the intestinal microbiome. Lucas-González et al. ^[8][29] concluded that high-fat foods such as pâté are excellent vehicles for preserving NEP, which could reach the colon intact and be metabolized by the intestinal microbiome. However, more studies are needed on lipid digestibility, colonic fermentation, and polyphenol transformations to achieve the complete health implications of fortifying meat products with persimmon flours.

Liu et al. ^[9][30] selected optimal deastringency methods and evaluated the bioaccessibility of polyphenols in Yongding persimmon peels treated with 12 combinations of CO₂ and ethanol. EP and NEP content after the deastringency treatments as well as the antioxidant capacity and bioaccessibility of the EP after in vitro digestion, were determined. The results indicated that the EP content decreased, and the NEP content increased with increasing ethanol and CO₂ concentration in the non-digested samples. After in vitro digestion, there was also a significant decrease in the EP and antioxidant capacity of persimmon peels. This could be related to a higher NEP formation after the digestion process. The ethanol (30%) and CO₂ vapor (70%) methods were the most effective, with the highest bioaccessibility of EP. Therefore, it could be considered the best deastringency method.

Recent studies investigated the recovery index of EP, soluble flavonoids, and antioxidant capacity of persimmon affected using drying methods—ultrasound-assisted vacuum drying (USV), freeze-drying (FD), infrared drying (ID), and hot air drying (HAD) ^[10][31]. The results showed that the USV, ID, and HAD led to a significant increase in the bioaccessibility of EP, soluble flavonoids, and antioxidant capacity compared to fresh persimmon. The samples obtained by FD did not show significant differences in the recovery index with respect to fresh persimmon. The recovery index increment was produced because of the heat treatment during the drying process. The heat facilitated the release of bioactive compounds from the food matrix. This would also explain the higher bioaccessibility obtained for ID and HAD because they are the drying processes with the highest thermal load. Therefore, the best dehydration processes to obtain higher bioaccessibility of EP, soluble flavonoids, and antioxidant capacity are HAD and ID.

Bas-Bellver et al. ^[11][32] analyzed the effect of the gastric, small intestine phase, and colonic fermentation on the phenolic compounds and the antioxidant capacity of Rojo Brillante persimmon powders obtained using the HAD and FD methods. In other studies, EP and antioxidant capacity increased after the gastric phase and decreased after the intestinal phase. As they stated, most of the solubilized polyphenolic compounds remained in the precipitate. The bioaccessibility of the EP of both samples obtained by both drying treatments showed no differences between them, whereas the bioaccessibility of the antioxidant capacity increased in the samples treated by freeze-drying. After the colonic fermentation of the predigested samples, a growth of beneficial bacteria such as Bifidobacterium and Faecalibacterium prausnitzii was observed. Likewise, positive correlations were detected between polyphenols and Actinobacteria, Akkermansia, and Ruminococcaceae; bacteria genera related to beneficial effects on the immune system and health status. Lactic acid bacteria, Streptococcus, and Lactobacillus also showed higher abundance after fermenting the digested persimmon samples. In addition, butyrate-producing bacteria such as Faecalibacterium and Ruminococcaeae also showed higher abundance after fermentations. Butyrate is a short-chain fatty acid produced by intestinal bacteria because of the fermentation of indigestible polysaccharides. This metabolite is a critical mediator of the colonic inflammatory response and a contributor to the immune system. Thus, persimmon powders could be used in food formulation to improve the content of bioactive compounds and could influence human health.

Matsumura et al. ^[12][33] investigated the in vitro antioxidant potential of NEP from Hohrenbo dehydrated persimmon using HAD. They performed the in vitro digestion divided into four phases: oral, gastric, small intestine, and large intestine and determined the antioxidant capacity in each phase. The antioxidant capacity in the oral phase was low but increased in the gastric and small intestine phases. However, the highest values of antioxidant capacity were obtained in the large intestine phase. In the large intestine phase, the intestinal microflora produced the fermentative decomposition of the non-extractable fraction of the dried persimmon, enhancing its antioxidant capacity. Moreover, the authors concluded that more studies are required to confirm the health benefits of NEP and to distinguish between the dietary functions of EP and NEP.

Hamauzu and Suwannachot ^[13][34] analyzed the EP and NEP fractions in Ichida-gaki persimmon samples dehydrated using natural drying. After simulating the gastric and small intestine phase in vitro, the NEP fraction presented a strong bile acid-binding capacity. Therefore, dehydrated persimmon with a large amount of NEP could act as a cholesterol-lowering agent.

Estévez-Santiago et al. ^[14][35] evaluated the bioaccessibility of provitamin A carotenoids from different fruits, including persimmon. The carotenoids evaluated were β-cryptoxanthin, β-carotene, and α-carotene in their trans/cis forms using HPLC quantification. The carotenoids bioaccessibility in persimmon was low, where β-carotene and α-carotene had the highest percentage of bioaccessibility. Estévez-Santiago et al. ^[14][35] explain that the effect of the food matrix affects the bioaccessibility of carotenoids, and bioaccessibility increases with the presence of a fat source. Fruit is rarely consumed with a fat source, as this mixture is not a common food offering. However, fruits are usually eaten as desserts after meals containing fat. This practice can have a positive effect on the bioaccessibility of carotenoids.

According to Cano et al. ^[15][36], the bioaccessibility of carotenoids involves two processes: (i) release of carotenoids from the food matrix and (ii) subsequent micellization. This is limited by many factors, such as the presence of lipids, processing (milling, mechanical grinding), or the type of food matrix. Only the carotenoids present in the micellar phase are considered bioaccessible. Cano et al. ^[15][36] evaluated the stability and bioaccessibility of carotenoids and carotenoid esters in the Rojo Brillante persimmon in fresh fruit and after high hydrostatic pressure and pasteurization treatments. The number of carotenoids before and after digestion was quantified using the HPLC technique, and their recovery and bioaccessibility indexes were calculated after the oral, gastric, and small intestine phases. The results in fresh persimmon showed low bioaccessibility and no micellization of carotenoids; traces were found in the micellar phase of the small intestine phase. This was related to the fiber content of persimmon that traps bioactive compounds and reduces micellization and bioaccessibility. Pressurized and thermally treated samples increased the overall carotenoid bioaccessibility to 54% and 25%, respectively. This increase in bioaccessibility could be because of structural modification (pressurized samples) or degradation plant of polysaccharides (pasteurized samples), such as pectin—present in persimmon tissue—releasing the carotenoids and favor the subsequent micellization.

García-Cayuela et al. ^[16][37] assessed the in vitro carotenoids recovery index and bioaccessibility in Rojo Brillante persimmon-based dairy products. Dairy products were formulated with whole milk (3.6% fat) or skimmed milk (0.25% fat) and with whole freeze-dried persimmon, pulp, or peel. On average, the total carotenoid recovery was approximately between 25–39%. This means that the total carotenoid content decreased between 66–75% after in vitro digestion in all the formulated samples. The carotenoids bioaccessibility was significantly higher in dairy products formulated with whole milk. Within the whole milk formulations, the highest amount of bioaccessible carotenoids was provided by dairy products, including peel, followed by those including whole persimmon and those with the pulp. Furthermore, these formulations significantly improved the bioaccessibility of provitamin A total carotenoids (β-cryptoxanthin, α-carotene, β-carotene, and lycopene). García-Cayuela et al. ^[16][37] suggested, as did Estévez-Santiago et al. ^[14][35], that a higher fat content in the product exerts a significant improvement in carotenoid bioaccessibility. The highest amounts of bioaccessible carotenoids were found in whole milk + whole persimmon and whole milk + peel. Therefore, these formulations would be the most suitable for developing functional foods for people with low vitamin A consumption.

Bas-Bellver et al. ^[11][32] determined the changes in persimmon carotenoids after FD and HAD treatments and during in vitro digestion. The total carotenoid content was slightly higher in the FD powders than in the HAD because of the absence of oxygen and the low temperature during the FD treatment. α-Cryptoxanthin was the most abundant carotenoid in both persimmon powders. Nevertheless, the degradation of the carotenoids analyzed was evidenced during in vitro digestion in both drying treatments. This degradation during digestion depended on the content and characteristics of fiber and lipids present in the food matrix. After colonic fermentation, the number of certain beneficial bacteria genera were slightly greater with the presence of the persimmon powder samples. There was a positive correlation with beneficial bacteria genera and a negative correlation with harmful bacteria, thus indicating that the presence of antioxidant compounds (polyphenols and carotenoids) is associated with a high and low abundance of these genera. Therefore, persimmon waste powders could be included in the food formulation to improve the content of carotenoids and could have a positive effect on human health.