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Pomegranate (Punica granatum L.) is an ancient fruit that is particularly cultivated in west Asia, though it is also cultivated in the Mediterranean region and other parts of the world. Since ancient years, its consumption has been associated with numerous health benefits. In recent years, several in vitro and in vivo studies have revealed its beneficial physiological activities, especially its antioxidative, antimicrobial and anti-inflammatory properties. Furthermore, human-based studies have shown promising results and have indicated pomegranate potential as a protective agent of several diseases. Following that trend and the food industry’s demand for antioxidants and antimicrobials from natural sources, the application of pomegranate and its extracts (mainly as antioxidants and antimicrobials), has been studied extensively in different types of food products with satisfactory results. This review aims to present all the recent studies and trends in the applications of pomegranate in the food industry and how these trends have affected product’s physicochemical characteristics and shelf-life. In addition, recent in vitro and in vivo studies are presented in order to reveal pomegranate’s potential in the treatment of several diseases.
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Foods 2020, 9, 122; doi:10.3390/foods9020122
Food Applications and Potential Health
Benefits of Pomegranate and its Derivatives
Panagiotis Kandylis * and Evangelos Kokkinomagoulos
Laboratory of Oenology and Alcoholic Beverages, Department of Food Science and Technology,
School of Agriculture, Aristotle University of Thessaloniki, P.O. Box 235, 54124 Thessaloniki, Greece;
* Correspondence:; Tel.: +30-2310-991678
Received: 31 December 2019; Accepted: 21 January 2020; Published: 23 January 2020
Abstract: Pomegranate (Punica granatum L.) is an ancient fruit that is particularly cultivated in west
Asia, though it is also cultivated in the Mediterranean region and other parts of the world. Since
ancient years, its consumption has been associated with numerous health benefits. In recent years,
several in vitro and in vivo studies have revealed its beneficial physiological activities, especially its
antioxidative, antimicrobial and anti-inflammatory properties. Furthermore, human-based studies
have shown promising results and have indicated pomegranate potential as a protective agent of
several diseases. Following that trend and the food industry’s demand for antioxidants and
antimicrobials from natural sources, the application of pomegranate and its extracts (mainly as
antioxidants and antimicrobials), has been studied extensively in different types of food products
with satisfactory results. This review aims to present all the recent studies and trends in the
applications of pomegranate in the food industry and how these trends have affected product’s
physicochemical characteristics and shelf-life. In addition, recent in vitro and in vivo studies are
presented in order to reveal pomegranate’s potential in the treatment of several diseases.
Keywords: extract; juice; peel; seed; antioxidant; polyphenols; health benefits; dairy; meat; food
1. Introduction
Pomegranate is the well-established fruit of a shrub (Punica granatum L.) that is particularly
cultivated in west Asia and in the region around the Mediterranean, as well as other parts of the
world, including America, where the climate is suitable for its growth [1]. The shrub normally grows
up to 5 m, but in some cases, it may reach a morphology of a tree that is as tall as 10 m, except for
dwarf cultivars that grow up to 1–2 m [2]. Climates that simulate that of Mediterranean (with high
sunlight-exposed mild winters and dry summers), seem to be ideal for the growth of pomegranate.
Most varieties are deciduous, although there have been reports of evergreen and conditionally
deciduous pomegranates, depending on the altitude and temperature of the zone. The fruit is
categorized as a fleshy berry. Its shape is nearly round, with a diameter up to 10 cm, and there is a
crown-shaped calyx at the top. Inside the leathery exocarp is a fleshy mesocarp, organized in
chambers that are separated by membranes. The arils contain the edible portion of the fruit. The
exocarp, namely the pomegranate peel, comprises around 50% of the whole fruit, while the edible
part consists of 10% seeds and 40% arils [3]. The whole pomegranate and its juice have an intense
color for which selected bioactive compounds are responsible, especially anthocyanins. Therefore,
the variation in color amongst different cultivars is mainly due to the different concentration of these
The scope of the current review is to point out pomegranate applications in food industry
concerning the product’s physicochemical characteristics and shelf life. Moreover, there is an effort
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to present the pomegranate’s potential against a number of diseases through in vitro and in vivo
2. General Description
2.1. History
The pomegranate originates in the Middle East, with findings such as fossilized leaves, branches
and seeds dating back to the early Bronze Age (3500–2000 BC). Scientists have placed it in the first
five positions in the list of the oldest cultivated fruits, along with the olive, grape, date palm and fig
[4], while references of pomegranate exist in the Koran and the Bible [5]. In many religions and
cultures, pomegranate is thought to be an auspicious symbol, mostly of life, luck, abundance and
fertility [6]. The process of the domestication of pomegranate took place during the prehistoric times,
when traders, sailors and missionaries are said to have been responsible for the introduction of
pomegranate to the Mediterranean region, Mexico and California. Its spread through Eurasia and
America demonstrates the versatility of the plant as far as climatic and soil conditions are concerned,
and this is actually the reason for the fruit’s current morphological conditions.
2.2. Taxonomy
The pomegranate is part of the Punicaceae family and the Punica genus, whereas two species
exist: Punica granatum and Punica protopunica. The latter is endemic to Socotra Island (Yemen) and is
considered to have played an important role in the evolution of the cultivated form of pomegranate,
since it is considered the ancestor of the genus Punica [5]. The genus Punica has distinctive
characteristics that place it in the order Myrtales, although the family under which it should be is
debatable [5]. Historically, due to early morphological studies, it is believed that the Punica genus
should be considered under Lythraceae [2], but there have been many controversies regarding its
classification into a family. However, due to its unique morphology and other features, such as fruits
with leathery pericarp, pulpy seeds with edible sarcotesta, an ovule with a multilayered outer
integument, and a unicellular archesporium, pomegranate has been found to differ from other typical
Lythraceae genera and has therefore been included in a separate family, Punicaceae [2]. The first
written description of the genus Punica dates back to 1753 and belongs to C. Linnaeus [2]. The current
scientific name Punica granatum can be translated to “seeded apple” (Punica—apple; granatum—
grainy) [5]. Due to the plant’s high tolerance to drought conditions, pomegranate is considered a
suitable option for the cultivation of fruit crops in arid zones.
2.3. Cultivars
There are many different cultivars of pomegranate (more than 500) spread all over the world.
However, the type of cultivars that have prevailed in certain regions reflects the preferences and taste
of the local populations, e.g., nonacidic cultivars are favored in India. The origin of the current
cultivars is covered by a shroud of doubt because most of them are derivatives of mutations with no
recordings of their origin. Exemptions are some cultivars that are the result of deliberate breeding.
In general, the same basic pomegranate fruit is known by different names in different regions,
and this is mainly due to the fact that husk and aril color can markedly vary when grown in different
regions. These differences mainly affect fruit size, husk color (ranging from yellow to purple, with
pink and red most common), aril color (ranging from white to red), seed hardness, maturity, juice
content, acidity, sweetness and astringency [7].
Some of the most important cultivars around the world are presented in Table 1.
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Table 1. Some of the pomegranate varieties around the world.
Country Variety References
China Dabaitian, Heyinruanzi, Tongpi, Bopi [8]
Egypt Arabi, Manfaloty, Nab ElGamal, Wardy [9]
Georgia Pirosmani, Rubin, Shirvani, Slunar, Vedzisuri, Imeretis Sauketeso [10]
Greece Hermione, Persephone, Porphirogeneti [11]
India Ganesh, Mridula, Bhagwa, Ruby, Alandi [12,13]
Iran Malas-e-Saveh, Rabab-e-Neyriz, Malas-e-Yazdi, Sishe Kape-Ferdos,
Naderi-e-Budrood [14]
Israel Rosh Hapered, Malisi, Wonderful, Asmar [13,15]
Italy Dente di Cavallo, Neirana, Profeta, A dente Molfetta, Ecotipo Turi,
Maddaloni Dolce, Giardino Chiuso Dolce [16,17]
Malta Blance, Dulce Colourada, Cagin [13,18]
Morocco Gjebali, Djeibi, Grenade Jaune, Grenade rouge, Bzou, Sefri, Chelfi [19]
Spain Mollar de Elche, Agri de albatera, Valenciana [13,20]
Tunisia Gabsi, Tounsi, Zehri, Mezzi, Jebali, Garoussi, Kalaii, Zaghouani [10,21]
Turkey Cekirdksiz, Ernar, Fellahyemez, Hatay, Akanar, Hicaznar, Janarnar [10,13]
USA Wonderful, Early Foothill, Granada, Spanish sweet, Ruby red [13,18,22]
2.4. Composition
Pomegranate is a well-known source of valuable nutritional substances. It contains hydrolysable
tannins, condensed tannins, flavonols, anthocyanins, and phenolic and organic acids (Figure 1);
compounds that have been studied and related with numerous health benefits against diseases [23].
In addition, it is characterized by a low pH value (usually <4.0), a relatively high acidity (even up to
20 g of citric acid/L of juice), and a sugar content (mainly fructose and glucose) of 70–180 g/L. The
exact composition of the fruit depends on many factors, such as the cultivar, soil condition, climate,
ripening stage, cultivation techniques, processing conditions, and storage conditions (Table 2).
The edible part of the fruit is at least 50% of the fruit (40% arils and 10% seeds), and the rest is
the non-edible peel. Peels are source of phenolics, minerals and complex polysaccharides, while arils,
apart from water (85%), contain sugars, pectin, organic acids, phenolics, and flavonoids—principally
anthocyanins. Seeds contain proteins, crude fibers, vitamins, minerals, pectin, sugars, polyphenols,
isoflavones, and the oil that is derived from them (12%–20%) is characterized by a high content of
polyunsaturated fatty acids such as linolenic and linoleic acids, as well as other lipids such as punicic
acid, oleic acid, stearic acid, and palmitic acid [24].
The family of hydrolysable tannins contains two members, ellagitannins and gallotannins,
which can be hydrolyzed into ellagic and gallic acid, respectively. On the one hand, ellagitannins are
mostly present in the pericarp, seeds, flowers, and bark, while, on the other hand, gallotannins are
mostly present in the leaves. Punicalagin, a substance belonging in the family of ellagitannins, is
responsible for more than the half pomegranate juice’s antioxidant effect [25]. Following the digestion
path, ellagitannins are converted by the intestinal flora into urolithins. Other substances that are
present in pomegranate juice are phenolic acids, mainly gallic acid and ellagic acid (which belong to
hydroxybenzoic acids), as well as caffeic acid, chlorogenic acid, and p-coumaric acid (which belong
to hydroxycinnamic acids) [24].
Another constituent that plays a major role in the pomegranate as a functional food is
anthocyanins. These water-soluble plant pigments belong to the family of flavonoids and are
responsible for the color of the fruit and its juice. They have been thoroughly studied for their
numerous effects on health, such as their antioxidant, anti-inflammatory and antiproliferative
properties, meaning that they can contribute to the prevention of several diseases [26]. Flavonoids,
including flavonols, anthocyanins and phenolic acids, are mainly found in the peel and juice of
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It has been reported that the main phenolic compounds in pomegranate juice are anthocyanins,
whereas the main phenolic compounds that are found in the mesocarp and pericarp are hydrolysable
tannins [27]. It has also been reported that the pomegranate peel has a higher antioxidant capacity
than the arils and seeds of the fruit [28], thus making it a potent source of bioactive compounds. This
is in accordance with other studies that have indicated that the pomegranate peel has a higher
concentration of phenolic compounds in comparison with pomegranate juice [29].
Figure 1. Major polyphenols, organic acids, alkaloids, and lignans of the pomegranate fruit.
Table 2. Physicochemical characteristics of pomegranate varieties’ juices.
Characteristic Sweet
(°Brix) 10.0–16.5 12.0–15.0 13.0–16.0 15.7–17.5 16.2 ± 0.2
pH 4.0–4.2 3.6–3.7 2.9–3.6 2.8–3.6 3.6 ± 0.1
(g/L) 4.0–6.8 8.2–11.4 14.8–24.5 11.0–13.0 3.8 ± 0.2
Fructose (%w/v) 4.1–6.0 3.9–4.0 3.5–4.0 7.8–9.1 8.2
Glucose (%w/v) 4.3–6.4 4.3–4.4 3.4–3.9 7.3–8.4 7.0
Total sugars (%w/v) 8.5–12.4 8.3–8.4 7.2–7.9 15.3–17.5 15.2
Several varieties from Iran [30];
Total soluble solids;
Titratable acidity (g citric acid/L of juice).
The bioactive health effects of pomegranate have been attributed to the broad range of
phytochemicals that it contains. The most predominant phytochemical in pomegranate, as was
already described, is considered to be polyphenols—mainly hydrolysable ellagitannins and
anthocyanins [24]. However, it has been proven that there is a synergistic effect among compounds
that further increases their bioactivity. For example, quercetin and ellagic acid show better inhibition
properties against cancer cell growth in comparison to each of the substances alone [33].
Usually, the characterization of a matrix, and especially of the compounds to be studied, is based
on previously published works. Nowadays, along with advancements in technology, it is possible to
create databases with properties of known substances. An example of this is high resolution mass
spectroscopy, where the analyzed substance can be identified based on a database that has been
constructed and allows for the identification of new compounds beyond those already known [34].
A recent study [35] characterized pomegranate aril anthocyanin extracts by high pressure liquid
chromatography (HPLC) coupled with high resolution mass spectroscopy (HRMS), and the five most
dominant anthocyanins were delphinidin-3,5-diglucoside, cyanidin-3,5-diglucoside, pelargonidin-
3,5-diglucoside, delphinidin-3-glucoside, and cyanidin-3-glucoside.
Foods 2020, 9, 122 5 of 22
3. Health Benefits
Fruits, in general, play a major role in the maintenance of a balanced diet. They provide plenty
of macro- and micronutrients, as well as bioactive compounds that promote health. Over the past few
decades, there have been many studies indicating the importance of fruit consumption in the
prevention of health-associated risks, as well as campaigns for the incorporation of fruit in the diets
of children.
Numerous studies concerning the potential health benefits, in addition to the nutritional value,
of the pomegranate and its constituents have been conducted. Encouraging findings have increased
the interest shown in this specific fruit over the past few years. Pomegranate, being rich in bioactive
compounds like polyphenols, has shown many health-related properties, such as antioxidant, anti-
inflammatory and antihypertensive, through in vivo and in vitro studies. The health-promoting
properties of the fruit are considered to mainly be due to the presence of punicalagin and, to a lesser
extent, to other metabolites, such as flavonols and anthocyanins [36]. Several studies have brought
up the potential contribution of pomegranate in the treatment of cancer, diabetes and heart disease.
3.1. In Vitro Studies
Several in vitro studies have been conducted by mainly using pomegranate juice and extracts in
order to associate them with numerous health benefits (Table 3).
Table 3. Recent health-related pomegranate in vitro studies.
Derivative Effect References
whole fruit extract H2O2-induced oxidative stress; apoptosis;
natural antioxidants for skin health [37]
whole fruit extract antimicrobial activity against 29 clinical
Clostridium difficile isolates [38]
juice extract inhibition of a-glucosidase activity [39]
extract and juice prebiotic effect [40]
juice lipogenesis and lipolysis [41]
juice inhibition of lipase, α-glucosidase and dipeptidyl
peptidase-4 [42]
peel extract inhibition of renal cell carcinoma growth [43]
peel extract anti-neurodegenerative [44]
peel extract apoptosis and metastasis in prostate cancer cells [45]
peel and juice extract inhibition of cariogenic bacteria [46,47]
peel and fruit extract stimulates osteoblastic differentiation
(osteoporosis) [48,49]
peel polysaccharide immunostimulatory effect [50]
punicalagin antiproliferative activity against human lung,
breast, cervical and prostate cancer cells [51–53]
punicalagin papillary thyroid human carcinoma cell death [54]
punicalagin inhibition of lipopolysaccharide-induced memory
impairment (Alzheimer’s disease) [55]
punicalagin attenuates osteoclast differentiation (osteoporosis) [56]
products (juice, extract, oil)
photo-chemopreventive effect in human
reconstituted skin [57]
urolithins inhibition of neuroinflammation (Alzheimer’s
disease) [58]
3.1.1. Prebiotic Effect and Antimicrobial Activity
One of the most important health-related functions of the pomegranate and its derivatives is
their effect on gut microbiota and their potential use as antimicrobial agents. It is well known that
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ellagitannins, the most abundant group of polyphenols in pomegranate, are hydrolyzed in ellagic
acid in the gut before being further metabolized by the colon microbiota to form urolithin A and B
[38]. This has been associated with the prebiotic potential of the pomegranate and its products.
Indeed, in an in vitro study with fecal bacteria, pomegranate by-products enhanced the growth of
Bifidobacterium spp. and Lactobacillus spp. acting as a prebiotic [59]. Pure cultures of Bifidobacterium
and Lactobacillus strains have been proven capable of utilizing ellagic acid and glycosyl ellagic acid
[40]. Pomegranate by-products, such as gallic acid, ellagic acid and glucose units, are used by fecal
bacteria to produce urolithins and increase the production of short chain fatty acids like acetate,
propionate and butyrate [59]. In a similar study, pomegranate juice and extracts were used in in vitro
stool cultures and were proven to enhance the growth of Bifidobacteria and Lactobacilli while
simultaneously inhibiting the growth of the Bacteroides fragilis group, Clostridia, and
Enterobacteriaceae [40]. Furthermore, pomegranate by-products and punicalagins were found to
inhibit the growth of pathogenic Clostridia and Staphyloccocus aureus in human gut bacteria cultures
[60]. These results may reveal the potential prebiotic activity of pomegranate juice and extracts on
human gut microflora. The prebiotic effect of pomegranate juice has been evaluated by using the
simulated gastrointestinal digestion of different pomegranate juices with lactic acid bacteria,
resulting in the increased bio-accessibility of phenolic compounds and ensuring the survival of lactic
acid bacteria (which may be due to metabolism of the ellagitannins, epicatechin, and catechin) [61].
3.1.2. Anticarcinogenic Effect
Pomegranate extracts have also been evaluated for their anticarcinogenic activity against
numerous cancer types. More specifically, pomegranate extracts have been shown to block nuclear
factor kappa B (NF-κB) activity in a prostate cancer model [62] and renal cell carcinoma [43] in vitro.
Therefore, pomegranate extracts may be used as dietary adjuncts to manage patients with small,
localized, incidentally identified renal tumors, and this may lead to the avoidance of nephrectomy
[43]. Pomegranate peel extracts and punicalagin, a polyphenol from pomegranate fruit, have shown
growth inhibition on prostate cancer cells and anti-proliferative activity via the induction of apoptosis
[45,51]. Additionally, in vitro studies have revealed that punicalagin induces the cell death of
papillary thyroid carcinoma cells [54], inhibits cell proliferation in a non-small lung carcinoma cell
line [52], and exerts a strong anti-proliferative activity against the human lung, breast, and cervical
cancer cell lines [53]. The pomegranate and its products have been associated with the prevention of
cancer metastasis. In a recent study, the main molecular targets of pomegranate that are associated
with cancer metastasis were reviewed [63]. These targets include (i) molecules that are involved in
cell–cell and cell–extracellular matrix adhesions, (ii) pro-inflammatory and pro-angiogenic
molecules, (iii) modulators of cytoskeleton dynamics, and (iv) regulators of cancer cell anoikis and
chemotaxis. Furthermore, the antimetastatic effect of pomegranate may be attributed to molecular
changes in the extracellular matrix.
3.1.3. Skin Health
Pomegranate phenolics may be used as natural antioxidants for cosmeceutical applications for
skin health, as a recent in vitro study showed their protective effects against H2O2-induced oxidative
stress and cytotoxicity in human keratinocyte HaCaT cells [37]. In addition, pomegranate products
(juice, extract and oil) that are derived from the remaining material after pomegranate fruit squeezing
for juice production have presented photo-chemopreventive effects [57]. More specifically,
pomegranate products have been shown to inhibit UVB-mediated DNA and protein damage,
increased proliferating cell nuclear antigen and tropoelastin levels along with the degradation of
extracellular matrix proteins in human reconstituted skin.
3.1.4. Obesity, Diabetes, Alzheimer’s Disease, Osteoporosis and Dental Health
In recent years, obesity has become a worldwide health problem, and several studies have
focused on it. Pomegranate juice and some specific components, like ellagic acid and punicalagin,
Foods 2020, 9, 122 7 of 22
have presented the ability to inhibit amine oxidases, α-glucosidase, dipeptidyl peptidase-4, lipase,
triglyceride accumulation, and adipogenesis-related genes, as well as to decrease lipogenesis and
lipolysis in mouse and human adipose cells. These results have shown the great potential of
pomegranate juice and its components to be used as a functional food for the prevention of diseases
that are associated with obesity, diabetes and dyslipidemias [41,42]. In addition, pomegranate juice
extract and ellagitannins have been shown to inhibit α-glucosidase activity in vitro and to reduce
starch digestibility under simulated gastrointestinal conditions, confirming the great potential of
pomegranate juice to improve postprandial hyperglycemia, which is linked to type II diabetes [39].
Several studies have proposed the use of pomegranate, and especially its derivative punicalagin
and urolithins, as a potential nutritional strategy in slowing the progression of neurodegenerative
disorders such as Alzheimer’s disease [64]. Urolithins inhibit neuroinflammation [58], while
punicalagin inhibits lipopolysaccharide-induced memory impairment via anti-inflammatory and
anti-amylogenic mechanisms [55].
Pomegranate extracts (peel and fruit) stimulate osteoblastic differentiation [48,49], while
punicalagin attenuates osteoclast differentiation in vitro [56]; therefore, pomegranate juice or extracts
might be useful as agents for the treatment of osteoporosis. In addition, the regular consumption of
pomegranate may benefit the skeletal tissues of the host [49].
Pomegranate has also been proposed for the maintenance of dental health. Streptococcus mutans
is one of the major microorganisms of dental flora, and it is capable of producing acids, soluble
extracellular polysaccharides, and insoluble extracellular polysaccharides, as well as forming
biofilms. An in vitro study showed that pomegranate peel extracts are capable of inhibiting the
growth of cariogenic bacteria at high concentrations (up to 12.5–25.0 mg/mL); however, these
concentrations are difficult to maintain in the oral cavity because of the constant saliva flow. In lower
concentrations, these extracts have been shown to inhibit biofilm formation, acid production, and
extracellular polysaccharides production by S. mutans, showing these extracts’ potential to prevent
dental caries [46]. In another study, pomegranate peel and juice extracts presented inhibitory effects,
not only against S. mutans but also against Rothia dentocariosa, which has been found on the carious
lesions of human teeth and may cause several diseases like endocarditis, pneumonia and infections
of the peritoneum and lung [47].
3.2. Studies Using Mice Models
Apart from in vitro studies that have used pomegranate juice and extracts, there have also been
several studies that have used mice models (Table 4).
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Table 4. Recent health-related pomegranate studies that used mice models.
Derivative Effect References
fruit of progression of cognitive and behavioral
impairments in Alzheimer’s disease [65]
whole fruit extract anti-inflammatory and antioxidant effects [66]
whole fruit extract apoptosis and inflammation in liver cells [67]
peel polysaccharide weight loss and immune organ index of
immunosuppressed mice [68]
peel polysaccharide protection against CCl4-induced liver injury [69]
pomegranate aril extract inhibition of contact hypersensitivity of allergic
dermatitis [70]
juice hypoxia-induced fetal growth and apoptosis in the
placenta in pregnant mice [71]
juice neuroprotection and protection against oxidative
damage in Parkinson’s disease rat model [72]
juice antileishmanial activity, probably by boosting the
endogenous antioxidant activity in female BALB/c mice [73]
leaf total serum cholesterol and triglycerides of
hyperlipidemic mice [74]
peel extract contribution in prevention and treatment of Giardia
lamblia infection [75]
peel extract preventing bone loss associated with ovariectomy in
mice [48]
3.2.1. Obesity, Diabetes
The pomegranate and especially its extracts have attracted the attention of the research
community due to their numerous health benefits, some of them associated with obesity. Several
mouse intervention studies have demonstrated that pomegranate extracts can decrease inflammation
and LDL (low-density lipoprotein) cholesterol in high-fat diet-induced obese mice [76,77] and can
reduce hepatic lipid peroxidation and serum glucose levels in healthy rats, in addition to improving
glycemic control and increased relative beta cell number in alloxan-induced diabetic rats [78,79]. In a
recent study, the combination of pomegranate extracts with inulin led to enhanced cholesterol-
lowering effects [80]. In addition, in the same study, the mechanism of the pomegranate extracts’
action was revealed—more specifically, they lowered cholesterol by increasing bile acid synthesis.
Furthermore, punicalagin reduces the high-fat diet-induced accumulation of cardiac triglyceride and
cholesterol in obese rats via adenosine monophosphate (AMP)–activated protein kinase (AMPK)
activation [81]. Finally, pomegranate leaf extracts can inhibit lipid absorption and reduce blood
triglycerides and total cholesterol in hyperlipidemic mice by inhibiting lipase activity [82].
3.2.2. Prevention and Treatment of Infections
The pomegranate and its products have been evaluated as agents for the prevention and even
treatment of several bacterial or virus infections in mice model systems. Coccidiosis, the most
prevalent disease, especially in poultry farms, causes widespread economic loss. The use of
pomegranate peel extracts on the outcome of coccidiosis in mice has been found to attenuate
inflammation and injury of the jejunum that is induced by Eimeria papillata infections [83]. In a similar
study, treatment with a pomegranate peel extract decreased the pathogenicity of Citrobacter rodentium
infections in mice, suggesting an alteration of the microbiome, making it more resistant to Citrobacter
rodentium [82]. Citrobacter rodentium mimics many aspects of human enteropathogenic Escherichia coli
infections and is therefore used in several studies with mice. A pomegranate peel extract (containing
punicalin, punicalagin, and ellagic acid) reduced Citrobacter rodentium infection-induced weight loss
and colon damage that correlated with a decreased mortality and reduced colonization of the spleen
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[84]. In addition, a pomegranate peel extract proved to be valuable in the prevention and treatment
of Giardia lamblia infection (giardiasis) of the human small intestine [75]. These studies indicate that
pomegranate polyphenols may mitigate the pathogenic effects of food-borne bacterial pathogens.
3.2.3. Other Health Benefits
The addition of pomegranates in the diet may slow the progression of cognitive and behavioral
impairments in Alzheimer’s disease [65], while pomegranate extracts have been shown to have anti-
inflammatory and antioxidant effects on cecal ligation and puncture-induced acute liver injury [66];
they have also been shown to protect against arsenic-induced inflammation and apoptosis in the liver
cells of male Swiss albino mice [67]. Another important product of the pomegranate with several
health benefits is the pomegranate peel polysaccharides (rhamnose, glucuronic acid, galacturonic
acid, glucose and xylose), which may be used in efficacious adjacent immunopotentiating therapy or
an alternative means in lessening chemotherapy-induced immunosuppression; they can also be
utilized as immunostimulants for the food and pharmaceutical industries [68]. Several studies have
shown that pomegranate peel polysaccharides may enhance the immunomodulatory effect, induced
by cyclophosphamide, of immunosuppressed mice [68], exhibit a strong protective effects against
CCl4-induced liver injury in mice [69], and, at low doses, alleviate contact hypersensitivity symptoms,
suggesting that they may provide beneficial effects on allergic contact dermatitis at physiologically
relevant doses in humans [70].
3.3. Human Studies
The significance of pomegranate health benefits has been revealed by its adaption in several
human-based studies (Table 5). The consumption of pomegranate juice for a period of eight weeks
showed beneficial effects on blood pressure, serum triglycerides, high-density lipoprotein
cholesterol, oxidative stress and inflammation in hemodialysis patients [85]. In patients with type 2
diabetes, a consumption of 1.5 mL/kg body weight reduced serum erythropoietin level after three
hours [86], while a 200 mL/day consumption for six weeks reduced systolic and diastolic blood
pressure without affecting the lipid profile [87]. In addition, the daily consumption of pomegranate
juice (230 mL) has been associated with the stabilization of the ability to learn visual information over
a 12 month period [88]. The consumption of pomegranate juice has also been proposed to athletes,
and a systematic study for a 21 day period showed an improvement in malondialdehyde and
carbonyls levels, and, thus, a decrease of the oxidative damage caused by exercise [89]. Finally,
pomegranate juice has been associated with a reduction of inflammation, muscle damage, and an
increase of platelets blood levels in healthy people [90]. A 30 day supplementation with pomegranate
extracts in individuals with overweight and obesity beneficially affected body weight, serum glucose,
insulin, triglyceride, total cholesterol, LDL–C, HDL–C (high-density lipoprotein–cholesterol) and
LDL–C to HDL–C proportion, while also acting as an anti-inflammatory agent, lowering
inflammatory and lipid peroxidation biomarkers [91]. An eight week supplementation with
pomegranate peel extracts attenuated the systolic and diastolic blood pressure in patients with type
2 diabetes and also presented hypolipemic, hypoglycemic, and antioxidative potential [92]. Finally,
clinical studies with pomegranate seed oil in type 2 diabetic patients have resulted in reductions in
the levels of fasting blood sugar, interleukin-6 and TNF-α (tumor necrosis factor-α); however, no
significant changes have been observed in insulin and lipid profiles [93,94].
Foods 2020, 9, 122 10 of 22
Table 5. Recent health-related pomegranate studies in humans.
Derivative Subject Effect References
whole fruit extract overweight and
obese patients
anti-inflammatory effect; body
weight, serum glucose, total
cholesterol, LDL; HDL
juice hemodialysis
improved blood pressure, serum
triglycerides, HDL, oxidative stress
and inflammation
juice humans with
type 2 diabetes serum erythropoietin level [86]
juice humans with
type 2 diabetes systolic and diastolic blood pressure [87]
juice healthy adults maintains visual memory skills [88]
juice endurance-based
athletes modulation of fat and protein damage [89]
juice active healthy
systolic blood pressure, creatinine
and muscle damage parameters [90]
seed oil humans with
type 2 diabetes levels of fasting blood sugar [93,94]
peel extract humans with
type 2 diabetes
hypoglycemic, and
antioxidative potential [92]
peel extract patients with
systolic blood pressure, LDL, total
cholesterol; HDL [95]
women with
acute coronary
reverts high-density lipoprotein-
induced endothelial dysfunction and
postprandial triglyceridemia
4. Applications in Food Products
The pomegranate, as has been mentioned above, is considered to be a fruit with many beneficial
properties that mainly affect health. In addition, many of its sensory properties, such as color and
aroma, present great interest in the food industry and can be utilized in many ways. Many researchers
have studied the effect of pomegranate addition in the properties of several foods products, such as
dairy products (Table 6), films and coatings for food packaging (Table 7), meat and fish products
(Table 8), and cereal and nuts products (Table 9).
Table 6. Recent studies on the effect of the addition of pomegranate derivatives to dairy products.
Derivative Product Effect References
juice kefir-type viscosity; acidity [97]
juice powder yogurt total phenolics; antioxidant
activity; solid-like behavior [98]
peel extract cheese lipid oxidative stability; storage
quality [99]
peel extract
powder fermented milk total phenolics; antioxidant activity [100]
peel extract
powder cheese antioxidant activity; shelf life [101]
peel extract
powder freeze-dried yogurt total phenolics; antioxidant activity [102]
seed powder yogurt antioxidant activity; fatty acid
profile improvement [103]
Foods 2020, 9, 122 11 of 22
Table 7. Recent studies on the application of pomegranate derivatives to films and coatings.
Derivative Product Effect References
peel extract zein-based film (cheese) tensile strength; antioxidant and
antimicrobial activity [104]
peel extract
chitosan coating (rainbow
trout, pacific white shrimp,
improvement of functional
characteristics of coatings;
improvement of sensory
characteristics and shelf life of food
peel powder starch-based films better mechanical properties;
antimicrobial activity [109]
peel extract chitosan/locust gum
coating (oranges)
inhibition of Penicillium digitatum;
shelf-life of oranges [110]
peel extract surimi-based films superior mechanical properties;
improved thermal stability [111]
juice bitter vetch seed protein
antioxidant activity; improvement of
physicochemical properties [112]
Table 8. Recent studies on the effect of the addition of pomegranate derivatives to meat and fish
Derivative Product Effect References
peel powder meatballs antioxidant activity; lipid and protein
oxidation; microbial quality [113]
peel powder beef sausage quality criteria improvement; improvement
of cooking characteristics [114]
juice powder raw ground chicken heat resistance of E. coli [115]
peel extract pacific white shrimp lipid oxidation; melanosis; microbial
growth [116]
extract fish patties shelf-life [117]
extract pork sausage
controlling microbial growth and oxidation;
shelf-life [118]
Table 9. Recent studies on the effect of the addition of pomegranate derivatives to cereal and nut
Derivative Product Effect References
peel extract hazelnut paste shelf life; delay oxidation [119]
peel extract cookies shelf life; antioxidant activity;
panelist acceptance (odor, color) [120]
seed powder gluten-free bread specific volume and springiness;
antioxidant activity [121]
seed powder gluten-free cake antioxidant activity, protein and fiber;
peroxide value [122]
seed powder gluten-free sheeted pasts antioxidant activity; cooking and
textural parameters [123]
4.1. Dairy Products
Pomegranate juice, in the form of powder, may be used in yogurt production, mainly as a
replacer of sucrose content. The addition of pomegranate juice powder (5%) has been shown to lead
to a product with an increased total phenolic content, an increased antioxidant activity, and a higher
in vitro bio-accessibility. Furthermore, it has also been shown to positively affect the sensory
characteristics of the product, resulting in a more solid-like behavior mainly due to phenolic–protein
Foods 2020, 9, 122 12 of 22
interactions [98]. In a similar study with kefir-like products, the addition of fresh juice (5%) resulted
in products with an increased viscosity and acidity; however, the addition of honey was necessary in
order to improve the sweetness [97].
The addition of a pomegranate peel extract is another way to add the beneficial properties of
pomegranate to dairy products. This extract is mainly used to increase the antioxidant activity of the
products, as well as their storage shelf life [100,101]. In addition, it has been used in cheese production
and has resulted in improved lipid oxidative stability and storage quality [99]. However, the addition
of this extract may lead to negative alterations of the sensory characteristics of the products, mainly
due to its high astringency and bitterness [101]. In general, the pomegranate peel extract may be used
as a promising natural preservative in fermented dairy products, though it should be used in low
concentrations in order to avoid the adversarial effect on sensory attributes. The addition of honey
may reduce these effects and improve the acceptability of these products, as in the case of freeze-
dried yogurt [102].
Pomegranate seed powder, which is rich in conjugated linolenic acids, has also been
incorporated in dairy products like yogurt. Compared to a control, yogurt enriched with 0.5% (w/v)
pomegranate seed powder showed similar nutritional and pH values, higher antioxidant activities,
desirable fatty acid and conjugated linolenic acids contents, and lower atherogenicity indexes [103].
4.2. Films and Coatings
No wad ays , the re is an in crea se of inte res t fo r the development of novel food packaging materials
and, especially, edible packaging materials. Pomegranate components have been used in the
development of such products due to their increased phenolic content and antioxidant properties.
Several films and coatings have been developed by incorporating pomegranate peel extracts. A zein-
based film has been produced by incorporating pomegranate peel extracts at concentrations up to 75
mg/mL of film [104]. The addition of pomegranate peel extracts leads to the increased tensile strength,
elongation at break, total phenolic content and antioxidant activity of zein films, whereas film
solubility and water vapor transmission rate decrease and thickness remains constant. This film has
been shown to present inhibitory activity against several pathogenic bacteria and has been used for
the packaging of cheese, inhibiting the growth of spoilage microorganisms but not affecting lactic
acid bacteria. In addition, cheese, with zein-pomegranate packaging, has low protein and lipid
oxidation products during storage compared to cheese that is packaged with zein film without
pomegranate peel extracts.
Chitosan is a cationic polysaccharide that is obtained by the deacetylation of chitin, and, due to
its biodegradability, biocompatibility, antimicrobial activity and non-toxicity, is considered a very
promising and eco-friendly material for different purposes, including food coatings systems [105]. In
addition, pomegranate peel extracts have been proven capable of improving the functional
characteristics of chitosan-based materials by enhancing the desired properties for their potential
application as food coatings [105]. Chitosan-based coatings with incorporated pomegranate peel
extracts have been used in several products, such as rainbow trout [106], pacific white shrimp [107]
and strawberries [108]. In all studies, an improvement in sensory characteristics of the final product
has been reported in combination with an extension of shelf life. More specifically, in the case of
pacific white shrimps, an inhibition of melanosis has been reported, while a decrease of lipid and
protein oxidation has been reported in rainbow trout.
Pomegranate peel powder has also been used for the preparation of edible films based on starch
[109]. The powder has been used as an antimicrobial and reinforcing agent. The new film has
presented inhibitory actions against both Staphylococcus aureus and Salmonella. The addition of
pomegranate peel powder in a starch based matrix has also exhibited better mechanical properties
by enhancing the stiffness, modulus, tensile strength and drop impact strength of the matrix. Another
edible coating material based on chitosan or/and locust bean gum with an incorporated pomegranate
peel extract was developed to control the growth of Penicillium digitatum and to reduce the
postharvest decay of oranges [110]. The results showed that the addition of a pomegranate peel
extract reduced disease incidence by up to 49% on oranges that were artificially inoculated with P.
Foods 2020, 9, 122 13 of 22
digitatum. Pomegranate peel extracts have also been used to formulate surimi-based edible films with
superior mechanical and water barrier properties and improved thermal stability for food packaging
[111]. The antioxidant activity of bitter vetch seed protein edible films was increased with the addition
of pomegranate juice to the film, which formed a solution that resulted in a material with great
potential in the active packaging of food systems [112]. Apart from antioxidant activity, the presence
of pomegranate juice has also been shown to affect some physicochemical properties of films. More
specifically, the films have shown higher total soluble matter, elongation at break, and water vapor
permeability, as well as a lower tensile strength, in comparison with control films prepared in the
absence of pomegranate juice. In addition, film morphology has been shown to markedly change,
with the film surface becoming considerably smoother and with a high number of pores. The
interactions in the film forming solution between bitter vetch proteins and the phenolic compounds
that are contained in pomegranate juice may be responsible for the observed changes in film
4.3. Antimicrobial and Antifungal Agent in Fruits and Juices
The great antimicrobial activity of pomegranate has attracted the interest of researchers to use
the fruit as a natural antimicrobial agent or even a preservative in fruits and their juices. In vitro
studies of pomegranate peel extracts have revealed their strong antifungal activity against Botrytis
cinerea, Penicillium digitatum and Penicillium expansum [124]. Furthermore, when used in artificially
inoculated fruits, pomegranate has proven very effective in inhibiting P. digitatum and Penicillium
italicum in lemons, P. italicum in grapefruits, and P. expansum in apples. However, pomegranate
extracts have also been used in fruit juice due to their antimicrobial properties. For example, a
commercial pomegranate extract (POMELLA®, PE) has successfully been used against Alicyclobacillus
acidoterrestris cells and spores in apple juice [125].
4.4. Meat and Fish Products
Meat products are very susceptible to undesirable alterations during processing and storage,
which result in extensive flavor changes, color loss, and protein structure damage, all of which reduce
sensory parameters and consumer acceptability [126]. All these undesirable changes are mainly
caused by three different biochemical pathways—lipid oxidation, protein decomposition, and
microbial contamination—that are more pronounced in minced meats [127]. Therefore, pomegranate
has been evaluated as an additive in meat products in order to suppress the development of these
effects [128].
Lyophilized pomegranate peel nanoparticles, which have a high phenolic content and
antioxidant capacity, were evaluated as antioxidant and antimicrobial additives (up to 1.5%) in
meatballs during storage at 4 °C for up to 15 days. The results demonstrated that lyophilized
pomegranate peel nanoparticles were more effective in retarding lipid oxidation and improving the
microbial quality and cooking characteristics of meatballs compared to samples with 0.01% butylated
hydroxytoluene (BHT) and without any treatment [113]. Furthermore, these samples were more
sensorially acceptable. In a similar study, the use of pomegranate peel powder (up to 3%) was proven
to be effective as a natural preservative in producing high quality beef sausage samples during a
storage period of 12 days at 4 °C [114]. The addition of pomegranate peel powder caused a high
storage stability and reduced values of the thiobarbituric acid and total volatile nitrogen of prepared
beef sausage samples during refrigerated storage. The microbiological criteria of the prepared beef
sausage samples with pomegranate peel powder were also improved. In addition, improvements of
cooking characteristics, e.g., cooking loss, cooking yield, change in diameter, and change in length,
were also reported. A high-ellagic acid commercial pomegranate powder has also been used to
reduce the heat resistance of Escherichia coli O104:H4 in ground chicken [115]. Indeed, the time to
reach a 5.0 log reduction reached a minimum at a pomegranate powder concentration of 1%,
producing a 50% decrease in lethality time in comparison to that without added pomegranate
powder. This result, in combination with the reported inhibition of formation of carcinogenic
Foods 2020, 9, 122 14 of 22
aromatic amines by a pomegranate seed extract [129], implies that pomegranate formulations might
concurrently inhibit both pathogens and heterocyclic amines in processed meat and poultry products.
Pomegranate peel extracts could potentially be used as natural antioxidant and antibacterial
agents in fish products. For example, when shrimps were soaked in methanolic pomegranate peel
extracts for 15 min, melanosis, microbial growth, and lipid oxidation could be retarded for up to six
days of refrigerated storage [116]. The inhibitory activity followed a dose-dependent manner. In
another study, fish patties made with natural extracts, including pomegranate, showed a lower lipid
oxidation and, as a result, had an extended shelf life for 11 days of storage under retail display
conditions [117]. Furthermore, pomegranate presented a high inhibition against Listeria
4.5. Cereal and Nuts Products
Pomegranate peel extracts, either in crude or encapsulated form, were mixed with hazelnut
paste in order to extend the shelf life of the product through the inhibition of lipid oxidation [119].
An inhibition of lipid oxidation with a reduced formation of peroxides and a limited solubility of the
crude extract in the high lipid content matrix of hazelnut paste were reported. In a similar study,
pomegranate peel extracts, which were encapsulated by spray-drying when using orange juice
industry by-products as wall materials, were used to fortify cookies with an increased phenolic
content and oil oxidation stability [120]. The antioxidant activity of the enriched cookies remained at
high levels throughout the whole storage time, and they were preferred for their color and odor by
the panelists during sensory evaluation.
Pomegranate seed powder was incorporated in gluten-free bread in order to increase its total
phenolic content and antioxidant activity [121]. The results showed that pomegranate seed powder
increased the specific volume and springiness of gluten-free breads, whereas their hardness and
chewiness decreased significantly with increasing powder additions. In addition, decreases of
lightness and yellowness of crumb and crust color, as well as an increase of redness, were reported.
In general, the optimum gluten-free bread with the best physical characteristics and high antioxidant
properties was found with the use of 7.5% of pomegranate seed powder. Following that trend,
pomegranate seed powder has also been used for the production of gluten-free cake [122] and gluten-
free (GF) sheeted pasta [123]. Gluten-free cake (containing 25.75% pomegranate seed powder and
0.97% transglutaminase) showed higher total antioxidant activity, ash, fiber, protein and moisture
contents, as well as a lower peroxide value, volume index and porosity [122]. In the case of sheeted
pasta, an increase of the antioxidant activity reported, but the addition of pomegranate seed powder
affected cooking and textural parameters. In general, the lowest concentration of pomegranate seed
powder had the lowest effect, and, therefore, gluten-free pasta that was incorporated with up to 7.5%
of pomegranate seed powder resulted in a good acceptability [123].
5. Conclusions and Future Perspectives
In recent years, the food industry’s demand for antioxidants from natural sources has
continuously grown, especially now with the increased numbers of adverse toxicological reports on
many synthetic compounds. Therefore, pomegranate, which presents extremely high antioxidant and
antimicrobial properties, has a great potential for applications in food products. The application of
pomegranate and its extracts, mainly as antioxidants and antimicrobials, has been extensively studied
in different types of food products and has shown very promising results. In addition, many studies
have shown that these additives can positively affect the overall sensory quality, and hence the shelf
life, of food products.
Though pomegranate is a food and is therefore regarded as safe, this judgement is not applied
to its extracts, such as its peel and seed extracts, and further research is needed to determine their
safe limits [128]. Therefore, several studies have been carried out and must continue to be carried out
in order to ascertain the safe use of these edible natural compounds.
On the other hand, pomegranate juice and the wide variety of compounds derived from it have
been the focus of many in vitro and in vivo studies that have revealed their beneficial physiological
Foods 2020, 9, 122 15 of 22
activities, especially their antioxidative, antimicrobial and anti-inflammatory properties. These
studies have concluded that the regular consumption of pomegranate fruit, juice, or even its
compounds added in other food products acts beneficially for one’s health and may even protect
against or improve the course of several diseases like obesity, diabetes, cardiovascular diseases, and
even some cancer types.
Future studies should be focused on the identification of the mechanisms that are associated
with the previously mentioned activities of pomegranate and its products, its possible synergistic
effects with other compounds of foods, and, most importantly, its possible interactions with the gut
microflora of hosts. All these studies will provide all the necessary scientific evidence that is required
in order to fully understand the potential of pomegranate as a source of natural food preservatives
and a therapeutic agent.
Author Contributions: Conceptualization, P.K.; writing—original draft preparation, E.K. and P.K.; writing—
review and editing, P.K.; supervision, P.K.; project administration, P.K.; funding acquisition, P.K. All authors
have read and agreed to the published version of the manuscript.
Funding: We acknowledge support of this work by the project “Research Infrastructure on Food Bioprocessing
Development and Innovation Exploitation—Food Innovation RI” (MIS 5027222), which is implemented under
the Action “Reinforcement of the Research and Innovation Infrastructure”, funded by the Operational Program
“Competitiveness, Entrepreneurship and Innovation” (NSRF 2014–2020) and co-financed by Greece and the
European Union (European Regional Development Fund).
Conflicts of Interest: The authors declare no conflict of interest. The funders had no role in the design of the
study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to
publish the results.
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... The market demand for pomegranate fruit and its derived products, primarily in the form of juice, minimally processed fruits, jam, and dietary supplements, has increased greatly over the last decade. An important factor contributing to the expansion of its popularity, commercial production, and consumption habits has been the emergence of scientific evidence demonstrating the health-promoting benefits of this fruit (Kandylis and Kokkinomagoulos, 2020). ...
... Ellagic acid is the main molecule present in pomegranate peel exhibiting anticancer activity (Puneeth and Sharath, 2020), whereas the anthocyanins are known for their antioxidant, anti-inflammatory, and chemopreventative properties . Moreover, the magnitude of the antioxidant and antitumor activities of pomegranate peel extract is stronger than the sum of the individual activities of its constitutive bioactive molecules, indicating a possible synergistic effect resulting from the mixtures of phenolic compounds present in the pomegranate (Orgil et al., 2014;Kandylis and Kokkinomagoulos, 2020). ...
Pomegranates are rich in phenolic compounds and known for their antioxidant, anti-inflammatory, and anticancer properties. The highest concentration of these compounds is found in the peel (exocarp and mesocarp), which constitutes about 50% of the whole fresh fruit. These bioactive phytochemicals exhibit a broad spectrum of antimicrobial effects against both Gram-negative and Gram-positive bacteria, as well as fungi. In the present paper, the chemical composition and antimicrobial activity of the peel (exocarp and mesocarp) from seven Punica granatum varieties (Wonderful, Mollar de Elche, Primosole, Sassari 1, Sassari 2, Sassari 3, and Arbara Druci) grown in Sardinia (Italy) were evaluated. Polar phenols, flavonoids, condensed tannins, and anthocyanin contents were evaluated by extraction with water at 20 and 40 °C. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) was used to characterize each variety according to the chemical composition of the pomegranate peel extracts (PPEs). The antimicrobial and antibiofilm activities of each PPE were further tested in vitro against Staphyloccocus aureus, Listeria monocytogenes, Salmonella bongori, Escherichia coli, Lacticaseibacillus casei Shirota, and Limosilactobacillus reuteri. Gram-positive species were more sensitive than Gram-negative to the extracts tested. Antimicrobial activity was shown against S. aureus and L. monocytogenes strains, whereas less, even no activity was found against Sa. bongori and E. coli strains. The PPEs from Mollar de Elche, Primosole, and Sassari 3 showed the highest antimicrobial activities at concentrations that varied from 0.19 to 1.50 mg/mL, with biofilm activity being reduced by more than 70%. These activities were positively related to the punicalagin, flavonoid, and chlorogenic acid content of the extracts. Finally, regarding the pro-technological bacterial strains, La. casei Shirota and Li. reuteri 17938 showed very low, even no sensitivity to the used of the specific PPEs with high concentrations. This study proposes a formulation of pomegranate peel extract that valorizes agro-industrial waste in the context of sustainability and circular economy. Pomegranate extracts should be considered potential sources of natural, plant-derived antimicrobials, providing an alternative to artificial antimicrobial products.
... Functional foods are the subject of increased research interest in order to determine the diverse attributes of foods beyond basic nutrition, such as their effects on and biotransformation by constituents of the GIT [34,35]. Pomegranate is one such functional food consumed in various forms (fruit, juice or extract), which has documented health benefits and encompasses a host of beneficial compounds that are further metabolized into bioactive metabolites in the GIT [11,36]. While the benefits of POM have been postulated for centuries, the beneficial constituents have only recently been identified and studied using scientific methods, including clinical trials [11]. ...
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Despite rising interest in understanding intestinal bacterial survival in situ, relatively little attention has been devoted to deciphering the interaction between bacteria and functional food ingredients. Here, we examined the interplay between diverse beneficial Lactobacillaceae species and a pomegranate (POM) extract and determined the impact of this functional ingredient on bacterial growth, cell survival, transcription and target metabolite genesis. Three commercially available probiotic strains (Lactobacillus acidophilus NCFM, Lacticaseibacillus rhamnosus GG and Lactiplantibacillus plantarum Lp-115) were used in growth assays and flow cytometry analysis, indicating differential responses to the presence of POM extract across the three strains. The inclusion of POM extract in the growth medium had the greatest impact on L. acidophilus cell counts. LIVE/DEAD staining determined significantly fewer dead cells when L. acidophilus was grown with POM extract compared to the control with no POM (1.23% versus 7.23%). Whole-transcriptome analysis following exposure to POM extract showed markedly different global transcriptome responses, with 15.88% of the L. acidophilus transcriptome, 19.32% of the L. rhamnosus transcriptome and only 2.37% of the L. plantarum transcriptome differentially expressed. We also noted strain-dependent metabolite concentrations in the medium with POM extract compared to the control medium for punicalagin, ellagic acid and gallic acid. Overall, the results show that POM extract triggers species-specific responses by probiotic strains and substantiates the rising interest in using POM as a prebiotic compound.
... Although PP is richer in phenolic content than pomegranate juice [182], PJ also contains a variety of phenolic compounds (anthocyanins, tannins, and phenolic acids) and has antioxidant properties [183]. Pomegranate seed is another by-product that derives from the PJ production, which contains crude protein, crude lipids, dietary fiber, minerals, and phenolic compounds and shows antioxidant activity [184]. ...
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Pomegranate is a fruit bearing-plant that is well known for its medicinal properties. Pomegranate is a good source of phenolic acids, tannins, and flavonoids. Pomegranate juice and by-products have attracted the scientific interest due to their potential health benefits. Currently, the medical community has showed great interest in exploiting pomegranate potential as a protective agent against several human diseases including cancer. This is demonstrated by the fact that there are more than 800 reports in the literature reporting pomegranate’s anticancer properties. This review is an update on the research outcomes of pomegranate’s potential against different types of human diseases, emphasizing on cancer. In addition, perspectives of potential applications of pomegranate, as a natural additive aiming to improve the quality of animal products, are discussed.
... Its bark power possesses diuretic, prostaglandin enhancing and coronary risk factor modulating properties. Pomegranate, Punica granatum L. belongs to the Punicaceae family and is the smallest plant family that includes 1 genus and 2 species, including the following: Punica granatum (edible pomegranate) is indigenous to Iran and Mediterranean regions, and Punica protopunica (inedible) is endogenous to Socotra islands in Pacific Ocean (Kandylis et al., 2020). Pomegranate has extensively been used as a source of traditional medicine. ...
... Its fruit and juice are considered tasteful and healthy food. The pomegranate peel represents about 40-50% of the total fruit weight, and although it was previously considered waste, it contains numerous and diverse bioactive substances, as recently reported [289][290][291]. Therefore, its recycling not only overcomes the biowaste problems but also provides a source of valuable compounds, such as ellagitannins, flavonoids, and anthocyanins. ...
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Neurodegenerative diseases, characterized by progressive loss in selected areas of the nervous system, are becoming increasingly prevalent worldwide due to an aging population. Despite their diverse clinical manifestations, neurodegenerative diseases are multifactorial disorders with standard features and mechanisms such as abnormal protein aggregation, mitochondrial dysfunction, oxidative stress and inflammation. As there are no effective treatments to counteract neurodegenerative diseases, increasing interest has been directed to the potential neuroprotective activities of plant-derived compounds found abundantly in food and in agrifood by-products. Food waste has an extremely negative impact on the environment, and recycling is needed to promote their disposal and overcome this problem. Many studies have been carried out to develop green and effective strategies to extract bioactive compounds from food by-products, such as peel, leaves, seeds, bran, kernel, pomace, and oil cake, and to investigate their biological activity. In this review, we focused on the potential neuroprotective activity of agrifood wastes obtained by common products widely produced and consumed in Italy, such as grapes, coffee, tomatoes, olives, chestnuts, onions, apples, and pomegranates.
... In this context, some studies support the benefits of breads enriched with fiber and antioxidant substances from pomegranate peels for a healthy and nutritious diet (Sayed-Ahmed, 2014; Sulieman Abdel Moneim et al., 2016). Greek authors describe examples of possible applications of bioactive compounds from pomegranate fruit byproducts, including the peels, and for obtaining various types of food products with satisfactory results (dairy products, films and packaging coatings, meat and fish products, cereals and nuts (Kandylis and Evangelos, 2020). ...
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The wealth of epidemiological evidence in the scientific world underscores the possibility that a plant-based diet can reduce the prevalence of common diseases such as diabetes, cardiovascular disease, cancer, and stroke. The therapeutic effects of plant sources are partly explained by phenolic secondary metabolites or polyphenolic compounds. Therefore, polyphenolic compounds, which are widely distributed in plants, are of great interest for the development of effective specific drugs with antioxidant and anti-inflammatory effects. Moreover, polyphenol compounds have no harmful effects due to their natural biocompatibility and safety. Numerous studies have highlighted the potential of some industrial food wastes from plant material processing, including apple peels and mashed potatoes, grape skins, tomato and carrot peels, pomegranate peels and seeds, and many others. These byproducts are considered low-cost sources of natural biological compounds, including antioxidants, which have beneficial effects on human health. The polyphenol complex of pomegranate peel (Punica granatum L.), which makes up half of the pomegranate fruit, has more pronounced antioxidant and anti-inflammatory properties than other parts. And the most important active components of pomegranate peel, which are found only in this plant, are punicalagin, followed by ellagic acid and gallic acid. It is known that these polyphenolic compounds of pomegranate peel have the most pronounced therapeutic effect. Several studies have shown the protective effect of ellagic acid, punicalagin, against oxidative stress damage caused by free radicals. The potential of pomegranate peel as an antioxidant and therapeutic component in various biological systems is high, according to scientific sources. However, despite extensive research in recent years, a review of sources has shown that there is insufficient evidence to support the therapeutic effects of polyphenolic compounds from pomegranate peels. The role of pomegranate peel polyphenolic compounds, including flavonoids, as antioxidants in various biological systems also requires further research. Of particular importance are the mechanisms by which antioxidants influence the cellular response against oxidative stress. The purpose of this review was to report our current knowledge of plant polyphenolic compounds and their classification, and to evaluate the potential of phenolic compounds from pomegranate peels with significant antioxidant and therapeutic effects.
... It is this last therapeutic effect that interests us, since in traditional Mexican medicine it is widely used for this purpose [16]. Current science has tried to verify the mechanisms of action of these effects, finding sufficient evidence that different parts of the pomegranate have an antinociceptive (analgesic) effect in preclinical and clinical models [17]. Pomegranate peel and juice have been shown to have a good antinociceptive effect, which is attributed to the presence of polyphenols such as ellagitannins (and their metabolites), anthocyanins, free organic acids, terpenes, and alkaloids [18]. ...
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Pharmacological treatment of pain often causes undesirable effects, so it is necessary to look for natural, safe, and effective alternatives to alleviate painful behavior. In this context, it is known that different parts of pomegranate have been widely consumed and used as preventive and therapeutic agents since ancient times. For example, it has been shown to have an antinociceptive effect, however, there are many varieties. Each part has been found to display unique and attractive pharmacological activities. The content of the active phytochemicals in pomegranate depends on the cultivar, geographical region, the maturity, and the processing method. In this context, the effects of various pomegranate varieties and other parts of the pomegranate (e.g., peel and juice) on pain behavior have not been examined. The aim was to evaluate and compare the antinociceptive effect of ethanolic extracts (PEx) and lyophilized juices (Lj) of three varieties of pomegranate in the formalin test. In addition, computer-aided analysis was performed for determining biological effects and toxicity. Peels were extracted with ethanol and evaporated by rotary evaporation, and juices were filtered and lyophilized. Wistar rats (N = 48) were randomly distributed into 8 groups (n = 6) (Vehicle, Acetylsalicylic Acid, PEx1, PEx2, PEx3, Lj1, Lj2, and Lj3). The formalin test (2%) was carried out, which consists of administering formalin in paw and counting the paw flinches for 1 h, with prior administration of treatments. All samples have an antinociceptive effect (phase 1: 2.8–10%; phase 2: 23.2–45.2%). PEx2 and Lj2 had the greatest antinociceptive effect (57.8–58.9%), and bioactive compounds such as tannins and flavonoids showed promising pharmacodynamic properties that may be involved in the antinociceptive effect, and can be considered as a natural alternative for the treatment of nociceptive and inflammatory pain.
... Pomegranate (Punica granatum L.) is a deciduous fruit tree typically grown in subtropical and tropical regions of the world [1]. The growing awareness of the health benefits of the fruit and its numerous food derivatives has recently widened the global demand for this species [2,3]. Pomegranate is also appreciated in agriculture for its environmental adaptability, such as tolerance to drought and suboptimal edaphic conditions [1]. ...
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Pomegranate (Punica granatum, L.) is a fruit tree that is increasingly popular worldwide due to the health-related properties of the fruit juice. While several studies highlighted the rich phytochemical diversity, few efforts have been devoted to an integrative understanding of the level of diversity of this species. This study investigated the diversity of 40 pomegranate accessions in an Indian ex situ collection by using twenty-nine morphological traits, six biochemical parameters, and twenty-nine Simple Sequence Repeats (SSR) markers. Among the evaluated traits, fruit volume (23.34% CV), fruit weight (21.12% CV), and fruit color (*a) (22.69 % CV) largely contributed to the morphological classification. Based on Mahalanobis D2 distance and Tocher’s clustering, the 40 pomegranate accessions were grouped into eight clusters, partly consistent with their origin. Specifically, cultivars introduced from foreign countries were present in distinct clusters. The SSR marker analysis generated 66 alleles. The observed heterozygosity values ranged from 0.05 to 0.63, with a mean value of 0.30. Maximum molecular genetic dissimilarity was observed between ‘IC-318720′ and ‘Gul-e-Shah Red’ (0.30). The neighbor-joining dendrogram separated wild accessions from cultivated varieties. The combination of morphological, biochemical, and molecular characterization allowed for comprehensively characterizing the pomegranate diversity and provided information on the relationships between the different aspects of the diversity. This work also suggests that the origin of the accessions is an important factor of discrimination and that the level of admixture between local and foreign material is currently limited.
... The secondary metabolites present in the peel part like phenolic compounds include (gallic acid ellagic acid, and caffeic acid), flavonoids such as catechin, gallocatechin, and epicatechin, and hydrolyzable tannins like punicalagin [8] according to some in vitro and in vivo studies, these compounds possess various kinds of biological and health benefits such as antioxidants, anti-inflammatory, antimutagenic, anticarcinogenic, and antihypertensive benefits, not only that their presence includes various other treatments such as cardiovascular problems, diabetes, and obesity. [9] There are various herbal products available in the market but the quantification and identification of the concentration in a particular species are necessary for quality and purity purposes. As there is an increase in the demand for herbal/herbs, common people use them as self-medication to cure common disorders, the content variation in an active constituent of marketed herbal/Ayurvedic products represents a major challenge to controlling the quality of herbal medicines for quality control, safety, efficacy of herbal marketed products the qualitative and quantitative analysis are the useful techniques that are related to the marker compound/active constituent which is present in the plant. ...
Background: Punicalagin is the main phenolic compound present in pomegranate (Punica granatum), it possesses various kinds of activities which is very essential as a dietary supplement, herbal supplements, or nutraceuticals are widely available in the market and are used clinically for various therapeutic activities, in the recent years, especially in the pandemic period of COVID-19. Hence, it is necessary to standardize herbal medicines for quality control, quantitative analysis for purity, and routine analysis. The punicalagin shows potential antiviral activity against the SARS-COV-2 virus, the literature review reveals that punicalagin is the area of interest during the recent research studies, and the present work deals with the quantitative analysis of punicalagin from high-performance thin-layer chromatography (HPTLC) in marketed herbal preparation and the in-house preparation. Methods: The method development and quantitative analysis of punicalagin in pomegranate are developed using the solvent system chloroform: ethyl acetate: formic acid (4:3:3 v/v/v), and the method is successfully developed. Results: The punicalagin is quantified at 257 nm, acid (4:3:3). The content found in the various samples in PGGO is 3.207 mg, in PGBB is 1.257 mg, in PGNV is 1.743 mg, in PGWE is 807.6μg, in PGDF is 835.2 μg, and in in-house is 867.2 μg of punicalagin, from 1 g of each sample. Conclusion: The method was successfully developed, but there was no method developed for punicalagin in HPTLC, this is the novel approach we have done, and the method can be used for routine analysis.
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Pomegranate juice is a rich source of ellagitannins (ETs) believed to contribute to a wide range of pomegranate’s health benefits. While a lot of experimental studies have been devoted to Alzheimer disease and hypoxic-ischemic brain injury, our knowledge of pomegranate’s effects against Parkinson’s disease (PD) is very limited. It is suggested that its neuroprotective effects are mediated by ETs-derived metabolites—urolithins. In this study, we examined the capability of pomegranate juice for protection against PD in a rat model of parkinsonism induced by rotenone. To evaluate its efficiency, assessment of postural instability, visualization of neurodegeneration, determination of oxidative damage to lipids and α-synuclein level, as well as markers of antioxidant defense status, inflammation, and apoptosis, were performed in the midbrain. We also check the presence of plausible active pomegranate ETs-derived metabolite, urolithin A, in the plasma and brain. Our results indicated that pomegranate juice treatment provided neuroprotection as evidenced by the postural stability improvement, enhancement of neuronal survival, its protection against oxidative damage and α-synuclein aggregation, the increase in mitochondrial aldehyde dehydrogenase activity, and maintenance of antiapoptotic Bcl-xL protein at the control level. In addition, we have provided evidence for the distribution of urolithin A to the brain.
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Sausage made from pork meat, emmer wheat (Triticum dicoccum Schübler), almond (Prunus dulcis Mill.), and hazelnut (Corylus avellana L.) was integrated with a mix of Punica granatum and Citrus spp. extracts to evaluate the possible effects on the growth and oxidation of spoilage microorganisms. Two concentrations of the mix were added, respectively, during sausage-making, and the final products were compared with a control group, without the extract mix, during storage. The use of the mix, especially at 10 g/1000 g of the whole ingredients, delayed the pH drop and thiobarbituric acid-reactive substances (TBARs) value during storage. Total viable count, lactic acid bacteria and psychrotrophic microbial counts were also affected, as the extract mix lowered the maximum growth rate of the microbial population considered. The sensory analyses revealed an improvement in the shelf-life of 6 and 16 days, respectively, when 5‰ and 10‰ of the mix were used.
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Metastasis is the primary cause of mortality and morbidity among cancer patients and accounts for about 90% of cancer deaths. The most common types of treatment for cancer metastasis are chemotherapy and radiotherapy. However, such therapy has many serious side effects that could diminish the quality of life in patients. There is increased appreciation by the scientific community that natural compounds can be potential weapons in fighting against cancer. Interestingly, much evidence shows that pomegranate (Punica granatum) has great potential to inhibit tumor growth and metastasis. In this review, we discussed the molecular targets of pomegranate, specifically, those that are prerequisite for cancer metastasis. The search was performed in Google Scholar, Medline, Scopus, and PubMed using keywords such as metastasis, pomegranate, and signaling pathways. Some of the most important papers from the search results were included. Based on recent studies, some molecules, including those involved in cell-cell and cell-extracellular matrix adhesions, are affected by pomegranate. The other targets of pomegranate are modulators of cytoskeleton dynamics and regulators of cancer cell anoikis and chemotaxis. Furthermore, the antimetastatic effect of pomegranate may be attributed to molecular changes of the extracellular matrix. Pro-inflammatory and pro-angiogenic molecules are the other targets of pomegranate regarding cancer metastasis. A wide variety of molecules can be targeted by pomegranate to suppress tumor metastasis. A better understanding of the molecules regulated by pomegranate is needed to provide a rational basis for its clinical application.
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Background: Antioxidant nutrients such as the polyphenols in pomegranate juice may prevent neuronal damage from the free radicals produced during normal metabolism. Previous research in animals and a short-term clinical trial in middle-aged and older adults support the potential memory benefits of pomegranate juice; however, the long-term effects of pomegranate juice consumption on cognition have not been studied. Objective: In this study, we investigated the long-term effect of pomegranate juice on memory in nondemented middle-aged and older adults. Methods: We performed a 12-month, randomized, double-blind, placebo-controlled trial of pomegranate juice in middle-aged and older adults. Two hundred and sixty-one subjects (aged 50-75 y) were randomly assigned to consume pomegranate juice [8 oz (236.5 mL) per day] or a placebo drink (8 oz, matched constituents of pomegranate juice except for pomegranate polyphenols). Memory measures [Brief Visuospatial Memory Test-Revised (BVMT-R) and Buschke Selective Reminding Test (SRT)] were assessed at 6 and 12 mo and analyzed using a mixed-effects general linear model. Results: Twenty-eight subjects in the pomegranate juice group and 33 subjects in the placebo group dropped out before completing the study. Baseline variables in the 98 pomegranate juice and 102 placebo group subjects who completed the study did not differ significantly. Group by time interaction was statistically significant for BVMT-R Learning (F[2, 257]= 5.90, P = 0.003; between-group effect size [ES] = 0.45): the change within the pomegranate group was not significant (ES = 0.15), whereas the placebo group showed a significant decline (ES = -0.35). Changes in the other BVMT-R scores as well as the SRT measures were not significantly different between groups. Conclusions: Daily consumption of pomegranate juice may stabilize the ability to learn visual information over a 12-mo period. This trial was registered at as NCT02093130.
Pomegranate peel contains high levels of various phytochemicals. We evaluated the effects of pomegranate peel extract (PoPEx) consumption on plasma lipid profile, fatty acids (FA) level and blood pressure (BP) in patients with diabetes mellitus type 2 (DMT2). Thirty-seven subjects were recruited in this double blind, placebo controlled randomized trial. The study group (n = 19) received over 8 week’s capsules containing PoPEx twice a daily, while the placebo group received placebo. Treatment with PoPEx induced a significant lowering of both systolic and diastolic BP. The plasma levels of triglycerides, low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (LDL-C/HDL-C), and HbA1c were significantly decreased, while the level of HDL-C was significantly increased, compared with placebo intake. Moreover, the PoPEX treatment significantly improved the plasma lipids fatty acids content. It is concluded that consumption of PoPEx in DMT2 subject had favourable effects on some metabolic parameters, BP, lipid profile and plasma lipid FA composition.
Polyphenols are a broad class of plant secondary metabolites which carry out several biological functions for plant growth and protection and are of great interest as nutraceuticals for their antioxidant properties. However, due to their structural variability and complexity, the mass-spectrometric analysis of polyphenol content in plant matrices is still an issue. In this work, a novel approach for the identification of several classes of polyphenol derivatives based on ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry was developed. First, mass-spectrometric parameters were optimized in order to obtain a large set of diagnostic product ions for their high-confidence identification. The software Compound Discoverer 3.0 was then implemented with a comprehensive database of 45,567 polyphenol derivatives and with mass-spectrometric data for their building blocks, resulting in a specific tool for the semi-automatic identification of flavonoids, anthocyanins, ellagitannins, proanthocyanidins and phenolic acids. The method was then applied to the identification of polyphenols in industrial hemp (Cannabis sativa), a matrix whose use is recently spreading for pharmaceutical and nutraceutical purposes, resulting in the identification of 147 compounds belonging to the classes of flavonoids, proanthocyanidins and phenolic acids. The proposed method is applicable to the polyphenol profiling of any plant matrix and it is not dependent on data in the literature for their identification, allowing the discovery of compounds which have been never identified before.
The pomegranate fruit peel is a rich source of polyphenols including punicalins, punicalagins, and ellagic acids, but is considered an agricultural waste product. Pomegranate derived products have been reported to have a wide variety of health promoting benefits including antibacterial properties in vitro but there is limited evidence of their antibacterial properties in vivo. The purpose of this study was to test the in vivo antibacterial properties of a pomegranate peel extract (PPX) containing punicalin, punicalagin, and ellagic acid. C3H/He mice were orally pre-treated with water or PPX prior to infection with the mouse bacterial pathogen, Citrobacter rodentium (Cr) that mimics many aspects of human enteropathogenic Escherichia coli infections. Fecal excretion of Cr was monitored and mice were euthanized on day 12 post-infection to assess Cr colonization of the colon and spleen, histological changes, and gene expression. PPX-treatment reduced Cr infection induced weight loss and mortality that was observed in water-treated infected mice. However, Cr colonization of the colon and clearance was unaffected by PPX-treatment. Consistent with this, PPX treatment did not alter the potent Th1/Th17 pro-inflammatory response elicited by Cr infection. Significant colonization of the spleen was only seen in water-treated infected mice and was inversely correlated with the dose of PPX administered. PPX treatment decreased the extent of Cr-induced colon damage that correlated with decreased mortality and reduced colonization of the spleen. Thus, a pomegranate peel extract contains bioactive compounds that mitigate the deleterious effects of an in vivo infection with the model enteropathogenic bacteria, Cr.
Orange juice by-products are proposed as a "green" wall material for the encapsulation of pomegranate peel extract. Stability of crude and encapsulated peel extract was studied under accelerated storage conditions, in terms of phenolic content, antiradical activity, and color. The obtained extracts were used as biofunctional components in cookies, at a phenolics concentration of 5000 ppm. Their effects on phenolics content, antioxidant activity, color, and sensory attributes during baking and storage were examined. It was observed that a large amount of phenolic compounds was degraded during baking even if they were coated. However, encapsulation had a significant effect (p < 0.05) on the retention and the activities of phenolic compounds as compared to non encapsulated. Moreover, the results showed that the extracts could be incorporated in cookies without negatively affecting sensory quality.
Background: Pomegranate has antioxidant, cardioprotective, and anti-inflammatory properties. We designed a crossover study, aimed to determine if consumption of pomegranate juice (PJ) improves lipid profile and oxidative and inflammatory biomarkers of hemodialysis patients. Forty-one hemodialysis patients were randomly assigned to one of the two groups: PJ-treated group receiving 100 ml natural PJ immediately after their dialysis session three times a week and the control group receiving the usual care. After 8 weeks, a 4-week washout period was established and then the role of the groups was exchanged. Lipid profile, blood pressure, and oxidative and inflammatory biomarkers were measured before and after each sequence. Results: Based on the results of intention-to-treat analysis, triglycerides were decreased in PJ condition and increased in the controls. Conversely, high-density lipoprotein (HDL)-cholesterol was increased in PJ and decreased in the control group. Total and low-density lipoprotein (LDL)-cholesterol did not significantly change in either condition. Systolic and diastolic blood pressure significantly decreased in PJ condition. Total antioxidant capacity increased in PJ condition (P<0.001) and decreased in the controls (P<0.001). Conversely, malondialdehyde and interleukin-6 decreased in PJ (P<0.001) and increased in the control group (P≤0.001). The changes of these biomarkers were significantly different between the two conditions. Conclusion: Eight-week PJ consumption showed beneficial effects on blood pressure, serum triglycerides, HDL cholesterol, oxidative stress, and inflammation in hemodialysis patients. This article is protected by copyright. All rights reserved.
Biopolymer-based materials are potential candidates for food coatings application. In this study, pomegranate (Punica granatum L.) peel extract (PPE) at different concentrations was incorporated to chitosan/gelatin gels and the rheological, antioxidant and structural properties were evaluated. Due to its high phenolic content, PPE enhanced the antioxidant capacity of chitosan/gelatin mixtures. PPE addition extended linear viscoelastic range and enabled the samples to easily flow under the applied shear rate. Rheological properties indicated that both viscosity and activation energy of materials containing natural compounds are highly dependent on temperature. Scanning electron microscopy (SEM) images revealed the influence of PPE concentration in the scaffolds pores size. Findings of this study proved that PPE was capable to improve the functional characteristics of chitosan/gelatin-based materials enhancing the desired properties for their potential application as food coatings.