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Received: 12 Feb 2021. Received in revised form: 22 Aug 2021. Accepted: 09 Sep 2021. Published online: 27 Sep 2021.

From Volume 13, Issue 1, 2021, Notulae Scientia Biologicae journal uses article numbers in place of the traditional method of continuous pagination through the volume. The journal will continue to appear quarterly, as before, with four annual numbers.

Notulae Scientia Biologicae Volume 13, Issue 3, Article number 11085

DOI:10.15835/nsb13311085 ReRe

ReReviewviewviewview ArticleArticleArticle Article

Pomegranate, fruit of the Pomegranate, fruit of the Pomegranate, fruit of the

Pomegranate, fruit of the desert, a functional food, and a healthy diet desert, a functional food, and a healthy diet desert, a functional food, and a healthy diet desert, a functional food, and a healthy diet Mohamad H. SHAHRAJABIAN

1a

*, Wenli SUN

1b

, Qi CHENG

1,2

1Chinese Academy of Agricultural Sciences, Biotechnology Research Institute, Beijing 100081, China;

[email protected] (*corresponding author); [email protected]

2Hebei Agricultural University, College of Life Sciences, Baoding, Hebei, 071000, China; Global Alliance of HeBAU-CLS&HeQiS for BioAl-Manufacturing, Baoding, Hebei 071000, China; [email protected]

a,bThese authors equally contributed to this paper

Abstract Abstract Abstract Abstract

Traditional medicinal plants contain various ranges of chemical contents and they have become popular because of effectiveness, frequently inadequate provision of modern medicine, preferences and cultural beliefs.

Pomegranate belongs to the family of Punicaceae, and its various pharmacological activities are due to presence of wide range of bioactive compounds. The current searching was done by the keywords in main indexing systems including PubMed/MEDLINE, Scopus, and Institute for Scientific Web of Science as well as the search engine of Google Scholar. The keywords were traditional medicine, health benefits, pharmaceutical science, pomegranate, punicalin, punicalagin, and ellagitannins. Major polyphenols in peel and juice of pomegranate are flavonoids such as flavonols (catechin, epicatechin, gallocatechin), condensed tannins, phenolic acids such as gallic, ellagic and caffeic, hyrolysable tannins such as ellagitannins and gallotannins. The main organic acids in pomegranate juice are malic and citric, and in seed is fatty acids (punicic). The major alkaloids and lignans in peel are punigratane and isolariciresinol, respectively. Pomegranate fruit has been proven to act against various diseases like cancer, cardiovascular disorders, diabetes, AIDS, Alzheimers disease, male infertility, inflammation, coronary heart disease, and aging. The review summarizes the beneficial impacts of pomegranate which is recommended for consumption. Pomegranate is a high potential natural functional food due to its high pharmacological activities as an ancient efficacious natural drug.

Keywords:

Keywords:

Keywords:

Keywords:

ellagitannins; health benefits; pomegranate; punicalagin; traditional medicine

Introduction Introduction Introduction Introduction

Pomegranate occurrence and classification

Population rise, inadequate supply of drugs, prohibitive cost of treatments, side effects of several synthetic drugs and development of resistance to currently used drugs for infectious diseases have led to increased emphasis on the use of plant materials as a source of medicines (Shahrajabian

et al

., 2021; Sun

et al

., 2021a,b,c). Herbal medicines proved to be the major remedy in traditional system of medicine (Shahrajabian

et al

., 2020a,b,c,d,e). Pomegranate (

Punica granatum

L.) which is a perennial fruit tree from the Punicaceae native in Iran, has been considered a functional fruit in many countries especially Iran, India, Turkey and China (Sharma

et al

., 2011; Soloklui

et al

., 2012). Its name come from the Latin name of the fruit

Malum granatum

, which means granular apple; and the most important producers are Iran, India, Turkey, China, the USA and

AcademicPres Notulae Scientia Biologicae

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2

etc (El Barnossi

et al

., 2021). Pomegranate has been known for hundreds of years as a healing food (Mohapatra, 2014; Tanveer

et al

., 2015). It has shown positive health properties due to the presence of bioactive constituents such as polyphenols, tannins and anthocyanins (Pirzadeh

et al

., 2020). As a functional food and nutraceutical source, pomegranate fruit quality depends on climate and growing conditions (Mirzapour and Khoshgoftarmanesh, 2013; Rahimi

et al

., 2017); moreover, it is also considered as an ancient medicine (Yisimayili

et al

., 2019). On the basis of the Bible and the Koran, pomegranate has been a symbol of fertility (Mars, 2000; Ismail

et al

., 2014). In Iran, it is one of the most important Iranian horticultural products, which is usually cultivated in arid and semi-arid regions (Tatari

et al

., 2020). The pomegranate seeds are rich in crude protein, crude lipids, dietary fiber and minerals such as K, P, Mg and Ca (Dadashi

et al

., 2013). In Iran, Alak was the most promising cultivar due to highest fruit size, fruit weight, and juice and least skin percentage, Sour- Sweet, Rabab, and Black Skin cultivars showed the highest content of total anthocyanins, total phenolics, and ascorbic acid, and total soluble solid, which are suitable for fresh consumption and human health benefits (Asadi-Gharneh

et al

., 2017). The peal and arils of the fruits of Black Skin are being used in Persian traditional medicine (Asadi-Gharneh

et al

., 2017). The pomegranate has narrow and lance-shaped leaves which are glossy and leathery. The attractive scarlet, white or variegated flowers are over an inch across and have 5 to 8 crumpled petals and a red, fleshy, tubular calyx which persists on the fruit. The flowers may be solitary or grouped in twos and threes at the ends of the branches. The pomegranate is self-pollinated as well as cross-pollinated by insects.

Cross-pollination increases the fruit set and wind pollination is insignificant. The wide fruit is crowned at the base by the prominent calyx, the tough, leathery skin or rind is typically yellow overlaid with light or deep pink or rich red. Its classifications are on the basis of agronomical characteristics, especially color and shape (Ozkan, 2005; Orhan

et al

., 2014). The cracking of mature fruit is an important physiological disorder which causes great economic loss to pomegranate. The pomegranate seed is the whole grain and constitutes the edible part of the fruit (Melgarejo

et al

., 2020). The peel is the main by-product after juice processing (Mphahlele

et al

., 2019). It has been reported that higher fruit temperature, firmness, and peel thickness decreased bruise damage to the pomegranate fruit, and both storage time and increased radius of curvature increased the bruise volume and bruise area, respectively (Shafie

et al

., 2015). Chinese cultivars have some unusual features such as spur- type growth habit, double flowers and white flowers (Verma

et al

., 2010). Seedless fruits contain soft-seeded compared to old varieties (Stover and Mercure, 2007). The aim of this article is survey and introduce the most important health benefits of pomegranate with considering its chemical constituents.

Pomegranate nutritional composition and chemical constituents Pomegranate nutritional composition and chemical constituents Pomegranate nutritional composition and chemical constituents Pomegranate nutritional composition and chemical constituents

The most important known compounds of pomegranate are amino acids such as lysine, methionine, cysteine, isoleucine, leucine, phenylalanine, tyrosine, histidine, aspartic, glutamic, serine, glycine, arginie, alanine, and proline; minerals such as calcium (Ca), magnesium (Mg), potassium (K), sodium (Na), phosphorus (P), iron (Fe), zinc (Zn), manganse (Mn), copper (Cu), and selenium (Se); Vitamins such as thiamine (B1), riboflavin (B2),

L

-Ascorbic acid (C), α-Tochoferol (E), and retinol (A); Fats such as myristic, palmitic, srearic, arachidic, behenic, stearoleic, gadoleic, erucic, ecosapentaenoic, docosatetraenoic and etc (Hasnaoui

et al

., 2011; Ahmad

et al

., 2018; Ma

et al

., 2019). Pomegranate’s nutrient values for 100 g have been shown in Table 1. Nutrient content of pomegranate peel (per 100 g) is presented in Table 2.

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3 Table 1.

Table 1.

Table 1.

Table 1. Pomegranate’s nutrient values for 100 g (Ahmad et al., 2018)

Composition Content

Water 77.93g

Energy 83 kcal

Protein 1.67g

Total lipid (Fat) 1.17g

Ash 0.53g

Carbohydrates 18.70g

Fiber 4.0g

Sugars 13.67g

Calcium 10mg

Iron 0.3mg

Magnesium 12mg

Phosphorus 36mg

Potassium 236mg

Sodium 3mg

Ascorbic acid 10.2mg

Choline 7.6mg

Table 2.

Table 2.

Table 2.

Table 2. Nutrient content of pomegranate peel (per 100 g) (Ahmad et al., 2018)

Composition Content

Total solid 94.50

Moisture 5.40

Total sugars 17.70

Reducing sugars 4.34

Protein 4.90

Crude fiber 16.30

Fat content 1.26

Ash 3.40

Proximate composition of pomegranate seeds is percentage moisture (8.6%), total lipids (27.2%), crude protein (13.2%), crude fiber (35.3%), pectin (6%), total sugars (4.2%), and ash (2%); trace minerals present in pomegranate seeds are iron (1.3 ppm), sodium (6 ppm), magnesium (12.4 ppm), potassium (45.2 ppm), zinc (1 ppm), and copper (1.2 ppm) (Khan

et al

., 2017). Nutritional values of pomegranate seeds are shown in Table 3. Fatty acids found in pomegranate seeds are presented in Table 4. The name, peel color, aril color, taste and origin of 31 pomegranate cultivars in Iran are mentioned in Table 5.

Table 3.

Table 3.

Table 3.

Table 3. Nutritional values of pomegranate seeds (Khan et al., 2017)

Compounds Nutritional value

Energy 72 calories

Carbohydrates 16.3 grams

Protein 1.5 grams

Fat 1 gram

Fiber 3.5 grams

Sugar 11.9 grams

Vitamin K 14.3 micrograms (17.9% DV)

Vitamin C 8.9 milligrams (14.8% DV)

Foliate 33 micrograms (8.3% DV)

Potassium 205 milligrams (5.9% DV)

Vitamin B6 0.07 milligrams (3.5% DV)

Phosphorus 31 milligrams (3.1% DV)

Percent DV indicates daily values.

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4 Table 4.

Table 4.

Table 4.

Table 4. Fatty acids found in pomegranate seeds (Khan et al., 2017)

Fatty acids Values (%)

Caproic acid 2.16

Punicic acid 65.3

Capric acid 0.95

Lauric acid 6.62

Myristic acid 7.56

Myristoleic acid 0.41

Palmitic acid 4.8

Palmitoleic acid 0.47

Stearic acid 2.3

Linoleic acid 6.6

Oleic acid 5.13

Table 5.

Table 5.

Table 5.

Table 5. The name, peel color, aril color, taste and origin of 31 pomegranate cultivars in Iran (Nemati et al., 2012)

Cultivars Peel color Aril color Taste Origin

‘Shirine Dane Sefide

Ferdos’ Red Red Sweet Khorasgan

‘Torsheshahvare

Kashmar’ Red Red Sour Khorasgan

‘Shishe Kab’ Red Red Sweet-sour Khorasgan

‘Mazarie Bajestan’ Pink Yellow Sweet-sour Khorasgan

‘Dom Anbaroti’ White Yellow Sour Khorasgan

‘Shirin Dane

Ghermeze Ferdos’ Pink Red Sweet Khorasgan

‘Khazar Bajestani’ Red Red Sweet-sour Khorasgan

‘Leili Post Nazok’ Red Red Sweet-sour Khorasgan

‘Leili Post Koloft’ Pink Yellow Sweet-sour Khorasgan

‘Torshe Shahvare

Ferdos’ Red Red Sour Khorasgan

‘Bazmanie Post

Nazok’ Pink Pink Sweet-sour Sistan o Balochestan

‘Savehei Post Sefid’ White Pink Sweet-sour Sistan o Balochestan

‘Savehei Post

Ghermez’ Pink Yellow Sweet-sour Sistan o Balochestan

‘Malase Porbare

Saravan’ Pink Pink Sweet-sour Sistan o Balochestan

‘Malase Mamolie

Sarjo’ Red Red Sweet-sour Sistan o Balochestan

‘Shekanare Post

Koloft’ White Pink Sweet Mazandaran

‘Vahshie Janghalie

Ghaemshahr’ Red Yellow Sweet-sour Mazandaran

‘Mahalie Parande

Gorgan’ White Red Sour Mazandaran

‘Post SefideDezfol’ Red Red Sour Khozestan

‘Malase Dane Siyahe

Ramhormoz’ White Red Sweet-sour Khozestan

‘Malase Post Sorkh’ Red Red Sweet-sour Khozestan

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5

‘Shirine Post

Ghermez’ Red Red Sweet Azarbaejan

‘Shirine Post Sefid’ Pink Pink Sweet Azarbaejan

‘Malase Post Nazok’ White Yellow Sweet-sour Azarbaejan

‘Zagh Yazdi’ Red Red Sour Yazd

‘Zagh Yazdi’ Red Red Sweet-sour Yazd

‘Malase Yazdi’ Black Yellow Sweet Yazd

‘Gorje Shahvar’ Pink Pink Sweet Yazd

‘Agha Mohammadali’ Red Red Sweet Markazi

‘Alake Shirine Saveh’ Red Red Sweet Markazi

‘Malase Saveh’ Red Red Sweet-sour Markazi

Several bioactive compounds were extracted by the pomegranate peels which can be employed for the preparation of nutraceuticals (Turrini

et al

., 2019). Around 153 different phytochemicals have been found in pomegranate which have ability to fight against various diseases (Karimi

et al

., 2017). Its fruit peel contains phenolic compounds including ellagic acid, ellagitannins, lignins, catechin, rutin, punicalagin and epicatechin (Fischer

et al

., 2011; Glazer

et al

., 2012; Rosas-Burgos

et al

., 2017), and the peel consists of cellulose, ligning, pectin and proteins (Hasnaoui

et al

., 2014; Abid

et al

., 2017). Rowayshed

et al

. (2013) also reported catechins, phenol gallic acid, caffeic acid, ellagic acid, p-coumaric acid and resocenol compounds in pomegranate peels powder. Peels and membranes of pomegranate fruits can be recommended as a source of highly and lowly methyl-esterified pectic polysaccharides (Shakhmatov

et al

., 2019). The most abundant compounds in pomegranate in Mexico were hexanol, (Z)-3-hexen-1-ol, hexanal, 4-terpineol, α-terpineol, and 2-ethyl-1- hexanol, and in the peel, high concentration of color, phenols, flavonoids, and antioxidants were observed (Escarcega

et al

., 2020). Pomegranate exerts antiproliferative, anti-invasive and antimetastatic effects, induces apoptosis through modulation of Bcl-2 proteins, increases p21 and p27, and downregulates cyclin-cdk network (Faria and Calhau, 2011). Pomegranate seed oil is a rich source of rare conjugated fatty acids (punicic acid) (Paul

et al

., 2020). Ellagic acid (EA) is one of the most important biological molecules found in pomegranate which may induce vasorelaxation, oxygen free radical scavenging, hypolipidemic, anti-inflammatory and anti- carcinogenic activities (Usta

et al

., 2013). Pomegranates have the potential to cause toxicity to ruminants, because large amounts of toxic gallic acid can potentially be produced through rumen fermentation of punicalagin (Read

et al

., 2019). Concentrated pomegranate peel extract supplementation increases milk antioxidant capacity which have higher benefits in individuals with lower natural productivity capacity (Argov- Argaman

et al

., 2020). Pomegranate juice powder can replace some or all sucrose in fermentation matrix for the production of functional yogurt (Pan

et al

., 2019). There are 11 volatile organic compounds namely 1- hexanol, [Z]-3-hexen-1-ol, 1-octanol, α-terpineol, β-myrcene, limonene, [E]-α-bergamotene, β-caryophyllene, hexanal, [E]-2-hexenel, and guaiacol are common to pomegranate juices and seeds; hexalin, phenylacetaldehyde, 3-methyl butanal, and methyl-(1-methylethenyl) benzene are found just in seeds (Guler and Gul, 2017). Pomegranate juices has similar or higher sweetness than apple, orange and sour cherry juice (Topalovic

et al

., 2020). The fruit quality of pomegranate is a balance between taste attributes and nutraceutical compounds (Tozzi

et al

., 2020). It contains significant amounts of phenolic ingredients, and the antioxidant and anti-inflammatory impacts of pomegranate poly phenols have been confirmed previously (Yan

et al

., 2017;

Pontonio

et al

., 2019; Morvaridzadeh

et al

., 2020). Pomegranate peel polysaccharides (PPP) is a good source for dietary supplement application, which has good antioxidant activity

in vivo

(Wu

et al

., 2019). A positive correlation between antioxidant activity and total phenolic content was reported (Derakhshan

et al

., 2018).

The reason of the bright color of pomegranate flowers is a type of the flavonoids, which is anthocyanins (Zhang

et al

., 2011; Ben-Simhon

et al

., 2015). The pomegranate peel polysaccharides are composed of rhamnose, glucuronic acid, galacturonic acid, glucose and xylose in the molar percentage of 0.71%, 27.07%, 22.05%, 22.12%, and 28.05%, respectively (Wu

et al

., 2019). Habibnia

et al

. (2012) found that the predominant fatty acids in Iranian pomegranate was punicic acid, and beta-sitosterol and γ-tochopherol were the main sterol and

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6

tochopherol present in the extracted oil, respectively. The pomegranate peel, seed and whole fruit powder consists of moisture content, ash, protein, crude fiber, fat and minerals such as sodium, calcium, magnesium, potassium, phosphorus and iron (Sharma

et al

., 2018). Pomegranate seed oil (PSO) nanoemulsion is widely used as a promising delivery system for α-tocopherol (Sahafi

et al

., 2021). Pomegranate ellagitannins may inhibit α-flucosidase activity

in vitro

possibly affecting in

vivo

starch digestion (Bellesia

et al

., 2015). Its juice could be beneficial as a dietary supplement in patients receiving chemotherapy medications (Bakir

et al

., 2015).

The polyphenols are useful indicators to differentiate the geographical localities of pomegranate peel which can be used to predict their antioxidant activities (Kam

et al

., 2013). Pomegranate flower consist of triterpenoids, asiatic acid and ursolic acid; pomegranate juice consists of catechin, ascorbic acid, iron, glucose and amino acids;

pomegranate leaves consist of flavones, tannins, luteolin and glycosides; pomegranate seed oil consists of sterols, ellagic acid, 95% punicic acid and fatty acids; pomegranate root and bark consist of piperidine alkaloids, ellagitannins and punicalin; and pomegranate rind consists of flavonols, quercetin rutin and fatty acids (Huang

et al

., 2005; Lan

et al

., 2009). Principle constituents of pomegranate root and bark are ellagitannins, piperidine alkaloids, pyrrolidine alkaloid and pelletierine alkaloids (Neuhofer

et al

., 1993; Gil

et al

., 2000). The most important constituents of pomegranate leaves are carbohydrates, reducing sugars, sterols, saponins, flavanoids, tannins, piperidine alkaloids, flavones, glycoside and ellagitannins (Nawwar

et al

., 1994; Chaitra

et al

., 2012).

Lignins, sterols and terpenoids are the most important active phytochemicals in seed, bark and leaves (Lansky and Newman, 2007), alkaloids in bark and leaves, and fatty acids and triglycerides in seed oil (Lansky and Newman, 2007). Simple gallyol derivatives and organic acids have been reported in leaves and juice, respectively (Ender

et al

., 2002). Flavonols is one of the main phytochemicals in rind, fruit (Mirdehghan and Rahemi, 2007), and bark and leaves (Lansky and Newman, 2007; Jaiswal

et al

., 2010). Anthocyanins and anthocyanidins, catechin and procyanidins have been found in juice and rind (Jasiwal

et al

., 2010), estrogens in seeds and peel extracts (Kho

et al

., 2010), and essential oils in seeds (Abbasi

et al

., 2008). Name of different compounds along with their parts are shown in Table 6. Nozohour

et al

. (2018) reported that the main phytochemicals identified in the ethanolic extracts of the pomegranate peel and seed are furfural, heptacosane, 5-hydroxymethylfurfural, ellagic acid, ellagic acid, 3,3/-di-O-methyl, ellagic aci, 3,3/,4/-tri-Omethyl, punicalagin, pyrogallol, gallic acid, catechin, epicatechin, gallocatechin, gallocatechin-(4,8)-catechin, ascorbic acid, linoleic acid, stigmasterol, and gamma-sitosterol (Tanaka

et al

., 1986; Schubert

et al

., 1999; Amakura

et al

., 2000; Hornung

et al

., 2002; Wang

et al

., 2004; Nozohour

et al

., 2018).

Table 6.

Table 6.

Table 6.

Table 6. Name of different compounds along with their parts (Ahmad et al., 2018)

Pomegranate part Chemical compounds

Peels Gallic acid, Ellagic acid, Punicalin, Punicalagin, Caffeic acid, Ellagitannins, Pelletierine, alkaloids, Luteolin, Kaempferol, Quercetin

Seeds 3,3,-Di-O-methylellagic acid, 3,3,,4,-Tri-O-methylellagic acid, Punicic acid, Pleic acid, Palmitic acid, Stearic acid, Linoleic acid, Sterols, Tocopherols, Sex steroids Juice Simple sugars, Aliphatic organic acids, Gallic acid, Ellagic acid, Quinic acid,

Flavonols, Amino acids, Minerals, EGCG, Ascorbic acid Leaves Carbohydrates, Reducing sugars, Sterols, Saponins, Flavanoids, Tannins,

Piperidine alkaloids, Flavone, Glycoside, Ellagitannins Root and Bark Ellagitannins, Piperidine alkaloids, Pyrrolidine alkaloid,

Pelletierine alkaloids

Flower Gallic acids, Ursolic acid, Triterpenoids,

Fatty acids

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7

Potential Pharmaceutical and Health Benefits of Pomegranate in Traditional Medicine and Potential Pharmaceutical and Health Benefits of Pomegranate in Traditional Medicine and Potential Pharmaceutical and Health Benefits of Pomegranate in Traditional Medicine and Potential Pharmaceutical and Health Benefits of Pomegranate in Traditional Medicine and Modern Medicine Industry

Modern Medicine Industry Modern Medicine Industry Modern Medicine Industry

In traditional medicine, it may helpful for treating diseases such as ordinary diarrhea, dysentery, and stomach disorders (Lansky

et al

., 2000), and tannin content of pomegranate seed is usually used to treat women vaginal discharge and wound healing (Amin, 1991). The effect of pomegranate on different types of cancer such as bladder cancer (Lee

et al

., 2013), breast cancer (Adams

et al

., 2010; Sturgeon and Ronnenberg, 2010), colon cancer (Kohno

et al

., 2004; Waly

et al

., 2014), leukemia (Joseph

et al

., 2012), liver cancer (El-Ashmawy

et al

., 2016; Song

et al

., 2016), lung cancer (Khan

et al

., 2007), prostate cancer (Lucci

et al

., 2015; Deng

et al

., 2017), skin cancer (Afaq

et al

., 2010; George

et al

., 2011) have been reported. It has reported that pomegranate juice has the highest antioxidant activity among all various food types (Guo

et al

., 2003). Pomegranate juice powder (PJP) rich in phenolic compounds was used as some or all sucrose in the fermentation matrix for the preparation of set yogurts (Pan

et al

., 2019). It has been reported in many researches that polyphenols present in pomegranate imparts significant anti-inflammatory and anti-oxidant properties for prevention of various diseases (Guo

et al

., 2003; Lee

et al

., 2010). Sharma

et al

. (2017) reported that pomegranate has stronger anti- oxidant activity compared to β-carotene, ascorbic acid and vitamin E than green tea, and also can affect pathways involved in cancer development like cellular transformation and angiogenesis (Khan

et al

., 2008).

The dietary supplementation with 200 and 300 mg/kg pomegranate peel extract (PPE) may increase the antioxidant potential and quality indices of broilers breast meat, and the antioxidant potential of PPE was equal to that of α-Toc in refrigerated meat (Saleh

et al

., 2017). The potentiated virucidal activity of pomegranate rind extract (PRE) by co-administered zinc (II) has potential as a multi-action novel topical therapeutics against

Herpes simplex

virus (HSV) infections, like as cold sores (Houston

et al

., 2017). The usage of pomegranate extracts orally at the dose of 1500 mg/kg showed the potential of increasing sexual behavior in rats (Katana

et al

., 2019). The pomegranate peel is a promising feedstock for second generation ethanol production (Demiray

et al

., 2018). On the basis of one study, 2 g/kg supplementation of pomegranate peel powder meal may improve the water binding capacity of broiler breast meat because of reduced cooking loss of the meat (Akuru

et al

., 2020). Pomegranate peel and seed methanolic extracts have notable total flavonoid and phenolic contents and also antioxidant activity, which can protect the liver against histo-pathological and some enzymatic changes induced by the Methotrexate (MTX) in rats (Doostan

et al

., 2019). Pomegranate peel extract was capable to boost the functional characteristics of chitosan/gelatin-based materials enhancing the desired properties for their potential application as food coatings (Bertolo

et al

., 2020). Pomegranate molasses has anti-inflammatory (Lee

et al

., 2010), antidiabetic properties (Xu

et al

., 2009), and important role to reduce the risk of cardiovascular diseases (El Darra

et al

., 2017). Ridzwan

et al

. (2020) reported the potency of pomegranate extract as a non-opioid substitution therapy for both

in-vitro

and

in-vivo

studies;

in-vitro

studies showed using of pomegranate extract treatment may be effective in decreasing the μ-opioid receptor (MORs) and cyclic adenosine monophosphate (cAMP) protein levels in U-87 cells at a concentration of 0.125 mg/mL.

Pomegranate peel extract consumption in diabetes mellitus type 2 subject may have favourable impacts on some metabolic parameters, blood pressure, lipid profile and plasma lipid fatty acids composition (Grabez

et al

., 2020). Pomegranate peel extract can be used as alternative therapy for blastocystosis and for improving novel anti-Blastocystis drugs (Abdel-Hafeez

et al

., 2016). Pomegranate juice shows microbicidal properties for both oral hygiene and chemo-preventive in immune deficiency and cardiovascular diseases (Faria and Calhau, 2011), with tremendous anti-atherogenic and anti-anti-atherosclerotic characteristics for decreasing high blood pressure and density lipoprotein oxidation (Turk

et al

., 2008).

Rashidi

et al

. (2013) reported that concentrated pomegranate juice consumption was not effective on blood glucose and lipid profiles concentrations in type 2 diabetic patients. Pomegranate seed oil demonstrated and important therapeutic effect in the treatment of ovarian ischemia and reperfusion injury (Yayla

et al

., 2018). Pomegranate juice can be recommended as a suitable transport medium for avulsed teeth, and 1% of its juice was as effective as Hank’s balanced salt (HBS) for maintaining PDL cell viability (Tavassoli-Hojjati

et al

.,

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8

2014). Pomegranate seed extract exhibited therapeutic potential for avoidance memories, because it is a potent phytoestrogenic and antioxidant which may have compensating effects for peripheral estrogen deficit (Sarkaki

et al

., 2015). Black pomegranate peel extract could effectively suppress angiogenesis potentially through a vascular endothelial growth factor (VEGF) dependent mechanism (Dana

et al

., 2015). Natural pomegranate juice is also a potent inflammatory, and anti-thrombocytopenia treatment among elderly population (Achraf

et al

., 2018). Saleh

et al

. (2018) reported that the antioxidant potential of pomegranate pomace extract supplementation was equal to that of α-tocopherol acetate in refrigerated meat. Martinez

et al

. (2019) concluded that natural extracts from pomegranate, rosemary, and hydroxytyrosol delayed the lipid oxidation, and addition of it to fish products contributed to extend the shelf life to fish. The whole fruit extract of pomegranate has cardioprotective effect against Dox-induced cardiotoxicity in rats (HassanpourFard

et al

., 2011). Pomegranate peel extract was found to have strong anti-inflamatory activity by the reduction in the levels of Interlukin-6 (IL-6) and tumor Necrosis Factor-α (TNF-alfa), and rich in phenolic and flavonoids which may enhance its reducing activity and free radical scavenging ability (Qabaha

et al

., 2019).

Pomegranate juice has the potential as a nutraceutical to improve health span and lifespan in human beings (Balasubramani

et al

., 2014). The pomegranate vinegar may prevent a high-fat diet (HFD)-induced obesity and obesity-related cardiac complications because of anti-inflammatory and anti-adiposity properties of vinegar (Bounihi

et al

., 2017). Under accelerated oxidation conditions, pomegranate peel metahanolic extract have the potential capability to improve the shelf life of edible oils in comparison with the most powerful synthetic antioxidant [tert-butyl hydroquinone (TBHQ)-200 ppm)] (El-Hadary and Taha, 2020).

The pomegranate peel extract can be used in the treatment of oral candidiasis with no negative effects following administration in the rats (Bassiri-Jshromi

et al

., 2018). Pomegranate seed oil (PSO) clearly attenuate hexachlorobutadiene (HCBD)-induced nephrotoxicity (Bouroshaki

et al

., 2010). A decrease in hematotoxic and genotoxic effects induced by pomegranate peel is due to its powerful antioxidant capacity (Elwej

et al

., 2016). The fruits of some pomegranate genotypes could be used to obtain extracts very rich in punicalagins and that these substances could be used as an alternative to synthetic products to control plant disease and improve the quality of the plant products, avoiding the impact of synthetic chemicals on the environment (Rongai

et al

., 2019). The pomegranate peel extract showed anti-herpes simplex virus-1 (HSV) activity, probably by inhibiting the adsorption stage with SI value of 7.7 (Moradi

et al

., 2015). Pomegranate peel pectin can act as an effective emulsifier, and can be used as a novel polysaccharide emulsifier in the food industry (Yang

et al

., 2018).

The antimetastatic effect of pomegranate may be attributed to molecular changes of the extracellular matrix (Ahmadiankia, 2019). The most notable pharmaceutical benefits of pomegranate have been shown in Table 7.

Table 7.

Table 7.

Table 7.

Table 7. Pharmaceutical benefits of pomegranate

Health benefits Mechanisms and impacts Reference

Acute Pancreatitis

The higher doses of three fractions (250 and 500 mg/kg for pomegranate freeze-dried power and pomegranate seeds extract and doses of 100, 200 μL/kg for pomegranate seed oil fraction) significantly reduced amylase and lipase activity in serum, pancreatic pancreatic myeloperoxidase activity, edema, leukocyte infiltration and vacuolization in comparison to

the control group.

Minaiyan et al. (2014)

Alzheimer

Pomegranate extract is more efficacious as a protectant than a therapeutic measure in reducing histopathological hallmarks in

Alzheimer’s disease.

Almuhayawi et al. (2020)

Anti-depressant effects

The aqueous extract of pomegranate (AE-PG) administered by intraperitoneal route induced anti-depressant like effects, and the mechanism

of action involved the activation of the Estrogen receptor β (ERβ) and the

Valdes-Sustaita et al. (2021)

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9

serotonergic system.

Anti-diabetes effects

a. Pomegranate seed oil (PSO) has a protective effect against diabetes complications in rats, and also significantly reversed streptozotocin (STZ)-induced depletion in thiol content and

histological abnormality.

Mollazadeh et al. (2016)

b. No significant impacts of pomegranate supplementation on metabolic parameters in patients with type 2 diabetes mellitus (T2DM)

was found.

Jandari et al. (2020)

c. Pomegranate juice consumption as an antioxidant may have a contribution in changing fasting blood sugar, lipid profiles,

lipoprotein oxidation and human serum paraoxonase (PON1) activity.

Parsaeyan et al. (2012)

d. Consumption of 2000 mg pomegranate seed oil (PSO) per day for 8 weeks had no impact on fasting blood sugar (FBS), insulin resistance

and lipid profile in diabetic patients.

Faghihimani et al. (2016)

Anti-diarrheal activity

a. Its extract showed a concentration- dependent inhibition of the spontaneous

movement of the isolated rat ileum and attenuated acetylcholine-induced contractions.

Qnais et al. (2007) b. Its extract also caused a dose-dependent

decrease of gastrointestinal transit and significantly protected rats against castor oi-

induced diarrhea enteropooling.

Qnais et al. (20070

Anti-cancer activity

a. Pomegranate extracts inhibit the growth of breast, prostate, colon and lung cancer cells in

culture.

Polyphenols from pomegranate has been used for prevention of prostate cancer.

Adhami and Mukhtar (2006) Adhami et al. (2009) Nallanthighal et al. (2016) Boggula and Peddapalli (2017) b. The extracts derived from pomegranates had

significant concentration-dependent antiproliferative and pro-apoptotic effects against MCF-7 (ER+) and MD-MBA-231 or MD-MBA-435 (ER-) breast cancer cell lines.

Mehta and Lansky (2004)

c. Pomegranate extract suppresses the melanocyte and melanin synthesis through

inhibiting tyrosinase activity which is important in treatment of skin cancer.

Yoshimura et al. (2005)

d. The photo chemo preventive effects of pomegranate against UVA and UVB irradiations in normal human epidermal keratinocytes (NHEK) as a test system has

been proved.

Syed et al. (2006)

e. Pomegranate fruit extracts (PFE) dose- dependently inhibited NF-κB-dependent

reporter gene expression associated with proliferation invasion, and motility in aggressive breast cancer phenotypes while

decreasing RhoC and RhoA protein expression.

Khan et al. (2009)

f. Pomegranate juice gains lots of attractions due to its remedial and preventative roles against prostate cancer because of its ability in inhibiting cell growth and inducing apoptosis.

Koyama et al. (2010) g. Pomegranate extract decreased the

expressions of genes of the enzyme involved in the synthesizing androgen and at the same

time downregulate the hypoxia-inducible factor 1-α (HIF-1α) to constrain angiogenesis

in prostate cancer.

Sartippour et al. (2008)

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10

h. The inhibitory effects of pomegranate juice on progression of prostate cancer as well as its role on increasing adhesion and decreasing migration of the live cells has been confirmed.

Wang et al. (2012)

i. Pomegranate extract suppresses cancer stem cells characteristics in part due to inhibition of

epithelial-to-mesenchymal which can be exploited in the prevention of breast cancer.

Nallanthighal et al. (2017)

j. Ellagic acid induced a greater effect than luteolin, suggesting that ellagic acid might be a

promising candidate for further preclinical testing for treatment of human ovarian cancer.

Liu et al. (2017) k. Black peel pomegranate is a worthy bio-

agent in silver nanoparticle biosynthesis and treatment of cancer.

Khorrami et al. (2019) l. The MTT assay showed 94.53% inhibition

on the oral cancer cell lines and clonogenic assay showed decrease in the colonies after

treating with the peel extract.

Jesse Joel et al. (2019)

m. Pomegranate juice possesses a promising inhibitory effect on bladder cancer (BC) development, probably due to its anti-oxidant

and anti-inflammatory properties. It can correct the expression of pro-inflammatory cytokines (interleukin 6 and hypoxia-inducible

factor 1), it also press angiogenesis by down- regulation of hypoxia-inducible factor and supports apoptosis through reduction of the

tumor suppressor gene p53.

Mortada et al. (2020)

n. Dwarf pomegranate extracts showed potent growth inhibitory activities in human prostate cancer cells (DU145), which appear to be mediated by a pro-apoptotic mechanism.

Amri et al. (2020) o. Nano-pomegranates have great potential in

anti-breast cancer treatment, because MCF-7 cells have shown remarkable efficiencies of

enhancing cellular uptake, inhibition and necrosis and apoptosis at in vivo rat

experiments.

Wang et al. (2020)

p. The pomegranate fruit fleshy pericarp acts as a natural agent to synthesize silver nanoparticles (AgNPs) which can be

considered as an anticancer agent.

Govindappa et al. (2021)

q. Pomegranate extract and tangeretin may be effective in preventing breast cancer

development.

Gul et al. (2021)

Anti-inflammatory and analgesic effect

a. The methanol extract Amrouz (MoEA) and methanol extract Sefri (MoES) have both analgesic and anti-inflammatory properties.

Ouachrif et al. (2012) b. Pomegranate juice may have an anti-

inflammatory effect in patients with type 2 diabetes (T2D), because it may reduce interlukin-6 and hs-CRP concentrations in

plasma.

Sohrab et al. (2014)

c. The phosphorylation of ERK1/2, p38, JNK and translocation of the NF-B p65 subunit into nuclei were inhibited by the pomegranate

flower ethanol (PFE) treatment, and PFE produced potential anti-inflammatory effect.

Xu et al. (2017)

d. Pomegranate peel extracts is a promising food supplement for dairy cattle, especially around calving, when the animals are more subject to oxidative stress and inflammatory

diseases.

Pomegranate supplementation significantly

Taheri Rouhi et al. (2017) Mastrogiovanni et al. (2020) Morvaridzadeh et al. (2020)

Wang et al. (2020)

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11

reduced hs-CRP, IL-6, and TNF-α.

Anti-inflammatory effects of pomegranate poly phenols have been confirmed.

e. Pomegranate (200 mg/kg) attenuate pain and inflammation by down-regulating the activation of TNF-R1, TNF-α, lL-1β, lL-6, NF-κB, oxidative stress markers and tissue

histology.

Karwasra et al. (2019)

f. Oral pretreatment with its dried extract produced statistically significant and dose dependent inhibition of edema induced when

compared to the control groups.

Bagri et al. (2010) g. Standardized pomegranate rind extract and

the equivalent ellagic acid (EA) dose- dependently reduced the croton oil-induced

mouse ear edema.

Mo et al. (2013)

Antioxidant activity

a. All parts of pomegranate had antioxidant activity with high total phenolic, flavonoid and

flavonol contents.

Fazeli et al. (2011) Surek and Nilufer-Erdil (2014)

Elwej et al. (2016) Lantzouraki et al. (2016) Derakhshan et al. (2018) Drinic et al. (2020) b. Pomegranate leaf, peel and seed exhibited

very strong antioxidant activity.

Kotamballi et al. (2002) Singh et al. (2002) c. Pomegranate peel polysaccharides has good

antioxidant activity in vivo, and it is a good natural source for dietary supplement

application.

The pomegranate juice contains potent antioxidant nutrients capable of reducing the

cytotoxicity of hypercholesterolemia and atorvastatin which enhance the structure and

function of the cerebellar cortex.

The pomegranate peel as a by-product has the potential to develop bio-functional edible films intended for packaging food products.

Wu et al. (2019) El-Sayyad et al. (2020) Moghadam et al. (2020)

d. The antioxidant capacity of pomegranate peel extract is 10 times higher than the pulp

extract.

Shams Ardekani et al. (2011) e. Pomegranate peel because of its high

antioxidant activity can be added to yoghurt for the development of freeze-dried yoghurt with functional ingredients on an industrial

scale.

Kennas et al. (2020)

Anti-microbial activity

a. Fresh pomegranate juice has antimicrobial activity, which might be attributed to its high polyphenol content and antioxidant capacity.

Sadeghian et al. (2011) Betanzos-Cabrera et al. (2015) b. The isolated compounds are economically

viable of safe antimicrobial agents that possess an inhibitory action to pathogenic H. pylori.

Pomegranate by-products have powerful antioxidant and antimicrobial activities.

Gould et al. (2009) Khalid et al. (2018) Andrade et al. (2019)

Nazeam et al. (2020) c. According to X-ray diffraction, pomegranate

peel retained its semi-crystalline structure in the film, which can shown its importance as an edible film and food grade packaging material.

Ali et al. (2019)

Anti-bacterial activity

a. The hydro-alcoholic extract (HAE) from pomegranate presents antibacterial activity against selected microorganisms, and maybe a possible alternative for the treatment of dental

plaque bacteria.

Pomegranate peel extracts enhances immunity

Menezes et al. (2006) Jagdale et al. (2019) Shahid et al. (2019) Monir et al. (2020)

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12

and increased the protection against pathogenic bacteria.

b. The total phenolic and flavonoid content of pomegranate has positively associated with the antibacterial activities of the fractions with

chloroform extract exhibiting lowest antibacterial activity against Escherichiacoli (MIC 25 mg/ml), and the methanol fraction exhibiting the highest antibacterial effect against Staphylococcusaureus (MIC 0.19

mg/ml).

Mahboubi et al. (2015)

c. The pomegranate peel extracts showed antibacterial activities against Pseudomonasaeruginosa and

Staphylococcusaureus.

Nozohour et al. (2018)

d. Because of its antibacterial effects, pomegranate peel is a potential source of

natural preservatives for the control of Cronobactersakazakii in food.

Yemis et al. (2019)

Anti-aging activity

Pomegranate anthocyanins could be used as a safe, stable, homogeneous, nonirritant and effective topical anti-aging drug formulation

for aged people.

Abdellatif et al. (2020)

Anti-apoptotic activity

The methanolic extract of pomegranate peel has beneficial influences and could be able to inhibit Al-induced oxidative stress and histopathological alterations in liver and

kidney of female rats.

Abdel Moneim et al. (2013)

Anti-bacterial effects

a. All pomegranate extracts contain high levels of phenolics and exhibited antibacterial

activity against Bacillus subtilis, Staphylococcus aureus, Escherichiacoli and

Salmonella typhimurium.

Nuamsetti et al. (2012)

b. Pomegranate peel extract contains bioactive compounds which mitigate the deleterious impacts of an in vivo infection with the model

enteropathogenic bacteria Citrobacter rodentium (Cr).

Smith et al. (2020)

Anti-angiogenic effects

Pomegranate peel extract (PPE) showed anti- angiogenic effects and it could be mediated in part through peroxisome proliferator-activated

receptors (PPARs) dependent pathway.

Dana et al. (2016)

Anti-hepatotoxic effects

The hepatoprotective potential of the acetone extract of Punica granatum fruits on tissue

defense systems during isoniazid- and rifampicin induced hepatotoxicity in rats was

found.

Yogeeta et al. (2007)

Nausea and vomiting

Pomegranate seems to be more effective than vitamin B6 in the treatment of Nausea and

vomiting pregnancy (NVP).

Abdolhosseini et al. (2017)

Natural preservative and anti-atherogenic supplementation

a. Polyphenolic fraction of pomegranate juice can act as antiatherogenic supplementation and natural preservative for meat and fatty foods through direct inhibition of LDL

oxidation.

Faisi et al. (2018)

b. The pomegranate peel phenolics may improve stored meat products quality, such as

instrumental color retaining, limitation of

Derakhshan et al. (2018) He et al. (2019) Smaoui et al. (2019)

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13

microflora growth, retardation of lipid and protein oxidation.

Nephroprotective effects

a. The prophylactic consumption of pomegranate juice for 14 days could show nephroprotective effects by reducing oxidative

stress and potassium depletion.

Alimoradian et al. (2017)

b. Pomegranate juice may lead to the stabilization of kidney function despite using

captopril and gentamicin.

Alimoradian et al. (2017)

Skin health

a. The pomegranate extract and its phenolics may ameliorate the adverse effects against H2O2-induced oxidative stress and cytotoxicity

in keratinocytes supports their utilization as natural cosmeceuticals for skin health.

Liu et al. (2019)

b. Pomegranate peel extract can prolong the shelf-life of bighead carp fillets for about 2 days, and it can be considered as a promising

preservative in aquatic products.

Zhuang et al. (2019) c. Pomegranate extract showed effectual at

protecting human skin fibroblasts from cell death following UV exposure.

Pacheco-Palencia et al. (2008) d. Pretreatment of epiderm with pomegranate-

derived products resulted in inhibiting of UVB-induced; collagenase gelatinase,

stromelysin, marilysin, elastase and tropoelastin.

Afaq et al. (2009)

Anti-liperoxidant activity

Owing to the high anti-liperoxidant property of pomegranate, acetone extract may have

possible application in the food industry.

Zhang et al. (2007)

Anti-obesity effects

a. A significant decrease in feed consumption and body weight of female rats after exposure them to a diet containing 20% of pomegranate

extract (6%) for 37 days.

Cerda et al. (2003)

b. The pomegranate lead extract in a mouse model of high-fat diet-induced obesity, and the

effects appear to be partly mediated by inhibiting pancreatic lipase activity and

suppressing energy intake.

Lei et al. (2007)

Anti-viral effects

The crude pomegranate peel extract and its n- butanol and ethyl acetate fractions had the highest inhibitory effect against influenza A

virus with IC50 value of 6.45, 6.07 and 5.6 μg/ml in Madin-Darby Canine Kidney

(MDCK) cells, respectively.

Moradi et al. (2019)

Anti-ulcer effects

The pomegranate peel extract, especially sour summer has curative potential as an antiulcer, possibly via its high antioxidant activity.

Moghaddam et al. (2013)

Oral health management

a. Pomegranate juice is efficacious against

dental plaque microorganisms. Kote et al. (2011) b. Hydroalcoholic extract was effectual against

dental plaque microorganisms. Menezes et al. (2006)

Sexual behavior

a. Administration of the pomegranate extract orally at the dose of 1500 mg/kg produced significant augment of sexual activity in male

rats.

Lydia et al. (2019)

b. Pomegranate juice consumption led to an

increase in epididymal sperm concentration, Turk et al. (2008)

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14

sperm motility, spermatogenic cell density, and the diameter of seminiferous tubules and germinal cell layer thickness; it also decreased

the abnormal sperm rate when compared to the control group.

c. Ellagic acid has a protective effect against testicular and spermatozoa toxicity induced by

cyclosporine A.

Turk et al. (2010)

Vertigo

Pomegranate concentrated juice as a stomach tonic led to the improvement of the digestive

symptoms and vertigo.

Monfared et al. (2019)

Wound healing

a. The extract of the top layer of the peel significantly improved the wound healing process, but the pulp showed no promising

impacts.

GhasemiPirbalouti et al. (2010) Elzayat et al. (2018) Sheikh Asadi et al. (2018) b. The ethanol extract of pomegranate exocarp

has the higher amounts of tannins and flavonoids, compounds that are known to be

beneficial for wound healing.

Ghaleh Mohammadi and Mirghazanfari (2019)

c. 10% standardized pomegranate extract accelerates the healing of deep second-degree

burn wound, and pomegranate standardized with 40% ellagic acid is a promising for the

healing of burn wound skin.

Lukiswanto et al. (2019)

The most important biological effects of methanol extract of pomegranate fruits are antiestrogenic in breast, no induction of proliferation in endometrial, ovarian, and cervical cancer cells, suppressed TNFα- mediated endothelial cell apoptosis, estrogen inducible gene expression was not altered, reduced LDL cholesterol levels cardioprotective effect, no DNA adduct formation or oxidative DNA damage and has osteoprotective effects (Sreekumar

et al

., 2014). Fruit peel administration showed a noteworthy amelioration of abnormalities related Cd-nephrotoxicity (El-Habibi, 2013), and flower extract has protective role and ameliorate nephrotoxicity induced by gentamicin (El-Daly, 2016). The methanolic extract of peels was a potent inhibitor for

Listeria monocytogenes

,

S. aureus

,

Escherichia coli

, and

Yersinia enterocolitica

(Al-Zoreky, 2009;

Devatkal

et al

., 2013). Extracts from fruit skin showed good antibacterial activity against

S. aureus

and

P.

aeruginosa

(Sadeghian

et al

., 2011); and tannin from the pericarp is a very effective constituent against genital herpes virus (HSV-2) (Zhang

et al

., 1995). Acidity of pomegranate juice and concentrated liquid extract (POMxl) solutions contributed to rapid anti-influenza activity (Sundararajan

et al

., 2010), and treated mice with pomegranate peel significantly showed reduction in parasitemia as compared to untreated control (Mubaraki

et al

., 2016). Water extracts from arils has shown antibacterial effects against

Bacillus megaterium

,

P. aeruginosa

,

S. aureus

,

Corynebacterium xerosis

,

E. coli

,

Enterococcus faecalis

and

Micrococcusluteus

(Duman

et al

., 2009), and the aqueous and methanol extracts from whole fruit showed antibacterial effects on

S. typh

,

Salmonella typhimurium

, and

Salmonella paratyphi

(Pasha

et al

., 2009). Nascimento

et al

. (2000) showed antibacterial effects of ethanol extracts of the whole fruit on

P. aeruginosa

, and

B. subtilis

; and Salgado

et al

. (2009) indicated the antibacterial effects of raw extract of pomegranate whole fruit on

P. aeruginosa

,

E.

coli

,

Enteroccoccus faecalis

,

Enterobacter aerogenes

,

S. aureus

and

Microccocus luteus

. The most important health benefits of pomegranate are shown in Figure 1.

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15 Figure 1.

Figure 1.

Figure 1.

Figure 1. The most important health benefits of pomegranate

Conclusions Conclusions Conclusions Conclusions

Pomegranate is native to Persia and Mediterranean zone which has been widely used in many countries and cultures, especially in west and center of Asia. Nutrient content of pomegranate peel is total solid, moisture, total sugars, reducing sugars, protein, crude fiber, fat content and ash. Fatty acids found in pomegranate seeds are caproic acid, punicic acid, capric acid, lauric acid, myristic acid, myristoleic acid, palmitic acid, palmitoleic acid, stearic acid, linoleic acid and oleic acid. Chemical compounds in pomegranate peels are gallic acid, ellagic acid, punicalin, punicalagin, caffeic acid, ellagitannins, pelletierine, alkaloids, luteolin, kaempferol and quercetin. Chemical constituents in pomegranate seeds are 3,3,-Di-

O

-methylellagic acid, 3,3,,4,-Tri-

O

- methylellagic acid, punicic acid, pleic acid, palmitic acid, stearic acid, linoleic acid, sterols, tocopherols and sex steroids. Chemical compounds in pomegranate juice are simple sugars, aliphatic organic acids, gallic acid, ellagic acid, quinic acid, flavonols, amino acids, minerals, EGCG, and ascorbic acid. Pomegranate leave contains carbohydrates, reducing sugars, sterols, saponins, flavanoids, tannins, piperidine alkaloids, flavone, glycoside, and ellagitannins. The main chemical compounds in root and bark are ellagitannins, piperidine alkaloids, pyrrolidine alkaloid, and pelletierine alkaloids. Flower chemical constituents are gallic acids, ursolic acid, triterpenoids, and fatty acids. The most important potential benefits of pomegranate are antioxidant, cancer prevention, Alzheimer ,s disease protection, reduce inflammation in the gut and improve digestion, a powerful anti-inflammatory fruit, positive contributes to osteoarthritis and cartilage damage, heart-healthy juice, may lower systolic blood pressure, antiviral effects, improve learning and memory, a good source for potential fertility aid, a traditional remedy for diabetes, rich in different vitamins such as vitamin C, E, K., and a good source of folate and potassium.

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16 Authors’ Contributions

Authors’ Contributions Authors’ Contributions Authors’ Contributions

All authors contributed equally to literature research, writing manuscript, etc.

All authors read and approved the final manuscript.

Acknowledgements Acknowledgements Acknowledgements Acknowledgements

This work was supported by the National Key R&D Program of China (Research grant 2019YFA0904700). This research was also funded by the Natural Science Foundation of Beijing, China (Grant No. M21026).

Conflict of Interests Conflict of Interests Conflict of Interests Conflict of Interests

The authors declare that there are no conflicts of interest related to this article.

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