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Recent Patents on Inflammation & Allergy Drug Discovery 2018, 12, 24-38
REVIEW ARTICLE
ISSN: 1872-213X
eISSN: 2212-2710

Inflammation
& Allergy
The Promising Pharmacological Effects and Therapeutic/Medicinal Appli- Drug Discovery

cations of Punica Granatum L. (Pomegranate) as a Functional Food in

Humans and Animals

4
Muhammad Saeed1, Muhammad Naveed2, Jannat Bibi3, Asghar A. Kamboh , Muhammad A. Arain5,
Recent Patents of Inflammation & Allergy Drug Discovery

Qurban A. Shah5, Mahmoud Alagawany6, Mohamed E. A. El-Hack6, Mervat A. Abdel-Latif7, Mohd. I. Yatoo8,
Ruchi Tiwari9, Sandip Chakraborty10 and Kuldeep Dhama11,*
1
Department of Animal Nutrition, College of Animal Sciences and Technology, Northwest A&F University, Yangling,
71200, P.R. China; 2Department of Clinical Pharmacy, School of Basic Medicine, and Clinical Pharmacy, China Pharma-
ceutical University, Nanjing, Jiangsu Province, 211198, China; 3Department of Physical Education, Shaanxi Normal Uni-
versity, China; 4Department of Veterinary Microbiology Faculty of Animal Husbandry and Veterinary Science Sindh Agri-
culture University, 70060 Tandojam, Pakistan; 5Faculty of Veterinary and Animal Sciences, Lasbela University of Agricul-
ture, Water and Marine Sciences, Uthal, Balochistan 3800, Pakistan; 6Poultry Department, Faculty of Agriculture, Zagazig
University, Zagazig 44511, Egypt; 7Department of Nutrition and Clinical Nutrition, Faculty of Veterinary Medicine, Da-
manhour University, Damanhour 22516, Egypt; 8Division of Veterinary Clinical Services Complex, Faculty of Veterinary
Sciences and Animal Husbandry, Shuhama, Srinagar-190006, Jammu and Kashmir, India; 9Department of Veterinary Mi-
crobiology and Immunology, College of Veterinary Sciences, UP Pt. Deen Dayal Upadhayay Pashu Chikitsa Vigyan Vish-
wavidyalay Evum Go-Anusandhan Sansthan (DUVASU), Mathura, India - 281001, India; 10Department of Veterinary Mi-
crobiology, College of Veterinary Sciences and Animal Husbandry, R.K. Nagar, West Tripura, India; 11Division of Pathol-
ogy, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, 243 122, Uttar Pradesh, India
Abstract: Background: Punica granatum L. (pomegranate), is a shrub mostly available in the Mediterranean
Sea region. The fruits have gained the substantial attention among researchers due to their promising
biological activities including anti-inflammatory, antibacterial, antidiarrheal, immune modulatory, antitumor,
wound healing and antifungal that have been attributed to various constituents of seeds, bark, juice, pericarp,
and leaf of this tree across the globe. The phenolic compounds of pomegranate have been documented to
possess numbers of prophylactic and therapeutic utilities against various pathological infections as well as
non-infectious disorders.
Objective: The current review expedites the pharmacological role of Punica granatum L. in curing elements
related to infectious and non-infectious disorders.
Methods: The current review is based on literature and patents already available on various scientific data-
bases highlighting the role of Punica granatum along with its therapeutic potentials against infectious and
non-infectious disorders. The databases included under study were PubMed, Med line, PubMed Central, Sci-
ARTICLE HISTORY
ence Direct and few other scientific databases. The information obtained through these diverse databases is
Received: November 21, 2017 compiled, critically interpreted and presented in the current study.
Revised: February 11, 2018
Accepted: February 15, 2018
Results: Multi-dimensional beneficial application of pomegranate plant is recorded. The pomegranate seed oil
has phytoestrogenic compounds and the fruit is rich in phenolic compounds with strong antioxidant activity. The
DOI: fruit and bark of pomegranate are used against intestinal parasites, dysentery, and diarrhea in different animals
10.2174/1872213X12666180221154713 and human models. Since the ancient time the juice and seeds had considered the best therapy for throat and
heart disorders. Ellagic acid is one of the main components of pomegranate with potent antioxidant activity.
Results from different studies reported that Punica granatum L or its byproducts can be used as natural food
additives in human and animal nutrition in order to boost immunity, microbial safety and provide the housing
environment without affecting body weight gain. In addition, Punica granatum L. byproducts can modulate
immune function and gut microbiota of broiler chickens as well as reduce the odorous gas emissions from ex-
creta. Naturally occurring polyphenols in a pomegranate can be a potential alternative medicine for the preven-
tion of avian Colibacillosis diseases and can also be used as an intestine astringent to relieve diarrhea and enteri-
tis in chickens.
Conclusion: The present review gives the insight towards major components of pomegranate as well as their
pharmacological activities against pathological disorders. In spite of many beneficial properties of Punica
granatum L., more research evidence on a molecular basis is needed to find out the molecular mechanism of
action in various animals and human models to validate the usefulness of Punica granatum L. as a potent
therapeutic agent.
Keywords: Animal, human, medicinal aspects, nutritional value, performance, pharmacological effects, Punica granatum L.
*Address correspondence to this author at the Division of Pathology, ICAR- 1. INTRODUCTION
Indian Veterinary Research Institute (IVRI), Izatnagar, Bareilly-243 122,
Uttar Pradesh, India; Tel: +91 9837654996; Fax: 0581-2302188; The European Union has initially restricted and later on
E-mail: kdhama@rediffmail.com banned non-essential use of antibiotics from 2006 to be used

2212-2710/18 $100.00+.00 © 2018 Bentham Science Publishers

Pomegranate as a Functional Food and its Therapeutic Perspectives
as antibiotic growth promoters in food animal production to
reduce the pooling of resistant genes because of the gradual
increase in the development of resistant strains toward certain
antibiotics, residual toxicity in food chain, adverse reactions
and side effects [1-4]. A minimal residual limit of some anti-
biotics has been established. Non-judicial use of synthetic
antibiotics in human illnesses has been severely criticized.
Therefore, human health practitioners and animal nutritionist
are seeking out to alternate products that can improve the
health, reduce the disease burden and also modulate the gut
health in both animals and human population [1, 2, 5-7]. Vari-
ous experimentations had been done using various medicinal
plants/botanicals, herbs and their products (extracts and pow-
ders) as alternative feed supplements, functional foods, nu-
traceuticals, immunomodulators, antimicrobials and health
protective agents in different animal species including live-
stock, poultry and pets, as well as safeguarding health of hu-
mans, which have shown the positive and promising effects
[8-20].
Phytobiotics are secondary plant metabolites such as fla-
vonoids, steroids, alkaloids, terpenes, tannins, phenolics, and
essential oils present in plants as normal constituents or as a
result of pathogen attack [21]. These have been used in a
number of human and animal model studies and surprising
results have been achieved in all aspects of health, wellbeing,
and performance [22-28]. In the current century, phytobiotics
has gained more interest as potential alternatives to antimicro-
bials showing also their antioxidant, immunomodulatory and
therapeutic effects of various diseases and disorders [29-37].
Additionally, studies are also reported that the phytobiotics
enhance growth performance, feed utilization (feed conversion
efficiency) as well as an immune response while reducing
intestinal harmful bacteria and fecal noxious gas emissions
[34, 38-43]. Recent reports have also shown plant and herb
metabolites/extracts to be effective against important and
emerging viral pathogens such as Zika virus and other viruses
[35, 44, 45]. Nutraceuticals from fruits and vegetables have
been shown to possess several health benefits [6, 46].
Pomegranate is a fruit of the Punicaceae family, used for
a variety of purposes e.g. fresh juice in-house but also in
food industries as an additive to the manufacturing of dyes,
cosmetics [47, 48]. Several products are nowadays made of
this fruit to enhance human health. In addition, its by-
products as peels, rinds, and seeds, which may cause envi-
ronmental pollution, are used in animal nutrition [49, 50].
Punica granatum L. peels (account for half of its weight)
contain several phytobiotics such as hydrolyzable tannins
(ellagitannin, punicalagin, punicalin and pedunculagin), fla-
vonoids, anthocyanins and other phenols [50-53]. In addi-
tion, hot water extract of pomegranate peels is rich in pheno-
lic compounds [54]. In vitro studies reported that Punica
granatum L. peel and seed extracts have antimicrobial activ-
ity as they are rich in phenolic compounds [55, 56]. Addi-
tionally, oral administration of Punica granatum L. rind
powder suspension can enhance humoral and cellular immu-
nity in laboratory animals [57]. The plant extract had anti-
oxidant, anti-inflammatory, cardioprotective, anti-neoplastic,
cancer preventive, and neuroprotective effects [13, 58-60].
Extracts of P. granatum peels were effective to combat dif-
ferent types of bacteria and may be used to control bacterial
infections due to its polyphenol content [61, 62]. The poly-
Recent Patents on Inflammation & Allergy Drug Discovery 2018, Vol. 12, No. 1 25
phenols found in P. granatum have an effective
anti-
inflammatory,
antioxidant,
and
anti-carcinogenic activity
[50, 63] and promote wound healing [64, 65]. Also, the seed
oil of pomegranate which contains a high concentration of
punicic acid had immunomodulatory activity in mice [66,
67]. Moreover, P. granatum peel extract has been reported
for improving biochemical and histological parameters in
mice challenged with Staphylococcus aureus [68]. Despite
Punica granatum L. has beneficial activities further research
regarding its use in livestock nutrition as well as a human
dietary supplement is needed. Studies have demonstrated
that there is the difference in the concentration of final avail-
ability of bioactive constituent phenolic compounds present
in fresh natural and commercially available market juice of
pomegranate and such adulteration need to be reduced. With
the help of High-Performance Liquid Chromatography
(HPLC) from pomegranate pericarp, aqueous extract (WE)
with water and alcoholic extract with alcohol (AE) were pre-
pared to contain ellagitannins punicalagin A and punicalagin
B as a chief ingredient while punicalin as a small constituent.
The study suggested that before marketing the pomegranate
fruit juice these important polyphenols should be standard-
ized to make them available in optimum percentage to pro-
vide desired health effects as claimed by manufacturers [69].
Literature documented that pomegranate and its components
such as seeds, leaves, bark, fruit, and juice have various
pharmacological and therapeutic properties [70].
After reviewing the systematic literature from PubMed,
Google Scholar, Science Direct, and other resources, it was
revealed that different parts of pomegranate like seeds, bark
juice, pericarp, and leaf have gained the interest and high-
lighted the invaluable results in different animal species and
human disease models. Despite the amazing beneficial effects
of pomegranate, there is currently lack of research regarding
its potential use in human nutrition and poultry feed. So the
objective of this reappraisal gives new insight to human re-
searchers, veterinary advisor, and animal nutritionist to con-
duct more research on this fruit and its byproducts to evaluate
its beneficial effects and recommended as a safe natural die-
tary additive for humans as well as a feed additive in poultry
feed to replace the synthetic antibiotics.
2. PHYTOCHEMICALS IN PUNICA GRANATUM L.
Chemical studies on pomegranate suggested that it con-
tains different phytochemicals. The juice is rich in anthocyan-
ins, gallic acid, ellagic acid, caffeic acid, quercetin, catechins,
and rutin; the seed oil is rich in fatty acids, punicic acid, el-
lagic acid, and sterols; the pericarp (peel, rind) is rich in cate-
chin, fatty acids, punicalagins, rutin, quercetin, flavones, gallic
acid, flavonones, flavonols, and anthocyanidins; leaves are
rich in tannins (punicalin and punicafolin), and flavone gly-
cosides like apigenin and luteolin. Ursolic acid, gallic acid,
triterpenoids like Asiatic acid and maslinic are found in flower
while ellagitannins (punicalin and punicalagin) and numerous
piperidine alkaloids are formed in roots and bark [58]. Exam-
ples of the phytochemical structures are illustrated in Fig. (1).
3. HABITAT AND TRADITIONAL USES OF POME-
GRANATE FRUIT
Pomegranate and all its parts are considered to be an ef-
fective medicinal plant in Egypt, Greece, and China. Punica
26 Recent Patents on Inflammation & Allergy Drug Discovery 2018, Vol. 12, No. 1 Saeed et al.

O
O

HO
HO OH

HO

Punicic acid CH3 Gallic acid

OH OH
O
OH
HO O

HO O
HO OH

OH
O OH
OH O
O
OH Ellagic acid
Quercetin
HO

HO O
OH
O
O
HO O
O O
O O
OH
O
HO
O O
HO OH

HO OH
OH
OH OH
Gallotannin

Fig. (1). The important phytochemicals content in pomegranate.

granatum L. is mainly grown in arid and semi-arid regions of Table 1. Chemical Analysis and Secondary Metabolites Con-
India, Iran, Mediterranean countries including Turkey, centration of Punica granatum L.
Egypt, Tunisia, Spain, Morocco, etc. [71, 72]. Pomegranate
trees may attain a height of 30 feet, with narrow, oblong,
Item Concentration
opposite leaves which are 3-7
2cm (length and width) in
dimension, bearing pink, bright red or orange flowers con- Chemical analysis, %
taining four to five petals. A thick layer comprising of
rounded hexagonal edible fruit with a diameter of 5-12cm, Crude protein 60.8
which weighs 200g approximately, covers seeds. They are Moisture 90.41
widely used for the treatment of parasitic and fungal infec-
tions, dysentery, diarrhea as well as stomatitis. Also, the hull Ether extract 20.63
and root extracts are suggested to be useful for treating infer-
Crude ash 20.82
tility and gynecological problems. Moreover, it is effective
in snakebite, diabetes, burns and leprosy treatment [58]. Ad- Calcium 10.5
ditionally, the ancient Chinese civilization pays special atten-
tion to pomegranate and it is found in the traditional folk’s Sodium 0.67
medicine that its red juice known as a soul concentrate, is Magnesium 0.79
homologous to human blood and act as an anti-aging factor
[58]. The beneficial activities of pomegranate and its by- pH 3.56
products on different organs are presented in Fig. (2). Analy- Iron (ppm) 0.06
ses of chemical constituents of pomegranate are shown in
Table 1. [73] Total polyphenols (mg/g) 145.91

Hydrolysable tannins (mg/g) 14.26

4. BIOLOGICAL PROPERTIES AND THERAPEUTIC
APPLICATIONS Total flavonoids (mg/g) 57.59

Since very early pomegranate has been popular to be
used as functional food and source of neutraceuticals being
enriched in antioxidant, anticarcinogenic, anti-obesity, anti-
tumor, and anti-inflammatory medicinal properties. Its seeds,
fruits, juice and peel all possess therapeutic health-promoting
constituents in the form of various bioactive compounds
Source: Ahmed et al. [73].
such as ellagic acid, ellagitannins, punicalagins, punicic acid,
flavonoids, anthocyanidins, anthocyanins, estrogenic fla-
vonols, other fatty acids and flavones suitable for remedial
applications [58]. When used along with other drugs or
Pomegranate as a Functional Food and its Therapeutic Perspectives
Pomegranate
Fatty acid accumulation
Cardiac fibrosis Heart
Atherogenesis
Fatty liver
Insulin sensitivity Liver
Lipid peroxidation
Diabetic nephropathy
Kidney
Oxidative stress
Inflammation
GIT
a-Glucosidases
Fig. (2). Beneficial activities of pomegranate and its byproducts on different organs [58].
health supporting compounds in combination synergistic
effects have been reported. However, more research should
be done to assess the final metabolic outcome and the
bioavailability of bio-active constituents to the cells within
the body. Pomegranate intake has proved its potential in cor-
recting disorders of cancer, insulin resistance within the
body, high blood pressure, high cholesterol level, oxidative
stress, hyperglycemia, chronic inflammatory diseases includ-
ing intestinal inflammation, obesity, cardiovascular disor-
ders, etc. [74, 75]. Several studies reported the antimicrobial,
antioxidant, anti-inflammatory, anticancer as well as immune
stimulant activities of pomegranate. These are summarized
in Table 2. [76-93]
For pomegranate, just like many other medicinal plants
and fruits, their biological effects, therapeutic/medicinal ap-
plications, dietary and beneficial health usages, various use-
ful products, and methods of utilization have been patented
by several researchers as presented in Table 3 [40, 94-126].
Specifically, the use of pomegranate as anti-inflammatory
agent [94, 95, 101, 105, 112-114, 116, 117]; anti-allergic
agent [95, 98, 104, 108, 111, 115, 121]; analgesic [99]; anti-
resorptive and bone building dietary action [40, 100, 101];
anti-dermatological disorders [106, 107]; anti-angiogenic
[110, 119]; treating rhinitis and sinusitis [99] have been pat-
ented. Novel anti-wrinkle and anti-aging nano-formulations
and method of preparation using novel nano co-delivery sys-
tem were patented by Orza [103]. They can be used effec-
tively for treating and preventing inflammation of mucosal
Recent Patents on Inflammation & Allergy Drug Discovery 2018, Vol. 12, No. 1 27
Cataractogenesis
Eyes
AGE formation
Aldol reductase
Neuron
Oxidative stress
Blood Blood glucose
Insulin, HDL
TG, cholesterol , LDL
Blood vessel
Atherogenesis
Preserve b-cells
Pancreas Regenerate b-cells
Insulin secretion
Adipose tissue
Obesity
Adipocyte differentiation
tissues in the body [105]. Effective methods and specific
compositions prepared from pomegranate fruit extracts are
available for treating dermatological skin disorders [106,
107]. Extracts obtained from pomegranate showed anti-
angiogenic properties due to gallic acid and its derivatives by
inhibiting the angiogenesis in fat tissues [110]. Resolvins
and protectins as oxygenated metabolites derived from
Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid
(DHA) have been shown to possess potent anti-inflammatory
and immunoregulatory properties, hence an appropriate for-
mulation of fish oil and pomegranate fruit juice in an oil-in-
water emulsion form can be used for the treatment and reso-
lution of inflammation [113]. Herbs in combination with
methotrexate can be used for treating diseases and inflamma-
tory conditions [114]. These are quite effective as chemical
or synthetic agents of patented repute [115-121] for a variety
of biological activities. If compared with red wine and green
tea, Pomegranate Juice (PJ) possesses strong antioxidant
potential, which is due to ellagitannins and hydrolyzable
tannins. The PJ effectively lessens the macrophage oxidative
stress, diminishes free radicals and reduces lipid peroxida-
tion. Ellagitannins block some inflammatory markers to
check the cellular inflammation.
5. ANTIOXIDANT ACTIVITY
Antioxidant activities render various beneficial health
aspects in both humans and animals [127]. Recently some
28 Recent Patents on Inflammation & Allergy Drug Discovery 2018, Vol. 12, No. 1 Saeed et al.

Table 2. Summary of Different Studies on the Biological Effects of Pomegranate.

Effects Punica Granatum Part References

Gastroprotective Pomegranate peel extract [47]

Hypoglycemic Pomegranate flower [52]

Antioxidative Pomegranate peel extract [76-79]

Pomegranate peel extract

Neuroprotective [79, 80]
Pomegranate juice

Anti-inflammatory Pomegranate fruit extract [80, 81]

Antimicrobial Pomegranate peel extract [61, 83]

Pomegranate peel flour

Antifungal Pomegranate peel extract [84]

Inhibits methicillin-resistant S. aureus Pomegranate fruit peel [85]

Antiplasmodial Pomegranate fruit rind [86]

Anthelmintic Pomegranate peel extract [87]

Cardiovascular protection Pomegranate juice [88, 89]

Reduces oxidative stress Pomegranate juice [89]

Antidiarrheal Pomegranate peel aqueous extract [90]

Anticancer Pomegranate fruit, pulp and peel extract Pomegranate seed oil [91, 92]

Inhibits microbial adherence Pomegranate gel [93]

Table 3. Summary of The Patents on Biological Effects of Pomegranate.

Patent Name of Inventor Application Number Year References

Anti-resorptive and bone building dietary supplements Da, C.S.R., Fast, D.J., Gellenbeck, K.W., WO2008051594 2008 [40]
and methods of use Krempin, D.W., Lin, Y., Murray, M.A., Rana, J.,
Rebhun, J.F., Roh-Schmidt, H., Wilkins, L.M.

Compositions, kits, apparatus, and methods for inhibit- Levin, B.H. US20010004644 2001 [94]
ing cephalic inflammation

Dietary food supplement containing natural cyclooxy- Nair, M.G., Wang, H., Dewitt, D.L., Krempin, US6818234 2004 [95]
genase inhibitors and methods for inhibiting pain and D.W., Mody, D.K., Qian, Y., Groh, D.G.,
inflammation Davies, A.J., Murray, M.A., Dykhouse, R.,
Lemay, M.

Biotype diets system: predicting food allergies by Power, L.W. US7601509 2005 [96]
blood type

Anti-allergy composition and related methods Menon, G.R., Fast, D.J., Krempin, D.W., US7384654 2008 [97]
Goolsby, J.N.

Anti-allergy composition and related method Menon, G.R., Fast, D.J., Rozga, L.A., Lin, Y., US7384656 2008 [98]
Krempin, D.W., Goolsby, J.N.

Dietary food supplement containing natural cyclooxy- Nair, M.G., Dewitt, D.L., Wang, H., Krempin, US 8337914 2012 [99]
genase inhibitors and methods for inhibiting pain and D.W., Mody, D.K., Groh, D.G., Murray, M.A.,
inflammation Lemay, M., Qian, Y., Davies, A.J., Dykhouse, R.

Anti-resorptive and bone building dietary supplements Krempin, D.W., Murray M.A., Lin, Y., EP20110176493 2012 [100]
and methods of use Gellenbeck K.W., Da C.S.R., Wilkins L.M.,
Roh-schmidt, H., Jatinder, R., Rebhun, J.F.,
Fast, D.J.
Table (3) contd….
Pomegranate as a Functional Food and its Therapeutic Perspectives Recent Patents on Inflammation & Allergy Drug Discovery 2018, Vol. 12, No. 1 29

Patent Name of Inventor Application Number Year References

Anti-resorptive and bone building dietary supplements Krempin, D.W., Krempin, L., Murray, M.A., US9446087 2016 [101]
and methods of use Lin, Y., Gellenbeck, K.W., Da, C.S.R., Wil-
kins, L.M., Roh-Schmidt, H., Rana, J.,
Rebhun, J.F., Fast, D.J.

Lip gloss Wilson US9295635 2016 [102]

Novel anti-wrinkle and anti-aging nanoformulations Orza, A.I. US20170157005 2017 [103]
and method of preparation using novel nano
co-delivery system

Edible oil blend composition for use by humans with Syal, R., Richard, K. WO2017011891 2017 [104]
food allergies & intolerances

Methods and materials for treating and preventing Ponikau, J. WO9920261. 1999 [105]
inflammation of mucosal tissue

Methods and compositions for treating dermatological Murad, H. WO2000064472 2000 [106]
disorders with fruit extracts

Method of treating dermatological disorders with fruit Murad, H. US6630163 2003 [107]
extracts

Antiallergic agent Yukinaga, N., Yoshihiko, N. JP1998000346468 2000 [108]

Methods of treating allergic reactions Ashley, R.A. WO03099270 2003 [109]

Angiogenic agents from plant extracts, gallic acid, and Greenway, F., Liu, Z., Wolthering, E. US20070031332 2007 [110]
derivatives

Method of treating ocular allergy Klimko, P.G., Beauregard, C. US8034839 2011 [111]

Methods of treating inflammation Schultz, J.R., Turner, C. WO2011116245 2011 [112]

Use of a composition comprising fish oil and juice for Mathisen, J.S. WO2014209132 2014 [113]
the treatment of inflammation

Molecular and herbal combinations with methotrexate Jaggi, M., Singh, A., Shraibom, N., Steinberg, E. WO2017003430 2017 [114]
for treating diseases and Inflammatory ailments

Allergens modified with polysarcosines Garman, A.J., Wheeler, A. EP0038154 1983 [115]

Use of OB-101 to treat inflammation Chiou, G.C.Y. US5344829 1994 [116]

Controlled release of N-acetylcysteine (NAC) for re- Arad, Y., Dong, L.C. US20110244045 2011 [117]
duction of systemic and/or vascular inflammation

1-Kestose for treating allergy and atopic dermatitis. Koga, Y., Shibata, R., Aiba, Y., Fukumori, Y., EP1878738 2011 [118]
Takeda, H.

Anti-angiogenic extracts from pomegranate Greenway, F., Liu, Z., Wolthering, E. US8334000 2012 [119]

Methods and compositions for treating skin Gioffre, A.J. WO2015116529 2015 [120]

Composition and uses thereof Davidson, V.P. WO2016187643 2016 [121]

Pomegranate extract having a high ellagic acid content, Lee, H.Y. US8986749 2015 [122]
and use of the pomegranate extract

Formulations containing pomegranate seed oil, Rosa Sofer, T., Meyerf, T. WO2016070194 2016 [123]
canina fruit oil, and Inula viscosa oleoresin or extract

Pomegranate extracts from pomegranate flesh, and Lee, H.Y. WO2010076913 2010 [124]
composition for improving
Postmenopausal syndrome comprising effective
amount of the same

Pomegranate extract for use in treating rhinitis and sinusitis Hugo, B.E., Arie, Y., Itzhak, B. WO2013132487 2013 [125]

Pomegranate derived cell culture and methods for Hagay, Y., Azachi, M., Yatuv, R. WO2015102003 2015 [126]
preparing and using the same
30 Recent Patents on Inflammation & Allergy Drug Discovery 2018, Vol. 12, No. 1
studies added to the evidence of antioxidant effects of pome-
granate [128-130]. Kumar et al. [128] noted that HgCl2
treated rats showed increased oxidative stress as evidenced
by increased activity of erythrocyte PMRS 153%, lipid per-
oxidation 31%, and AOPP 290%. There was a significant (p
< 0.01) decrease (25%) in plasma antioxidant capacity and
intracellular glutathione (75%). Supplementation with PPE
protected rats from HgCl2 induced oxidative damage. Pome-
granate peel extract supplementation to control rats increased
antioxidant defense.
Zhao et al. [129] demonstrated that the combination of
PomE and Ex showed additive benefits on inhibition of
HFD-induced body weight increase and improvement of
HFD-induced immune dysfunction, including (a) attenuating
the abnormality of histomorphology of the spleen, (b) in-
creasing the ratio of the CD4+: CD8+ T cell subpopulations
in splenocytes and Peripheral Blood Mononuclear Cells
(PBMC), (c) inhibition of apoptosis in splenocytes and
PBMC, (d) normalizing peritoneal macrophage phenotypes
and (e) restoring immunomodulating factors in serum. We
also found that immune dysfunction in HFD-fed rats was
associated with increased inflammatory cytokine secretion
and oxidative stress biomarkers and that the combination of
PomE and Ex effectively inhibited the inflammatory re-
sponse and decreased oxidative damage.
Amri et al. [130] investigated beneficial effects of Pome-
granate Seeds Oil (PSO), leaves (PL), juice (PJ) and peel
(PP) on brain cholinesterase activity; brain oxidative stress
and lipid profile in high-fat-high fructose diet (HFD) in-
duced-obese rat and found that PSO, PL, PP, and PJ inhib-
ited cholinesterase activity in a dose-dependent manner.
Pomegranate leaves extract displayed the highest inhibitory
activity by IC50 of 151.85mg/ml upon in vitro study. For in
vivo study, HFD regime induced a significant increase of
cholinesterase activity in the brain by 17.4% as compared to
normal rats. However, the administration of PSO, PL, PJ,
and PP to HDF-rats decreased cholinesterase activity in brain
respectively by 15.48%, 6.4%, 20% and 18.7% as compared
to untreated HFD-rats. Moreover, HFD regime caused a sig-
nificant increase in brain stress, brain and body weight, and
lipid profile disorders in blood. Furthermore, PSO, PL, PJ
and PP modulated lipid profile in blood and prevented accu-
mulation of lipid in brain and body evidenced by the de-
crease of their weights as compared to untreated HFD-rats.
In addition, administration of these extract protected the
brain from stress oxidant, evidenced by the decrease of
Malondialdehyde (MDA) and Protein Carbonylation (PC)
levels and the increase in Superoxide Dismutase (SOD) and
Glutathione Peroxidase (GPx) activity.
Polyphenols are the predominant compounds present in
pomegranate including flavonoids, condensed and
hydrolyzable tannins in addition to alkaloids as pelletitierine.
Hydrolyzable tannins constitute about 90% of the antioxidant
activity of polyphenols found in the juice [76]. The strong
antioxidant potential is due to the presence of high concen-
tration of polyphenolic compounds such as punicalagins,
punicalins, anthocyanins, unique fatty acids, gallagic acid
and ellagic acid, among which few after metabolism within
the biological system turned to urolithins are responsible for
in vivo antioxidant effect [131]. The antioxidant activity of
Saeed et al.
the juice equals three times as that of red wine and green tea
due to the high concentration of polyphenol. Pomegranate
fruit extract is rich in flavonoids, which have antioxidant
activity via decreasing MDA and hydroperoxides concentra-
tions, and enhancement of catalase, SOD, GPx, and glutathi-
one reductase activities in the liver [77]. Moreover, the anti-
oxidant activity of anthocyanins (delphinidin, cyanidin, and
pelargonidin) present in Pomegranate Fruit Extract (PFE)
was higher than other natural antioxidants such as vitamin E
(
-tocopherol), vitamin C, as well as vitamin A [132, 133].
6. ANTI-INFLAMMATORY ACTIVITY
Recently, Danesi and Ferguson [134]. Sahebkar et al.
[135], Zarfeshany et al. [136] and Colombo et al. [137] re-
viewed anti-inflammatory effects of Pomegranate. Park et al.
[138] found that the Pomegranate Peel Extract (PPE) attenu-
ated the production of ROS and the expression of TNF-
,
IL1, MCP-1, and ICAM-1, but not VCAM-1, in THP-1 cells
stimulated by PM10 (100μg/ml). Pomegranate peel extract
also attenuated the adhesion of PM10-stimulated THP-1 cells
to EA.hy926 endothelial cells. Pomegranate peel extract con-
stituents, punicalagin and ellagic acid, attenuated PM10-
induced monocyte adhesion to endothelial cells, and punica-
lagin was less cytotoxic compared to ellagic acid. This study
suggests that PPE and punicalagin may be useful in alleviat-
ing inflammatory reactions due to particulate matter. Jianjun
et al. [115] found that 10-100μg/ml PFE decreased the pro-
duction of NO (IC50 value
=
31.8μg/ml), PGE2 (IC50
value
=
54.5μg/ml), IL6 (IC50 value
=
48.7μg/ml), IL1
(IC50 value
=
71.3μg/ml) and TNF-
(IC50 value =
62.5μg/ml) in LPS-stimulated RAW 264.7 cells signifi-
cantly. A mechanism-based study showed that phosphoryla-
tion of ERK1/2, p38, JNK and translocation of the NF-B p65
subunit into nuclei were inhibited by the PFE treatment.
These results show that PFE produced a potential anti-
inflammatory effect by modulating the synthesis of several
mediators and cytokines involved in the inflammatory proc-
ess.
Pomegranate extract, which is rich in polyphenols, can
inhibit the expression of IL6 and IL8 through NF-kB modu-
lation of [81]. In addition, it inhibits the expression of IL1B
and IL6 important in the dentistry [139, 140]. The standard
marker of pomegranate anti-inflammatory effect is granatin
B [41]. Phytochemicals in the form of polyphenols present in
pomegranate amend the inflammatory cell signaling in colon
cancer cells and hence can be explored to reduce the cancer
proliferation in the body [141]. Many pomegranate-based
anti-inflammatory formulations/products have been patented
also [91-97]. Marques et al. [142] evaluated anti-
inflammatory effects of PLE in LPS-Induced peritonitis and
found that the levels of TNF-
in acute inflammation were
suppressed in the hydroalcoholic extract-treated rats.
7. ANTI-CANCEROUS ACTIVITIES
In experiment 7, 12-dimethylbenz[a]anthracene (DMBA)
is used as a carcinogen to induce cancer in murine mammary
gland organ culture and pomegranate fermented juice poly-
phenols were used as the chemopreventive agent. Findings
reported a significant reduction of 47% in the cancerous le-
sion produced due to the carcinogen. Based on results further
Pomegranate as a Functional Food and its Therapeutic Perspectives
clinical trials on a human were advocated for the assessment
of chemopreventive and adjuvant therapeutic potentials of
pomegranate in cases of human breast cancer [143]. Whole
pomegranate seed oil and pomegranate fermented juice
polyphenols both have shown chemo-preventive potential in
a mouse mammary organ culture against breast cancer as
they reduced the occurrence of breast tumors in ten days of
treatment [144]. The study performed over HT-29 human
colon cancer cell line reported that phytochemicals present in
PJ modulate the inflammatory cell signaling by inhibiting
propagation of cancer cell and apoptosis by alteration of cel-
lular transcription factors and signaling proteins. Results
showed that PJ and its ellagitannins in the concentration of
50mg/L reduced the phosphorylation of the p65 unit and
abolished the activity of NFkB, inhibited the TNF-alpha in-
duced COX-2 protein expression by 79%, total pomegranate
tannin extract (TPT) by 55% and punicalagin by 48% [141].
Pomegranate fruit extract, as a chemopreventive/chemo-
therapeutic agent, is effective in preventing human lung can-
cer as evident from the study over human lung carcinoma
A549 cells and also in athymic nude mice in a dose-
dependent manner upon oral administration. Pomegranate
fruit extract in the concentration of 50-150 microg/ml when
used for 72 h, growth of carcinoma cells was arrested in G0-
G1 phase of the cell cycle showing reduction in the protein
expressions of cyclins D1, D2, E, declined Cyclin-
Dependent Kinase (CDK) 2, cdk4 and cdk6 expression and
activation of WAF1/p21 and KIP1/p27. Treatment with PFE
inhibited binding activity of NF-kappaB with DNA and di-
minish phosphorylation of MAPK proteins, phosphorylation
of Akt at Thr308, degradation and phosphorylation of Ikap-
paBalpha, inhibit PI3K, NF-kappaB, IKKalpha, Ki-67 and
PCNA to lessen the cancerous growth significantly in lung
cells [145].
8. GLUCOSE AND LIPID METABOLISM ACTIVI-
TIES
Diverse metabolic effects of pomegranate fresh juice (PJ)
and seed powder (PS) have been studied by Rouhi et al.
[146]. They noted that PJ and PS treatment had slight but
non-significant reduction of plasma glucose concentration,
and no impact on plasma insulin compared to Diabetic Con-
trol (DC) group. PJ lowered the plasma Total Cholesterol
(TC) and Triglyceride (TG) significantly, and Low-Density
Lipoproteins (LDL) non-significantly compared to DC
group. In contrast, PS treatment significantly raised plasma
TC, LDL, and High-Density Lipoproteins (HDL) levels
compared to the DC rats. Moreover, the administration of PJ
and PS significantly reduced the levels of plasma inflamma-
tory biomarkers, which were actively raised in diabetic rats.
Only PJ treated group showed significant repairment and
restoration signs in islets of Langerhans. Besides, PJ pos-
sessed preventative impact against 2, 2-diphenyl-1-
picrylhydrazyl (DPPH) radicals almost 2.5 folds more than
PS.
Punica granatum L. may have a cholesterol-lowering
activity to protect against cardiovascular and other chronic
diseases [147, 148]. Punica granatum flowers are being
prescribed in Unani and Ayurvedic medicines for the
treatment of diabetes disorders [149]. Pomegranate flowers
extracts had a protective effect on serum lipid profile and
Recent Patents on Inflammation & Allergy Drug Discovery 2018, Vol. 12, No. 1 31
activities of antioxidant status in streptozotocin-induced
diabetic rats. Lipid profile of rats' model showed an increase
in serum total cholesterol, glucose level, LDL, triacylglyc-
erol, VLDL, lipid peroxidation level as well as a decrease in
HDL. The change of these parameters may explain the use of
pomegranate fruit as a dietary supplement to protect against
chronic atherogenic and impaired glucose metabolic disor-
ders [150]. Pomegranate Leaf Extract (PLE) showed anti-
obesity effects in a mouse model in which hyperlipidemia
and obesity was induced because of using high-fat diet.
Study involved male and female both ICR mice weighing 20
percent higher due to fat diet than the control group of
normal diet mice. In test group 400-800mg/kg/day of PLE
was provided for 5 weeks. Regularly measured parameters
included daily food intake, body weight serum total
cholesterol (TC), triglyceride (TG), glucose and High-
Density Lipoprotein Cholesterol (HDL-C) levels were
measured. Results after 5 weeks were very encouraging in
terms of reduction in body weight, appetite of obese mice,
energy intake, various adipose pad weight percents, serum
TC, TG, glucose levels and TC/HDL-C ratio. The
mechanism included inhibition of pancreatic lipase activity
to suppress energy intake and hence PLE is suggested as
promising appetite suppressant agent which can help in re-
ducing obesity in some time if it is of high fat diet origin
[151]. Similarly, another study showed that when PSO was
fed to mice for 12 weeks, its administration resulted in
decreased body weight, less body fat mass without affecting
the feed and/or energy intake in fat diet induced obese mice.
Mechanism explained that punicic acid metabolism played a
significant role and hence dietary supplementation of
pomegranate seed oil improved peripheral insulin sensitivity
in the high fat diet induced obese mice and will be helpful in
reducing the obesity [152].
9. ANTIMICROBIAL ACTIVITIES
Most of the methanolic extract of pomegranate fruit peels
were found to have antimicrobial activity against Staphylo-
coccus aureus and other gram-negative bacteria; Listeria
monocytogenes, Escherichia coli and Yersinia enterocolitica.
The antimicrobial activity is due to high phenols content of
peels rich samples [61]. The mixture of PJ and polyphenols
was reported to protect against food-borne viral infection.
Accumulation of ellagitannins and punicalagins (from
pomegranate products provided by POM Wonderful (Los
Angeles, CA) in the intestine modulated gut microbiota and
inhibited the growth of pathogenic clostridia and Staphylo-
coccus aureus without any adverse effect on gut microbiota
[153]. An in vitro study was conducted to assess and
compare the in vitro antifungal efficacy of Punica granatum
with Acacia nilotica, Cuminum cyminum and Foeniculum
vulgare against Candida albicans. Extract was prepared
from powdered pomegranate peel and other plants and
sterilized filter papers discs soaked in 30μl of the extract
were inoculated over Sabourauds dextrose agar plate
containing culture of Candida and observed for zone of
inhibition. After incubation of 48h, maximum zone of
inhibition of 22mm diameter was recorded from Punica
granatum and proved the significant anti-fungal potential of
pomegranate over other studied herbs [154].
32 Recent Patents on Inflammation & Allergy Drug Discovery 2018, Vol. 12, No. 1
10. STUDIES IN HUMANS
Mycosis is a becoming more common and highly resis-
tant to traditional treatments. As described by [155] the juice
derived from pomegranate possesses strong anti-
hypertensive, antioxidant, and anti-atherosclerotic properties.
Currently, several research findings have indicated that the
use of pomegranate has exhibited beneficial effects on car-
diovascular risk in diabetic [148, 156] blood pressure [22,
135] obese [157, 158] and hypertensive patients [159]. Clini-
cal trials performed over human population suggested the
curative effects of PJ against diabetes, cardiovascular disease
and prostate cancer [131]. Literature documented that PJ can
be used as cancer-chemopreventive and cancer-chemo-
therapeutic agent against prostate cancer in humans if sup-
plemented in diet [160]. Pomegranate prevents and cures
cancers by antiproliferative, anti-invasive and antimetastatic
effects. It modulates Bcl-2 proteins to induce apoptosis,
causes increase in p21 and p27 along with down-regulation
of cyclin-CDK network [161]. Results from clinical studies
conducted over human beings in last ten years reported that
peels, flowers, and seeds fractions of pomegranate have posi-
tive impact in correcting diabetic Type 2 by lowering the
oxidative stress either by neutralizing the generated Reactive
Oxygen Species (ROS) or by increasing the activities of an-
tioxidant enzymes, enhancing metal chelation and by reduc-
ing resistin formation and lipid peroxidation. It also influ-
enced transcriptional factors as nuclear factor B and perox-
isome proliferator-activated receptor
by their up-regulation
or down-regulation [162]. Compounds mainly punicalagin,
ellagic, gallic, oleanolic, ursolic, and uallic acids are impor-
tant anti-diabetic bio-molecules present in PJ. Similarly, tan-
nins and anthocyanins are potent antioxidant polyphenols
which effectively reduce the incidence of Type 2 diabetes.
Such evidences recommend the therapeutic use of PJ for
managing type 2 diabetes [161, 163]. Pomegranate flowers,
seeds and juice specifically showed hypoglycemic activity as
they are capable of preventing Type 2 diabetes via perox-
isome proliferator-activated receptor gamma binding and
also diminished nitric oxide production. Pomegranate bioac-
tive molecules responsible for antidiabetic properties are
comprised of oleanolic, ursolic and gallic acids present in
pomegranate fruit juice [164].
As described by Malik and Mukhtar [165], dietary ad-
ministration of fresh PFE exhibited the inhibition of tumor
growth together with a decrease in serum Prostate-Specific
Antigen (PSA) levels. The most promising properties of
pomegranate thus far are associated with its valuable effects
on cardiovascular disorders, metabolic syndrome, and diabe-
tes in human being [134]. In another finding that the PFE
like PSO and PJ, have been verified in human skin cell cul-
tures and skin cancer models of laboratory animals and indi-
cate the enormous potential for inhibiting ultraviolet B in-
duced skin cancer [147]. The ingestion of punicalagin that
obtained from the pomegranate’s husk, exhibited very robust
antioxidant action by reducing the growth of oxidative DNA
products and shows anti-cancer potential against lung cancer
[166]. Like this the ellagic acid, and punicalagin that are
being considered the chief elements of the P. granatum peel,
exhibit potent anti-proliferative action. In one study anti-
proliferative properties of pomegranate peel were evaluated
against different types of cancer cells including lung cancer,
Saeed et al.
and results show that the anti-cancer activities of P.
granatum are not exclusively limited to the edible part of the
P. granatum fruit [167]. As reported by Fleck et al. [168]
who found that punicalagin that derived from pomegranate
could be used in wound healing therapy. The pomegranate
could be adopted as a food supplement to augment the lon-
gevity, growth and fertility rate in numerous species of labo-
ratory animals and as well as in human beings, but the dos-
age should be very cautiously adjusted to avoid detrimental
effects [169].
11. STUDIES IN ANIMALS
Several scientific studies have investigated the protective
effect of pomegranate fruit as well as different nonedible
parts of pomegranate tree on organs such as heart [170] liver
[152, 171] and skeletal muscle in an obese rat model [172]. It
is well known that Reactive Oxygen Species (ROS) affect
lethally to the sperms during freeze thawing which results in
disruption of membrane integrity, decreasing sperm motility,
and also cause DNA damage [173]. To overcome these dele-
terious effects of ROS, adding antioxidant like pomegranate
extract to the semen extender may consider as a promising
choice without having any negative effects on semen quality
and fertility [174]. Pomegranates having a substantial
amount of polyphenolic compounds including condensed
tannins, flavonoids, and hydrolyzable tannins (gallotannins
and ellagitannins) that had attributed to potential antioxidant
action including lowering of ROS [70]. Punicalagin is the
outmost abundant ellagitannins that also known as a most
numerous polyphenol among the pomegranate ellagitannins
that known to cause significant antioxidative effects of
pomegranate extract [50]. In another study, it was observed
that pomegranate extract had significantly improved sperm
motility, total count, viability, mitochondria activity, mem-
brane integrity, and reduced malondialdehyde concentration
(lipid peroxidation) and conclusively reported that pome-
granate extract can enhance the ram semen quality after
thawing [175]. Researchers have investigated the antiprolif-
erative and proapoptotic properties of PFE on oral admini-
stration in athymic nude mice against prostate cancer and
results reflected the antitumor effects of PFE [160].
12. ADDITIVE EFFECTS IN DIET
In avian species, there is a growing interest among re-
searcher to improving the growth, increasing feed utilization
and reducing mortality by supplementing a pomegranate-
derived additive to feed. Pomegranate-derived additives have
demonstrated its potential for enhancing growth performance
and health status of poultry without using growth-promoting
antibiotics. A recent Korean study reported that pomegranate
byproduct (PB; dried peel, seeds, and rind after extraction of
juice) in supplemental levels of 0.5 and 1.0% improved the
broilers’ immunity in a dose-dependent manner by increas-
ing the spleen and bursa indices and serum IgA and IgG lev-
els [73]. The study also demonstrated that 1.0% inclusion
level could positively modulate the gut microbial ecosystem
of broilers by increasing the Saccharomyces cerevisiae and
Bacillus spp. and decreasing the Escherichia coli and Salmo-
nella spp. Whereas, Ahmed et al. [176] reported that dietary
supplementation of PB up to 2% could improve the breast
and thigh muscle composition, fatty acid profile and decrease
Pomegranate as a Functional Food and its Therapeutic Perspectives
the TBARS values of broiler meat. In the study of Szymczyk
et al. [177] who fed PSO to broiler and resulted in a signifi-
cant combination of conjugated linoleic acid isomers into the
broiler’s breast meat lipids and gave a promising alteration in
the fatty acid composition of these lipids, maintaining com-
petitive production traits of broiler meat.
The Ellagic Acid (EA), a polyphenolic constituent that is
an exit in substantial amount in pomegranate fruits that was
fed at 75mg/kg and lower (P < 0.05) serum superoxide dis-
mutase activity [178]. In the experiment of Saleh et al. [78]
who fed broiler with pomegranate peel extract at 200 and
300mg/kg improved the antioxidative potential and also
quality characteristics of broilers breast meat. In conclusion,
the aforementioned study reported that the antioxidant poten-
tial of pomegranate peel extract was equal to that of
-
tocopherol in refrigerated meat. In another study, the combi-
natorial effects of Punica granatum and Terminalia chebula
(PgTc) extract were observed in chickens challenged with
Avian Pathogenic Escherichia coli (APEC). The results de-
clared a dose-dependent response of PgTc extract dosages
(0.15, 0.3 and 0.6g/kg BW for seven days) for improved sur-
vival rate and health status [81]. The study also reported a
significant effect of PgTc extract to modulate chickens’ im-
munity by reversing the over expression of TLR2, TLR4 and
TLR5; and inhibited the inflammation by reducing the pro-
inflammatory cytokines like IL8, IL1,
TNF-
, VCAM1
and ICAM1 [81]. In a layered study, Pomegranate Seed Pulp
(PSP) was used in inclusion levels of 5, 10 and 15%, results
demonstrated that 5% dietary inclusion of PSP is beneficial
in laying hens to improve egg production without any ad-
verse effects on egg weight, egg mass, eggshell ratio, egg-
shell weight, breaking strength, and yolk and albumen in-
dexes [179].
13. DIRECT ADDITIVE EFFECTS IN MEAT
A number of studies have used the direct application of
Punica granatum extract/juice in chicken meat and/or its
products and reported a marvelous effect in terms of im-
proved shelf-life and consumers’ acceptability. Lytou et al.
[180] reported a reduced number of spoilage microbes and
increased shelf-life of chicken breast fillets immersed in
pomegranate juice as compared to control group. Another
study reported that marination of chicken breast meat in
pomegranate fruit juice could potentially inhibit the protein
oxidation and reduce the bacterial growth and sensorial dete-
rioration up to 12 days of refrigerated storage at 4°C [181].
The pomegranate peel extract has a synergistic antioxidant
effect and extended the refrigerated shelf life of meat and
nugget [182]. The PJ had found the best inhibitory result on
the microbial growth and also on the chemical changes in
chicken's breast meat [183]. In another study, it was detected
that extracts of kinnow, as well as pomegranate's by-
products, are strong natural antioxidant source so the by-
products from pomegranate have potential that are being
used as strong natural antioxidants to reduce the oxidative
problems in poultry meat [182].
Promoting and supporting more researches on pomegran-
ate and its active principles / bioactive compounds, valida-
tion and clinical trials as well as exploring the recent ad-
vances in the scientific arena like biotechnology, proteomics,
Recent Patents on Inflammation & Allergy Drug Discovery 2018, Vol. 12, No. 1 33
nanotechnology, pharmacology and biomedicine) to opti-
mize the designing and production of valuable functional
foods, nutritional supplements, nutraceuticals, medicines,
drugs and pharmaceuticals, would help to exploit its multi-
dimensional beneficial effects and potential for safeguarding
health of humans and their companion animals [7, 184-187].
Advancement in the field of proteomics will allow exploring
the effect of Punica granatum on vital enzymes [188]. Last
but not the least the plant is a rich source of phytochemicals
which can also be studied very vividly to explore the phar-
macological as well as toxicological characters which will be
ultimately beneficial for mankind [189]. Of note, as noted
with other valuable plants and herbs, the antimicrobial poten-
tial of pomegranate need to be explored especially against
important / emerging pathogens having public health con-
cerns along with its effectiveness to counter general health
disorders like diabetes, cholesterol and heart problems, obe-
sity, others and also the deadly malady of cancers, which are
all presently the common health issues haunting health and
survival of the mankind.
CURRENT & FUTURE DEVELOPMENTS
Pomegranate gained more attention due to a rich source
of bioactive compounds and contains a variety of secondary
metabolites. It has promising biological activities, including
anti-inflammatory, antibacterial, antidiarrheal, immune
modulatory, antitumor, wound healing and antifungal that
have been reported with various constituents/extracts of
different parts (seeds, bark, juice, pericarp and leaf) of this
tree across the globe. This particular plant possesses the
property of influencing various signaling pathways viz., Bcl-
X; Mitogen Activated Protein Kinase (MAPK); c-Jun N-
terminal kinase (JNK) as well as caspases. As a result the
plant can be beneficial for treating as well as preventing ex-
tensively various types of diseases that include cancers of
prostate gland; breast; colon; skin; lung; blood. Not only this
Punica granatum can also possibly treat conditions viz., hy-
pertension; ischemia and perfusion of the myocardium; in-
flammation of the oral cavity; diabetes; infertility in males;
Alzheimer disease; brain injury in neonates; dysfunctions in
relation to erection and obesity. The Punica granatum L.
byproducts improved immunity and the intestinal microbial
ecosystem of broiler chickens along with also reduced odor-
ous gas emissions from poultry manure. It is well known that
pomegranate has got no botanical relative and it also pos-
sesses a very unite bunch of markers (both antigenic as well
as chemical). The potential of the plant to cause allergy
should be taken into consideration with utmost importance
and the users (potential) of the plant products should be
tested (spot tests should be performed) on routine basis. It is
of great worry that the preparations of the peel are genotoxic
in nature and such adverse property should be rigorously
investigated inspite of the fact that the plant has found its
safe application for centuries together in Ayurveda as well as
Chinese medicines. In spite of many beneficial properties of
Punica granatum L., there is currently a gap of research
knowledge that to be needed to further explore its pharma-
cological effects for a wide range of clinical applications in
the therapy of human and animal disorders. Investigations
are also required to find the potential application of the peel
to treat cancer. Research areas that need special emphasis
34 Recent Patents on Inflammation & Allergy Drug Discovery 2018, Vol. 12, No. 1
also include the investigation of appropriate dosages for
various animals and human diseases to maximize the bene-
fits without any detrimental effects.
ETHICS APPROVAL AND CONSENT TO PARTICI-
PATE
Not applicable.
CONSENT FOR PUBLICATION
Not applicable.
CONFLICT OF INTEREST
The authors declare no conflict of interest, financial or
otherwise.
ACKNOWLEDGEMENTS
All the authors of the manuscript thank and acknowledge
their respective Universities and Institutes.
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