Cultivation, chemical compositions and health benefits of jujube (Ziziphus jujuba Mill.)

Abstract

Medicinal plants have curative properties due to presence of various complex chemical substances and secondary metabolites. Jujube (Ziziphus jujuba Mill), belongs to Rhamnaceae family, is distributed throughout the eastern, southeastern and central parts of Iran. Different parts of jujube are being consumed all around the world because of their health benefits, as both food and herbal medicine. Fruits of this plant are widely used in Iranian folk medicine as antitussive, laxative agent and blood pressure reducer. Based on Iranian traditional medicine books, local traditional healers used powders of stem bark and leaves of jujube to cure wounds and oral wounds as aphthous. It is used traditionally as anti-diabetes, tonic, aphrodisiac, hypnotic-sedative and anxiolytic, anticancer, antifungal, antibacterial, antiulcer, anti-inflammatory, cognitive, antispastic, antifertility/contraception, hypotensive, antinephritic, cardiotonic, antioxidant, immunostimulant, and wound healing. The phytochemical and pharmacological results have revealed that flavonoid, polysaccharide, phenolic, vitamin C and triterpenic acid are the main active ingredients. Due to the high polyphenolic content and antioxidant capacity, this plant can be proposed for treatment of diabetic patients.

Full text

Cultivation, chemical compositions and health benefits of jujube
(Ziziphus jujuba Mill.)
Seied Mehdi Miri
Department of Horticulture, Karaj Branch, Islamic Azad University, Karaj, Iran
smmiri@kiau.ac.ir
Abstract
Medicinal plants have curative properties due to presence of various
complex chemical substances and secondary metabolites. Jujube
(Ziziphus jujuba Mill), belongs to Rhamnaceae family, is distributed
throughout the eastern, south-eastern and central parts of Iran. Different
parts of jujube are being consumed all around the world because of their
health benefits, as both food and herbal medicine. Fruits of this plant
are widely used in Iranian folk medicine as antitussive, laxative agent
and blood pressure reducer. Based on Iranian traditional medicine
books, local traditional healers used powders of stem bark and leaves of
jujube to cure wounds and oral wounds as aphthous. It is used
traditionally as anti-diabetes, tonic, aphrodisiac, hypnotic-sedative and
anxiolytic, anticancer, antifungal, antibacterial, antiulcer, anti-
inflammatory, cognitive, antispastic, antifertility/contraception,
hypotensive, antinephritic, cardiotonic, antioxidant, immunostimulant,
and wound healing. The phytochemical and pharmacological results
have revealed that flavonoid, polysaccharide, phenolic, vitamin C and
triterpenic acid are the main active ingredients. Due to the high
polyphenolic content and antioxidant capacity, this plant can be
proposed for treatment of diabetic patients.
Keywords: Ziziphus jujube, phytochemistry, anti-diabetes, antioxidant,
antibacterial, anticarcinogenic

Introduction
Traditional medicines are used by approximately 60% of the world's population. While the traditional
medicines are derived from medicinal plants, minerals, and organic matter, the herbal drugs are
prepared from only medicinal plants (Keshavarzi et al., 2013; Mahajan and Chopda, 2009). Medicinal
plants have curative properties due to presence of various complex chemical substances and secondary
metabolites (Alizadeh et al., 2017a; Asghari Lalemi et al., 2013; Aslani et al., 2015a & b; Keshavarzi
et al., 2013, 2014a & b, 2015a & b; Mahajan and Chopda, 2009; Nikdehghan et al., 2013a & b;
Roughani et al., 2018a & b; Shams Olshoara et al., 2017). The use of herbal medicine has recently
increased because of its effectiveness, limited side effects, and easy accessibility (Valavi et al., 2016).
Jujube (Ziziphus jujuba Mill) is native to China and originated in the middle and lower reaches of the
Yellow River and has been cultivated in China for more than 4000 years (Yao, 2013). It grows mostly
in Europe, southern and eastern Asia, and Australia, and is broadly distributed in Iran (Gao et al.,
2013; Kaeidi et al., 2015).
The fruit of this plant has gained wide attention in folk herbal medicine for the treatment of a wide
range of disorders (Kaeidi et al., 2015). The study on biological activities has supported the health
benefits of jujube as both food and medicinal herb (Chen et al., 2017). The main biologically active
components are vitamin C, phenolics, flavonoids, triterpenic acids, and polysaccharides.
Phytochemical studies of jujube fruits have showed their biological effects, such as anti-diabetes,
anticancer, anti-inflammatory, antiobesity, immunostimulating, antioxidant, hepatoprotective, and
gastrointestinal protective activities and inhibition of foam cell formation in macrophages (Gao et al.,
2013; Hemmati et al., 2015b).
Taxonomic description
Jujube (Ziziphus jujuba Mill) belongs to the Rhamnaceae family and is one of the most
important Ziziphus species (Tahergorabi et al., 2015). Jujube is a small tree of 6-9 m depending on
location with strong and hard wood (Yao, 2013). Trees are semi deciduous and much branched. The
bark has deep longitudinal furrows and is grayish brown or reddish in color. Usually the shrub or tree
is spinous, but occasionally unarmed (Mahajan and Chopda, 2009). Jujube has four types of shoots:
primary (extension) shoot, secondary shoot (side branches), mother-bearing shoot (fruiting spur), and
fruit-bearing shoot (branchlet) (Yao, 2013). Branchlets are densely white pubescent, especially when
young and tend to be zigzag. Branches spread erect, becoming flexuous and dull brown grey. Fruiting
branches are not deciduous (Mahajan and Chopda, 2009). Its leaves are shiny, ovate or oval in shape,
not branched, and alternate. Leaves are 2.5 to 5.5 cm long and 2 to 4 cm wide. Flowers are fragrant,
pale greenish yellow in color, and small with diameters ranging from 4 to 8 mm. A jujube flower has
five sepals, five petals, five anthers, and one ovary with two ovules. Flowers can appear singly or in a
cluster at each leaf axil. Jujube’s flower cluster (inflorescence) is a cyme with up to 13 flowers
depending on the cultivar and its position on the branchlet. Jujube fruit is a drupe with one pit (stone)
in the middle containing up to two seeds. Its fruit derives from its ovary and the nectary disk. Fruit
size varies from thumb-sized to golfball-sized depending on the cultivar. The fruit shape can be round,
oblong, oval, ovate, obovate, oblate, apple-like, or abnormally shaped (Yao, 2013). The pulp is acidic
and sweet, the fruit greenish, yellow or sometimes reddish (Mahajan and Chopda, 2009).
Climatic conditions
Jujubes adapt well to a wide range of soil and weather conditions. They grow from 0 to 2000 m
elevation, between lat. 18°14ʹ to 45° and long. 76° to 124°, and in soil pH 5.5 to 8.5. Jujubes could
tolerate 48.9 °C in the summer and withstood -30 °C in the winter. With its late-season start-up, it
avoids much of the late frost threat and, as a result, jujube trees rarely miss a crop. Jujube normally
leafs out 4 to 6 weeks later than most temperate tree fruit crops and it blooms even later and continues
blooming for 2 months or longer (Yao, 2013). The jujube trees adapt the drought conditions and

produce sufficient yield under severe drought conditions (Sulusoglu et al., 2014). The tree can survive
with an annual rainfall of only 200 mm, but for better fruit set and fruit quality, more precipitation or
supplemental irrigation is needed (Yao, 2013).
Propagation
The most widely used method of jujube propagation was by root suckers or grafting on sour jujube
rootstocks (Mousavi et al., 2017c; Yao, 2013). Researchers also tried softwood cuttings and tissue
culture propagation of jujubes (Mousavi et al., 2017a & b; Yao, 2013), but grafting is still the most
popular propagation method. Whip tongue grafting, bark grafting, and cleft grafting are the most
popular and successful grafting methods (Yao, 2013).
Medicinal uses
Different parts of jujube can be used for the curing of many kinds of illness including diabetes,
diarrhea, skin infections, liver complaints, urinary disorders, obesity, fever, pharyngitis, bronchitis,
anemia, insomnia, cancer, and also for blood purification and tonification of the gastrointestinal tract
(Tahergorabi et al., 2015). Jujube causes a decrease in the blood levels of glucose and lipids, and it has
been reported to make a significant decline in triglyceride, LDL and cholesterol levels (Hemmati et
al., 2015a).
The bark cures boil and is good for the treatment of dysentery and diarrhea. The leaves are antipyretic
and reduce obesity. The aqueous paste of the leaves is applied externally to relieve a burning sensation
(Mahajan and Chopda, 2009). Based on Iranian traditional medicine books, local traditional healers
used powders of stem bark and leaves of jujube to cure wounds and oral wounds as aphthous (Hamedi
et al., 2016). Roots are used to treat dysentery; they are given with cow's milk until the patient is cured
(Mahajan and Chopda, 2009).
Fruits are widely used in Iranian folk medicine as antitussive, laxative agent and blood pressure
reducer (Hamedi et al., 2016). The fruit is cooling, digestible, tonic, aphrodisiac, laxative and removes
biliousness, burning sensations, thirst, vomiting and is also good in treating tuberculosis and blood
diseases. It is employed as an antidote to aconite poisoning, abdominal pain in pregnancy and
externally in poultice and applications for wounds. The seeds cure eye diseases and are also useful in
leucorrhoea. The kernels increase flesh and strength and are sedative in activity (Mahajan and Chopda,
2009).
Phytochemistry
Carbohydrate
The major sugars found in the jujube fruit are glucose, fructose, sucrose, rhamnose, and sorbitol.
Dietary fiber and fructose contents of the jujube fruit play a role in the regulation of blood sugar levels
by slowing digestion (Tahergorabi et al., 2015). Polysaccharides are one of major biologically active
components of the jujube fruit and have various biological effects, including immunomodulatory,
antioxidant, antitumor, hepatoprotective, and hypoglycemic activities, and gastrointestinal-protective
effects (Ji et al., 2017). Presence of pectin-A in jujube fruit is reported. Chemically it contains 2, 3, 6-
tri-o-acetyl D lactose units. Pectin has a number of pharmaceutical properties such as binding bile
acid, lowering plasma cholesterol and anti diarrhoeal properties (Mahajan and Chopda, 2009). Zhao et
al. (2008) extracted water-soluble polysaccharides (WSPs) in Chinese jujube leaves, fruits and
flowers. Pectic polysaccharides were the major components in all WSPs since all extractions were
very rich in sugars such as uronic acid, arabinose and galactose.
Vitamin
Jujube fruits are very rich in vitamin C (Mahajan and Chopda, 2009; Mousavi et al., 2016) compared
to other edible fruits such as cherry (Momeni et al., 2015; Negini Kalkhoran et al., 2012), citrus
(Kiani Majd et al. 2013; Yaraei-Rostami et al. 2013a & b), grape (Tanha et al., 2015), quince (Naeimi
et al., 2018), pistachio (Nobari et al. 2012), plum (Alizadeh et al. 2017b), pomegranate (Amraei et al.,
2014; Jalili Moghadam et al., 2012; Khaiati et al. 2017), strawberry (Haghighat et al., 2015; Hosseini
et al., 2013) and walnut (Izan et al. 2013). The vitamin C content of mature fruit of 45 cultivars

ranged from 225 to 530 mg/100 g fresh weight (FW) plus ‘Youzao’ having the highest content of 820
mg/100 g FW at early mature stage. Jujube fruit also contains vitamin B1 (thiamine) and B2
(riboflavin). It is also known to have a high vitamin P (354 to 888 mg per 100 gm pulp) (bioflavonoid)
content. It enhances the action of vitamin C. One fruit per day would meet the diet requirements for
vitamin C and vitamin B complex for an adult man as recommended by FAO/WHO (Mahajan
and Chopda, 2009). However, most of the vitamin C gets lost during the sun-drying process, and on
average only 10% remains. So, for the benefit of vitamin C, eating fresh jujube fruit is much better
than eating dried fruit (Yao, 2013).
Fatty acid
Dried pulp of jujube is a source of essential unsaturated fatty acids. The main fatty acids in the jujube
are oleic, linoleic (omega-6), palmitic, and palmitoleic acids (Tahergorabi et al., 2015).
Alkaloids
Alkaloids are distributed in all parts of Ziziphus species. The cyclic peptide alkaloids, mauritine A,
mucronine D, amphibine H, nummularine A-B, sativanine A-H, and -K, frangulanine, jubanine A-C,
scutianine C-D and ziziphine A were isolated from stem bark of jujube (Mahajan and Chopda, 2009;
Tripathi et al., 2001). The alkaloids coclaurine, isoboldine, norisoboldine, asimilobine, iusiphine and
iusirine were isolated from leaves. Cyclopeptide and peptide alkaloids from jujube were found to show
sedative effects. The seeds of Z. jujuba var. Spinosa also contain cyclic peptide alkaloids sanjoinenine,
franguloine and amphibine-D and four peptide alkaloids; sanjoinine-B, -D, -F and -G2 (Mahajan
and Chopda, 2009). Adouetine-X, frangulanine and jubanine F-J which are active (sedative) ingredient
cyclopeptide alkaloids were isolated and characterized from the root bark of jujube (Kang et al., 2015;
Mahajan and Chopda, 2009).
Glycosides
I. Flavonoid glycosides/spinosins: Three flavonoids as spinosin, 6′″‐sinapoylspinosin, 6′″‐
feruloylspinosin were isolated and purified from Z. jujuba (Bai et al., 2010). Also, eight flavonoid
compounds were isolated from the seeds of Z. jujuba var. Spinosa. On the basis of chemical and
spectral analyses, their structures were elucidated as swertish, puerarin, 6‴-feruloylspinosin, apigenin-
6-C-β-d-glucopyranoside, spinosin, 6‴-feruloylisospinosin, isospinosin, and isovitexin-2″-O-β-d-
glucopyranoside (Cheng et al., 2000). Li et al. (2013) recognized two new flavonoids, 8-formyl-3′,4′-
dihydroxy-6,7-dimethoxyflavone and 8-formyl-4′-hydroxy-3′,6,7-trimethoxyflavone from the fruits
of Z. jujuba. Five flavone C-glycosides from the methanol extract of the degrease seeds of Z. jujuba
var. Spinosa were isolated though various column chromatography methods including silica gel,
MPLC and HPLC. The structures were elucidated as 6"-feruloyl-6'''-vanillylspinosin, 6",6'"-
diferuloylspinosin, spinosin, swertisin and isoswertisin (Chen et al., 2015). A total of six flavonoids
(five flavonols and one chalcone) were identified in jujube fruit and leaves. Total flavonoid contents of
leaves were approximately 900-fold higher than that of fruit. Quercetin 3-O-rutinoside (rutin) and
quercetin 3-O-robinobioside were the predominant flavonols in fruit and leaves of jujube. In
particular, rutin had the highest content in leaves. Phloretin 3',5'-di-C-glucoside (chalcone type) was
detected only in leaves (Lee et al., 2016).
II. Glycosides/saponins: Different parts of jujube that is seeds, leaf and stem contain glycosides. The
saponins isolated from the seeds include jujubosides A, B, A1 B1 and C, acetyljujuboside B and
protojujubosides A, B and B1. The saponin, ziziphin, was extracted from the dried leaves. It has a
structure, 3-O-a-L-rhamnopyranosyl (1-2)-a-arabinopyranosyl 20-O-(2,3)-di-O-acetyl-a-L-
rhamnopyranosyl jujubogenin. A saponin from jujube leaves and stem was isolated. It was assigned
the structure 3-O-((2-O-α-D-furopyranosyl-3-O-β-D-glucopyranosyl)-α-L-arabinopyranosyl)
jujubogenin. They are being widely researched for cancer prevention and cholesterol control. Saponins
showed adjuvant and hemolytic, sedative, anxiolytic and sweetness inhibiting properties. Jujuboside
A, is also known to be a noncompetitive inhibitor of calmodulin and is thought to be linked to its
sedative properties (Mahajan and Chopda, 2009).
Terpenoids
The triterpenoic acids have been isolated from the fruits of Z. jujube, some of them are colubrinic acid,
alphitolic acid, 3-Ocis-p-coumaroylalphitolic acid, 3-O-transpcoumaroylalphitolic acid, 3-O-cis-p-
coumaroylmaslinic acid, 3-O-trans-pcoumaroylmaslinic acid, oleanolic acid, betulonic acid, oleanonic

acid, zizyberenalic acid, betulinic acid, zizyberanal acid, zizyberanone, zizyberanalic acid and ursolic
acid (Guo et al., 2009; Mahajan and Chopda, 2009). Betulin, 2α-hydroxyursolic acid, ceanothic acid,
2-O-protocatechuoyl alphitolic acid, caffeoyl alphitolic acid and ceanothic acid dimethyl ester were
also characterized in jujube (Mahajan and Chopda, 2009).
Pharmacological properties
Antidiabetics effect
Atherogenic dyslipidemia, characterized by an increased level of lipoprotein and a decreased level of
adiponectin, is a major risk factor for cardiovascular diseases in diabetic patients. Jujube extract is
beneficial in ameliorating oxidative stress and atherogenic risk of diabetic rats (Hemmati et al.,
2015b). Also, it has been able to increase significantly HDL-C with no effect on total cholesterol and
LDL-C. This beneficial effects of jujube extract in diabetic rats may be associated with increase in
adiponectin level (Hemmati et al., 2015a). Postprandial hyperglycemia plays an important role in the
development of type 2 diabetes. Inhibition of alpha-amylase was led to a delay in breaks down of
starch and glycogen and prevented a rapid rise in blood sugar. Due to the high polyphenolic content
and antioxidant capacity and significant inhibitory effect of jujube on alpha-amylase, this plant can be
proposed for treatment of diabetic patients (Afrisham et al., 2015). Valavi et al. (2016) revealed that
hydroalcoholic extract of jujube could improve diabetes by influencing lipid peroxidation and
changing the antioxidant capacity. Z. jujube fruit infusion has had beneficial effects on glycosylated
haemoglobin and lipid profile in type 2 diabetes mellitus patients (Yazdanpanah et al., 2017). Hussein
et al. (2006) reported that extracts of Z. spina christi and Z. jujuba have beneficial effects on diabetic
rats. They reduced hyperglycemia, hyperlipidemia and lipid peroxides that associate diabetes. Besides,
they were safe towards liver and kidney functions. The effect of Z. jujuba was more pronounced than
that of Z. spina christi.
Hypnotic-sedative and anxiolytic effect
Flavonoids and saponins from seed of jujube showed sedative and hypnotic effects, which caused a
significant reduction of walking time and coordinated movement ability of mouse, significantly
prolonging its sleeping time. They are known to depress activity of the central nervous system which
reduces anxiety and induces sleep. It was found that it produced sleep, but was not anticonvulsant or
muscle relaxant. The inhibitory effect of Jujuboside A on rat hippocampus was demonstrated. Jujube
was found to increase pentobarbital-induced sleep time and to reduce free movement on mice (Chen et
al., 2017). Anxiolytic effects in mice of a polyherbal substance containing seed extract of jujube were
reported. Both sanjoinine A and nuciferine, alkaloids obtained from fruit, prolonged the sleeping time
produced by hexobarbital. When sanjoinine was heated it was found to produce an isomer of even
greater sedative effect (Mahajan and Chopda, 2009).
Neuroprotective activity
Among different types of flavonoids in jujube, kaempferol 3-O-rutinoside possessed neuroprotective
activity against oxidation insult and prevention of Aaggregation. Quercetin 3-O-rutinoside was shown
to have anti-Aβ aggregation effect. Both (-)-catechin and (-)-epicatechin showed inhibition of
Aβ aggregation and Aβ-induced toxicity. In addition, kaempferol 3-O-rutinoside showed protective
effect on permanent focal cerebral ischemia and on neuronal cultures, as well as in reducing memory
dysfunction, energy metabolism failure, and oxidative stress in multi-infarct dementia model rats
(Chen et al., 2017). Kaeidi et al. (2015) concluded that the aqueous extract of jujube protects against
hyperglycaemia-induced cellular toxicity. This could be associated with the prevention of ROS
generation and neural apoptosis. Moreover, they suggested that it has a therapeutic potential to
attenuate diabetes complications such as neuropathy.
Sweetness inhibitors
Triterpenoid sweetness inhibitors were isolated from jujube. Extracts from the leaves of jujube have
been found to suppress sweet taste sensation in fly (Pharma regina), rat and hamster. Antisweet
substances isolated from jujube included jujubasponins II, III, IV, V and VI from the leaves,
jujuboside B from the leaves and seeds and ziziphus saponins I-III from dried fruit. Ziziphin and
jujubosaponins II and III, the only three of the anti-sweet saponins from this plant with acyl groups,

were up to 4 times more active in suppressing the sweet taste of sucrose than the other anti-sweet
constituents and thereby reducing obesity in diabetic or overweight people. The saponin,
ziziphin suppressed the sweetness induced by D-glucose, D-fructose, stevioside, glycine, sodium
saccharin, aspartame and naringin dihydrochalcone. It however showed no suppressive effect on the
sour taste of hydrochloric acid and the bitter taste of quinine indicating that ziziphin is highly specific
to sweet taste. Ziziphin was found to inhibit the sweet taste receptors in humans. The mechanism
which ziziphin used was identified as taste modification (Mahajan and Chopda, 2009).
Anticancer activity
Triterpenic acids and polysaccharides of jujube fruit have antiproliferative and anticancer effects on
various cancer cell lines (Tahergorabi et al., 2015). Huang et al. (2007) investigated the mechanism of
anti-cancer activity of jujube in human hepatoma cells (HepG2) and suggested that the chloroform
fraction of extract induced a concentration dependent effect on apoptosis and a differential cell cycle
arrest in HepG2 cells. The in vitro cytotoxicities of the triterpenoic acids extracted from jujube were
tested against tumour cell lines. The lupane-type triterpenes showed high cytotoxic activities. The
cytotoxic activities of 3-O-p-coumaroylalphitolic acids were found to be better than those of non-
coumaroic triterpenenoids. These results suggest that the coumaroyl moiety at the C-3 position of the
lupane-type triterpene may play an important role in enhancing cytotoxic activity. The triterponic acid,
betulinic acid, extracted from jujube showed selective toxicity against cultured human melanoma cells.
It is thought that betulinic acid may also be effective against other types of cancer. Considerable in
vitro evidence has demonstrated that betulinic acid is effective against small- and non-small-cell lung,
ovarian, cervical, and head and neck carcinomas. Betulinic acid induces apoptosis in sensitive cells in
a p53- and CD95-independent fashion (Mahajan and Chopda, 2009). Hoshyar et al. (2015) indicate
that the aqueous extract of Z. jujube fruit exhibited a preventive effect against anaemia, lymphocytosis
and neutrophilia in rats and could be useful for treating mammary tumours in humans.
Antimicrobial activity
Ethanol extract of the jujube root showed significant inhibitory activity on fungi Candida albicans, C.
tropicalis, Aspergillus flavus, A. niger and Malassezia furfur (strains 1374 and 1765). Additionally,
extract of root bark exhibited antibacterial activity against 20 bacteria. Betulinic acid isolated from
stem bark has also been found to retard the progression of HIV 1 infection that is antiviral
activity (Mahajan and Chopda, 2009). Ethanolic extracts from jujube fruits have effective
antimicrobial impact against Escherichia coli, Staphylococcus aureus as well as C. albicans and A.
fumigatus, so as it revealed more effective antimicrobial activity compared to common antibiotic like
Vancomycin, and it is appropriate candidate for treatment of microbial infections, especially pediatric
infectious diseases (Daneshmand et al., 2013). Also, methanolic crude extracts had potent antibacterial
agent against E. coli, Salmonella typhi and Pseudomonas aeruginosa (Shad et al., 2013).
Antiulcer activity
Jujube leaves extract possesses significant and dose dependent antiulcer activity that can be attributed
to its cytoprotective and antisecretory action (Ganachari and Kumar, 2004). The root was also found to
have antiulcerogenic effect, which could be related to its antioxidant potential (Alam et al., 2016).
Anti-inflammatory and antispastic effect
Triterpenic acids were considered as active ingredients for the effect on anti-inflammatory and
anticancer activities (Chen et al., 2017). Ziziphus leaves possess significant anti-inflammatory
properties against carrageenan-induced rat paw oedema (Hovanet et al., 2016a).
Antiallergic activity
Jujube was shown to have strong anti-allergic activity. The anti-allergic activity of the aqueous
extracts of leaves was studied by measuring its inhibitory effect on hyaluronidase (bovine testes)
activation in vitro (Mahajan and Chopda, 2009). Naik et al. (2013) evaluated anti-allergic and anti-
anaphylactic activity of ethanolic extract of jujube fruits in rodents. They suggested that the observed
anti-allergic and anti-anaphylactic activity of extract may be largely through the stabilization of mast
cells by the membrane presence of phytoconstituents (steroidal saponins and flavonoids).
Permeability enhancement activity
Delivery of certain classes of drugs such as peptides creates problems in transportation across cell
membranes and subsequent diminished bioavailability. To overcome this barrier, permeability

enhancers can be used to aid the passage of drugs across cell membranes. To assess the permeability
enhancing activity of jujube, an aqueous extract of seeds was compared to two members of a known
series of permeability enhancement agents belonging to the alkyl glycosides (Eley and Dovlatabadi,
2002).
Cognitive activities
Jujube was reported to improve learning and memory in ovariectomized rat model, and the effect of
which might be due to an increase of estrogen in the blood, as well as the levels of nitric oxide and
acetylcholine in the brain. Oleamide (cis-9octadecenoamide) was found to attenuate the scopolamine-
induced amnesia in mice, a useful in vivo model for Alzheimer disease (Chen et al., 2017). Methanolic
extract of jujube was showed 34.1 % activation effect on choline acetyltransferase in vitro, an enzyme
that controls the production of acetylcholine which appears to be depleted in the brains of Alzheimer
patients. Using sequential fractionation the active ingredient was found to be oleamide which showed
65% activation effect (Mahajan and Chopda, 2009).
Antifertility/contraceptive property
The ethyl acetate extract of jujube bark was found to effect antisteroidogenic activity and hence
fertility in adult female mice. It was found to arrest the normal estrus cycle of adult female mice at
diestrus stage and reduced the wet weight of ovaries significantly. Hematological profiles, biochemical
estimations of whole blood and serum remained unaltered in extract-treated mice. Normal estrus cycle
and ovarian steroidogenisis were restored after withdrawal of treatment. Antifertility activities of
crude extracts were found to be reversible in rat (Mahajan and Chopda, 2009). The petroleum ether
extract of jujube leaves was evaluated for anti-fertility activity in the adult male mouse. Extracts were
found to produce significant inhibition of sperm motility and cause reduction in viability of sperm cell.
It is evident that jujube severely affects male animal fertility parameters and its antifertility effects are
reversible (Rekha and Chandrashekhara, 2014).
Hypotensive and antinephritic effect
Jujube has been found to stimulate nitric oxide release in vitro, in cultured endothelial cells and in
vivo, in the kidney tissues of rats. It may contribute to hypotensive (reduction of blood pressure) and
antinephritic (reduction of inflammation of the kidney) action, possibly by increasing renal blood flow
(Mahajan and Chopda, 2009).
Cardiovascular activity
Betulinic acid and jujuboside B could be the active components showing beneficial effects on
cardiovascular system (Chen et al., 2017).
Immunostimulant effects
Jujube polysaccharides were proposed to be main active ingredients contributing to its immune-
modulating and hematopoietic functions (Chen et al., 2017). Water-soluble polysaccharides of Z.
jujuba cv. Dongzao revealed immunobiological activities especially in fruits and flowers (Zhao et
al., 2008). The leaf extract of jujube was also found to stimulate chemotactic, phagocytic and
intracellular killing potency of human neutrophils at 5-50 µg/ml (Mahajan and Chopda, 2009).
Antioxidant effects
The flavonoid and polysaccharide could account for antioxidative effect of jujube (Chen et al., 2017).
A comprehensive and an exhaustive account on 70 antioxidant Korean medicinal plants have been
reported and were confirmed antioxidant effect of Z. jujuba (in vitro) (Mahajan and Chopda, 2009).
Shad et al. (2013) and Al-Saeedi et al. (2016) also demonstrated that the leaf and fruit extracts
of jujube exhibited significant antioxidant activity.
Wound healing activity
The methanol bark extract of jujube demonstrated a significant increase in protein and wound closure.
Any one of the phytochemical constituents in extract may be responsible for the wound healing
activity. Flavonoids and tannins are known to promote wound healing process mainly due to their
astringent and antimicrobial properties, hence it can be inferred that the wound healing activity of the
methanol bark extract of jujube observed is partly to its flavonoids and tannin contents, which seems
to be responsible for wound contraction and increased rate of epithelization (Sampath Kumar et al.,
2012). Wound healing properties of root and leaves of jujube have also been reported (Chopda et al.,
2014; Hovanet et al., 2016b).

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and prune cultivars and genotypes in Karaj. M.Sc Thesis of Horticultural Science, Islamic Azad University-
Karaj Branch.
Al-Saeedi, A.H. Humaid Al- Ghafri, M.T. and Amzad Hossain, M. (2016). Comparative evaluation of total
phenols, flavonoids content and antioxidant potential of leaf and fruit extracts of Omani Ziziphus jujuba L.
Pacific Science Review A: Natural Science and Engineering. 18(1): 78-83.
Amraei, A. Miri, S.M. and Souri, M.K. (2014). The effect of spray on boric acid on cracking and quantitative
and qualitative characteristics of fruit of five pomegranate genotypes in Kuhdasht. M.Sc Thesis of
Horticultural Science, Islamic Azad University-Karaj Branch.
Asghari Lalemi, S. Naghavi, M.R. and Miri, S.M. (2013). Morphological study and Trigonellin levels in 7 native
Trigonella monantha ssp noeana ecotypes. First National Conference on Medicinal Plants and Sustainable
Agriculture, Hamedan, Iran.
Aslani, M. Alizadeh, M.A. Miri, S.M. and Seiedian, S.E. (2015a). Study of morphological traits, shoot and
essential oil yields of Tanacetum pinnatum species. 2nd National Congress on Herbal Drugs & National
Seminar in Medicinal and Aromatic Plants. Shahr-e-Kord, Iran.
Aslani, M. Alizadeh, M.A. Miri, S.M. and Seiedian, S.E. (2015b). Study of morphological traits, shoot and
essential oil yields of Tanacetum tabrisianum species. 2nd National Congress on Herbal Drugs & National
Seminar in Medicinal and Aromatic Plants. Shahr-e-Kord, Iran.
Bai, H.L. Wang, J. Liu, C.M. and Li, L. (2010). Isolation and purification of flavonoids from Ziziphus jujuba by
high‐speed counter‐current chromatography. Journal of the Chinese Chemical Society.57(5A): 1071-1076.
Chen, J. Liu, X. Li, Zh. Qi, A. Yao, P. Zhou, Zh. Dong, T.T.X. and Tsim, K.W.K. (2017). A review of
dietary Ziziphus jujuba fruit (jujube): developing health food supplements for brain protection. Evidence-
Based Complementary and Alternative Medicine. 2017: Article ID 3019568.
Chen, K.X. Zhao, L.M. Ji, C.J. and Tan, N.H. (2015). Flavone C-glycosides from seeds of Ziziphus jujuba var.
spinose. Zhongguo Zhong Yao Za Zhi. 40(8): 1503-1507.
Cheng, G. Bai, Y. Zhao, Y. and Xu, X. (2000). Flavonoids from Ziziphus jujuba Mill var. Spinosa.
Tetrahedron. 56(45): 8915-8920.
Chopda, M.Z. Nemade, N.V. and Mahajan, R.T. (2014). Wound healing activity of root of Ziziphus jujuba Mill
in rat model. World Journal of Pharmacy and Pharmaceutical Sciences. 3(9): 830-836.
Daneshmand, F. Zare-Zardini, H. Tolueinia, B. Hasani, Z. and Ghanbari, T. (2013). Crude extract from Ziziphus
Jujuba fruits, a weapon against pediatric infectious disease. Iranian Journal of Pediatric Hematology
Oncology. 3(1): 35-40.
Eley, J.G. and Dovlatabadi, H. (2002). Permeability enhancement activity from Ziziphus jujuba. Pharmaceutical
Biology. 40: 149-153.
Ganachari, M.S. and Kumar, Sh. (2004). Anti-ulcer properties of Ziziphus jujuba Lam leaves extract in rats.
Journal of Natural Remedies. 4/2: 103 -108.
Gao, Q.H. Wu, Ch.S., and Wang, M. (2013). The jujube (Ziziphus Jujuba Mill.) fruit: A review of current
knowledge of fruit composition and health benefits. Journal of Agricultural and Food Chemistry. 61(14):
3351-3363.
Guo, Sh. Tang, Y.P. Duan, J.O. Su, Sh.L. and Ding, A.W. (2009). Two new terpenoids from fruits of Ziziphus
jujuba. Chinese Chemical Letters. 20(2): 197-200.
Haghighat, F. Miri, S.M. and Hassani, D. (2015). Study of qualitative and quantitative properties and yield of
some cultivars of strawberry. M.Sc Thesis of Horticultural Science, Islamic Azad University-Karaj Branch.
Hamedi, Sh. Shams-Ardakani, M.R. Sadeghpour, O. Amin, Gh. Hajighasemali, D. and Orafai, H. (2016).
Designing mucoadhesive discs containing stem bark extract of Ziziphus jujuba based on Iranian traditional
documents. Iranian Journal of Basic Medical Sciences. 19(3): 330-336.

Hemmati, M. Asghari, S. Zohoori, E. and Karamian, M. (2015a). Hypoglycemic effects of three Iranian edible
plants; jujube, barberry and saffron: Correlation with serum adiponectin level. Pakistan Journal of
Pharmaceutical Sciences. 28(6): 2095-2099.
Hemmati, M. Zohoori, E. Mehrpour, O. Karamian, M. Asghari, S. Zarban, A. and Nasouti, R. (2015b). Anti-
atherogenic potential of jujube, saffron and barberry: anti-diabetic and antioxidant actions. EXCLI
Journal. 14: 908–915.
Hoshyar, R. Mohaghegh, Z. Torabi, N. and Abolghasemi, A. (2015). Antitumor activity of aqueous extract
of Ziziphus jujube fruit in breast cancer: An in vitro and in vivo study. Asian Pacific Journal of
Reproduction. 4(2): 116-122.
Hosseini, M. Miri, S.M. and Souri, M.K. (2013). Effect of phenyl phthalamic acid and potassium nitrate
spraying on quantitative and qualitative characteristics of strawberry ‘Gaviota’. M.Sc Thesis of
Horticultural Science, Islamic Azad University-Karaj Branch.
Hovaneţ, M.V. Ancuceanu, R.V. Dinu, M. Oprea, E. Budura, E.A. Negreş, S. Velescu, B.S. Duţu, L.E. Anghel,
I.A. Ancu, I. Moroşan, E. and Şeremet, O.C. (2016a). Toxicity and anti-inflammatory activity of Ziziphus
jujuba Mill. leaves. Farmacia. 64(5): 802-805.
Hovaneţ, M.V. Oprea, E. Ancuceanu, R.V. Duţu, L.E. Budura, E.A. Şeremet, O.C. Ancu, I. and Moroşan, E.
(2016b). Wound Healing Properties of Ziziphus jujuba Mill. leaves. Romanian Biotechnological Letters.
21(5): 11842-11849.
Huang, J. Heyduck, R. Richins, R. VanLeeuwen, D. O’Connell, M. and Yao, S. (2017). Jujube cultivar vitamin
C profile and nutrient dynamics during maturation. HortScience. 52(6): 859-867.
Huang, X. Kojima-Yuasa, A. Norikura, T. Kennedy, D.O. Hasuma, T. and Matsui-Yuasa, I. (2007). Mechanism
of the anti-cancer activity of Zizyphus jujuba in HepG2 cells. The American Journal of Chinese Medicine.
35(3): 517-32.
Hussein, H.M. El-Sayed, E.M. and Said, A.A. (2006). Antihyperglycemic, antihyperlipidemic and antioxidant
effects of Zizyphus spina christi and Zizyphus jujuba in alloxan diabetic rats. International Journal of
Pharmacology. 2(5): 563-570.
Izan, J. Hadavi, E. and Miri, S.M. (2013). Effect of tissue culture derived treatments on the rate of bud-take in
Persian walnut (Juglans regia L.). M.Sc Thesis of Horticultural Science, Islamic Azad University-Karaj
Branch.
Jalili Moghadam, Z. Mostafavi, M. and Miri, S.M. (2012). Quantitative and qualitative study of ten genotypes of
pomegranate and comparison of their shelf life in the storage. M.Sc Thesis of Horticultural Science,
Islamic Azad University-Karaj Branch.
Ji, X. Peng, Q. Yuan, Y. Shen, J. and Xie, X. (2017). Wang, M. Isolation, structures and bioactivities of the
polysaccharides from jujube fruit (Ziziphus jujuba Mill.): A review. Food Chemistry. 227: .349-357.
Kaeidi, A. Taati, M. Hajializadeh, Z. Jahandari, F. and Rashidipour, M. (2015). Aqueous extract of Zizyphus
jujuba fruit attenuates glucose induced neurotoxicity in an in vitro model of diabetic neuropathy. Iranian
Journal of Basic Medical Sciences. 18(3): 301–306.
Kang, K.B. Ming, G. Kim, G.J. Ha, T.K. Choi, H. Oh, W.K. and Sung, S.H. (2015). Jubanines F-J, cyclopeptide
alkaloids from the roots of Ziziphus jujuba. Phytochemistry. 119: 90-95.
Keshavarzi, M. Rezaie, M.B. and Miri, S.M. (2013). Study of Stachys lavandulifolia Vahl application in Iran. 3rd
National Congress on Medicinal Plants, Amol, Iran.
Keshavarzi, M. Rezaie, M.B. and Miri, S.M. (2014a). Chemical composition of the essential oils extracted
Stachys lavandulifolia Vahl in Iran. 3rd National Congress on Medicinal Plants, Mashhad, Iran.
Keshavarzi, M. Rezaie, M.B. and Miri, S.M. (2014b). Quantitative and qualitative evaluation of the essential oil
of different populations of Stachys lavandolifolia Vahl. in Iran. Second National Conference on Medicinal
Plants and Sustainable Agriculture, Hamedan, Iran.
Keshavarzi, M. Rezaie, M.B. and Miri, S.M. (2015a). Evaluation of morphological and phytochemical of
Stachys lavandulifolia Vahl in field conditions. 4rd National Congress on Medicinal Plants, Tehran, Iran.
Keshavarzi, M. Rezaie, M.B. and Miri, S.M. (2015b). Phytochemical composition of the essential oil of different
populations of Stachys lavandulifolia Vahl in Iran. 4rd National Congress on Medicinal Plants, Tehran,
Iran.
Keshavarzi, M. Rezaie, M.B. and Miri, S.M. (2016). The comparision of morphological and phytochemical
evaluation in some population of Stachys lavandulifolia Vahl. in different provinces under field conditions.
Eco-phytochemical Journal of Medicinal Plants. 14(2): 78-87.
Khaiati, N. Miri, S.M. and Kalantari, S. (2017). Study of the effect of salicylic acid and Shirazi thyme essence on
improving the storage life of pomegranate fruit Malas-e-Saveh. M.Sc Thesis of Horticultural Science,
Islamic Azad University-Karaj Branch.

Kiani Majd, S. Miri, S.M. and Kalantari, S. (2013). Effect of pre-and post-harvest treatment of salicylic acid on
shelf life of Pearl Tangelo mandarin. M.Sc Thesis of Horticultural Science, Islamic Azad University-Karaj
Branch.
Lee, M.K. Kim, H.W. Kim, Y.J. Lee, S.H. Jang, H.H. Jung, H.A. Kim, S.B. Lee, S.H. Choe, J.S. and Kim, J.B.
(2016). Profiling of flavonoid glycosides in fruits and leaves of jujube (Zizyphus jujuba var. inermis
(Bunge) Rehder) using UPLC-DAD-QTOF/MS. Korean Journal of Food Preservation. 23(7): 1004-1011.
Li, G. Wu, L. Wei, J. Xu, S. Huang, H. Gao, X. and Hu, Q.F. (2013). Two new flavonoids from the fruits
of Ziziphus jujuba. Chemistry of Natural Compounds. 49(4): 617-620.
Mahajan, R.T. and Chopda, M.Z. (2009). Phyto-pharmacology of Ziziphus jujuba Mill- A plant review.
Pharmacognosy Review. 3(6): 320-329.
Momeni, H. Bouzari, N. and Miri, S.M. (2015). Study of some morphological, pomological and biochemical
characteristics in some Iranian native sour cherry genotypes. M.Sc Thesis of Horticultural Science, Islamic
Azad University-Karaj Branch.
Mousavi, S.S. Miri, S.M. and Moradi, P. (2016). Study of jujube micropropagation in in vitro conditions. M.Sc
Thesis of Horticultural Science, Islamic Azad University-Karaj Branch.
Mousavi, S.S. Miri, S.M. and and Moradi, P. (2017a). Effect of medium and indole butyric acid (IBA) on in
vitro rooting of jujube. 2nd International and 10th National Biotechnology Congress of Islamic Republic of
Iran, Karaj, Iran.
Mousavi, S.S. Miri, S.M. and and Moradi, P. (2017b). Effects of media and benzyl adenine (BA) on in vitro
shoot multiplication of jujube. 2nd International and 10th National Biotechnology Congress of Islamic
Republic of Iran, Karaj, Iran.
Mousavi, S.S. Miri, S.M. and and Moradi, P. (2017c). Optimization of micropropagation of jujube (Ziziphus
jujuba cv. Tian-yuzao). Journal of Agronomy and Plant Breeding. 13(4): 1-11.
Naeimi, Kh. Abdollahi, H. and Miri, S.M. (2018). Evaluation of vegetative and reproductive characteristics of
quince germplasm in north west of Iran (Ardabil). M.Sc Thesis of Horticultural Science, Islamic Azad
University-Karaj Branch.
Naik, S.R. Bhagat, S. Shah, P.D. Tare, A.A. Ingawale, D. and Wadekar, R.R. (2013). Evaluation of anti-allergic
and anti-anaphylactic activity of ethanolic extract of Zizyphus jujuba fruits in rodents. Revista Brasileira de
Farmacognosia. 23(5): 811-818.
Negini Kalkhoran, M. Bouzari, N. Miri, S.M. and Imani, A. (2012). Study of pomological and morphological
characteristics of some sweet cherry cultivar and genotypes using UPOV descriptor. M.Sc Thesis of
Horticultural Science, Islamic Azad University-Karaj Branch.
Nikdehghan, S. Naghavi, M.R. Miri, S.M. (2013a). Morphological evaluation of different subspecies of
marjoram (Origanum vulgare) from Iran. 8th National Horticultural Science Congress of Iran, Hamedan,
Iran (in Farsi).
Nikdehghan, S. Naghavi, M.R. and Miri, S.M. (2013b). Variety of essential oil compounds between 6 ecotypes
of Marjoram (Origanum vulgare ssp. Viride) native of Iran. First National Conference on Medicinal Plants
and Sustainable Agriculture, Hamedan, Iran.
Nobari, F. Afshari, H. and Miri, S.M. (2012). Physiological analysis of cold resistance in commercial pistachio
cultivars of Damghan. M.Sc Thesis of Horticultural Science, Islamic Azad University-Karaj Branch.
Rekha, S. and Chandrashekhara, S. (2014). Anti fertility effect of Ziziphus jujuba Mill. World Journal of
Pharmacy and Pharmaceutical Sciences. 3(3): 1363-1370.
Roughani, A. Miri, S.M. Hassandokht, M.R. Moradi, P. and Abdossi, V. (2018a). Agro-morphological study on
several accessions of garden cress (Lepidium sativum-Brassiaceae) in Iran. Pakistan Journal of Botany.
50(2): 655-660.
Roughani, A. Miri, S.M. Hassandokht, M.R. Moradi, P. and Abdossi, V. (2018b). Morphological variation of
some Lepidium draba and L. latifolium populations. Taiwania. 63(1): 41-48.
Sampath Kumar, Ch. Arutla, R. Swaroopa, D. and Sridhar Rao, K. (2012). Wound healing potential of Ziziphus
jujuba bark extract on albino rats. International Journal of Research in Ayurveda and Pharmacy. 3(6): 830-
832.
Shad, A.A. Ahmad, Sh. Ullah, R. AbdEl-Salam, N.M. Fouad, H. Ur Rehman, N. Hussain, H. and Saeed, W.
(2014). Phytochemical and biological activities of four wild medicinal plants. The Scientific World Journal.
2014: 857363.
Shams Olshoara, Y. Javadi, H. Miri, S.M. (2017). Evaluation of cytogenetic diversity of eight populations of
three Astragalus species. 6th Congress of Agriculture and Sustainable Natural Resources, Tehran, Iran.
Sulusoglu, M. Cavusoglu, A. Dede, N. and Unver, H. (2014). Morphological, pomological and nutritional traits
of jujube (Zizyphus jujuba Mill.). 49th Croatian & 9th International Symposium on Agriculture, Valamar
Lacroma Dubrovnik, Crotia.

Tahergorabi, Z. Abedini, M.R. Mitra, M. Fard, M.H. and Beydokhti, H. (2015). “Ziziphus jujuba”: A red fruit
with promising anticancer activities. Pharmacognosy Reviews. 9(18): 99-106.
Tanha, M. Miri, S.M. and Hadavi, E. (2015). Investigation of spraying calcium chloride and salicylic acid on
quantitative and qualitative characteristics of grape cultivar of Bidaneh Sephid. M.Sc Thesis of Horticultural
Science, Islamic Azad University-Karaj Branch.
Tripathi, M. Pandey, M.B. Jha, R.N., Pandey, V.B. Tripathi, P.N. and Singh, J.P. (2001). Cyclopeptide alkaloids
from Zizyphus jujuba. Fitoterapia. 72(5): 507-510.
Valavi, M. Mezginejad, F. Haghighi, F. Hemmati, M. Zarban, A. and Rabiei Gask, E. (2016). Effectiveness of
aqueous and alcoholic extracts of barberry, jujube, and saffron against oxidative stress in Streptozotocin-
induced diabetic rats. Modern Care Journal. 13(3): e11162.
Yao, Sh. (2013). Past, present, and future of jujubes- Chinese dates in the United States. HortScience. 48(6):
672–680.
Yaraei-Rostami, M. Ghasemnezhad, M. Miri, S.M. and Ghodsvali, A. (2013a). Effect of foliar spray with
salicylic acid and waxing treatment on quality and storage life of orange fruit cv. Moro. 8th National
Horticultural Science Congress of Iran, Hamedan, Iran.
Yaraei-Rostami, M. Ghasemnezhad, M. Miri, S.M. and Ghodsvali, A. (2013b). Effect of foliar spray with
salicylic acid and waxing treatment on quality and storage life of orange fruit cv. Thamson Navel. 8th
National Horticultural Science Congress of Iran, Hamedan, Iran.
Yazdanpanah, Z. Ghadiri‐Anari, A. Vahidi Mehrjardi, A. Dehghani, A. Zare Zardini, H. and Nadjarzadeh, A.
(2017). Effect of Ziziphus jujube fruit infusion on lipid profiles, glycaemic index and antioxidant status in
type 2 diabetic patients: A randomized controlled clinical trial. Phytotherapy Research. 31(5): 755-762.
Zhao, Z. Liu, M. and Tu, P. (2008). Characterization of water soluble polysaccharides from organs of
Chinese Jujube (Ziziphus jujuba Mill. cv. Dongzao). European Food Research and Technology. 226(5):
985-989.