Jujube / Ber (Hindi) / K`ool (Bengali)

General features: The scientific name is Ziziphus jujuba. In Hindi, it is named Ber but in Bengali it is commonly called K`ool (কুল ). This perennial fruit plant belongs to the Rhamnaceae family of Ziziphus genus. Considering the appearance, it can be counted to be a plant or even shrub that grows wildly in warm or temperate climates. Indian jujube is classified as Ziziphus mauritania which also belongs to the same Rhamnaceae family of identical genus [1]. The fruit, ziziphus jujuba carries few other names, Chinese date / Red date which have different outlook compared to its Indian or Bengali counterpart. The English names of Indian jujube are Indian Plum. Indian jujube prefers warm tropical or subtropical climate to grow but the others tend to grow in moderate or temperate conditions. Indian types are smaller in size, grow wildly and found in the eastern or southern states of India. The plant is considered being the native of India even though Chinese categories breed in India also [2]. Besides the South Asian nations like China, Malaysia, Cambodia, Thailand, Vietnam and Laos, Jujube grow in Caribbean islands, Africa, Australia, Jamaica, Venezuela, Fiji, Pacific islands, and many of the Latino nations [3]. It is a thorny perennial plant / shrub reaching ~ 40 ft height having 15 inches or more diameter trunk which spreads pinnacles with many drooping branches. The fruits have variable shapes and sizes, often rounded or oval, or oblong, or even obovate with 1 – 2.5 inches in length. The flesh is white and crisp. The green underripe fruits are juicy and tasty, spreading pleasant aroma. The fruit skin is very glossy and smooth. The seed is identical to olive pit. The leaves are shiny green and ovate, 2 – 3 inches long and 1.3 inches wide having three veins at base with fine toothed margin. The flowers are tiny, 0.25 inches wide and have five yellowish-green petals. Seemingly, the plant has been domesticated in South Asia since almost 9000 BC. More than four hundred cultivars have been selected / identified so far [4]. The fruits synthesize various Phyto-ingredients like saponins, flavonoids, and alkaloids which detoxify blood, eliminates harmful toxins preventing numerous blood diseases. The small berry like fruits are loaded with important minerals like potassium, manganese, iron, and zinc. It improves the hemoglobin level preventing the occurrence of anemia and subsequently regulates adequate blood flow in the body. In a way, Jujube fruits have multitude of beneficial role on health [5]:

  1. Improving mental health and brain function
  2. Helping controlling blood pressure
  3. Acting as antiinflammatory, antiallergic, and antimicrobial agent
  4. Acting as antioxidant
  5. Controlling diabetes   
  6. Improving digestive health
  7. Relieving cough
  8. Acting as anticancer agent
  9. Enabling to detoxify blood
  10. Preventing osteoporosis
  11. Acting as anti-aging agent

History of Jujube: The source of name is found from the ancient Greek language. Afterward it was modified in Classical Latin language, Zizyphum meaning fruit and Zizyphus, the tree. Further modification occurred also in Roman language and finally settled by the French converting to ‘Jujube’ which is accepted now also in English. The legendary Karl Linnaeus, the inventor of binomial naming, named it Rhamnus ziziyphus in his book “Species Plantarum” in 1753 AD. But in 2011, a new name has been proposed and finally accepted to be Zizyphus jujuba [6]. Jujube has been considered to be the native of both India and China. In India although regarded as a fruit but mostly popularized to be a vegetable for making “Achar”, the tasty condiments enable to make food far more delicious. It is highly popularized in China. Jujube’s name has been noted in Chinese poems around 1046 – 771 BC. In ancient Chinese medical book (Huangdi Neijing), jujube has been documented (475 – 221 BC) to be one of the most valuable fruits or herbs of China. It is also enumerated to be one of the superior herbal medicines that can prolong life providing nourishment, regulating digestive system, and improving sleep behavior. Jujube is known being consumed for thousands of years in the Asian and other tropical nations.[7].

Folk uses: The leaves, stem, and fruits are consumed for different medicinal reasons. Normally, people are quite fond of fruits for its alluring deliciousness. But besides the delicacy they also serve numerous medicinal actions providing antitussive, laxative, and blood pressure lowering effects. The extract of stem bark and leaves exhibit a number of activities by acting as antidiabetic, tonic, aphrodisiac, hypnotic, sedative, anxiolytic, anticancer, antifungal, antibacterial, antiulcer, antiinflammatory, antispastic, antifertility, hypotensive, antinephritic, antioxidant, immunostimulant, and wound healing effects including the oral wound [7]. Recent studies indicate that all these effects are exerted by selective phytochemicals synthesized within various plant parts. The major active phytocomponents are Vitamin C, flavonoids, phenolics, triterpene acids, alkaloids, and a few polysaccharides. Additionally, fruits show Antiobesity, antiinflammatory, hepatoprotective, and gastrointestinal protective effects including the inhibition of foam cell formation in macrophages [7,8].

Medicinal uses: In general Jujube fruits and plant parts are effective either to control or cure number of ailments that includes diabetes, diarrhea, skin infection, urinary problems, liver problems, fever, obesity, bronchitis, pharyngitis, insomnia, anemia, cancer, blood purification, and gastrointestinal problems. It also reduces triglycerides, LDL, and cholesterol levels in the circulating blood. The fruits can prevent vomiting. It is also often used in treating tuberculosis or even employed to act as an antidote for aconite poisoning. The seeds have the ability to cure eye diseases and are useful to treat leukorrhea. The kernel provides sedative actions. The fruits have anxiolytic effects on the nervous system and provides neuroprotective actions against any impairments caused by stress or toxins. It stimulates neuronal differentiation, increasing the expression of neurotrophic factors thereby helping promote learning and memory functions in brain [8,9].

Phytochemical components and pharmacological role: The major phytocomponents are varieties of sugars / carbohydrates, vitamins, fatty acids, alkaloids, saponins, glycosides, and terpenoids.

Sugars and carbohydrates – Jujube has an appreciated amount of dietary fiber in addition to glucose, fructose, sucrose, rhamnose, and sorbitol. High dietary fiber helps regulate blood sugar by slowing down digestion [10]. On the other hand, polysaccharides exert a number of biological effects like antioxidant, immunomodulatory, antitumor, gastroprotective, hepatoprotective, and hypoglycemic. The fruit has Pectin – A (2-3-6-tri-O-acetyl D-lactose). Pectin binds bile acid thereby enables to lower cholesterol. In addition, it has an antidiarrheal effect. The water-soluble fractions are enriched with uronic acid, arabinose, and galactose. Jujube fruits are a good source of Magnesium (10 mg / 100g), Phosphorous (23 mg / 100 g), Sodium (3.0 mg / 100 g), Potassium (250 mg / 100 g) and Zinc (0.05 mg / 100 g) [10].

Vitamins – Jujube is extremely rich in vitamin C in comparison to any other fruits. The average vitamin C of jujube ranges from 225 – 530 mg / 100 g fresh weight during the early maturing stage. The fruits also produce vitamin B1 (Thiamin) and B2 (Riboflavin). It also contains high levels of flavonoids often described as vitamin P, 354 – 888 mg / 100 gm pulp. In a way, one piece of fresh fruit can meet the daily requirements for vitamin C, and B complex for an adult. Noticeably, sun-drying process lowers the levels [5,10].

Fatty acids – The essential fatty acids isolated from the dried pulp of jujube are Oleic (mono unsaturated Omega – 9), linoleic (poly unsaturated Omega – 6), palmitic (saturated fatty acid), and palmitoleic (monounsaturated omega – 7 fatty acid) [11].

Alkaloids – Uniquely, a large number of cyclic peptide alkaloids have been isolated from the jujube plant. Noticeably, they are distributed all over the plant parts [8]. It is interesting to know that a large majority cyclic peptide alkaloids are synthesized mainly within the plants of Rhamnaceae family although others also produce but to a lesser level [5]. From the stem bark extract, the cyclic peptide alkaloids isolated are Mauritine A, Mucronine D, Amhibine H, Nummularine A-B, Sativanine  A-H-K, Frangulanine, Jujubine A-C, Scutianine C-D, and Ziziphine A [5,12,13].

Other alkaloids identified from the leaves are Coclauirine, Isoboldine, Nor-isoboldine, Asimilobine, Iusiphine, and Iusrine [5].

The seeds also contain several cyclic peptide alkaloids which are Sanjoinenine, Amhibine D and Frangulanine along with four of its isomers.

A majority of them exhibit many pharmacological actions which particularly includes sedative and analgesic properties. In addition, many of them exhibit parasite / antiplasmodial and antimicrobial effects particularly against Plasmodium falciparum (Malaria) and Myobacterium tuberculosis [5,8,11-13].

 Terpenoids – A large number of triterpene acids are isolated from the jujube fruits. The most noticeable ones are colubrinic acid, amphibolic acid, 3-O-cis-p-coumaroylalphitolic acid, 3-O-trans-p-coumaroyl-alphitolic acid, 3-O-cis -coumaroyl-maslinic acid, 3-O-trans -coumaroyl-maslinic acid, betulinic acid, Oleanonic acid, Zizyberenalic acid, Zizybernal acid, Zizibernanone, and Ursolic acid. Several of them are identified to exist with their esters [7,8,14,15].

Approximately, eleven triterpenoid acids have been identified so far from jujube fruits. An overwhelming majority of them exhibit cytotoxic activities on various tumor cells like, K562 (leukemia), B16(F-10) (mouse melanoma), SK-MEL-2 (human melanoma), PC-3 (metastatic human prostate carcinoma), LOX-IMVI (human melanoma-special type), and A549 (human lung adenocarcinoma). Interestingly, cytotoxic actions are more pronounced in the case of coumaroic triterpenoids than the others indicating coumaroic moiety at C-3 position of lupane triterpenes exert dominant role on cytotoxic actions [5,7,8]. On the other hand, those having oleanane moiety show anticomplement behavior against classical pathway of complement activations inhibiting hemolytic effects. Contrarily, lupane types are uniquely inactive in that regard [5,8]. There are also a few glycosides and saponins identified from seeds, leaves, and stems. They are Jujubosides A / B / A1 / B1/ C, acetyljujubosides B, and  protojujubosides A / B / B1. The majority of them play numerous biological roles. Jujuboside B can inhibit platelet aggregation, melanogenesis mediated by α- melanocyte hormone mediated melanogenesis [15]. It prevents proliferation of breast cancer cells in vitro and in vivo [16]. Further, Jujuboside A prevents excitatory signaling pathway during sleep-loss induced memory impairment via GABAergic mechanism [9,17]. Jujuboside B inhibits platelet aggregation and prevents α- melanocyte stimulated hormone (α- MSH) mediated melanogenesis. Studies also indicate that it is able to prevent proliferation of breast cancer cells both in vivo and in vitro [16 ]. Ursolic acid is a pentacyclic triterpene that has large potential as a therapeutic agent. It acts as an antiinflammatory, antioxidant, antiviral, serum lipid lowering, and anti-neoplastic agent. It promotes apoptosis inhibiting cancer cell proliferation via multiple mechanism eg, ROCK/PTEN and p53 pathways as well as suppressing NF-κβ while increasing Caspase – 3, 8 and 9 action [5].

Jujube fruits synthesize large amounts of phenolics (275 – 540 mg / 100 g of gallic acid equivalent) which is higher than cherries, apples, guava, persimmon, and red grape. Regarding flavonoids the level is also very high (62 – 285 mg / 100g).

Flavonoids have been known for their beneficial role on health mostly acting as antioxidant and scavenging harmful free radicals also inhibiting the lipid peroxidation thereby protecting health from cardiovascular problems. Flavonoid glycosides also show numerous advantageous health effects. Swertsin can act as antidiabetic agent. It induces islet differentiation generating beta cells. It is also an antagonist to adenosine receptor. So, it might provide protection against neurological problems like spinal injuries, Alzheimer’s disease, or Parkinson disorders [Riviera-Oliver M, Diaz- Rios M, Life Sci, 2014, 101(0), 1 – 9]. It also exhibits antiinflammatory and antioxidant effects [9,17].  

Besides the above phyto-ingredients jujube fruits are uniquely enriched with nucleosides and nucleobases (287.79 – 1239.23 µg /g) when studied using 43 cultivars each comprising of 49 samples. It has been established that nucleosides and its bases can regulate or modulate numerous physiological actions like inhibiting the platelet aggregation, exhibiting antiarrhythmic, antiseizure, antioxidant, and antitumor actions [7,9,14,17].

Pharmacological effects and health benefits: History indicates that Jujube plants and fruits are in use for a long period of time. Its health benefits are observed through historically acquired knowledge and from folk medicinal use. A majority of actions have been recorded in the laboratory. Below is the description of some of the important pharmacological effects.

Antidiabetic effect –  It has been noticed that postprandial hyperglycemia has an important role in type-2 diabetes. The inhibition of α – amylase hinders the breakdown of starch and glycogen preventing quick rise of blood sugar. The large phenolic content and due to its subsequent antioxidant role, the methanolic extract of Jujube fruits exerts considerable inhibitory role on pancreatic α – amylase enzyme, enabling to lower glucose level in the blood [8]. So, it can be used as a therapeutic measure in treating type-2 diabetes. The constant infusion of fruit extract shows beneficial effect on glycosylated hemoglobin level and lipid profile for the type-2 diabetic patients [18,19].

Cardiovascular actions – Atherogenic dyslipidemia characterized by elevated level of lipoproteins and subsequent lowering of adiponectin exerts high risk for cardiovascular diseases. The condition elevates triglyceride, LDL, apolipoprotein B and oxidized LDL along with succeeding lowering of the HDL. All these jointly produce a huge risk regarding cardiovascular problems [9,11,21]. Additionally, it has been noticed that long term consumption of Jujube extract at low level can prevent hypertension  induced by the nitric oxide (NO) deficiency. The steroidal saponin, Jujuboside B, plays a protective effect in this case. It promotes NO generation by enhancing the expression of endothelial nitric oxide synthase (eNOS) activity causing rapid Ca+2 influx while depleting the intracellular Calcium store within cells. The event reduces vascular tension. Thus, Jujuboside increases extracellular Ca+2 influx via endothelial transient receptor potential cation (TRPC) channels, phosphorylates eNOS, promotes NO generation in vascular endothelial cells, induces vasodilation via endothelial dependent hyperpolarization through K+ channels. Overall, this natural compound can improve endothelial dysfunction enabling to treat vascular diseases. Betulinic acid, another triterpene  also shows cardioprotective behavior in the case of myocardial ischemic injury. The underlying mechanism is highly complex but majorly caused due to its powerful antioxidant role, including scavenging action of reactive oxygen species (ROS) [9,11].

Anticancer effect – It is already established that triterpenes and its polysaccharides have antiproliferative as well as anticancer actions on numerous cell lines. Among them the lupane type is found to be the most efficient. When compared to the others regarding cytotoxicity, 3-O-p- coumaroyl-alphatolic acids are seen more effective than the non-coumaroyl ones. So, the coumaroyl moiety at C-3 position of lupane structure have an important role in cytotoxicity. The chloroform extract of jujube fruits enriched with triterpenes induces dosedependent apoptosis and differential cell cycle arrest in HepG2 cells (human liver carcinoma cell line), MCF-7 and SKBR3 (human breast cancer cell lines). Betulinic acid isolated from the fruits produce selective toxicity against cultured human melanoma cells. It is also effective for small and non-small cell lung cancer, ovarian, cervical, and head and neck carcinomas. The compound exerts apoptosis in p53 and CD95-independent ways [7,9,11,15].

Antiinflammatory effect – The antiinflammatory effect of jujube fruits and leaves extract has been verified in laboratory by animal experiments. It has been noticed that fractions enriched with triterpenes and flavonoids are majorly responsible for the antiinflammatory actions. The effect is mediated by the inhibition of nitric oxide (NO) generation due to reduction of nitric oxide synthase (NOS) expression [5,7].

Anti-allergic actions – Extracts from fruits and leaves have strong antiallergic properties. The aqueous extract of leaves and ethanolic extract of fruits exhibit potent anti-allergic effects. The conclusion is based on the experiments that the anti-allergic or anti-anaphylactic actions are owing to the presence of steroidal saponins along with flavonoids and its glycosides enabling to stabilize the mast cells by interacting with the cell membranes. The oral administration of either extract are tested in a variety of ways. Additionally, the extract inhibits tracheal contraction induced by Acetylcholine and Histamine. The extract also have a free radical scavenging role which might be involved also in the process [5,7].

Antioxidant effect – The flavonoids, polysaccharides, phenolics and anthocyanins in fruit extract are liable for its antioxidative role. It has been noticed that both fruits and leaves extract exhibit potent antioxidant properties. Interestingly, peels of the cultivars indicate highest effects where the predominant antioxidants are protocatechuic acid, gallic acid, chlorogenic acid, and caffeic acid. As a cautionary measure, even the jujube fruits are loaded with natural antioxidants, but one should be aware of the necessary metabolic function of reactive oxygen species (ROS). Its large removal can upset the cell signaling pathways opening the risk of unwanted chronic diseases [5,21].

Inhibition of foam cell production in macrophages – It has been reported that pentacyclic triterpenoids from Jujube are able to inhibit the generation of foam cells in macrophages induced by acetylated LDL. The identified major active ingredients are triterpenoids like oleanonic acid, pomolic acid, and pomonic acid. The – CO2H group at C-28 position plays an important role in the inhibition of foam cell generation in human macrophages [22].

Neuroprotective effect – Traditionally, jujube acts as neuroprotective herbal medicinal component by offering calming sensation of mind that leads to improve the quality of sleep. It exerts neuroprotective action while protecting neuronal cells against neurotoxin induced stress, stimulating neuronal differentiation, increasing the expression of neurotrophic factors thus promoting learning behavior and memory. Flavonoids and Jujuboside have been identified being the potentially active phytocomponents liable for those neuro-biological actions. Due to its significant neuroprotective role jujube can be a good health supplement for preventing or treating many neurological problems. It is also noticed that Jujube extract also offers anxiolytic activity. Further, Jujuboside A, a saponin can induce sedative and hypnotic action, prolonging the sleeping time. In other words, it can cure insomnia. Experiments have further demonstrated that this compound or the extract stimulates the expression of GABAA receptor subunits in hippocampal neurons of rats. It also improves the behavioral disorders in dementia model induced by administering Aβ1-42 amyloid Beta peptide in mouse [9,23].

Wound healing action – The bark extract by methanol shows significant increase of protein synthesis and subsequent wound closure. The identified ingredients are mostly flavonoids and tannins which help contraction of wounds by enhancing the rate of epithelization. Similar effects are also noticed in the case of extracts made from roots and leaves [8,24].

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