INTRODUCTION:

Ziziphus is a genus comprising many species that can be found in a variety of warm and subtropical climates.¹ Ziziphus species are versatile plants utilized as foods, folkloric medicines, and to protect the environment.² The different species of this genus already have multiple medicinal purposes mainly attributed to insomnia and anxiety. The main bioactive compounds for the activities of this medicinal herb are mostly phenolics and carbohydrates.¹

Ziziphus jujube Mill. among many significant plants, Rhamnaceae family. Common names of this plant are Azufaifo (Spanish), Gingeolier (French), Acofeifeira (Germany), Ber (India), Giuggiolo (Italy) etc.³ Other synonyms for this plant are Ziziphus vulgars Lam., Ziziphus sativa Gaetrn., Rhamnus ziziphus L., and Ziziphus zyzyphus (L.) Karsten. The plant has been cultivated for many years in China.

Nowadays, approximately 40 species of this plant are grown in different provinces of China. Jujube can produce strong wood with many medicinal properties, A small, graceful tree that yields honey, in addition to fruits.⁴ Various parts of the plant are utilised for numerous medicinal purposes. The leaves are antipyretic and reduce obesity, barks are useful in curing boils and treating dysentery and diarrhoea. The fruit produces a soothing effect, acts as a laxative and removes the burning sensation.⁵ According to the Iranian medicinal book, the plant stem bark, leaves, and fruits have many important medicinal values from ancient times.⁶ People of east, central, and southeast Iran called this plant ‘Anna’ and employed it in folk medicine to treat gastric ulcers and digestive problems since Avicenna’s prescription. In Southern Africa and Indian Subcontinent, it is commonly termed as ‘ber’.⁷ The plant also possesses various beneficial biological activities against fatigue, hyperhidrosis, liver problems, urinary problems, fever, immunomodulator⁸ and hypertension. The leaf of jujube has been used for many years to improve sleep, soothe the nerves, nourish the heart and reduce diarrhoea.⁹ The plant also drew substantial customers based on its copious of carbohydrates, nutrients, organic substances, and amino acids. The fruit can be consumed not only when fresh but also in a dehydrated state. Drying is an efficient technique to inhibit microbial growth in food. The drying process occurs naturally under sunlight or through the use of hot air.¹⁰ Eliminating moisture and stopping the growth of microbes, it lowers the weight and volume of food, extending its shelf life and lowering transportation and storage expenses.¹¹ The plant has many health-promoting properties and enriches many biological components, including polysaccharides, trace minerals, amino acids, and jujube fruits (Ziziphus jujuba Mill). are used in conventional medicine.¹² Jujube is ingested not only in its fruit form but also recommended as a tonic in compliance with Traditional Chinese Medicine for the nourishment of blood. Among the various commercially accessible jujube formulations, Guizhi Tang (GZT), devised by the esteemed Chinese medicine practitioner Zhang Zhongjing, is widely utilized globally. This formulation consists of jujube and four other medicinal herbs and continues to be commonly employed to address common colds, headaches, and fevers in Asian nations.¹³ Nowadays, there are varieties of plants that are being utilised for medicinal purposes such as Carum Carvi¹⁴, Achyranthes Aspera¹⁵, Remusatia Vivipara¹⁶, Striga orobanchioides¹⁷, Combretum albidum G. Don ^18,19 etc.

This review article highlights the ethnopharmacological, phytochemical distribution of constituents in various regions (e.g., leaves, bark, fruits, and seeds) of plant and pharmacological aspects of Ziziphus jujube Mill. The herbal marketed formulations of this plant have been summarized along with recent advancements in the pharmaceutical development of this extract. Since Ziziphus jujube Mill. possesses various pharmacological and biological properties, a detailed literature study of each activity has been presented in this article.

PLANT DESCRIPTION:

Jujube is a tiny tree with robust wood that grows to a height of 6-9 meters depending on the area. The bark has a deep longitudinal split and is greyish-brown or reddish in hue. The plant has four shoots i.e., extension shoot (primary), side branches (secondary), fruiting spur (mother bearing) and fruit-bearing shoot (branching). Leaves are 2.5-5.5cm long and 2-4cm wide, lustrous, ovate, or oval in form, non-branched, and deciduous. Flowers are small, carrying five petals, sepals and anthers, and having a single ovary with two ovules, varying in size from 4 to 8mm in diameter. Oval, round, oblong, oblate, and irregularly shaped jujube fruits are among the many shapes available. The fruit is a drupe with a single spit (stone) in the centre containing up to two seeds. The fruit can be as small as a thumb or as large as a golf ball.⁶ In recent times, approximately 40 cultivars are grown in different provinces of China. The plant also captivated a substantial clientele because it is abundant in carbohydrates, nutrients, organic elements, and amino acids.⁴ The view of unripened, ripened fruit and whole tree of Ziziphus jujube Mill. is shown in (

Fig.).

Fig. 1. Ziziphus jujube Mill. plant description (Ripened fruit, Tree and Unripen fruit)

CULTIVATION AND COLLECTION:

The plant was acquired for many years in China, as interpreted by its partnership with rice culture in the Book of Songs.⁴ Ziziphus jujube is a Chinese native plant that has spread over Australia, Europe, Eastern Asia, and Southern Asia. The plant has a low-temperature requirement and can survive up to 48.9°C in the summer and -38°C in the winter. It thrives in a diverse range of soil, and it is alkalinity and salinity-resistant, making it excellent for cultivation. The plant undergoes distinct growth stages throughout the entire year: Stage I spans from April to early May, encompassing bud burst to leaf. Then Stage II extends from mid-May to late June, involving flowering to fruit development. Followed by Stage III ranges from late June to late July, dedicated to fruit growth. Then, Stage IV takes place from early August to early September, focusing on fruit maturation. Followed by Stage V occurs from October to March, marking the period of hibernation.^6,20 The area dedicated to Ziziphus jujube cultivation spans 2 million hectares, yielding an annual output of nearly 5.47 million tons of dried jujube.²¹

CHEMICAL COMPOSITION:

Different components of the plant Ziziphus jujube have been utilised for different medicinal and beneficial purposes since ancient times. Different components of the plant consist of different chemical constituents as mentioned in (Table-1) with their respective structures.

Along with the chemical composition, the plant has nutrient value as well. According to the published reports, this plant tends to regulate the blood sugar level and satiating effect due to its dietary fibres and fructose presence.^22,23 Jujube is also rich in vitamin C.²² The investigation led by Usman revealed the existence of cardiac glycosides, alkaloids, phenols, tannins, and terpenes in the leaf ethanolic extract of Ziziphus jujube while in the aqueous extract, there were the existence of alkaloids, tannins, phenols, steroids, saponins and cardiac glycosides.²⁴ In a recent study, Zhi et al. they performed a genetic study employing mixed models to investigate the sugar-acid fractions of both Ziziphus jujube Mill. and wild jujube (Z. acido jujube). They employed the cover net control hybridization technique to crossbreed Ziziphus jujube Mill. and Z. acido jujube, resulting in an F1 population consisting of 179 hybrid progenies. The study unveiled the presence of acids, including malic, citric, oxalic magic, tartaric, succinic, and fumaric, in the fruit of the F1 hybrid population. Additionally, the fruit contained three primary sugar components: sucrose, fructose, and glucose.²⁵ Jujube fruit extraction with acid and alkaline also showed high values of polysaccharides with a high uronic acid value. ¹² Studies showed that the dry fruit of the pant also consists of polyphenols as per the estimation of Total phenolic and Total flavonoid content.²⁶

Luo et al. performed the genome-wide screening in Ziziphus jujube Mill. for the ribonuclease T2 gene family and its functional assessments. In the study, they discovered four members of Ribonuclease T2 viz. ZjRNase1, ZjRNase2, ZjRNase3 and ZjRNase1, ZjRNase4. Examination of the phylogenetic relationships unveiled that these four members of RNase T2 could be segmented in two classes (Class I and Class II). These studies proved to be useful in understanding the molecular mechanism for low production in hybrid seeds of jujube plant. A recent study examined, the chemical composition and antioxidant activity of ripe fruit juice, wine, and vinegar extracted from Ziziphus jujube Mill. were examined. Jujube vinegar was found to contain protocatechic, malic, chlorogenic, p-hydroxybenzoic, tartaric, caffeic, oxalic acid, and various organic acids. Ketone, ester, aldehyde, alcohol and terpene volatile aroma compounds were also found in jujube samples.²⁷

PHARMACOLOGICAL ACTIVITIES:

Ziziphus jujube Mill. the plant has multiple biological activities like antioxidant, antimicrobial, antidiabetic etc. The plant has been used for decades for its medicinal properties and as a food supplement, for healthy skin, and as a source of honey².

Anticancer Activity:

In an investigation, different types of extracts of Ziziphus jujube such as n-hexane (ZE1), chloroform (ZE2), crude ethyl acetate extract (ZE3), ethyl acetate (AcOEt) extract, and n-butanol extract were examined for their anticancer property. The extracts (ZE1, ZE2 and ZE4) were reported to inhibit the proliferation of cells in oestrogen receptor alpha-positive MCF-7 and oestrogen receptor alpha-negative SKBR3 breast cancer cell lines. ZEs didn’t affect cell viability of both non-malignant breast epithelial MCF-10A and normal human fibroblasts Bj1-hTERT cells. The most potent jujube extract, rich in triterpenic acids exhibited inhibitory effects on growth and induced programmed cell death in both malignant and non-malignant cells.³⁵ Huang et al. conducted research on the cytotoxic property of Ziziphus jujube and its fundamental mechanism of action in HepG2 cells (Human Hepatoma). They utilized fractions of the aqueous extract of Ziziphus jujube, successfully treated with chloroform, then by ethyl acetate, followed by butanol and finally water. The parameters selected to investigate the anticancer property Ziziphus jujube were cell cycle changes, ROS (reactive oxygen species) and mitochondrial membrane potential. The results showed that the most effective was chloroform fraction (CHCL₃-F). There was an escalation in ROS (Reactive Oxygen Species) levels, induction of programmed cell death, and a fall in mitochondrial membrane potential ability by Ziziphus jujube low concentrations and chloroform fraction also showed G1 and G2/M arrest.³⁶ In a recent investigation, the fruit triplet extractions for each growth stage (except Stages 1 and 2) were redissolved in dilute dimethyl sulfoxide and a total of eight stages (S1, S2, S3, S4, S5, S6, S7 and S8) of growth extract were examined for cytotoxic effect. Five different cell lines were used to test the extracts Hel299 (normal lung), A549 (lung cancer), U937 (histiocytic lymphoma) and Chang (normal liver). The results revealed that all growth stages were affected dose-related. In A456 lung cancer cells exhibited a decrease, HeLa cervical cancer cells were inhibited, whereas Hel200 normal lung cells were also inhibited. On the other hand, U937 cells had no effect and the growth of Chang normal liver cells was inhibited by the S5 extract.³⁷ In a recent study, the anticancer activity, of dried fruit was determined against nuclear sclerosis and disruption of hepatocellular carcinoma (HepG2) cells. The metabolomics techniques employed for the assessment of content determination and composition of dried jujube fruit. The results revealed that the phenolic metabolites in the fruit were found to be associated with nuclear fragmentation, HepG2 cell nuclear sclerosis, and rise in ROS (Reactive Oxygen Species).²¹ In another study, the anticancer property of Ziziphus jujube Mill. roots methanolic extract on HepG2 (human hepatocellular carcinoma) cell line was carried out in accordance with MTT assay method. The different isolates were scrutinized for cytotoxic effect against different cell lines and few of them showed anti-cancer activity the inhibitory concentration range from 1.9-5.9µM.³³

Antidiabetic Activity:

Shirdel et al. investigated hydro-alcoholic extract of Ziziphus jujube leaves for its antidiabetic activity with the help of different biochemical estimations from the blood of rats. The results revealed notable decrease in the level of serum glucose, triglycerides, cholesterol and VLDL. A notable decrease in LDL levels and an increase in HDL levels were observed during the result analysis. All the results revealed that hydro-alcoholic extract of leaves of Ziziphus jujube has an antidiabetic effect.³⁸ In a recent study, the phenolic pools were extracted using methanol from leaves of jujube and twelve phenolic compounds were identified. In vitro antioxidant activities like 2,2- diphenyl-1-picrylhydrazyl, oxygen radical absorbance, nitric oxide radical scavenging activity, metal chelation, cupric ion reducing antioxidant activity, iron reducing power and alpha-amylase, alpha-glucosidase inhibition showed by total phenolics. The findings demonstrated that the total phenolic content was notably greater in Ziziphus jujube in comparison to the second plant, Moringa oleifera Lam. Additionally, the extract exhibited robust biological activity, displaying effectiveness in chelating/reducing iron or cupric forms. The extract also demonstrated efficacy in scavenging free radicals, and it exhibited inhibitory effects on enzymes, as evidenced by lower IC₅₀ and EC₅₀ values.³⁹ In a separate investigation two saponins SZJ-1 and SZJ-2, primarily consisting of jujuboside A, spinosyn, betulinic acid, and jujuboside B, these were isolated and extracted from Ziziphus jujube. The findings indicated that both saponins significantly enhanced glucose consumption and improved the levels of SOD (Superoxide dismutase), HK (Hexokinase) and PK (Pyruvatekinase) in insulin resistant HepG2 cells. Moreover, they led to a reduction in malondialdehyde (MDA) content, suggesting potential benefits in mitigating oxidative stress in insulin-resistant cells. These results indicated that the saponins present in Ziziphus jujube improved the insulin-resistant symptoms.⁴⁰

Antimicrobial Activity:

Abd-Alrahman et al. conducted research on the anti-bacterial property of the ethanolic extract of Ziziphus jujube seeds against six bacterial strains. This was determined by assessing the minimal inhibitory concentration (MIC). The extracts for antimicrobial activity were evaluated by a modified Kirby-Bauer18 disc diffusion technique. Brantner and Grein (1994) described the microdilution broth technique for determining the lowest inhibitory concentration. The 50% w/v ethanol extract of Ziziphus jujube was examined for antimicrobial activity at two different concentrations (50µl and 100µl) against six different bacterial strains. The obtained MIC values of different bacterial strains suggested a broad antimicrobial activity of the plant. ² In a recent investigation, Usman et al. explored antimicrobial property of ethanolic and aqueous extract of Ziziphus jujube leaves against two bacteria S. aureus and E. coli. The bacteria were isolated by using broth dilution and agar well diffusion from vaginal swabs. Ethanolic extract at doses 50 and 100 mg/ml exhibited inhibitory zones against S. aureus ranging from 13.00 to 15.00mm, and against E. coli ranging from 7.00 to 10.00 mm, respectively. Meanwhile, the aqueous extract, at concentrations of 50 and 100mg/ml, showed inhibitory zones against S. aureus within the range of 9.00 to 11.00mm and against E. coli ranging from 6.00 to 8.00 mm, respectively. At the Minimum Inhibitory Concentration (MIC) of 100 mg/ml, the strains of S. aureus exhibited higher susceptibility to the extract.²⁴ In a recent study, metabolomics approach was used to estimate the content and composition, and the antimicrobial activity of the phenolic compounds present was identified. The findings indicated that the phenolic compounds extracted from jujube fruit exhibited significant antibacterial activity, effectively inhibiting the growth of S. aureus, E. coli, and C. albicans.²¹ In another study, jujube fruits obtained from five different Tunisia provenances were (Sfax, Choutrna, Regueb, Mahdia and Mahres) investigated for antibacterial activity of various methanol extracts from Ziziphus jujuba was evaluated by using culture media of S. aureus ATCC 25923 and Listeria monocytogenes ATCC 070101121, as well as two gram-negative bacteria, Aeromonas hydrophila and Kleibsella pneumoniae ESA 8. Antibacterial tests were conducted using the agar well diffusion method after dissolving the extracts in sterile water. The determination of MIC for extract was performed through the microdilution broth method. The results indicated that the maximum inhibition was observed against S. aureus strains, especially in Sfax powder extracts, with inhibition zones ranging from 12 to 20mm.⁴¹ In recent investigation the 50% ethanol leaves extract of jujube used against three Gram-positive and three Gram-negative bacteria for its antibacterial activity by estimating its Minimum inhibitory concentration. The results revealed the antibacterial activity of the extract in concentration of 50mg/mL for Gram-positive bacteria and concentration of 25- 50mg/mL for Gram-negative activity.⁹

Antioxidant Activity:

Wojdylo et al. studied the antioxidant activity of 4 Spanish jujube cultivators (MSI, GAL, PSI and DAT) by using FRAP and ABTS methods. They found total twenty five polyphenolic compounds with the help of LC-MS-QToF and quantified by UPLC-PDA-FL. They classified them as 13 flavanols, 1 flavanone, 10 flavan-3-ols and 1 dihydrochalcone. The results stated that MSI and GAL fruit cultivators had highest and lowest antioxidant capacity, with PSI and DAT fruits cultivators had intermediate values.²⁹ Zhang et al. studied the flavonoid extract antioxidant activity of Ziziphus jujube Mill. and used ultra-high-pressure extraction to achieve maximum yield of flavonoid extract. They measured the antioxidant properties using DPPH and ABTS methods. They tested the extract for antioxidant properties compares to the ultrasound-assisted extraction extract (UAE) and results showed that UHPE (ultra-high-pressure extraction) has stronger antioxidant activity.⁴² In another study, the intake in different doses of water extract gave transcriptional expression in NAD(P)H (Nicotinamide adenine dinucleotide phosphate), glutamate-cycteine ligase modifier subunit, glutathione S-transferase, glutamate-cysteine ligase catalytic subunit and quinine oxidoreductase for anti-oxidation.⁴³ In a recent investigation jujube wine, jujube vinegar and jujube juice were used to estimate the antioxidant activity. The antioxidant activity TEAC was determined by the ABTS method. Results showed that the TEAC content of jujube vinegar surpassed the content of jujube juice and jujube wine. The investigation suggested that the jujube vinegar because of its extended shelf life it is an important product for food.²⁷ In another study, the extracts were taken of different growth stages of (S1- S8) Ziziphus jujube fruit. The same method of the previous article was used in this article. The different extracts of Ziziphus jujube Mill. fruits of each growth stage showed results for the antioxidant property.³⁷ In a separate study, Ziziphus jujube Mill. fruit powder by using DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging method explored for its antioxidant activity. The tested four different jujube fruits from five provenances Sfax, Choutrna, Regueb, Mahdia and Mahres. The results showed that antioxidant from decrease in concentration required for 50% inhibition IC₅₀ values i.e., from 175mg/ml (Sfax) to 55mg/ml (Mahdia) as compare to standard the BHT (77.86mg/ ml). ⁴¹

Antiatherogenic Activity:

Hemmati et al. investigated the antiatherogenic properties of hydro-alcoholic extract and aqueous extract of the jujube plant in rats. Different biochemical parameters were estimated for the same. Serum levels of very low-density lipoprotein, lipid, and fasting blood glucose were significantly lowered. Treated groups with the extract of Jujube plant also showed reduced level of lipid peroxidation, increased antioxidant activity, increased serum adiponectin levels and decreased lipid lipoprotein levels. These all-biochemical parameters showed the beneficial effects of Jujube plant extract in atherogenic and diabetic animal models.⁴⁴

Anxiolytic Activity:

Peng et al. worked on an ethanolic extract of semen Ziziphus Jujube for anxiolytic activity, that was studied on ICR mice with different dosages. For the evaluation, behavioural tests were conducted, and the findings revealed a rise in the percentage of open arm entries of the elevated plus maze and a drop in the proportions of entries in close arm of elevated plus maze. The results also showed induction of sleeping time in mice by hexobarbital, along with reduction in the locomotor activity.⁴⁵

Neuroprotective Activity:

Chen et al. examined neuroprotective activity by use of chemical standardised water of jujube to the 24 hours cultured astrocytes. The results revealed stimulated expression of glial cell derived neurotrophic factor, nerve growth factor and brain derived neurotrophic factor in dose-dependent manner. Using protein kinase as a pre-treatment, the neurotrophic factor expression generated by jujube was reduced by the inhibitor H89. The extract also exhibited antioxidant properties as it induced the transcriptional production of anti-oxidation enzymes.⁴³

Anti-inflammatory Activity:

Pethari and Saxena conducted a study to check the anti-inflammatory effect of hydroethanolic extract of Ziziphus jujube fruit employing paw edema carrageenan-induced paw edema. The hydroethanolic extract, administered at a dose of 350mg/kg orally (p.o), demonstrated significant inhibition of inflammation compared to the standard drug diclofenac sodium.⁴⁶ Mesaik et al. tested the anti-inflammatory activity of an ethanolic extract of jujube fruits on carrageenan-induced paw oedema in female wistar rats. Diclofenac sodium was utilized as the standard anti-inflammatory medicine for comparison. The results revealed substantial prevention of edema in both the left and right paws. According to the findings, ethanolic extract of jujube fruit exhibited anti-inflammatory properties.⁴⁷

Anti-diarrheal Activity:

Mesaik et al. studied the anti-diarrheal activity of jujube fruit ethanolic extract using a diarrheal mouse model induced by Castor oil and Escherichia coli. Graded doses of the extract showed no significant effect. However, the highest dose of 1200mg/kg demonstrated a notable impact on defecation and watery stools compared to the control group, resulting in a 60% reduction in diarrhoea.⁴⁷ Rao and Lakshmi, investigated the antidiarrheal activity of aqueous extract from leaves of Ziziphus jujube with the help of castor oil and magnesium sulphate induced diarrhoea model in rats. Results revealed the anti-diarrheal activity by showing significantly inhibit the rate of defecation and consistency of faeces.⁴⁸

Wound healing Potential and anti-inflammatory activity:

In an investigation, the ethanolic extract of Romanian Ziziphus jujube leaves was analyzed for its chemical constituents. Moreover, the study explored the newly formulated lipophilic ointment contained 10% extract of dries jujube leaf for its anti-inflammatory activity. The pH of the ointment was measured to be 5.41–5.42. Acute cutaneous irritancy test on Albino rat and recurring application studies on Wistar rats demonstrated that the ointment was non-toxic. In comparison to the standard drug (Cicatrizin), the ointment displayed healing activity on rats and exhibited a reasonable anti-inflammatory response when compared to control group. However, when compared with indomethacin in a rat model of inflammation induced by intraplantar administration of kaolin, the ointment showed no significant effect.³⁰

Anti-atherosclerosis activity:

Fujiwara et al. reported methanol extract of Zizyphi fructus and Zizyphi semen foam cell inhibitory activity triggered by the acetylated LDL (low density lipoprotein) among the 50 crude extracts and based on that they reported the triterpenoids in Ziziphus jujube may therefore, useful in prevention of atherosclerosis. They also reported that the terpenoids like pomolic acid, pomonic acid and oleanoic acid were the major, and terpenoids containing a carboxylic acid at carbon-28 play a crucial role in the activity results.⁴⁹

Cardiovascular Diseases:

Farhadnejad et al., performed the randomised controlled clinical trial on 48 patients, aged 30-65 years randomly assigned to two groups intervention (n=24) received 30 gm Ziziphus jujube and control (n=24) group. The results indicated that there were no noticeable changes were noted in the 30mg recived group when compared to the control group in various parameters of cardiometabolic factors, including total cholesterol, fasting plasma glucose level, triglycerides, low and high-density lipoprotein-cholesterol levels, as well as IL-6 (Interleukin-6) and C-reactive protein levels. The findings concluded regular intake of Ziziphus jujube confer beneficial effects. In another study, the hydroalcoholic extract of Ziziphus jujube Mill. fruits were investigated for its ability to liberate nitric oxide. Nitric oxide plays a vital role in cardiovascular regulation, and the results revealed that Ziziphus jujube promotes the release of nitric oxide. The cardiovascular response of the extract was further examined in acute NG-nitro-L-arginine methyl ester (L-NAME)-induced hypertension in rats. The results demonstrated that low-dose (100mg/kg) long-term consumption weakened the cardiovascular response induced by L-NAME.^50,51

Immunomodulatory activity:

In an investigation, the immune-related response of two polysaccharide compounds extracted from the fruits of Zziphus jujube, namely Ju-B-2 and Ju-B-3, were examined. The results revealed that Ju-B-2 exhibited immune-related responses on proliferation of splenocytes at doses exceeding 30µg, while Ju-B-3 does not demonstrate a stimulatory effect.⁵²

Hypolipidemic activity:

The results of the study conducted by Mostafa et al. suggested that Ziziphus jujube Mill. fruits powder demonstrated cholesterol-lowering and anti-obesity effects at various doses. The study involved a randomized sample of 83 individuals, comprising 41 men and 42 women aged 20 to 57 years (mean age 32±13). Subjects were grouped in three types of groups because of their BMI (Body Mass Index), and they were provided with a specific questionnaire. Anthropometric measurements were taken, and blood samples were collected for various analyses, including AST (aspartate aminotransferase, ALT (alanine aminotransferase) done to determine the lipid profile. The results revealed the significant reduction in fat percentage, body mass index, body weight, Low-density lipoprotein cholesterol and total cholesterol level in all groups. The consumption of 30 g/day Ziziphus jujube Mill. fruits powder showed significant reduction in triglycerides (TC).⁵³

Other Beneficial Effects:

Lee et al. reported that lupin-type triterpenes, such as betulinic acid and betulonic acid, exhibited high cytotoxic activity, and 3-O-trans-p-coumaroyl alphitolic acids were found to be more effective than noncoumaroic triterpenoids. Additionally, they observed that oleanane-type triterpenes displayed significant anticomplement activity with IC50, whereas ceanothane-type and lupine-type triterpenes were inactive. Furthermore, the effects of Ziziphus jujube on blood circulation have also been documented. The pre-incubation of jujube extract at 37℃ for 5 minutes in platelet-rich plasma was stated to inhibit the aggregation of platelets induced by thrombin (0.4 U/ml), collagen (2 mg/ml), and arachidonic acid (100mM).¹³

Kubota et al. performed study for anti-obesity activity of Ziziphus jujube. They found that the extract of Z. Jujube inhibited glycerol-3-phosphate dehydrogenase activity and lipid accumulation without impacting 3T3-L1 preadipocytes cell viability. Results also indicated that the chloroform fraction of the Z. Jujube extract exhibited the most inhibitory effect during fractionation with organic solvents. The study suggested that the chloroform fraction of the Z. Jujube extract may block adipogenesis. Additionally, the mechanism of action of jujube (Ziziphus jujube) based on the network pharmacology in appetite stimulation was discovered. The Traditional Chines medicine integrative database (TCMID) and Traditional Chinese Medicine Systems Pharmacology (TCMSP) were used to find the action targets and the active compounds of jujube. Utilizing the cytoHubba plug-in and identifying hub genes, significant protein nodes and subnetworks were forecasted. According to the findings, a collective of 16 active constituents were recognized, with 131 action targets specifically associated with appetite and appetite management. MCODE analysis ruled out three important targets. Jujube ingredients displayed high binding activity against the primary targets, according to molecular docking. Based on the findings, the key active ingredients in jujube were investigated for their potential role in appetite regulation across a variety of components, targets, and channels.⁵⁴

In an investigation, in a double blinded trial carried out on lactating women, the impact of Ziziphus jujube fruit lotion on the healing of breast fissures was investigated. The study recorded the existence or absence of nipple discharge on the 7th and 14th day postpartum. The results indicated significance differences among the control group (applied breast milk) and the group that applied Ziziphus jujube lotion. The study concluded that the Ziziphus jujube fruit lotion is effective in healing nipple fissures.⁵⁵

CONCLUSIONS:

Ziziphus jujube is one of the most crucial Chinese herbal plants with the great importance and well-known plant worldwide. The tree has many medicinal values as well as pharmacological aspects for future medicinal uses. This review article combines the ethnopharmacological, preliminary evidence of modern pharmaceuticals and nutritional value data of the jujube plant, review literature used for this article confirms the phytochemical and biological importance of the plant. There is a lot of research ongoing on the medicinal plants for their anticancer activity. There are no recent studies which investigated the clinical difference of different varieties of Ziziphus jujube cultivators. There have no studies with the fruit part of the plant, researchers studied the other parts like barks, seeds, and leaves. This article opens the scope for researchers to study different aspects of Ziziphus jujube plant parts.

FUTURE PROSPECTS:

The plant Ziziphus jujube has a variety of chemical constituents and those are effective in the treatment of various diseases: many pharmacological activities are yet unknown. This article can help new researchers comprehend those tasks for the most effective research with this plant. Various parts of the plant have various chemical constituents that might be used to care for illnesses and open up new research in the future.

FUNDING:

No financial support from any organization or university was taken. We appreciate all the authors contributing to this article's editing, reading, and writing support.

CONFLICT OF INTEREST:

The authors have no competing interests to declare regarding the publication of this paper.

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Received on 22.10.2024 Revised on 14.02.2025

Accepted on 08.04.2025 Published on 01.12.2025

Available online from December 06, 2025

Research J. Pharmacy and Technology. 2025;18(12):5981-5990.

DOI: 10.52711/0974-360X.2025.00864

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

S. No.	Plant Parts	Chemical Constituents	Structures
1	Seeds	Palatinol A, 7-ethyl-4-decen-6-one, linoleic acid, oleic acid, betulinic acid, 2,5-octadecadiynoic acid, lineoleoyl chloride, 13-heptadecyn-1-ol, methyl ester, spinosin, zizyphursolic acid, epiceanothic acid ^1,28
2	Fruits	Hydroxycinnamic acid like caffeic acid, p-coumaric acid, benzoic acid like p-hydoxybenzoic acid, gallic acid, quercetin-3-O-rutinoside-7-O-pentoside, rutin, epicatechin and ellagic acid ^20,29
3	Leaves	Protojujubosides A and B, saponin, ziziphin, triterpenic acids, flavonoids (quercetin-3-O-rutinoside), epicatechin, caffeic acid ^3,30
4	Bark	Epiafzelechin, epigallocatechin, catechin, epicatechin ^27,31
5	Roots	Alphitolic acid, 2-O-trans-p-coumaroyl alphitoloic acid, 2-O-protocatechuoyl alphitolic acid, 2-O-Benzoyl alphitolic acid, 2-O-vanilloyl alphitolic acid, ceanothic acid, epiceanothic acid, zizyberanalic acid ^22,32–34