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    Systematic evaluation of antioxidant capacities of the ethanolic extract of different tissues of jujube (Ziziphus jujuba Mill.) from China. Zhang Hao,Jiang Lu,Ye Shu,Ye Yubin,Ren Fazheng Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association Jujube (Ziziphus jujuba Mill.) has long been used for human consumption and medicinal purposes in China. It is recommended for some diseases in which radical species are produced as a result of oxidative stress. However, the systematic study on the antioxidant capacities of various tissues of jujube is still lacking. In order to address this, various tissues of three jujube varieties were characterized with respect to their antioxidant capacities and antioxidant compounds such as flavonoid, ascorbic acid, anthocyanin and phenolic. Antioxidant capacity was measured using the DPPH (2,2-diphenyl-1-picrylhydrazyl) and FRAP (ferric-reducing antioxidant power) assays. The phenolic acids were analyzed by high-performance liquid chromatography (HPLC). The results show that the peel of all cultivars has the highest antioxidant capacities, reflecting the highest content of total phenolics, flavonoids, and anthocyanins found in this part. In addition, the predominant phenolic acid in jujube was found to be protocatechuic acid, followed by gallic acid, chlorogenic acid and caffeic acid. The results obtained in this study clearly indicate that Chinese jujube has a significant potential to use as a natural antioxidant agent. 10.1016/j.fct.2010.03.011
    Cocktail enzyme-assisted alkaline extraction and identification of jujube peel pigments. Shen Dongbei,Kou Xiaohong,Wu Caie,Fan Gongjian,Li Tingting,Dou Jinfeng,Wang Hanbo,Zhu Jinpeng Food chemistry Jujube peel (JP) is rich in pigments, which appears red to deep red in color. This study optimized conditions for cocktail enzyme-assisted extraction of jujube peel pigments based on response surface method (RSM). A Box-Behnken design (BBD) was utilized to analyze the effects of buffer liquid volume (BLV), pH, temperature, and incubation time on the total polyphenols content (TPC), total flavonoids content (TFC) and color (L*, a*, b*). Optimal extraction conditions, for the highest concentrations of TPC, TFC and a* values, were 16 mL BLV, pH 7.0, temperature 43 °C, and incubation time 97 min. Finally, concentrations and identities of the eight main constituents (p-coumaric acid, (-)-epicatechin, quercetin-3-O-robinobioside, rutin, kaempferol 3-O-robinobioside, quercetin 3-O-α-l-arabinosyl-(1 → 2)-α-l-rhamnoside, quercetin 3-O-β-d-xylosyl-(1 → 2)-α-l-rhamnoside, quercetin) in jujube peel pigments were determined using UPLC-MS/MS. The study provides guidance for valorisation of jujube peel, specifically valuable food-safe pigments, during industrial production. 10.1016/j.foodchem.2021.129747
    Antihyperglycemic and antihyperlipidemic effects of Ziziphus vulgaris L. on streptozocin-induced [corrected] diabetic adult male Wistar rats. Solati Jalal,Soleimani Nastaran Acta diabetologica Herbal medicine and medical plants such as Ziziphus vulgaris L. are widely used for the treatment of diseases such as diabetes mellitus. We investigated the effects of water extracts of Ziziphus vulgaris L. fruit on serum glucose, triglycerides, LDL-cholesterol, HDL-cholesterol and activities of aminotransferase enzymes inreptozocin-induced diabetic adult male rats. Continuous supplementation of this water extract by gavage at doses of 0.25, 0.5, 1, 1.5 and 2 g/kg in 0.5 ml distilled water in diabetic rats resulted in a significant decrease of fasting blood glucose and LDL-cholesterol and triglyceride levels after 14 days. The levels of HDL-cholesterol and insulin, and activities of serum aminotransaminase enzymes, alanine aminotransferase and aspartate aminotransferase were not changed significantly in the extract-supplemented group compared to the control group. 10.1007/s00592-009-0166-8
    A novel peroxidase from Ziziphus jujuba fruit: purification, thermodynamics and biochemical characterization properties. Zeyadi Mustafa,Almulaiky Yaaser Q Scientific reports In this study, peroxidase from Ziziphus jujuba was purified using ion exchange, and gel filtration chromatography resulting in an 18.9-fold enhancement of activity with a recovery of 20%. The molecular weight of Z. jujuba peroxidase was 56 kDa, as estimated by Sephacryl S-200. The purity was evaluated by SDS, which showed a single prominent band. The optimal activity of the peroxidase was achieved at pH 7.5 and 50 °C. Z. jujuba peroxidase showed catalytic efficiency (Kcat/Km) values of 25 and 43 for guaiacol and HO, respectively. It was completely inactivated when incubated with β-mercaptoethanol for 15 min. Hg, Zn, Cd, and NaN3 (5 mM) were effective peroxidase inhibitors, whereas Cu and Ca enhanced the peroxidase activity. The activation energy (Ea) for substrate hydrolysis was 43.89 kJ mol, while the Z value and temperature quotient (Q) were found to be 17.3 °C and 2, respectively. The half-life of the peroxidase was between 117.46 and 14.15 min. For denaturation of the peroxidase, the activation energy for irreversible inactivation Ea*(d) was 120.9 kJmol. Thermodynamic experiments suggested a non-spontaneous (∆G*d > 0) and endothermic reaction phase. Other thermodynamic parameters of the irreversible inactivation of the purified enzyme, such as ∆H* and ∆S*, were also studied. Based on these results, the purified peroxidase has a potential role in some industrial applications. 10.1038/s41598-020-64599-9
    Fatty acid profile of peel and pulp of Spanish jujube (Ziziphus jujuba Mill.) fruit. Reche Juana,Almansa M Soledad,Hernández Francisca,Carbonell-Barrachina Ángel A,Legua Pilar,Amorós Asunción Food chemistry The fatty acid methyl esters (FAMEs) profiles of fruit peel and pulp of 4 Spanish cultivars of Ziziphus jujuba were studied. The FAMEs profile of the cultivar 'GAL' was studied under two farming practices, (i) organic, 'GAL-E' and conventional, 'GAL-T'. Eleven FAMEs were identified, the predominant ones were cis-palmitoleic acid (pulp) and oleic and palmitic acid (peel). When comparing the FAMEs profiles between organic and conventional 'GAL' peel jujube fruits, the 'GAL-E' (organic) presented a higher unsaturated/saturated ratio than the 'GAL-T' cultivar (conventional), while this relationship in the pulp was the opposite. The 'DAT' cultivar was interesting for its high palmitoleic acid content while the 'GAL-E' and 'GAL-T' cultivars had high contents of oleic, palmitic and linoleic acids. The LDA (linear discriminant analysis) model showed that the FAMEs contents could be used to discriminate the studied cultivars, and the agricultural practice, because all groups were clearly separated with no overlaps. 10.1016/j.foodchem.2019.05.147
    Triterpenoids from Ziziphus jujuba induce apoptotic cell death in human cancer cells through mitochondrial reactive oxygen species production. Shin Minna,Lee Bo-Mi,Kim Okwha,Tran Huynh Nguyen Khanh,Lee Suhyun,Hwangbo Cheol,Min Byung-Sun,Lee Jeong-Hyung Food & function Ziziphus jujuba var. inermis Rehder is an edible fruit-producing species of the Rhamnaceae family. In the present study, we isolated eight triterpenoids (1-8) from the fruits of Z. jujuba var. inermis and evaluated their apoptotic cell-death-inducing activities in human cancer cell lines (A549, PC-3, and MDA-MB-231). The structures of compounds 1-8 were determined by spectroscopic methods. Among these, four isomers of coumaroyl alphitolic acid showed potent cytotoxic activities on these cancer cells: 3-O-cis-p-coumaroyl alphitolic acid (3), 3-O-trans-p-coumaroyl alphitolic acid (4), 2-O-trans-p-coumaroyl alphitolic acid (5), and 2-O-cis-p-coumaroyl alphitolic acid (6). Moreover, compounds 3-6 induced apoptotic cell death in a concentration-dependent manner. We further investigated the apoptosis-inducing effects of compound 4 in PC-3 cells which triggered the cleavage of procaspase-3, procaspase-7, procaspase-8, bid, and PARP. Compound 4 increased both the mitochondrial reactive oxygen species (ROS) production and the phosphorylation of p38 MAPK (mitogen-activated protein kinase), but decreased the mitochondrial membrane potential. Pretreatment with Mito-TEMPO (a specific mitochondrial-targeted antioxidant) or a specific p38 inhibitor (SB203580) attenuated apoptotic cell death triggered by compound 4 which suggests that compound 4 may induce apoptotic cell death in these cancer cells by increasing the mitochondrial ROS production as well as the subsequent p38 MAPK activation. The study findings provide a rational base to use Ziziphus extracts for cancer treatments in traditional oriental medicine. 10.1039/c8fo00526e
    Physico-chemical and physiological changes during fruit development and on-tree ripening of two Spanish jujube cultivars (Ziziphus jujuba Mill.). Almansa Soledad,Hernández Francisca,Legua Pilar,Nicolás-Almansa María,Amorós Asunción Journal of the science of food and agriculture BACKGROUND:Few studies have been performed on changes in organoleptic, nutritive, functional, and physiological properties during jujube fruit development and on-tree ripening. In this work, a comparative study on the evolution of physical, chemical, nutritive, and physiological parameters and bioactive compounds of two Spanish jujube cultivars was performed. RESULTS:Both cultivars showed a non-climacteric ripening pattern, although the JM cultivar was smaller, sweeter, softer, and more highly coloured than the JG, which was characterised by having larger and firmer fruits, although less sweet and coloured. Both cultivars showed high TAA, which was highly correlated with the concentration of total phenols, giving them great functional properties. CONCLUSION:This fruit has little economic importance in Spain and it is just marginally grown for self-consumption or for ornamental purposes. Given the excellent properties of these fruits, it could be considered a fruit species of great interest, and commercial growth of these cultivars with high yields and fruits with high functional properties should be promoted. © 2016 Society of Chemical Industry. 10.1002/jsfa.7610
    A chemically standardized extract of Ziziphus jujuba fruit (Jujube) stimulates expressions of neurotrophic factors and anti-oxidant enzymes in cultured astrocytes. Chen Jianping,Yan Artemis L,Lam Kelly Y C,Lam Candy T W,Li Ning,Yao Ping,Xiong Aizhen,Dong Tina T X,Tsim Karl W K Phytotherapy research : PTR UNLABELLED:The fruit of Ziziphus jujuba Mill., known as jujube or Chinese date, is commonly consumed as a health supplement worldwide. To study the role of jujube in brain benefits, the expression of neurotrophic factors and anti-oxidant enzymes in the jujube-treated cultured astrocytes was determined. Application of a chemical standardized water extract of jujube in cultured astrocytes for 24 h stimulated the expressions of nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor in a concentration-dependent manner. The pre-treatment with H89, a protein kinase A inhibitor, attenuated the jujube-induced expression of neurotrophic factors. In parallel, the treatment of jujube water extract induced the transcriptional expressions of the enzymes responsible for anti-oxidation, i.e. NAD(P)H:quinine oxidoreductase 1, glutamate-cysteine ligase catalytic subunit, glutamate-cysteine ligase modifier subunit and glutathione S-transferase, in a concentration-dependent manner. These results proposed the benefits of jujube in regulating expressions of neurotrophic factors and anti-oxidant enzymes in cultured astrocytes. 10.1002/ptr.5202
    Cytotoxic Ceanothane- and Lupane-Type Triterpenoids from the Roots of Ziziphus jujuba. Kang Kyo Bin,Kim Jung Wha,Oh Won Keun,Kim Jinwoong,Sung Sang Hyun Journal of natural products Ziziphus jujuba, a plant in the family Rhamnaceae, is used in several Asian countries as a food and traditional medicine. Fifteen new ceanothane-type (1-15) and three new lupane-type triterpenoids (16-18) were isolated from the roots of Z. jujuba, as well as 12 previously known triterpenoids (19-30). Their structures were elucidated by 1D and 2D NMR spectroscopic and HR mass spectrometric data analysis. Compounds 12 and 13 were found to possess a rare E-ring γ-lactone structure, and 14 was assigned as the first 2,28-dinorlupane derivative isolated as a natural product. Twenty-five of the isolates were examined for cytotoxicity against human hepatocellular carcinoma HepG2 cells, and compounds 6-8, 14, 17, 23, 25, 29, and 30 showed cytotoxicity with IC50 values ranging from 1.9 to 5.9 μM. 10.1021/acs.jnatprod.6b00525
    Structurally diverse triterpenes obtained from the fruits of Ziziphus jujuba Mill. as inflammation inhibitors by NF-κB signaling pathway. Ruan Jingya,Sun Fan,Hao Mimi,Han Lifeng,Yu Haiyang,Lin Fanyou,Wang Lijuan,Cao Guohao,Zhang Yi,Wang Tao Food & function Twenty-nine triterpenes were obtained from the fruits of Ziziphus jujuba Mill. through various chromatography methods, and their stereo-structures were confirmed by spectroscopic methods. Among them, 2α,3β,20-trihydroxylupane-28-oic acid (1) was identified as a new compound, and the H and C NMR data of 7, 8 and 23, as well as the C NMR data of 17 are reported here for the first time. Meanwhile, the nitric oxide (NO) inhibitory activities of all compounds were examined in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. As results, compounds 2, 7, 10-13, 15, 16, 18-21, 26-29 were found to play important roles in suppressing NO production at 5 μM. The structure-activity relationships (SARs) on NO inhibition indicated that the ursolic and oleanolic acid skeletons, p-coumaroyl group substitution, six-membered A ring, and deoxygenation (loss of C[double bond, length as m-dash]O) in the C ring showed a more positive effect on the NO inhibitory activity of triterpenes, while the reduction of the A ring C[double bond, length as m-dash]O to OH was a negative factor. Moreover, it was found that compounds 15 and 19 could suppress the phosphorylation of IκBα and NF-κB/p65 to prevent it from shifting into the nucleus and downregulate the expression of inflammatory factors, such as iNOS, IL-6 and TNF-α. Our investigations revealed that the NO inhibitory effects of the active triterpenes obtained from Z. jujuba were mediated, at least in part, through the NF-κB signaling pathway. 10.1039/d1fo00117e
    Physico-chemical, nutritional, and volatile composition and sensory profile of Spanish jujube (Ziziphus jujuba Mill.) fruits. Hernández Francisca,Noguera-Artiaga Luis,Burló Francisco,Wojdyło Aneta,Carbonell-Barrachina Ángel A,Legua Pilar Journal of the science of food and agriculture BACKGROUND:Jujube fruit is eaten mostly fresh, but may be dried (Chinese dates and tea) or processed into confectionary recipes in bread, cakes, compotes, and candy. Given that the quality of jujube available on the market differs on account of various factors such as geographical environment, cultivar, processing conditions, and storage conditions, and that, for consumers, flavour and nutrition properties of jujube represent the major parameters in determining the quality of jujube, the main goal of this study were to determine the main physico-chemical properties of jujube fruits, sugars and organic acids profiles, protein, mineral constituents, volatile composition and sensory profile of jujube fruits. This would allow breeders to select cultivars with higher levels of nutrients and also enable increasing dietary intake by consumers. RESULTS:Investigations showed that jujube fruit weight ranged from 4.8 to 29.3 g fruit(-1) . Four sugars (glucose, fructose, sucrose and sorbitol) and four organic acids (citric, malic, ascorbic and succinic acids) were identified and quantified by high-performance liquid chromatography in jujube fruits. Potassium, calcium and magnesium were the major mineral constituents in jujube fruits. Fifteen volatiles compounds were found in the aroma profile of jujube fruits (nine were aldehydes, three terpenes, one ester, one ketone and one linear hydrocarbon). CONCLUSION:The results showed that Spanish jujube cultivars studied are a good source of vitamin C, and they have a low content of Na. The jujube cultivar with the most appreciated quality by consumers was GAL; the GAL fruits were sweet, crunchy, and had high intensities of jujube ID and apple flavour a long after-taste. Therefore, jujube grown in Spain has a great potential to be exploited for functional foods. © 2015 Society of Chemical Industry. 10.1002/jsfa.7386
    Research advances in bioactive components and health benefits of jujube ( Mill.) fruit. Lu Yang,Bao Tao,Mo Jianling,Ni Jingdan,Chen Wei Journal of Zhejiang University. Science. B Jujube ( Mill.), a highly nutritious and functional fruit, is reported to have various health benefits and has been extensively planted worldwide, especially in China. Many studies have shown that bioactive components derived from jujube fruit have significant nutritional and potential biological effects. In this paper, the latest progress in research on major bioactive compounds obtained from jujube is reviewed, and the potential biological functions of jujube fruit resources are discussed. As a dietary supplement, jujube fruit is well recognized as a healthy food which contains a variety of bioactive substances, such as polysaccharides, polyphenols, amino acids, nucleotides, fatty acids, dietary fiber, alkaloids, and other nutrients. These nutrients and non-nutritive phytochemicals obtained from jujube fruit have physiological functions including anticancer, antioxidant, anti-inflammatory, anti-hyperlipidemic, anti-hyperglycemic, immunoregulatory, neuroprotective, sedative, and antiviral functions. Of note is that new constituents, including alkaloids, dietary fiber, and other bioactive substances, as well as the antiviral, hypoglycemic, lipid-lowering, and neuroprotective effects of jujube fruit, are systematically reviewed here for the first time. Meanwhile, problems affecting the exploitation of jujube fruit resources are discussed and further research directions proposed. Therefore, this review provides a useful bibliography for the future development of jujube-based products and the utilization of jujube nutritional components in functional foods. 10.1631/jzus.B2000594
    Licorice (Glycyrrhiza spp.) and jujube (Ziziphus jujuba Mill.) formula for menopausal symptoms: Classical records, clinical evidence and experimental data. Coyle Meaghan E,Liu Jian,Yang Hongyan,Wang Kaiyi,Zhang Anthony L,Guo Xinfeng,Lu Chuanjian,Xue Charlie C Complementary therapies in clinical practice OBJECTIVES:This study sought to determine the most common oral herbal formula for menopausal symptoms in classical Chinese medicine textbooks and investigate its clinical effectiveness and potential mechanisms of action. METHODS:The most common formula used for menopause-like symptoms in past eras was identified from the Encyclopedia of Traditional Chinese Medicine. A systematic review of randomized controlled trials (RCTs) was undertaken and findings from relevant experimental studies were summarized. RESULTS:Licorice (Glycyrrhiza spp.) and jujube (Ziziphus jujuba Mill.) formula (LJF) was used in 63 of the 175 citations (36%) in the classical literature. Evidence from four RCTs showed that while LJF may improve sleep symptoms, there is insufficient evidence to provide recommendations for clinical practice. Experimental studies showed sedative, antidepressant-like, estrogenic and antiprogestogenic actions. CONCLUSIONS:LJF has a long history of use for menopause-like symptoms, but further research is needed to confirm its clinical effects and guide clinical decision-making. 10.1016/j.ctcp.2021.101432
    A standardized extract of the fruit of Ziziphus jujuba (Jujube) induces neuronal differentiation of cultured PC12 cells: a signaling mediated by protein kinase A. Chen Jianping,Maiwulanjiang Maitinuer,Lam Kelly Y C,Zhang Wendy L,Zhan Janis Y X,Lam Candy T W,Xu Sherry L,Zhu Kevin Y,Yao Ping,Lau David T W,Dong Tina T X,Tsim Karl W K Journal of agricultural and food chemistry The fruit of Ziziphus jujuba Mill., known as Chinese date or jujube, is consumed as a health supplement worldwide. To study the role of jujube in brain benefits, its effects on neuronal differentiation of PC12 cells were studied. Application of jujube water extract induced neurite outgrowth of PC12 cells, >25% of which were differentiated; this effect was similar to that of nerve growth factor. In parallel, the expressions of neurofilaments (NFs) in jujube-treated cultures showed a dose-dependent increase, with the highest inductions by ∼150% for NF68 and NF160 and by ∼100% for NF200. Application of H89, a protein kinase A inhibitor, attenuated jujube-induced neurite outgrowth of the cultures. Besides, using jujube extract induced the phosphorylation of cAMP responsive element binding protein on PC12 cells, which was blocked by H89. These results support the use of jujube as a food supplement for the prevention of neurodegenerative diseases in which neurotrophin deficiency is involved. 10.1021/jf405093f
    Optimization extraction, structural features and antitumor activity of polysaccharides from Z. jujuba cv. Ruoqiangzao seeds. Wu Zhen,Li Hong,Wang Yongde,Yang Dajian,Tan Hongjun,Zhan Yong,Yang Yong,Luo Yang,Chen Gang International journal of biological macromolecules As a discarded byproduct of jujube (Z. jujuba), its seeds contain various biological components. Response surface methodology was used to optimize ultrasound-assisted heating extraction conditions of polysaccharides from Z. jujuba cv. Ruoqiangzao seeds (ZJSPs). The optimal parameters were as follows: temperature 83.1 °C, time 100 min, ultrasonic power 140 W, and water-material ratio 33.5 mL/g, allowed a maximum yield of 1.97%. One main fraction (ZJSPs-1) was successfully purified by ion-exchange and gel-permeation chromatography. With a molecular weight of 342 kDa, ZJSPs-1 was composed of arabinose, glucose, xylose, galactose and rhamnose. The presence of pyranose-form sugars as well as both α- and β-configurations was validated by FT-IR and H NMR. TG/DSC indicated that ZJSPs-1 has a favorable thermal stability. XRD suggested that ZJSPs-1 exhibited both crystalline and amorphous portions. ZJSPs-1 was in aggregates of homogenous-dense honeycomb like structures observed by SEM and AFM. ZJSPs-1 possessed antitumor activities against HeLa cells in a dose- and time-dependent manner at 24 and 48 h with IC of 164.6 and 87.1 μg/mL, respectively. Fluorescent microscopic and flow cytometry revealed that ZJSPs-1 inhibited the proliferation of HeLa cells through apoptosis. Z. jujuba seeds are good sources for antitumor polysaccharides in pharmaceutical and food industries. 10.1016/j.ijbiomac.2019.06.020
    Response to Comment on Effect of drying of jujubes (Ziziphus jujuba Mill.) on the contents of sugars, organic acids, α-tocopherol, β-carotene, and phenolic compounds. Gao Qing-Han,Wang Min Journal of agricultural and food chemistry 10.1021/jf400098v
    The jujube (Ziziphus jujuba Mill.) fruit: a review of current knowledge of fruit composition and health benefits. Gao Qing-Han,Wu Chun-Sen,Wang Min Journal of agricultural and food chemistry The nutritional jujube ( Ziziphus jujube Mill.) fruit belonging to the Rhamnaceous family grows mostly in Europe, southern and eastern Asia, and Australia, especially the inland region of northern China. Jujube has a long history of usage as a fruit and remedy. The main biologically active components are vitamin C, phenolics, flavonoids, triterpenic acids, and polysaccharides. Recent phytochemical studies of jujube fruits have shed some light on their biological effects, such as the anticancer, anti-inflammatory, antiobesity, immunostimulating, antioxidant, hepatoprotective, and gastrointestinal protective activities and inhibition of foam cell formation in macrophages. A stronger focus on clinical studies and phytochemical definition of jujube fruits will be essential for future research efforts. This review may be useful for predicting other medicinal uses and potential drug or food interactions and may be beneficial for people living where the jujube fruits are prevalent and health care resources are scarce. 10.1021/jf4007032
    A Review of Dietary Fruit (Jujube): Developing Health Food Supplements for Brain Protection. Chen Jianping,Liu Xiaoyan,Li Zhonggui,Qi Airong,Yao Ping,Zhou Zhongyu,Dong Tina T X,Tsim Karl W K Evidence-based complementary and alternative medicine : eCAM The fruits of , known as jujube or Chinese date, are being consumed all around the world because of their health benefits, as both food and herbal medicine. Traditionally, one of the main functions of jujube, as described in herbal medicine, is to benefit our brain by calming down the mind and improving quality of sleep. Here, the activities of jujubes on nervous system are summarized and discussed. Jujube possesses neuroprotective activities, including protecting neuronal cells against neurotoxin stress, stimulating neuronal differentiation, increasing expression of neurotrophic factors, and promoting memory and learning. Flavonoid, cAMP, and jujuboside could be the potential bioactive ingredients to account for the aforesaid biological activities. These findings imply that jujube is a potential candidate for development of health supplements for prevention and/or treatment of neurological diseases. 10.1155/2017/3019568
    In vitro antioxidative and immunological activities of polysaccharides from Zizyphus Jujuba cv. Muzao. Zhang Li,Liu Xinquan,Wang Yongjie,Liu Guangpu,Zhang Zhen,Zhao Zhongxi,Cheng Huiling International journal of biological macromolecules Zizyphus jujuba has been used as a traditional Chinese medicinal herb since ancient time. Polysaccharides have been found to be important bioactive compounds in the jujube. This work was designed to investigate the physicochemical characteristics and bioactivities of polysaccharides purified from Zizyphus jujuba cv. Muzao. Water-soluble polysaccharides were extracted using an ultrasonically assisted extraction method. The purified polysaccharides (HJP) were obtained by deproteinization and decoloration. Three main fractions (HJP1, HJP2 and HJP3) were isolated using DEAE-Sepharose fast flow ion-exchange chromatography. The purified polysaccharides were found to consist of mannose, rhamnose, galactose, galacturonic acid, glucose and arabinose at various levels for different fractions. The HJP and its three main fractions displayed DPPH radical scavenging activities as well as relatively strong reducing power and HJP had stronger activities than homogeneous compositions. Moreover, the results from in vitro immunological activities studies indicated that HJP could improve the phagocytosis activity of THP-l cells and had effect on the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). In conclusion, the polysaccharides from Zizyphus jujuba cv. Muzao were discovered to have antioxidative and immunological activities. 10.1016/j.ijbiomac.2016.10.102
    The Seed of Zizyphus jujuba var. spinosa Attenuates Alzheimer's Disease-Associated Hippocampal Synaptic Deficits through BDNF/TrkB Signaling. Kwon Huiyoung,Jung In Ho,Yi Ji Hyun,Kim Jae Hoon,Park Jung Hoon,Lee Seungheon,Jung Ji Wook,Lee Young Choon,Ryu Jong Hoon,Kim Dong Hyun Biological & pharmaceutical bulletin Ziziphus jujuba is a plant, which bears fruits and seeds that are used for medicinal purposes in Traditional oriental medicine. The seed of Zizyphus jujuba var. spinosa (EZJ) has been also traditionally used for psychiatric disorders in Chinese and Korean medicines. Recent findings have indicated that EZJ improves memory impairment, a common symptom of various neurological diseases. However, the effects of EZJ on amyloid β (Aβ) toxicity, which is a main cause of Alzheimer's disease (AD), remain to be elucidated. To illuminate the potential anti-AD effect and mechanism in the mouse hippocampal tissue, we examined the effect of standardized EZJ on Aβ-induced synaptic long-term potentiation (LTP) deficit in the hippocampal tissue. EZJ blocked Aβ-induced LTP deficits in a concentration-dependent manner. Moreover, EZJ increased brain-derived neurotrophic factor (BDNF) level in naïve hippocampal slices. The finding that the blockade of BDNF receptor reduced the effect of EZJ suggests that EZJ ameliorates the Aβ-induced LTP deficit through BDNF/topomyosin receptor kinase B (TrkB) signaling. However, transcription or translation inhibitors failed to block the effect of EZJ, suggesting that BDNF synthesis is not required for the action of EZJ on LTP. Finally, we found that EZJ stimulates plasmin activity. In contrast, plasmin inhibitor blocked the effect of EZJ on the Aβ-induced LTP deficit. Our findings indicate that EZJ ameliorates Aβ-induced LTP deficits through BDNF/TrkB signaling. This phenomenon is induced by a regulatory effect of EZJ on the post-translation modification of BDNF. 10.1248/bpb.b17-00378
    Ethanol extract of the seed of Zizyphus jujuba var. spinosa potentiates hippocampal synaptic transmission through mitogen-activated protein kinase, adenylyl cyclase, and protein kinase A pathways. Jo So Yeon,Jung In Ho,Yi Jee Hyun,Choi Tae Joon,Lee Seungheon,Jung Ji Wook,Yun Jeanho,Lee Young Choon,Ryu Jong Hoon,Kim Dong Hyun Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:As the seed of Zizyphus jujuba var. spinosa (Bunge) Hu ex H.F. Chow (Rhamnaceae) has been used to sleep disturbances in traditional Chinese and Korean medicine, many previous studies have focused on its sedative effect. AIM OF THE STUDY:Recently, we reported the neuroprotective effect of the effect of Z. jujuba var. spinosa. However, its effects on synaptic function have not yet been studied. In this project, we examined the action of ethanol extract of the seed of Z. jujuba var. spinosa (DHP1401) on synaptic transmission in the hippocampus. MATERIALS AND METHODS:To investigate the effects of DHP1401, field recordings were conducted using hippocampal slices (400µm). Object recognition test was introduced to examine whether DHP1401 affect normal recognition memory. RESULTS:DHP1401 (50μg/ml) induced a significant increase in synaptic activity in Shaffer collateral pathway in a concentration-dependent manner. This increase of synaptic responses was blocked by NBQX, a broad spectrum α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, but not IEM-1460, a Ca-permeable AMPAR blocker. Moreover, U0126, a mitogen-activated protein kinase inhibitor, SQ22536, an adenylyl cyclase inhibitor, and PKI, a protein kinase A inhibitor, blocked DHP1401-induced increase in synaptic transmission. Finally, DHP1401 facilitated object recognition memory. CONCLUSIONS:These results suggest that DHP1401 increase synaptic transmission through increase of synaptic AMPAR transmission via MAPK, AC and PAK. 10.1016/j.jep.2017.02.009
    Separation and purification of saponins from Semen Ziziphus jujuba and their sedative and hypnotic effects. Jiang Jian-Guo,Huang Xiao-Juan,Chen Jian The Journal of pharmacy and pharmacology Semen Ziziphus jujuba (SZJ) has long been used in Chinese traditional medicine for the treatment of anxiety and insomnia because of its effect of decreasing monoaminergic system activity; saponins are thought to be the main bioactive factors. To investigate the sedative and hypnotic effects of saponins from SZJ, silica gel column chromatography and thin-layer chromatography were used to purify the crude extract of total saponins from SZJ. High-performance liquid chromatography showed that saponins from SZJ comprised two components, compounds I and II. Animal tests were conducted using these two compounds to compare their sedative and hypnotic effects. Results showed that both compounds had a significant effect (P < 0.05, P < 0.01) on walking time compared with that of the control group. Compound I had a significant effect on coordinated movement (P < 0.05). Both compounds prolonged the suprathreshold barbiturate induced sleeping time (P < 0.05). The number of sleeping animals increased by 30% and 20% for compounds I and II, respectively, under the subthreshold dose of sodium barbital. 10.1211/jpp.59.8.0017
    Ziziphus jujuba extract for the treatment of chronic idiopathic constipation: a controlled clinical trial. Naftali Timna,Feingelernt Haya,Lesin Yevgeni,Rauchwarger Ariela,Konikoff Fred Meir Digestion PURPOSE:To investigate the safety and efficacy of an extract of Ziziphus jujuba for chronic constipation.Constipated patients received liquid Z. jujuba or placebo for 12 weeks. Subjects completed questionnaires, a visual analog scale and transit time (TT) tests before and after treatment. RESULTS:Of 37 patients with a prolonged TT, 18 received the study drug and 19 a placebo. Two (12%) of the study and 16 (84%) of the control group dropped out due to severe constipation. The TT decreased from 12.2 particles for the study group to 3 particles at week 11. Symptom severity ratings decreased from 6 and 6.2 to 2 and 5, and the quality of life score improved from 1.9 and 2.3 to 1.3 and 1.4 in the study and control groups, respectively. CONCLUSION:Z. jujuba extract is an effective and safe treatment for chronic constipation. 10.1159/000190975
    Microbiome-metabolomic analysis of the impact of Zizyphus jujuba cv. Muzao polysaccharides consumption on colorectal cancer mice fecal microbiota and metabolites. Ji Xiaolong,Hou Chunyan,Zhang Xuelian,Han Lin,Yin Sheng,Peng Qiang,Wang Min International journal of biological macromolecules It is still uncertain whether the consumption of Zizyphus jujuba cv. Muzao polysaccharides (ZMP) alleviates colorectal cancer (CRC) through the gut microbiota. In this study, we investigated the mortality, colon length, inflammatory factors and cecal microbiota, metabolites of healthy and azoxymethane (AOM) and dextran sodium sulfate (DSS) in induced CRC mice, consuming ZMP. Fecal-microbiota composition was examined using 16S rDNA sequencing and fecal-metabolome profiles were evaluated by ultra-high performance liquid chromatograph mass spectrometry (UHPLC-MS). The results showed ZMP consumption prevented CRC mouse colon shortening, decreased their mortality, reduced pro-inflammatory cytokines, increased the concentration of total short-chain fatty acids (SCFAs) and modulated gut microbiota in their feces. ZMP also increased the richness of Bifidobacterium, Bacteroides and Lactobacillus. In addition, among 39 perturbed metabolites, carbohydrate and amino acid production were noticeably altered. Moreover, higher correlations were found between fluctuant gut microbiota and metabolites. These findings provide mechanistic insights into the impact of dietary Zizyphus jujuba cv. Muzao polysaccharides on host health. 10.1016/j.ijbiomac.2019.03.175
    The ethanol extract of Zizyphus jujuba var. spinosa seeds ameliorates the memory deficits in Alzheimer's disease model mice. Park Hye Jin,Jung In Ho,Kwon Huiyoung,Yu Jimin,Jo Eunbi,Kim Haneul,Park Se Jin,Lee Young Choon,Kim Dong Hyun,Ryu Jong Hoon Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:The seeds of Zizyphus jujuba var. spinosa (Bunge) Hu ex H.F. Chow (Rhamnaceae) have long been treated as hypnotic agent for sleep disturbances in traditional Chinese and Korean medicine and many previous studies have focused on its effect in central nervous system. AIMS OF STUDY:The present study aimed to provide evidence showing that the ethanol extract of Zizyphus jujuba var. spinosa seeds (EEZS), which may regulate plasmin activity, has the potential to serve as a therapeutic agent for AD. MATERIALS AND METHODS:Synaptic function was determined by measuring long-term potentiation (LTP) in Shaffer-collateral pathway of the hippocampus. Protein levels of plasmin or plasminogen were examined using western blotting. Plasmin activity was measured using ELISA. Cognitive functions were measured using passive avoidance and object recognition tests in the 5XFAD mice. RESULTS:Our in vitro analysis revealed that EEZS-treated hippocampal slices from 5XFAD mice, a mouse model of AD, showed significantly higher long-term potentiation levels than did vehicle-treated hippocampal slices from 5XFAD mice (P < 0.05). Additionally, EEZS significantly elevated the plasmin level and activity in the hippocampal slices from 5XFAD mice (P < 0.05). Co-treating the slices with EEZS and 6-aminocaproic acid, a plasmin inhibitor, blocked the ameliorating effects of EEZS on the synaptic deficits that were present in 5XFAD mice. Compatible with the in vitro study, the results of our in vivo investigation showed that administering EEZS orally to 5XFAD mice ameliorated their memory impairments. Orally administered EEZS also elevated the plasmin level and activity in the hippocampus of 5XFAD mice. CONCLUSIONS:Collectively, our findings suggest that EEZS alleviates the AD-like symptoms in 5XFAD mice by regulating of plasmin activity and EEZS may be a suitable treatment for AD. 10.1016/j.jep.2018.12.043
    Sugar transport played a more important role than sugar biosynthesis in fruit sugar accumulation during Chinese jujube domestication. Zhang Chunmei,Bian Yuan,Hou Sihao,Li Xingang Planta MAIN CONCLUSION:Sugar transport, including the symplasmic pathway in plasmodesmata and apoplasmic pathway mediated by sugar transporters, accelerated sugar accumulation in cultivated jujube, while sugar metabolism-related genes played weak roles in jujube domestication. The fruit of Chinese jujube (Ziziphus jujuba Mill.) is high in sugar concentration. By contrast, wild type-sour jujube (Z. jujuba Mill. var. spinosa Hu) contains markedly less sugar. It is unknown whether sugar transport or sugar metabolism drove sugar accumulation during jujube domestication. Using a combination of ultrastructural observations, phylogenetic analysis, testing for soluble sugars, and transcriptional analysis, the sugar accumulation mechanism was studied in the developmental stages of cultivated jujube and sour jujube. Our results indicate that the symplasmic transport pathway in plasmodesmata is present in cultivated jujube, but not in sour jujube. Sugar transporter genes have higher frequencies of duplication than sugar metabolism-related genes. Gene expression patterns indicate that sugar transporter genes, especially ZjSUT2, ZjSWEET1, ZjSWEET7, ZjSWEET11, ZjSTP3, and ZjSTP13a, rather than sugar metabolism-related genes showed higher expression levels in cultivated jujube versus sour jujube during fruit sugar accumulation. These findings suggest that sugar transport, including apoplasmic and symplasmic transport, rather than sugar biosynthesis, is associated with the difference in sugar accumulation between jujube and sour jujube, and that it may drive jujube domestication. This study provides valuable genetic information for jujube improvement, and offers new insights into fruit tree domestication related to sugar accumulation. 10.1007/s00425-018-2971-1
    Aqueous extract of Zizyphus jujuba fruit attenuates glucose induced neurotoxicity in an in vitro model of diabetic neuropathy. Kaeidi Ayat,Taati Majid,Hajializadeh Zahra,Jahandari Faranak,Rashidipour Marzieh Iranian journal of basic medical sciences OBJECTIVES:The neuroprotective effect of fruit aqueous extract of Ziziphus jujuba Lam on glucose-induced neurotoxicity in PC12 cells as an appropriate in vitro model of diabetic neuropathy was investigated. MATERIALS AND METHODS:Cell viability was determined by the MTT assay. Cellular reactive oxygen species (ROS) generation was measured by DCFH-DA analysis. Cleaved caspase-3, a biochemical parameter of cellular apoptosis, was measured by western blot analysis. RESULTS:Our data showed that a 4-fold elevation in glucose levels within the medium significantly reduced cell viability, increased intracellular ROS and caspase-3 activation in PC12 cells after 24 hr. Incubation of the high glucose medium cells with 300-μg/ml Z. jujuba fruit (ZJF) extract decreased the high glucose-induced cell toxicity and prevented caspase-3 activation and excited ROS generation. CONCLUSION:Thus, we concluded that the aqueous extract of Z. jujuba protects against hyperglycaemia-induced cellular toxicity. This could be associated with the prevention of ROS generation and neural apoptosis. Moreover, the results suggest that the ZJF has a therapeutic potential to attenuate diabetes complications such as neuropathy.
    Screening of a functional polysaccharide from Zizyphus Jujuba cv. Jinsixiaozao and its property. Li Jinwei,Shan Liang,Liu Yuanfa,Fan Liuping,Ai Lianzhong International journal of biological macromolecules Chinese jujube has been used as a kind of Chinese medicinal herb for a long time. In this paper, the polysaccharides from Zizyphus Jujuba cv. Jinsixiaozao (ZSP), one of the major Chinese jujube varieties, were extracted and purified sequentially so that its water-soluble immunobiological fractions were screened. The crude ZSP was found to dramatically increase thymus and spleen indices in mice, enhance the proliferation of splenocytes and peritoneal macrophages, and have potential anti-complementary activity. Immunobiological tests indicated that two fractions of ZSP, coded ZSP3c and ZSP4b, were the main active components. ZSP3c was rich in pectin with a degree of esterification (DE) of 49%, which may be related to its stronger immunological activity. 10.1016/j.ijbiomac.2011.04.006
    Structural characterization of polysaccharides from Zizyphus jujuba and evaluation of antioxidant activity. Chang S C,Hsu B Y,Chen B H International journal of biological macromolecules Fruit of Zizyphus jujuba Mill, a traditional Chinese herb widely consumed in Asian countries, has been reported to possess several vital biological activities. This study intends to develop an appropriate analytical method for isolation of polysaccharides from Z. jujuba fruits and evaluate their antioxidant activity. Initially, powdered Z. jujuba fruits were subjected to hot water extraction, followed by ethanol precipitation, deproteination, dialysis and fractionation in a DEAE-Sepharose CL-6B column. One neutral polysaccharide fraction (ZJPN) and 3 acidic polysaccharide fractions (ZJPa1, ZJPa2 and ZJPa3) were isolated with the average MW ranging from 40,566 to 129,518 Da. GC analysis revealed that 6 monosaccharides, namely, rhamnose, arabinose, xylose, mannose, glucose and galactose were present in polysaccharide fractions. The galacturonic acid content in polysaccharide fractions followed the order: ZJPa3>ZJPa2>ZJPa1>ZJPN. All the 4 polysaccharide fractions were found to be more effective in scavenging superoxide anions than hydroxyl radicals, while acidic polysaccharides showed a more pronounced effect in chelating ferrous ion. 10.1016/j.ijbiomac.2010.06.010
    Comparative pharmacokinetics of triterpenic acids in normal and immunosuppressed rats after oral administration of Jujubae Fructus extract by UPLC-MS/MS. Li Yao,Guo Sheng,Hua Tingting,Wang Yanyan,Wei Dandan,Zhao Ming,Su Shulan,Duan Jin-Ao Journal of chromatography. B, Analytical technologies in the biomedical and life sciences The fruit of Ziziphus jujuba (Jujubae Fructus) has been used as food and crude drug for thousands of years. Although several chemical and biological studies have revealed triterpenic acid as the main bioactive constituent of Jujubae Fructus responsible for immune-regulatory activity, only few pharmacokinetic studies have been conducted. To comprehend the kinetics of triterpenic acids and promote their curative application, a sensitive and efficient ultra-performance liquid chromatography coupled with mass spectrometry method (UPLC-MS/MS) was established. UPLC-MS/MS was applied for the simultaneous determination of ceanothic acid, epiceanothic acid, pomonic acid, alphitolic acid, maslinic acid, betulinic acid, and betulonic acid in normal and immunosuppressed rat plasma samples. After sample preparation, chromatographic separation was performed on an Acquity UPLC BEH C column (2.1 × 100 mm, 1.7 μm) with acetonitrile: methanol (1:1, v/v) and 0.5% ammonium acetate in water as mobile phase. The established method was validated and found to be specific, accurate, and precise for the seven triterpenic acids, and was successfully applied for the pharmacokinetic study of rat plasma samples. The results showed that the pharmacokinetic parameters (C, T, AUC, AUC and CLz/F) in the plasma samples of immunosuppressed rats were significantly different from those in normal rats, and might provide an insight for the clinical usage of triterpenic acids from Jujubae Fructus. 10.1016/j.jchromb.2018.01.026
    Fatty acids and carotenes in some ber (Ziziphus jujuba Mill) varieties. Guil-Guerrero J L,Díaz Delgado A,Matallana González M C,Torija Isasa M E Plant foods for human nutrition (Dordrecht, Netherlands) Several jujube varieties from the southeast of Spain were analyzed for fatty acid and carotene contents. Triglycerides having medium-chain fatty acids were most abundant in all samples. The main fatty acids were 12:0 (18.3 +/- 9.97), 10:0 (12.5 +/- 19.0), 18:2n6 (9.27 +/- 7.26), 16:1n7 (8.50 +/- 5.77), 16:0 (7.25 +/- 4.35), and 18:1n9 (5.34 +/- 2.52) on total saponifiable oil. The fruits yield 1.33 +/- 0.17 g/100 g saponifiable oil on a dry weight basis. Fatty acid profiles of fruits were found to be influenced by their developmental stage. Multivariable data analyses show that the samples could be grouped on the basis of their fatty acid content. Carotenes were found to be in good agreement with other fruits, varying from 4.12 to 5.98 mg/100 g on a dry weight basis. The contribution to vitamin value reach a mdium of 38 microg RE/100 g on a fresh weight basis. 10.1007/s11130-004-0017-2
    Activity-guided fractionation of the seeds of Ziziphus jujuba using a cyclooxygenase-2 inhibitory assay. Su Bao-Ning,Cuendet Muriel,Farnsworth Norman R,Fong Harry H S,Pezzuto John M,Kinghorn A Douglas Planta medica Bioactivity-guided fractionation of petroleum ether- and EtOAc-soluble extracts of the seeds of Ziziphus jujuba using a cyclooxygenase-2 assay as a monitor indicated that the triglyceride, 1,3-di-O-[9(Z)-octadecenoyl]-2-O-[9(Z),12(Z)-octadecadienoyl]glycerol (3), and a fatty acid mixture of linoleic, oleic and stearic acids, were the major active components. A new pentacyclic lupane-type triterpene derivative, 3-O-[9(Z)-octadecenoyl]betulinic acid (1), and betulinic acid (2) were also isolated and identified. All isolates as well as pure linoleic, oleic and stearic acids were evaluated for their inhibitory effects against both cyclooxygenases-1 (COX-1) and -2 (COX-2). 10.1055/s-2002-36354
    Mechanism of the anti-cancer activity of Zizyphus jujuba in HepG2 cells. Huang Xuedan,Kojima-Yuasa Akiko,Norikura Toshio,Kennedy David Opare,Hasuma Tadayoshi,Matsui-Yuasa Isao The American journal of Chinese medicine The Zizyphus jujuba fruit has been used as a traditional Chinese medicinal herb and considered to affect various physiological functions in the body for thousands of years. However, its anti-cancer activity and mechanism of action remain to be elucidated. We investigated the anti-cancer activity of Zizyphus jujuba Mill and its underlining mechanisms of action in human hepatoma cells (HepG2) and found that the extract of Z. jujuba decreased the viability of the cells. Further extraction of the initial Z. jujuba extract with organic solvents revealed that the chloroform fraction (CHCl(3)-F) was the most effective. Interestingly, the CHCl(3)-F induced not only apoptosis but also G1 arrest at a low concentration (100 mug/ml) and G2/M arrest at a higher concentration (200 mug/ml) by cell cycle assay. Apoptosis, an increase in intracellular ROS (reactive oxygen species) level, a decline of mitochondrial membrane potential at low Z. jujuba concentrations, and a ROS-independent mitochondrial dysfunction pathway at high concentrations were all observed. CHCl(3)-F-induced G1 arrest in HepG2 cells was associated with an increase in hypohosphorylation of Rb and p27(Kip1), and a decrease of phosphorylated Rb. However, CHCl(3)-F-induced G2/M arrest in HepG2 cells correlated with a decrease of the p27(Kip1) levels and generation of the phosphorylation of p27(Kip1), however the hypohosphorylation of Rb protein remained. Collectively, our findings suggest that the CHCl(3)-F extract of Z. jujuba extract induced a concentration dependent effect on apoptosis and a differential cell cycle arrest in HepG2 cells. 10.1142/S0192415X0700503X
    The pretreatment effects on the antioxidant activity of jujube polysaccharides. Qu Chenling,Yu Songcheng,Jin Huali,Wang Jinshui,Luo Li Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy Pretreatment is vital to keep the bioactivities of polysaccharides. In this paper, the effects of hot water, ultrasonic and microwave extraction, as well as the effects of protein and pigment removal steps, on the antioxidant activity of water soluble polysaccharides in jujube (WSPJ) were studied. Hydroxyl free radical (OH) scavenging activity was adopted to determine the antioxidant activity of WSPJ. The results showed that OH scavenging activity of WSPJ extracted by ultrasonic wave was higher than that extracted by hot water and by microwave. Furthermore, power parameter in both ultrasonic and microwave extraction affected the OH scavenging activity dramatically. On the other hand, Sevag reagent was better than trichloroacetic acid (TCA), TCA with 1-butanol (TCA-B) and hydrochloric acid for protein removal, and H2O2 was better than active carbon for pigment removal to keep the antioxidant activity of WSPJ. 10.1016/j.saa.2013.05.084
    The historical and current research progress on jujube-a superfruit for the future. Liu Mengjun,Wang Jiurui,Wang Lili,Liu Ping,Zhao Jin,Zhao Zhihui,Yao Shengrui,Stănică Florin,Liu Zhiguo,Wang Lixin,Ao Changwei,Dai Li,Li Xiansong,Zhao Xuan,Jia Chunxiang Horticulture research Jujube ( Mill.), or Chinese date, is the most important species of Rhamnaceae, a large cosmopolitan family, and is one of the oldest cultivated fruit trees in the world. It originates from the middle and lower reaches of the Yellow River, the 'mother river' of the Chinese people. It is distributed in at least 48 countries on all continents except Antarctica and is becoming increasingly important, especially in arid and semiarid marginal lands. Based on a systematic analysis of the unique characteristics of jujube, we suggest that it deserves to be recognized as a superfruit. We summarized historical research achievements from the past 3000 years and reviewed recent research advances since 1949 in seven fields, including genome sequencing and application, germplasm resources and systematic taxonomy, breeding and genetics, cultivation theory and techniques, pest control, postharvest physiology and techniques, and nutrition and processing. Based on the challenges facing the jujube industry, we discuss eight research aspects to be focused on in the future. 10.1038/s41438-020-00346-5
    Inhibitory effect of jujuboside A on glutamate-mediated excitatory signal pathway in hippocampus. Zhang Mu,Ning Gangmin,Shou Caihua,Lu Yinjun,Hong Dihui,Zheng Xiaoxiang Planta medica Jujuboside A (JuA) is a main component of jujubogenin extracted from the seed of Ziziphus jujuba Mill var spinosa (Bunge) Hu ex H F Chou (Ziziphus), which is widely used in Chinese traditional medicine for the treatment of insomnia and anxiety. Previously, we reported the inhibitory effects of JuA on hippocampal formation in vivo and in vitro, the present study was carried out to examine the effects of JuA on glutamate (Glu)-mediated excitatory signal pathway in hippocampus. Microdialysis coupled with high-performance liquid chromatography (HPLC) was used to monitor the changes of Glu levels in the hippocampus induced by penicillin sodium, or a mixture of penicillin sodium and JuA. The results showed that penicillin increased the hippocampal Glu concentration (p < 0.01) and a high dose of JuA (0.1 g/L) significantly blocked penicillin-induced Glu release (p < 0.05). Moreover, the effect of JuA on intracellular Ca2+ changes after the stimulation by Glu was studied in cultured hippocampal neurons with confocal laser scanning microscope (CLSM). It was found that Glu (0.5 mM) induced an intracellular [Ca2+]i increase (p < 0.01), and JuA significantly inhibited the Glu-induced Ca2+ increase. The calmodulin (CaM) antagonist trifluoperazine (TFP) showed a similar inhibitory effect as JuA. These observations suggested that JuA has inhibitory effects on Glu-mediated excitatory signal pathway in hippocampus and probably acts through its anti-calmodulin action. 10.1055/s-2003-42786
    Effects of water-soluble carbohydrate concentrate from Chinese jujube on different intestinal and fecal indices. Huang Ya-Ling,Yen Gow-Chin,Sheu Fuu,Chau Chi-Fai Journal of agricultural and food chemistry This study was to investigate the effects of water-soluble carbohydrate concentrate (WSCC) prepared from Chinese jujube ( Zizyphus jujuba) on different intestinal and fecal indices in a hamster model. WSCC contained carbohydrates (771 g kg(-1) of WSCC) including glucose, fructose, pectin polysaccharide, and hemicellulose. The administration of WSCC (5.0 and 15 g kg(-1) of diet) effectively ( P<0.05) shortened gastrointestinal transit time (by 34.2-57.3%), reduced cecal ammonia (by 58.1-60.3%), elevated total short-chain fatty acid concentrations in cecum (3-4-fold), increased fecal moisture (147-170%), reduced daily fecal ammonia output (by 31.9-75.8%), and decreased the activities of beta-D-glucuronidase (by 73.0-73.8%), beta-D-glucosidase (by 58.2-85.7%), mucinase (by 46.2-72.6%), and urease (by 31.9-48.7%) in feces. This study suggested that adequate consumption of jujube WSCC (at least 5.0 g kg(-1) of diet or 40 mg day(-1)) might exert favorable effects on improving the gastrointestinal milieu and reducing the exposure of intestinal mucosa to toxic ammonia and other detrimental compounds. 10.1021/jf072664z
    Regulation of GABA and 5-HT Receptors Involved in Anxiolytic Mechanisms of Jujube Seed: A System Biology Study Assisted by UPLC-Q-TOF/MS and RT-qPCR Method. Chen Liang,Zhang Xue,Hu Chun,Zhang Yi,Zhang Lu,Kan Juntao,Li Bo,Du Jun Frontiers in pharmacology The increase of the prevalence of anxiety greatly impacts the quality of life in China and globally. As the most popular traditional Chinese medicinal ingredient for nourishing health and tranquilizing mind, Jujube seed ( Mill., Rhamnaceae) (SZJ) has been proved to exert anxiolytic effects in previous reports. In this study, a system biology method assisted by UPLC-Q-TOF/MS and RT-qPCR was developed to systematically demonstrate the anxiolytic mechanisms of SZJ. A total of 35 phytochemicals were identified from SZJ extract ( Mill. var. spinosa [Bunge] Hu ex H.F. Chow), which interact with 71 anxiolytic targets. Protein-protein interaction, genes cluster, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were subsequently conducted, and results demonstrated that regulation of serotonergic and GABAergic synapse pathways were dominantly involved in the anxiolytic mechanisms of SZJ extract. The effects of SZJ extract on mRNA expressions of multiple GABA (gamma-aminobutyric acid type A) and 5-HT (serotonin) receptors subtypes were further validated in human neuroblastoma SH-SY5Y cells using RT-qPCR. Results showed that SZJ extract (250 μg/mL) significantly up-regulated the mRNA level of GABRA1 and GABRA3 as well as HTR1A, HTR2A, and HTR2B in non-HO treated SH-SY5Y cells. However, it exerted an inhibitive effect on the overexpressed mRNA of GABRA1, GABRA2, HTR1A, and HTR2A in HO treated SH-SY5Y cells. Taken together, our findings suggest that anxiolytic mechanisms of SZJ mostly involve the regulation of GABAergic and serotonergic synapse pathways, especially a two-way modulation of GABRA1, HTR1A, and HTR2A. Our current results provide potential direction for future investigation of SZJ as an anxiolytic agent. 10.3389/fphar.2020.01320
    Therapeutic Effects of Mill. Fruit in Traditional and Modern Medicine: A Review. Sobhani Zahra,Nikoofal-Sahlabadi Sara,Amiri Mohammad S,Ramezani Mahin,Emami Seyed A,Sahebkar Amirhossein Medicinal chemistry (Shariqah (United Arab Emirates)) Ziziphus jujuba Mill. belonging to the Rhamnaceae family, has been consumed since ancient times as a medicine and food. In the different traditional medical schools, Z. jujuba has been used to treat various diseases such as respiratory system diseases (asthma, cough, and laryngitis), gastrointestinal problems (constipation, colitis and liver diseases), as well as cardiovascular and genitourinary system diseases. From the perspective of Islamic traditional medicine (ITM), Z. jujuba fruit is an emollient, laxative, and maturative, it can purify blood and improve blood circulation, relieve internal heat and reduce inflammation. Some therapeutic uses of Z. jujuba such as antibacterial, antioxidant, sedative, hepato-protective, anti-hyperglycemic, and anti-hyperlipidemic activities have been shown in modern pharmacological studies. In the current study, traditional and ethno-medicinal uses, botany, phytochemistry and pharmacological activities of Z. jujuba were reviewed. 10.2174/1573406415666191031143553
    Cytoprotective effects of the aqueous extract of the Ziziphus jujuba fruit on TBHP-induced damage on human fibroblast cells. Arab Mina,Khorashadizadeh Mohsen,Abotorabi Zahra,Zarban Asghar Journal of basic and clinical physiology and pharmacology Background Oxidative stress plays a major role in the development of various human diseases. However, many antioxidant compounds can neutralize the excess of free radicals, protect the cells against their toxic effects and help prevent or treat a disease. This study investigated the cytoprotective effects of the aqueous extract of the Ziziphus jujuba fruit on the tert-butyl hydroperoxide (TBHP)-induced damage on human fibroblast cells. Methods Human fibroblast cells were pretreated with different concentrations (1, 2, 4, 8 mg/mL) of Z. jujuba for 24 h and exposed to 75 μM TBHP for another 24 h. Cell viability was determined by the MTT assay. The antioxidant activity was determined using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) methods, and the intracellular antioxidant activity was evaluated with the Cellular antioxidant activity assay. Results Our data showed that treatment with TBHP reduced cell viability of human fibroblast cells, while pretreatment with Z. jujuba increased cell viability in a dose-dependent manner. This indicated the cytoprotective effects of Z. jujuba. Pretreatment with Z. jujuba increased the antioxidant capacity and scavenged the TBHP-produced peroxyl radicals in the human fibroblast cell medium. Moreover, Z. jujuba increased the intracellular antioxidant activity of human fibroblast cells. Conclusions These results demonstrated that the aqueous extract of the Z. jujuba fruit can prevent TBHP-induced cellular toxicity by enhancing the antioxidant activity in cells and their medium. So, Z. jujuba has a therapeutic potential to attenuate oxidative stress-induced diseases. 10.1515/jbcpp-2019-0172
    Metabolite distribution and correlation studies of Ziziphus jujuba and Ziziphus nummularia using LC-ESI-MS/MS. Khan Muhammad Noman,Ul Haq Faraz,Rahman Saeedur,Ali Arslan,Musharraf Syed Ghulam Journal of pharmaceutical and biomedical analysis Ziziphus jujuba and Ziziphus nummularia are two important species of the genus Ziziphus. Both plants offer great commercial value and are consumed as food around the world and used for their medicinal values such as anti-inflammatory, antioxidant and hepatoprotective activities. Comprehensive chemical profiling of Z. jujuba and Z. nummularia was done through identification of major metabolites using HPLC-QTOF-MS/MS and quantification of eight analytes using HPLC-IonTrap-MS/MS analysis. A total of 53 compounds were identified from their high-resolution mass spectra in both positive and negative ionization modes. Among these, 52 compounds were found to be present in Z. jujuba, and 45 in Z. nummularia. Chemometric analysis was also performed to assess the distribution of identified compounds and to determine how the obtained data can be used to discriminate between the two species. Moreover, a method for the quantification of eight analytes including, 6″'-feruloylspinosin (1), apigenin (2), apigenin-7-O-glucoside (3), catechin (4), jujuboside A (5), jujuboside B (6), luteolin (7) and quercetin (8) was developed. The method expressed excellent accuracy with less than 3% error and good reproducibility with less than 4% RSD. The limit-of-detection (LOD) was also found to be very low ranging between 0.06 ng/mL to 4.10 ng/mL while limit-of-quantitation (LOQ) values were in the range of 0.17 ng/mL to 12.42 ng/mL. The analyte concentrations were found to be varying from 1.32 mg/kg to 645.76 mg/kg in both species. The developed method was used to identify and quantify marker compounds in fruit and whole plant samples of both species and in their herbal products as well. The present work is unprecedented, as there is no such extensive study targeting fruits, leaves and herbal formulations together using high-resolution techniques. The study will provide great utility in drug discovery, in taxonomical identification of these plants and to develop quality control protocols for their herbal formulations. 10.1016/j.jpba.2019.112918
    Anxiolytic effect of seed of Ziziphus jujuba in mouse models of anxiety. Peng W H,Hsieh M T,Lee Y S,Lin Y C,Liao J Journal of ethnopharmacology The aim of the present study was to investigate the ethanolic extract of Semen Ziziphi jujuba (SZJE) induced anxiolytic effect. The SZJE was orally administered to male ICR mice, at 0.5, 1.0 and 2. 0 g/kg, 30 min before the behavioral evaluation in the black and white test (BWT) and elevated plus maze (EPM). The SZJE at the dosage 0.5-2.0 g/kg increased the first time entry, total changes and times spent in the white chamber of the BWT. The SZJE at the dosage 0.5-1.0 g/kg increased the percentage of time-spent and the percentage of arm entries in the open arms of the EPM and decreased the percentage of time-spent and the percentage of arm entries in the closed arms of the EPM. Furthermore, the SZJE at the dosage of 1. 0 g/kg prolonged the hexobarbital-induced sleeping time in mice and decreased the locomotor activity in rats. These results suggested that SZJE possessed anxiolytic effect at lower dose and sedative effect at higher dose.
    Immunomodulatory effect of a formula developed from American ginseng and Chinese jujube extracts in mice. Yu Zhuo-ping,Xu Dong-dong,Lu Lai-feng,Zheng Xiao-dong,Chen Wei Journal of Zhejiang University. Science. B BACKGROUND:American ginseng (Panax quinquefolius L.) and Chinese jujube (Zizyphus jujuba Mill.) are commonly used in traditional Chinese medicine to enhance immune function. OBJECTIVE:The present study aimed to develop one Chinese prescription, Shenzao Cha (SZC), consisting of American ginseng and Chinese jujube, and systematically investigate its immunomodulation in healthy ICR mice. METHODS:Normal ICR mice received intragastric administration of SZC (1.3, 2.6, and 5.2 g raw material/kg body weight) once daily for four weeks, while a control group received the same amount of sterile water. RESULTS:SZC significantly increased the spleen and thymus indices and T-lymphocyte proliferation, while the T-lymphocyte proliferation in the 5.2 g/kg group was 1.4-fold higher than that in the control. Further, 1.3 g/kg SZC could markedly improve hemolytic activity by 25.2%, and 2.6 g/kg SZC increased the NK cell activity by 78.6% relative to the control. In addition, the activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), that participated in modulating oxidative stress, were significantly increased in the liver, spleen, thymus, and serum, while the contents of malondialdehyde were dramatically decreased. CONCLUSIONS:SZC exhibited potent immunomodulatory effects on innate and adaptive immunity in healthy ICR mice, as well as potential antioxidant activity for prevention of oxidative stress, which was suggested to partly contribute to the immune enhancement. 10.1631/jzus.B1500170
    Wild jujube polysaccharides protect against experimental inflammatory bowel disease by enabling enhanced intestinal barrier function. Yue Yuan,Wu Shuangchan,Li Zhike,Li Jian,Li Xiaofei,Xiang Jin,Ding Hong Food & function Dietary polysaccharides provide various beneficial effects for our health. We investigated the protective effects of wild jujube (Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou) sarcocarp polysaccharides (WJPs) against experimental inflammatory bowel disease (IBD) by enabling enhanced intestinal barrier function. Colitis was induced in rats by the intrarectal administration of TNBS. We found that WJPs markedly ameliorated the colitis severity, including less weight loss, decreased disease activity index scores, and improved mucosal damage in colitis rats. Moreover, WJPs suppressed the inflammatory response via attenuation of TNF-α, IL-1β, IL-6 and MPO activity in colitis rats. And then, to determine the effect of WJPs on the intestinal barrier, we measured the effect of WJPs on the transepithelial electrical resistance (TER) and FITC-conjugated dextran permeability in Caco-2 cell stimulation with TNF-α. We further demonstrated that the alleviation of WJPs to colon injury was associated with barrier function by assembly of tight junction proteins. Moreover, the effect of WJPs on TER was eliminated by the specific inhibitor of AMPK. AMPK activity was also up-regulated by WJPs in Caco-2 cell stimulation with TNF-α and in colitis rats. This study demonstrates that WJPs protect against IBD by enabling enhanced intestinal barrier function involving the activation of AMPK. 10.1039/c5fo00378d
    Comparison of the sedative and hypnotic effects of flavonoids, saponins, and polysaccharides extracted from Semen Ziziphus jujube. Jiang Jian-Guo,Huang Xiao-Juan,Chen Jian,Lin Qing-Sheng Natural product research Semen Ziziphus jujube (SZJ), the seeds of Ziziphus jujuba Mill. var. spinosa, is a kind of traditional Chinese medicine used for its action on insomnia. In order to analyze the effective component, we investigated and compared the sedative and hypnotic effects of three kinds of compounds, flavonoids, saponins, and polysaccharides. Flavonoids, saponins, and polysaccharides were extracted from SZJ and orally administered to mice separately at 17 g kg(-1) per day for certain days before animal tests. Spontaneous motility and coordinated movement tests were used to observe the effects of the three kinds of compounds on the mouse behavior, and sodium barbital-induced sleeping time of mouse were tested to analyze the effects of the three kinds of compounds on the sleep of mouse. Results show that flavonoids and saponins caused a significant reduction of walking time and coordinated movement ability of mouse, significantly prolonged its sleeping time at 40 mg kg(-1), ip, subthreshold dose and increased the sleeping number of animals at 50 mg kg(-1), ip, superthreshold dose induced by coeliac injection of sodium barbital. Polysaccharides did not show any significance in all animal tests. Comparative analysis showed that saponins had a more effective sedative and hypnotic function than that of flavonoids, polysaccharides did not show a sedative and hypnotic effect. 10.1080/14786410701192827
    Combination of Zizyphus jujuba and green tea extracts exerts excellent cytotoxic activity in HepG2 cells via reducing the expression of APRIL. Huang Xuedan,Kojima-Yuasa Akiko,Xu Shenghui,Kennedy David Opare,Hasuma Tadayoshi,Matsui-Yuasa Isao The American journal of Chinese medicine Hepatocellular carcinoma is a type of tumor highly resistant to available chemotherapeutic agents. The treatment of hepatocellular carcinoma remains a challenge that needs new approaches in the future. In a previous study, we demonstrated that the chloroform fraction (CHCl(3)-F) from Z. jujuba has anticancer activity in human liver cancer cells (HepG2), and that combining CHCl(3)-F with green tea extracts (GTE) results in enhanced effects of anticancer activity in the cells. To further understand the mechanism of the anticancer activity of combining CHCl(3)-F and GTE in HepG2 cells, we investigated whether the addition of a mixture of CHCl(3)-F and GTE would affect the expression of APRIL (a proliferation-inducing ligand), which was expressed in HepG2 cells from 4 hours of incubation in vitro. We have shown that CHCl(3)-F and GTE enhanced anti-cancer activity by reducing the expression of APRIL. We speculate that the CHCl(3)-F and GTE mixture might provide a lead to a new drug design to treat hepatocellular carcinoma in the future. 10.1142/S0192415X09006758
    Hair growth promoting effect of Zizyphus jujuba essential oil. Yoon Jung In,Al-Reza Sharif M,Kang Sun Chul Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association This study was undertaken to examine the efficacy of essential oil from seeds of Zizyphus jujuba for its potential role on hair growth by in vivo method. Essential oil was applied at different concentrations (0.1%, 1% and 10%) over the shaved skin onto the backs of BALB/c mice and monitored for 21 days. After 21 days, mice treated with 1% and 10% of oil produced a greater effect on the length of hair which were measured to be 9.96 and 10.02 mm, respectively, as compared to the control (8.94 mm). We measured the weight of hair/cm(2) area of dorsal skin and also evaluated hair thickness and hair follicles microscopically after plucking the hair immediately from the shaved area of mice and found the best results for 1% of essential oil-treated mice. From this study, it is concluded that Z. jujuba essential oil possesses hair growth promoting activity. 10.1016/j.fct.2010.02.036
    Hydroalcoholic extract of Zizyphus jujuba ameliorates seizures, oxidative stress, and cognitive impairment in experimental models of epilepsy in rats. Pahuja Monika,Mehla Jogender,Reeta K H,Joshi Sujata,Gupta Yogendra Kumar Epilepsy & behavior : E&B The anticonvulsant effect of the hydroalcoholic extract of Zizyphus jujuba (HEZJ) fruit (100, 250, 500, and 1000 mg/kg, orally) was evaluated in experimental seizure models in rats. The effect of HEZJ on seizure-induced cognitive impairment, oxidative stress, and cholinesterase activity was also investigated. HEZJ (1000 mg/kg) exhibited maximum protection (100%) against generalized tonic-clonic seizures in the pentylenetetrazole (PTZ) seizure model and and 66.7% protection against tonic hindlimb extension in the maximal electroshock (MES) seizure model. Significant impairment in cognitive functions was observed in both PTZ- and MES-challenged rats. Pretreatment with HEZJ resulted in significant improvement in learning and memory. HEZJ also reversed the oxidative stress induced by both PTZ and MES. The significant decrease in cholinesterase activity observed in the PTZ and MES models was significantly reversed by pretreatment with HEZJ. Thus, the present study demonstrates the anticonvulsant effect of HEZJ as well as amelioration of cognitive impairment induced by seizures in rats. 10.1016/j.yebeh.2011.05.013
    Anti-inflammatory activity of seed essential oil from Zizyphus jujuba. Al-Reza Sharif M,Yoon Jung In,Kim Hyo Jung,Kim Jong-Sang,Kang Sun Chul Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association This study was undertaken to evaluate the effect of essential oil from seeds of Zizyphus jujuba on TPA-induced skin inflammation in experimental mice. Exposure of TPA on the ear of the BALB/c mice caused a marked increase in both ear thickness and skin water content. The ear thickness was measured for TPA-induced ear was 0.54 mm, as compared to control (0.23 mm). Treatment with 1% and 10% of essential oil caused significant decrease in ear thicknesses which were measured to be 0.30 and 0.35 mm, as well as reduce the water content about 51% and 53% in the TPA-induced skin inflammation model, respectively. Furthermore, histological analysis clearly confirmed that Z. jujuba essential oil inhibited the inflammatory responses of skin inflammation in animal model. Therefore, our findings demonstrate that the essential oil of Z. jujuba seeds might accelerate the development of new drugs for various inflammatory diseases. 10.1016/j.fct.2009.11.045
    Zizyphus jujuba and its active component jujuboside B inhibit platelet aggregation. Seo Eun Ji,Lee So Young,Kang Sam Sik,Jung Yi-Sook Phytotherapy research : PTR The seeds of Zizyphus jujuba (SZJ), a famous oriental traditional medicine, have been reported to exhibit diverse activities in biological systems including the cardiovascular system. However, little information is available on its antiplatelet activity. This study was undertaken to investigate the antiplatelet effects of the ethanolic extract of SZJ (ESZJ) and of its principal components jujuboside A and B. In the in vitro platelet aggregation study, ESZJ exhibited significant and concentration-dependent inhibitory effects on collagen-, thrombin-, and AA-induced platelet aggregation. In addition, ESZJ-treated mice showed significantly the prolongation of bleeding times and the protection against thromboembolic attack. A comparison of the effects of jujuboside A and B on platelet aggregation revealed that only jujuboside B had potent inhibitory effects on collagen-, thrombin-, AA-, and ADP-induced aggregation. Jujuboside B also exhibited superior protection on thromboembolic model. Furthermore, jujuboside B had a significant inhibitory effect on collagen-induced thromboxane A2 production in rat platelets. This study describes the antiplatelet effects of ESZJ and of its active component jujuboside B, and its findings suggest that these agents be considered as components of preventive and therapeutic herbal drugs targeting cardiovascular diseases associated with platelet hyperaggregation. 10.1002/ptr.4809
    Antiproliferation of melanoma cells by polysaccharide isolated from Zizyphus jujuba. Hung Chi-Feng,Hsu Bo-Yang,Chang Shyh-Chung,Chen Bing-Huei Nutrition (Burbank, Los Angeles County, Calif.) OBJECTIVE:Zizyphus jujuba, a traditional Chinese herb rich in functional components such as polysaccharide, has been widely consumed in Asian countries. The objective of this study was to determine the antiproliferation effect of melanoma cells as affected by deproteinized polysaccharide (DPP) isolated from Z. jujuba. METHODS:Deproteinized polysaccharide was obtained through boiling water extraction, ethanol precipitation, deproteinization, and dialysis, and the molecular weight of DPP was determined by high-performance gel-filtration chromatography. Melanoma cell viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, the cell cycle was analyzed by flow cytometry, the formation of apoptotic bodies was observed under a fluorescence microscope at 450 nm, and caspase-3 and caspase-9 were measured by an assay kit. RESULTS:Deproteinized polysaccharide was composed of two fractions with average molecular weights of 143 108 and 67 633 Da. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test showed that the antiproliferation effect of DPP on melanoma cells followed a dose- and time-dependent course. The 50% inhibitory concentration of DPP in inhibiting melanoma cell growth was 3.99 ± 0.10 mg/mL after 24-h treatment but decreased significantly to 3.36 ± 0.14 mg/mL after 48 h. The cell cycle assay revealed melanoma cells to be arrested in G2/M phase. Moreover, with DPP treatment, the apoptotic bodies were generated, accompanied by an increase in caspase-3 and caspase-9 activity. CONCLUSIONS:This outcome suggested that DPP may be used as a potential anti-skin cancer agent for further in vivo and clinical trial experiments. 10.1016/j.nut.2011.05.009
    The memory ameliorating effects of DHP1402, an herbal mixture, on cholinergic blockade-induced cognitive dysfunction in mice. Kim Haneul,Lee Hyung Eun,Jung In Ho,Jeon Se Jin,Zhang Jiabao,Kwon Yubeen,Jang Dae Sik,Ryu Jong Hoon Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:The seeds of Ziziphus jujuba var. spinosa (Bunge) Hu ex H.F Chow (Rhamnaceae) and the roots of Codonopsis lanceolata (Siedbold & Zucc.) Benth. & Hook. f ex Trautv. (Campanulaceae), contained in the DHP1402, have long been used for treating dementia or hypomnesia as folk medicine. AIM OF THE STUDY:It has been reported that Z. jujuba var. spinosa and C. lanceolata are effective in improving cognitive function, but via different mechanisms. Therefore, in the present study, we evaluated the synergistic effects of Z. jujuba var. spinosa and C. lanceolata on scopolamine-induced memory impairment. MATERIALS AND METHODS:Scopolamine, a cholinergic muscarinic receptor antagonist, was used to induce cognitive dysfunction. We employed several behavioral tasks to estimate the synergistic effect of the seeds of Z. jujuba var. spinosa and the roots of C. lanceolata. In addition, we introduced the Western blotting, the antagonism passive avoidance task to investigate a synergistic effect of an herbal formulation. RESULTS:Synergistic effects of a combination of Z. jujuba var. spinosa and C. lanceolata at a 5:1 ratio [(w/w), DHP1402] were observed against cognitive dysfunction in the passive avoidance and Y-maze tasks. DHP1402 also ameliorated memory deficits in a dose-dependent manner in these behavioral tasks, as well as in the Morris water maze task. According to the Western blot results, the phosphorylation levels of protein kinase A (PKA), extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB) in the hippocampus were also increased in a synergistic manner after the administration of DHP1402. In addition, we found that the effects of DHP1402 on cognitive function were mediated by N-methyl-D-aspartate (NMDA) receptor signalling, based on the antagonism studies. Furthermore, we found that DHP1402 has inhibitory activity against acetylcholinesterase (AChE). CONCLUSION:DHP1402 attenuates cholinergic blockade-induced cognitive dysfunction through NMDA receptor modulation, PKA-ERK-CREB pathway activation, and AChE inhibition. Therefore, DHP1402 could be a candidate for alleviating cognitive dysfunction. 10.1016/j.jep.2017.09.013
    Zizyphus jujuba cv. Muzao polysaccharides enhance intestinal barrier function and improve the survival of septic mice. Zhou Hai-Cun,Guo Chang-An,Yu Wen-Wen,Yan Xin-Yan,Long Jian-Ping,Liu Zhi-Chang,Liang Xiao-Qin,Liu Hong-Bin Journal of food biochemistry This study aimed to examine the role of Zizyphus jujuba cv. Muzao polysaccharides (ZJPs) in protecting intestinal barrier function and the survival of septic mice. The sepsis mouse model was generated through cecal ligation and puncture (CLP) to observe the effect of ZJPs on the function of the intestinal barrier in the context of sepsis. We observed the clinical symptoms and survival time of the mice and evaluated serum inflammatory cytokines, intestinal pathological changes and intestinal permeability. Moreover, tight junction (TJ) proteins and apoptosis-associated proteins in intestinal tissue were examined. Finally, TLR4/NF-κB pathway-related proteins were measured in all groups. The results showed that pretreatment with ZJPs improved clinical and histological scores and reduced intestinal barrier permeability, and the levels of proinflammatory factors were decreased. Pretreatment with ZJPs also upregulated the levels of TJ proteins and downregulated the expression of proapoptotic proteins. Moreover, the activation of TLR4/NF-κB signaling was partly inhibited in septic mice by ZJPs pretreatment. The current study provides evidence that ZJPs have the potential to protect intestinal barrier function and improve the survival of septic mice via the attenuation of TLR4/NF-κB inflammatory signaling. PRACTICAL APPLICATIONS: This study reports the potential protective effect of ZJPs against cecal ligation and puncture (CLP)-induced sepsis. Our data reveal that CLP induced damage to the gut mucosal barrier, inflammation, and apoptosis in intestinal tissues. However, pretreatment with ZJPs improved clinical and histological scores, reduced intestinal barrier permeability, and decreased the levels of proinflammatory factors in mice. Pretreatment with ZJPs also upregulated the levels of TJ proteins and downregulated the expression of proapoptotic proteins. Moreover, the activation of TLR4/NF-κB signaling was partly inhibited in septic mice after ZJPs pretreatment. These findings provide evidence that pretreatment with ZJPs has the potential to attenuate CLP-induced gut damage in mice by restraining inflammation and apoptosis via the attenuation of NF-κB signaling. It provides a basis for further study of ZJPs in sepsis. 10.1111/jfbc.13722
    Characterization and hepatoprotective effect of polysaccharides from Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou sarcocarp. Yue Yuan,Wu Shuangchan,Zhang Huifang,Zhang Xuyan,Niu Yunhui,Cao Xiaoqin,Huang Fuwei,Ding Hong Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association The polysaccharides from Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou sarcocarp (PWJS) is evaluated for the chemical composition, antioxidant activity and hepatoprotective effect. The characteristics of PWJS were determined by FT-IR spectral and HPLC analysis. The antioxidant activity was investigated using in vitro systems. An in vivo study of PWJS against CCl4 induced liver injury was also conducted. HPLC analysis showed that PWJS is an acidic heteropolysaccharide, rich in glucose (38.59%), arabinose (23.16%), galacturonic acid (17.64%) and galactose (10.44%). PWJS displayed strong antioxidant activity in vitro. In the in vivo study, PWJS treatment lowered the serum levels of ALT and AST in CCl4-intoxicated mice. Additionally, levels of antioxidant enzymes (SOD and CAT) and GSH were elevated in liver damage mice by PWJS intervention, while content of MDA was lessened. Meanwhile, PWJS reverses the suppression of Nrf2 nuclear translocation, and increases the protein expression of HO-1, GSTα and NQO1 in liver damage mice. Hematoxylin-eosin staining showed that the condition of liver damage was mitigated. This study demonstrates that PWJS reverses hepatotoxicity in CCl4-intoxicated mice through the mechanisms of antioxidant activity, as well as an augmentation of the Nrf2 pathway in liver tissue. 10.1016/j.fct.2014.09.006
    Extract of Ziziphus jujuba Fruit (Jujube) Stimulates Expression of Enzymes Responsible for Heme Recycle via Anti-oxidant Response Element in Cultured Murine Macrophages. Chen Jianping,Lam Candy T W,Li Zhonggui,Yao Ping,Lin Huangquan,Dong Tina T X,Tsim Karl W K Phytotherapy research : PTR Jujube, the fruit of Ziziphus jujuba Mill., is a functional food and commonly used as a health supplement worldwide. To study the beneficial role of jujube in heme iron recycling during erythrophagocytosis, the expression of heme oxygenase-1 (HO-1), biliverdin reductase A and B, and ferroportin were determined in jujube-treated cultured RAW 264.7 macrophages. Application of a chemically standardized jujube water extract in cultured RAW 264.7 cells for 24 h stimulated the expressions of HO-1, biliverdin reductase A, biliverdin reductase B, and ferroportin in a concentration-dependent manner, having the maximal responses from twofolds to threefolds. A plasmid containing anti-oxidant response element, a regulator for HO-1 transcription, was transfected into RAW 264.7 cells. Application of jujube water extract onto the transfected macrophages stimulated the anti-oxidant response element-mediated transcriptional activity by twofolds. These results supported the potential capacity of jujube by regulating expressions of heme iron recycling genes in cultured macrophages. 10.1002/ptr.5526
    Hepatoprotective standardized EtOH-water extract of the leaves of Ziziphus jujuba. Bai Lu,Cui Xueqin,Cheng Ni,Cao Wei,Wu Yong,Guo Sen,Zhang Li,Ho Chi-Tang,Bai Naisheng Food & function The hepatoprotective activity of the EtOH-water extract of Ziziphus jujuba leaves was evaluated against CCl-induced hepatic damage in mice. The EtOH-water extract significantly alleviated liver damage as indicated by the decreased levels of serum ALT and AST and the decreased MDA content, the increased levels of SOD, GSH and GSH-Px, and the reduced pathological tissue injury induced by CCl. A quantitative analysis of fifteen major constituents (1-15) of the EtOH-water extract of the leaves of Z. jujuba was conducted by HPLC-DAD. Based on our research results, it can be concluded that the EtOH-water extract of the leaves of Z. jujuba is efficacious for prevention and treatment of CCl-induced hepatic injury in mice. Flavonoids might be the active ingredients responsible for the biological and pharmacological activities towards hepatoprotection. 10.1039/c6fo01690a
    A standardized extract of Ziziphus jujuba Mill protects against adriamycin-induced liver, heart, and brain toxicity: An oxidative stress and biochemical approach. Khajavi Rad Abolfazl,Entezari Heravi Nazanin,Kamkar-Del Yasamin,Abbasnezhad Abbasali,Jalili-Nik Mohammad,Shafei Mohammad Naser,Mohebbati Reza Journal of food biochemistry Due to the antioxidant effects of the Ziziphus jujuba Mill (Z. jujuba), we investigated the liver, heart, and brain-protective effects of this herb against toxicity induced by adriamycin (ADR). In this study, Wistar rats were divided into 1) control, 2) ADR and 3, 4, and 5) treated groups orally administrated three doses of Z. jujuba hydroalcoholic extract for 1 month. The liver, heart, and brain were removed for evaluation of the oxidative markers. Blood samples were evaluated to determine the levels of Lactate dehydrogenase, total and direct bilirubin, alkaline phosphatase, Aspartate transaminase, and Alanine aminotransferase. Administration of Z. jujuba significantly decreased the biochemical enzymes compared to the ADR. Oxidative condition in treated rats with different doses of Z. jujuba was improved compared to the ADR group. Z. jujuba could decrease the oxidative injury through invigoration of the tissues antioxidant system. The mentioned hepatic and cardiac parameters levels improved during extract administration. PRACTICAL APPLICATIONS: In the first stage, our findings and other supplementary works have shown that administration of jujube extract has prevented the effects of histotoxicity caused by adriamycin, so it seems that in the next stage, the effects of this herbal plant on patients with tissue toxicity caused by adriamycin should be evaluated and if the results are positive in pharmacological studies, it should be used as a complementary drug in the treatment of these patients. 10.1111/jfbc.13698
    Molecular mechanisms of polysaccharides from Ziziphus jujuba Mill var. spinosa seeds regulating the bioavailability of spinosin and preventing colitis. Liu Ying,Zhao Xiaotong,Lin Tingting,Wang Qing,Zhang Yanqing,Xie Junbo International journal of biological macromolecules In this study, the effect of Ziziphus jujuba Mill var. spinosa seeds (ZSS) polysaccharides on the bioavailability of spinosin in mice and its molecular mechanism were investigated. After continuously fed with ZSS polysaccharides 100 mg/kg·d for 28 consecutive days, the C57BL/6 mice absorbed spinosin at an obvious lower level compared with the control group. The expression levels of P-gp, MRP2 and Occludin in the colon were significantly increased. ZSS polysaccharides significantly regulated the composition of the gut microbiota, reducing the abundance of Bacteroidetes, and increasing the richness of Firmicutes and Verrucomicrobia. Moreover, ZSS polysaccharides can significantly regulate the expression levels of tight junction proteins and efflux transporters in Caco-2 cells. However, the gut microbiota culture supernatant showed no obvious biological activity in this regard. Furthermore, histopathological analysis revealed ZSS polysaccharides can alleviate TNBS-induced colitis, reduced inflammatory cell infiltration in mice. This immune regulation was related to the NF-κB and MAPK pathways in RAW264.7 cells. 10.1016/j.ijbiomac.2020.07.229
    Dietary supplementation with polysaccharides from Ziziphus Jujuba cv. Pozao intervenes in immune response via regulating peripheral immunity and intestinal barrier function in cyclophosphamide-induced mice. Han Xue,Bai Bingyao,Zhou Qian,Niu Jiahui,Yuan Jing,Zhang Huifang,Jia Jinyu,Zhao Wen,Chen Hong Food & function Ziziphus Jujuba cv. Pozao has been consumed as a traditional fruit with regional characteristics in China for a long time; however, fewer studies on polysaccharides from Ziziphus Jujuba cv. Pozao (JP) have been documented. This study aimed to evaluate the effect of oral administration of JP on cyclophosphamide-induced ICR mice for 28 days. The results showed that oral administration of JP could significantly improve the lymphocyte proliferation in the spleen and decrease the proportion of CD3+ and CD4+ and the ratio of CD4+/CD8+ in cyclophosphamide-induced mice in a dose-dependent manner. JP treatment also increased the levels of IL-2, IL-4, IL-10, IFN-γ, and TNF-α in serum and the intestine, and the improvement effects were proportional to the dose of JP. Similarly, JP significantly increased the levels of IgA and SIgA, as well as the expressions of Claudin-1 and Occludin in the intestine. Particularly, the expressions of Claudin-1 and Occludin were the best in the M-JP group. Furthermore, JP positively regulated the gut microbiota as indicated by the enriched microbiota diversity. At the phylum level, the relative abundance of Firmicutes was significantly decreased by JP, while that of Bacteroidetes was increased by JP treatment. More importantly, the ratio of Firmicutes/Bacteroidetes was significantly increased. And a high dose of JP is the most effective. At the genus level, the abundances of the Bacteroidales-S24-7-group, Lachnospiraceae, Alloprevotella, Alistipes and Bacteroides were increased by JP treatment. These results provided evidence for the regulating effect of JP on the peripheral immunity and intestinal barrier function in cyclophosphamide-induced hypoimmune mice. 10.1039/d0fo00008f
    Structural characterization and antioxidant activities of one neutral polysaccharide and three acid polysaccharides from Ziziphus jujuba cv. Hamidazao: A comparison. Yang Yanmin,Qiu Zhichang,Li Lingyu,Vidyarthi Sriram K,Zheng Zhenjia,Zhang Rentang Carbohydrate polymers A neutral polysaccharide (HJP-1a) and three acid polysaccharides (HJP-2, HJP-3 and HJP-4) were obtained from Z. jujuba cv. Hamidazao. HJP-1a was mainly composed of arabinose and galactose in a ratio of 56.9:20.0, with an average molecular weight of 3.115 × 10 g/mol. HJP-2, HJP-3 and HJP-4 were homogeneous heteropolysaccharides mainly containing galacturonic acid, arabinose and galactose, with average molecular weights of 4.590 × 10, 6.986 × 10 and 1.951 × 10 g/mol, respectively. Structural characterization indicated that the backbone of HJP-3 appeared to be mainly composed of →4)-α-d-GalpA (1→ and →2,4)-α-l-Rhap (1→ residues with some branches consisting of →5)-α-l-Araf (1→ residues and terminals of T-α-l-Araf (1→ and T-β-d-Galp residues. The four purified fractions displayed dose-dependent radical scavenging activity on ABTS radicals and reducing capacity, as well as excellent protective effect on HO-induced HepG2 cells and metronidazole-damaged zebrafish embryos, especially HJP-2 in vitro and HJP-1a in vivo. Therefore, the polysaccharides from Z. jujuba cv. Hamidazao could be used as a potential antioxidant in functional foods. 10.1016/j.carbpol.2021.117879
    Anti-inflammatory and cytotoxic activities of constituents isolated from the fruits of Ziziphus jujuba var. inermis Rehder. Tran Huynh Nguyen Khanh,Cao Thao Quyen,Kim Jeong Ah,Woo Mi Hee,Min Byung Sun Fitoterapia Three new sesquilignans, zijusesquilignans A-C (1-3), together with fifteen known compounds (4-18), were isolated from fruits of Ziziphus jujuba var. inermis Rehder (Rhamnaceae). Their chemical structures were established using spectroscopic analyses including 1D- and 2D-NMR, HR-EIMS, and ECD spectra. These compounds were assessed for their inhibitory effects on nitric oxide (NO) production. Of these compounds, 1-3 and 17 displayed inhibitory effects on NO production, with IC values ranging from 18.1 to 66.4 μM. Pretreatment with 1 and 17 significantly suppressed LPS-induced expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein in cells. Moreover, compounds 1-3, 7, 9, and 17 exhibited cytotoxic activities against three human tumor cell lines, with IC values ranging from 8.4 to 44.9 μM. 10.1016/j.fitote.2019.104261
    Hepatoprotective effects of polysaccharides extracted from Zizyphus jujube cv. Huanghetanzao. Liu Guangpu,Liu Xinquan,Zhang Yongchun,Zhang Fang,Wei Ting,Yang Min,Wang Kaiming,Wang Yongjie,Liu Na,Cheng Huiling,Zhao Zhongxi International journal of biological macromolecules Jujube polysaccharides have been proved to have various bioactivities. This study was designed to evaluate the chemical composition and hepatoprotective function of the polysaccharides extracted from Zizyphus jujube cv. Huanghetanzao (HJP). The composition of HJP was determined as heteropolysaccharides with galactose and arabinose being the main components. The pretreatment of mice with HJP significantly (p<0.01) reduced the activities of serum hepatic AST, ALT, and LDH induced by CCl4 or acetaminophen (APAP) while the commercial liver-injury treatment drug silybin did not show any prevention effects. Mechanistic study results indicate that the administration of the CCl4- or APAP-injured mice with HJP enhanced SOD and GSH-Px and decreased MDA, indicating that anti-oxidation and detoxification could be the pathways for the liver protection observed. In addition, the liver prevention and treatment effects of HJP on the liver damage induced by CCl4 or APAP obtained from the liver enzyme analyses were confirmed by the hepatic histopathology studies in mice. Therefore, HJP could be used as a prevention and treatment agent for liver injury induced by liver toxic chemicals and drugs. 10.1016/j.ijbiomac.2015.01.061
    Ethyl Acetate and Aqueous Fractions of Ziziphus jujuba Prevent Acute Hypertension Induced by Angiotensin II in Rats. Kamkar-Del Yasamin,Mohebbati Reza,Hosseini Mahmoud,Khajavirad Abolfazl,Shafei Mohammad N,Rakhshandeh Hassan Cardiovascular & hematological disorders drug targets BACKGROUND:The effect of hydroalcoholic extract of Ziziphus jujuba (ZJ) on hypertension has been reported previously. OBJECTIVE:This experiment investigates the effect of two ethyl acetate (EA, a polar and semi-polar compound) and aqueous fractions (AQ, a polar compound) of ZJ extract on cardiovascular parameters in acute hypertension induced by angiotensin II (AngII). METHODS:Rats were randomly divided into following groups (n=7 in each group): 1) Control; 2) AngII (50 ng/kg); 3) Losartan (LOS, 30 mg/kg) + AngII; 4, 5) ethyl acetate fraction (EA150 and EA300 mg/kg) + AngII and 6, 7) aqueous fraction (AQ150 and AQ300 mg/kg) + AngII. Rats were treated with both fractions and LOS orally for four weeks and in the experiment day (28th) AngII intravenously injected and cardiovascular parameters (Systolic Blood Pressure (SBP), Mean Arterial Pressure (MAP) and Heart Rate (HR)) directly were recorded by a power lab system. RESULTS:AngII could significantly increase SBP and MAP (P<0.001) and decrease HR with respect to the control and these responses were attenuated by LOS. The SBP and MAP in both doses of EA+ AngII and the higher dose of AQ fractions + AngII were significantly lower than the AngII group (P<0.05 to P<0.001). Bradycardia induced by AngII was also reduced by LOS and both fractions. The comparison of two fractions also showed that the effect of EA fraction is greater than the AQ. CONCLUSION:This study indicates that both fractions of the ZJ extract have a beneficial effect on hypertension. Because effect of EA was greater than AQ, we suggested that antihypertensive effects of ZJ mediated polar and nonpolar compounds. 10.2174/1871529X19666191119141400
    Antioxidant properties of jujube honey and its protective effects against chronic alcohol-induced liver damage in mice. Cheng Ni,Du Bing,Wang Yuan,Gao Hui,Cao Wei,Zheng Jianbin,Feng Fan Food & function The antioxidant potential of jujube honey, one of the most widely consumed honeys in China, has never been determined fully. In this study, jujube honey from six geographical origins in China was analyzed for individual phenolic acid, total phenolic content, and the antioxidant effect in chronic alcohol-related hepatic disease in mice. The results showed that jujube honey from Linxian of Shanxi province contained higher phenol levels, exhibited DPPH antioxidant activity, ferric ion reducing antioxidant power (FRAP) and protective effects against DNA damage. Treatment with jujube honey (Shanxi Linxian) for 12 weeks significantly inhibited serum lipoprotein oxidation, reduced the impact of alcoholism on aspartate aminotransferase (AST) and alanine aminotransferase (ALT). It also inhibited the generation of 8-hydroxy-2-deoxyguanosine (8-OHdG), lowered the levels of malondialdehyde (MDA) and increased the activity of hepatic glutathione peroxidase (GSH-Px). The study indicates that jujube honey exerts potent antioxidant activity and significant protection in hepatic disorders associated with chronic alcoholism. The protective effect is attributed to its antioxidant mechanisms and inhibition of oxidative degradation of lipids. 10.1039/c3fo60623f
    The testicular protective effects of standardised hydroalcoholic extract of Ziziphus jujuba Mill against adriamycin-induced toxicity. Mohebbati Reza,Kamkar-Del Yasamin,Shahraki Samira,Khajavi Rad Abolfazl Andrologia In this study, because of the anti-inflammatory and antioxidant effect of the Ziziphus jujuba (ZJ), we assessed the protective properties of the ZJ extract against testis toxicity caused by Adriamycin in the rat. Twenty rats were grouped into (a) control, (b) Adriamycin, (c) ZJ group and (d) treatment group in which Adriamycin was administrated and the ZJ hydroalcoholic extract was used for three weeks. On the 21st day, two testes were removed to determine the oxidation markers and pathological evaluation. The levels of sex hormones were determined. Epididymis also was crushed, and its spermatozoa were evaluated as concentration, motility and normality. Adriamycin increased oxidative stress markers as well as Luteinising hormone, and follicle-stimulating hormone and decreased testosterone levels compared to control. In the treated group, the levels of the above markers improved. The decreased number and motility of spermatozoa in treatment group increased, and the increased rate of abnormal spermatozoa in this group decreased. Pathological evaluations also show the healing process of damaged testicular tissue in the group receiving the ZJ extract. The ZJ extract relatively improves oxidative stress, sperm characteristics, hormonal alternation and pathological changes. These findings reveal the probable role of ZJ effective compounds in repairing tissue damage. 10.1111/and.13974
    Hypoglycemic effects of three Iranian edible plants; jujube, barberry and saffron: Correlation with serum adiponectin level. Hemmati Mina,Asghari Somaye,Zohoori Elham,Karamian Mehdi Pakistan journal of pharmaceutical sciences One of the most common disorders of the endocrine system is diabetes mellitus. This disease is associated with dyslipidemia. Adiponectin is a protein hormone that secreted by adipocytes and has an important role in regulating of glucose and fatty acid metabolic pathways. This study was designed to investigate the changes in serum level of adiponectin in diabetic rats treated with hydroalcoholic extracts of three medicinal plants; jujube (Ziziphus jujuba), barberry (Berberis vulgaris) and saffron (Crocus sativus) in comparison with quercetin. Streptozotocin -induced diabetic male rats were gavaged with specified doses of the extracts (25 and 100mg/kg) for two weeks. At the end of treatment period, fasting blood specimens were collected. The levels of adiponectin, fasting blood sugar (FBS), total Cholesterol, triglycerides, HDL-C and LDL-C were measured. Statistical analysis showed that serum levels of triglyceride and VLDL decreased significantly (P<0.05) in all treated groups. FBS level in all treated groups, decreased significantly and reach to normoglycemic level (P<0.05). Except Jujube, other plant extracts had no effect on cholesterol. Jujube in two doses (25 and 100mg/kg) could increased significantly HDL-C (P<0.05) with no effect on total cholesterol and LDL-C. Serum adiponectin level increased in all treated groups. These beneficial effects of C. sativus, B. vulgaris and Z. jujube extracts and quercetin in diabetic rats may be associated with increase in adiponectin level.
    Optimized Extraction of Phenolics from Jujube Peel and Their Anti-inflammatory Effects in LPS-Stimulated Murine Macrophages. Wang Bini,Hui Yuanyuan,Liu Longgang,Zhao Aiqing,Chiou Yi-Shiou,Zhang Fuxin,Pan Min-Hsiung Journal of agricultural and food chemistry The extraction of phenolics from jujube peel (PJP) was optimized using response surface methodology (RSM). A Box-Behnken design was utilized to analyze the effects of NaOH concentration, temperature, and extraction time on the total phenolic content (TPC). The results showed that RSM could be an adequate approach for modeling the extraction of PJP. The optimal extraction condition for the highest TPC was obtained with 3.4 M NaOH concentration for 67 min at 50 °C. Not only PJP but also phenolics from the jujube seed (PJS) contain considerable amounts of phenolics, particularly flavonoids. Quercetin and galangin were found to be the predominant phenolics. PJP markedly down-regulated the levels iNOS and COX-2 proteins in macrophages by inhibiting the activation of NF-κB through interfering with the MAPK signaling pathways. Compared to PJS, PJP presented higher anti-inflammatory activities, reflecting increased amounts of TPC and total flavonoid content (TFC). These findings suggest that PJP could be a potential source of anti-inflammatory agents. 10.1021/acs.jafc.8b06309
    A panoramic view on phytochemical, nutritional, and therapeutic attributes of Ziziphus mauritiana Lam.: A comprehensive review. Prakash Om,Usmani Shazia,Singh Ruchi,Singh Namrata,Gupta Amresh,Ved Akash Phytotherapy research : PTR Ziziphus mauritiana (Rhamnaceae), commonly known as Indian jujube, is a pharmacologically diverse medicinal plant. A plethora of active phytochemical constituents of this plant has been revealed so far, namely, berberine, quercetin, kaempferol, sitosterol, stigmasterol, lanosterol, diosgenin, and so forth. Several studies demonstrated the exploration of pharmacological potential of various parts such as fruits, leaves, and stems of the plant as antioxidant, cytotoxic, antimicrobial, anti-diarrhoeal, antidepressant, immunomodulator, and hepatoprotective. This review gives a unique summary including phytochemistry, nutritional value, and significant pharmacological importance of Z. mauritiana. The literature search was carried out via search engine PubMed, Science Direct, and so on. The data were heterogeneous in terms of leaves, stem, roots, and fruits which were used for different experimental findings, which made the comparison a lengthy task. Study findings suggested that the extracts from this plant may possess numerous types of pharmacological activities. As the search for novel drugs from botanical sources continues, there is need for future investigations to isolate and characterize pharmacologically active agents that confer medicinal properties on Z. mauritiana, as well as to elucidate the structures of these agents by which they exert their healing properties and to scientifically validate the existing traditional practices concerning its health benefits. 10.1002/ptr.6769
    Ethnobotanical Survey of Medicinal Plants Used by Traditional Healers to Treat Diabetes in the Taza Region of Morocco. Naceiri Mrabti Hanae,Bouyahya Abdelhakim,Naceiri Mrabti Nidal,Jaradat Nidal,Doudach Latifa,Faouzi My El Abbes Evidence-based complementary and alternative medicine : eCAM Type 2 diabetes is one of the noncommunicable diseases that is becoming a pandemic in Africa. In Morocco, traditional healers have started to use herbal medicines for the treatment of diabetes either individually or in combination with food. The current study aimed to perform an ethnobiological survey of antidiabetic plants use in the Taza region of Morocco. A total of 193 traditional healers were interviewed using a semistructured questionnaire. Data collected were analyzed utilizing the use value (UV), fidelity level (FL), and relative frequency citation (RFC) indices. Forty-six plant species belonging to 28 families were recorded for the treatment of diabetes in the Taza region of Morocco. The most frequently cited plant species are , , and Lamiaceae, Asteraceae, and Fabaceae were the most reported families. Leaves are the most used part of plants to prepare drugs, the decoction is the preferred mode of preparation, and remedies are often administered orally. Interestingly, and were reported as new medicinal plants used to treat diabetes in the Taza region of Morocco. People in the Taza region still rely on indigenous plants for their basic healthcare needs. Further research should be carried out to validate the antidiabetic effect of the newly reported plant species. This validation can be investigated by the determination of bioactive compounds and evaluation of their and antidiabetic effects. 10.1155/2021/5515634
    Triterpenoids Isolated from Ziziphus jujuba Enhance Glucose Uptake Activity in Skeletal Muscle Cells. Kawabata Kyuichi,Kitamura Kenji,Irie Kazuhiro,Naruse Shoma,Matsuura Tomohiro,Uemae Tomoyuki,Taira Shu,Ohigashi Hajime,Murakami Shigeru,Takahashi Masakazu,Kaido Yoko,Kawakami Bunsei Journal of nutritional science and vitaminology Jujube (Ziziphus jujuba Mill.), a traditional folk medicine and functional food in China and South Korea, is known for its beneficial properties, which include anti-cancer, anti-oxidative, and anti-obesity effects. To assess the anti-hyperglycemic effect of jujube in this study, we investigated the glucose uptake-promoting activity of jujube in rat L6 myotubes. After determining that the jujube extract induces muscle glucose uptake, we identified the following active compounds by bioassay-guided fractionation: betulonic acid, betulinic acid, and oleanonic acid. Ursonic acid, known to be present in jujube, was semi-synthesized from ursolic acid and also observed to enhance glucose uptake. These four triterpenic acids induced glucose uptake in a glucose transporter 4-dependent manner. Comparison experiments of jujube fruits from three countries, namely, China, South Korea, and Japan, revealed that Japanese jujube has a higher content of active triterpenoids and is the most potent enhancer of glucose uptake. 10.3177/jnsv.63.193
    Metagenomic analysis of gut microbiota modulatory effects of jujube (Ziziphus jujuba Mill.) polysaccharides in a colorectal cancer mouse model. Ji Xiaolong,Hou Chunyan,Gao Yonggang,Xue Yuqiang,Yan Yizhe,Guo Xudan Food & function Accumulating evidence has reported that the gut microbiota could play important roles in the occurrence and progression of colorectal cancer. The nondigestible plant polysaccharides have always been fermented by the intestinal microbiota. Polysaccharides, the predominant functional composition found in jujube fruit, has been shown to inhibit carcinogenesis in animal models. However, the molecular mechanisms involved in polysaccharides preventing carcinogenesis are still uncharacterized. The aim of this study was to investigate the modulatory effects of jujube polysaccharides (JP) on intestinal microbiota, and the influence of JP on the gut flora structure was then analyzed using an AOM/DSS-induced colitis cancer mouse model, using high-throughput sequencing. Contrasted with control group, the addition of JP could ward off colon cancer by ameliorating colitis cancer-induced gut dysbiosis. In addition, there was a significant decrease in Firmicutes/Bacteroidetes post JP treatment. What's more, KEGG pathways of metabolic pathways, ATP-binding cassette (ABC) transporters and two-component system enriched the most differentially expressed genes after JP intervention for 13 weeks. These results suggested that JP showed prebiotic-like activities by positively modulating intestinal microbiota and affecting certain metabolic pathways contributing to host health. In conclusion, our results demonstrated an appreciable capability of JP to restore the gut microbiota profile altered by AOM/DSS, indicating the potential of jujube polysaccharides as promising prebiotic candidates for the prevention and treatment of colorectal cancer. 10.1039/c9fo02171j
    Ziziphus jujube ameliorated cavernosal oxidative stress and fibrotic processes in cavernous nerve injury-induced erectile dysfunction in a rat model. Resim Sefa,Koluş Eyüp,Barut Osman,Kucukdurmaz Faruk,Bahar Abdulkadir Yasir,Dagli Hasan Andrologia The aim of this study was to investigate potential antioxidant and antifibrotic effects of Ziziphus jujube (ZJ) in a cavernosal nerve injury (CNI)-induced erectile dysfunction (ED) rat model. Forty-eight male rats were assigned to six-sized groups as group 1: sham-operated; group 2: sham-operated + low-dose ZJ (200 mg/kg); group 3: sham-operated + high-dose ZJ (400 mg/kg); group 4: CNI + distilled water; group 5: CNI + low-dose ZJ; and group 6: CNI + high-dose ZJ. At the end of 2 weeks, intracardiac blood was taken and rats were sacrificed. For biochemical analysis, cavernosal transforming growth factor-beta-1, collagen type I and type 3, fibronectin, α and β actin were examined in plasma and cavernosa. Superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and prolidase levels were measured in serum to evaluate antioxidant effect of ZJ. Histopathological examination of tissues revealed that highest fibrosis rate was in group 4 (66.84%). Collagen 1 and 3, alpha and beta actin, fibronectin levels were significantly different among groups (p < .05). Differences between plasma SOD, CAT, MDA and prolidase were also significant among those groups (p < .05). In this study, antioxidant and antifibrotic effects of ZJ were determined in the corporal tissue after CNI. It is thought that ZJ may be beneficial on ED patients especially after radical pelvic surgeries. 10.1111/and.13632
    Experimental and Clinical Pharmacology of Ziziphus jujuba Mills. Rodríguez Villanueva Javier,Rodríguez Villanueva Laura Phytotherapy research : PTR Ziziphus jujuba Mills, 'annab' in Iran, 'ber' in India or 'pomme sourette' in France, is a species whose fruit (known warmly as 'the fruits of life' in China) has been consumed for centuries for its nutritional value. The food industry used it as a food additive and flavoring. The dry seeds, the crude leaves and the stem bark are still used in ethnopharmacology to treat digestive disorders and gastric ulcers as antitussive, laxative and hypotensive drugs; even now, it is used in China to treat children who suffer from typhoid fever, furuncle and ecthyma. In Taiwan, the dry seeds for the variety spinosa (Suan Zao Ren) are the second most commonly prescribed and used phytomedicine for insomnia. Its popularity and production have increased worldwide in recent years, especially in Europe. The European Pharmacopoeia Commission has been unable to elaborate upon the EP monograph on Ziziphi spinosae semen as was planned. The EMA has not made its recommendations yet. Is it still a gap in the scientific knowledge? Or is difficult for traditional Chinese medicinal herbs to fulfill the style and quality parameters that are required? Copyright © 2017 John Wiley & Sons, Ltd. 10.1002/ptr.5759
    A Review of Edible Jujube, the Fruit: A Heath Food Supplement for Anemia Prevalence. Chen Jianping,Tsim Karl W K Frontiers in pharmacology The fruits of , commonly known as jujube, red date or Chinese date, are taken as fresh or dried food, and as traditional medicine worldwide due to high nutritional and health values. Traditionally in China, jujube is considered as a medicinal fruit that is being used in treating blood deficiency. In this review, the beneficial effects of jujubes on the hematopoietic functions are summarized and discussed. As illustrated in cell and animal models, the application of jujube extract possessed beneficial effects, including regulation of erythropoiesis via activation of hypoxia inducible factor-induced erythropoietin, potential capacity in recycling heme iron during erythrophagocytosis and bi-directional regulation of immune response. Thus, the blood-nourishing function of jujube is being proposed here. Flavonoid, polysaccharide and triterpenoid within jujube could serve as the potential active ingredients accounting for the aforementioned health benefits. Taken together, these findings provide several lines of evidence for further development of jujube as supplementary products for prevention and/or treatment of anemia. 10.3389/fphar.2020.593655
    Isolation, structures and bioactivities of the polysaccharides from jujube fruit (Ziziphus jujuba Mill.): A review. Ji Xiaolong,Peng Qiang,Yuan Yuepeng,Shen Jing,Xie Xueying,Wang Min Food chemistry Jujube (Ziziphus Jujuba Mill.) has been eaten as a fruit and nutraceutical food in China for thousands of years. Recent phytochemical and pharmacological studies have shown that the 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. Although the extraction and purification of jujube polysaccharides are tedious processes, including different steps of liquid- and solid-phase separation, the polysaccharides have been structurally characterized. However, the relationships between the structures and activities of the jujube polysaccharides are not well established. The purpose of the present review is to appraise the previous and current literature on the extraction, purification, structural characterization, and biological activities of jujube polysaccharides. This review should provide a useful bibliography for the further investigation, production, and application of jujube polysaccharides in functional foods and therapeutic agents. 10.1016/j.foodchem.2017.01.074
    Comparison of structural characterization and antioxidant activity of polysaccharides from jujube (Ziziphus jujuba Mill.) fruit. Ji Xiaolong,Hou Chunyan,Yan Yizhe,Shi Miaomiao,Liu Yanqi International journal of biological macromolecules The aim of this paper was to prepare purified fractions of polysaccharides from jujube (Ziziphus jujuba Mill.) fruit and further compare their structural characteristics and antioxidant activities. Firstly, three purified jujube polysaccharides, named PZMP1, PZMP2 and PZMP3, were successfully prepared by DEAE-Sepharose Fast Flow and Sephacryl S-300 columns. Then, their characteristics were studied and then compared by using chemical testing, high-performance gel permeation chromatography (HPGPC), gas chromatography (GC), Fourier transform infrared spectroscopy (FT-IR), methylation analysis, NMR spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM) and atomic force microscopy (AFM). Thereafter, their antioxidant activities were also contrasted. The data achieved demonstrated that the three jujube polysaccharides derived from different adsorption capacity of DEAE-Sepharose Fast Flow and Sephacryl S-300 columns possessed different structural characteristics and antioxidant activity, and with higher galacturonic acid content could exhibit better antioxidant bioactivities, which could provide certain directions for the functional and medicinal purposes development of jujube polysaccharides. 10.1016/j.ijbiomac.2020.02.018
    Characterization of the antioxidative polysaccharides from Ziziphus jujube cv. Goutouzao and its tumor-inhibitory effects on human colorectal carcinoma LoVo cells via immunocyte activation. Liang Qian,Wang Xingyu,Yang Shuo,Yu Linhong,Gao Qiaohui,Yang Xingbin,Zhao Yan Journal of food biochemistry Colorectal cancer, the most common malignancy in Asian and west world, is listed as the fourth lethal neoplastic disease with increasing incidence worldwide. Recently, Ziziphus jujube were reported with hepatoprotective, antihypertensive, and hypoglycemic functions. The polysaccharides from Ziziphus jujube was considered as the main component for these bioactivities. In this study, polysaccharides from Ziziphus jujube cv. Goutouzao (GZSP) was comprehensively investigated, and characterized as a heteropolysaccharide with antioxidant activity. Besides, it can stimulate the viability of immune cells RAW 264.7, which in turn inhibited the proliferation of colorectal carcinoma cells (LoVo) by inducing apoptosis, arresting cell cycle in G0/G1, and increasing intracellular ROS, as demonstrated by Flow Cytometric analyses. The results suggest that, different from chemotherapeutic modalities, GZSP can exert antitumor effects by activating immune reaction, providing more evidence for the development of GZSP-based functional foods and anticancer drugs serving as human colon cancer prevention. PRACTICAL APPLICATIONS: Natural products from medicinal and edible plant are great sources of phytochemicals beneficial to human health, such as tea polyphenols, carotenoids, and phytosterols, etc. In this study, GZSP, the polysaccharides from a well-received fruit, Ziziphus jujube cv. Goutouzao, has been comprehensively investigated. The results show that GZSP fights against free radicals commonly found in human circulation, a property that enables it to be used as an antioxidant food additive with jujube flavor. More importantly, GZSP impedes neoplastic progression by activating immune response, as evidenced by the inhibition of colorectal carcinoma (LoVo) cells. Comparing with chemotherapies usually imposing cytotoxicity on normal tissues, natural product GZSP is able to exert the antiproliferative effects on carcinoma cells with minimal side-effects. Therefore, GZSP-based functional foods and anticancer drugs with the purpose of preventing human colon cancer formation are promising to be developed. 10.1111/jfbc.13462
    The protective effects of Ziziphus vulgaris L. fruits on biochemical and histological abnormalities induced by diabetes in rats. Goli-malekabadi Najmeh,Asgary Sedigheh,Rashidi Bahman,Rafieian-Kopaei Mahmood,Ghannadian Mostafa,Hajian Shabnam,Sahebkar Amirhossein Journal of complementary & integrative medicine BACKGROUND:Diabetes mellitus arises from a deficient production and action of insulin. Ziziphus vulgaris L. (jujube) is a medicinal plant that is known to have anti-diabetic actions. The aim of the present study was to investigate the protective effects of jujube fruit powder and extract against biochemical imbalances in streptozotocin (STZ)-induced diabetes. METHODS:Diabetes was induced in rats using intraperitoneal injection of STZ at a dose of 60 mg/kg body weight (bw). Jujube powder (1 g/kg bw) and extract (1 g/kg bw) were administered daily via gavage, from two weeks prior to three weeks after STZ injection. Serum concentrations of glucose, insulin, and lipids and histological changes of the pancreas tissue were assessed at the end of study. RESULTS:The kaempferol content of jujube extract was found to be 0.013 ± 0.0005% (w/w). Two weeks of supplementation with jujube powder resulted in a significant reduction of serum glucose levels compared with the non-diabetic control group prior to STZ treatment. Both jujube preparations prevented serum insulin decrease following STZ treatment, increased antioxidant capacity, and reduced total cholesterol, high-density lipoprotein cholesterol, triglycerides, and malondialdehyde levels. Jujube powder reduced serum low-density lipoprotein cholesterol and C-reactive protein concentrations while jujube extract had no effect on these parameters. Histopathological examination revealed a significant attenuation of pancreatic inflammation in the jujube-treated animals. CONCLUSIONS:The present findings suggest a protective role of jujube supplementation, in particular in the powdered form, against diabetes-induced biochemical and histopathological abnormalities. 10.1515/jcim-2014-0010
    Effect of Ziziphus jujube Fruit Infusion on Lipid Profiles, Glycaemic Index and Antioxidant Status in Type 2 Diabetic Patients: A Randomized Controlled Clinical Trial. Yazdanpanah Zeinab,Ghadiri-Anari Akram,Mehrjardi Alireza Vahidi,Dehghani Ali,Zardini Hadi Zare,Nadjarzadeh Azadeh Phytotherapy research : PTR This study was designed to assess the effects of Ziziphus jujube fruit (ZJF) infusion on lipid profiles, glycaemic control and antioxidant status in patients with type 2 diabetes mellitus (T2DM). In this randomized controlled clinical trial, 116 participants with T2DM (older than 30 years) were assigned to consume a balanced diet or diet plus ZJF infusion (10 g/100 mL boiling water) three times/day before main meals for 12 weeks. Diet was designed to be energy restricted (500 kcal/day deficit from estimated energy requirements), and macronutrient content was similar in both groups (55% carbohydrate, 15% protein and 30% fat). The consumption of ZJF infusion compared with the control group was associated with significant improvement in glycosylated haemoglobin (-0.68 ± 0.65 vs. -0.44 ± 0.55%; p = 0.03), total cholesterol (-24.29 ± 28.89 vs. -11.21 ± 29.98 mg/dL; p = 0.02), triglycerides (-43.3 ± 39.26 vs. -27.16 ± 46.84 mg/dL; p = 0.05), low-density lipoprotein cholesterol (-19.85 ± 27.62 vs. -6.55 ± 27.82 mg/dL; p = 0.01), low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (-0.56 ± 0.80 vs. -0.2 ± 0.72; p = 0.01) and total cholesterol to high-density lipoprotein cholesterol ratios (-0.73 ± 0.94 vs. -0.35 ± 0.77; p = 0.02). ZJF had beneficial effects on glycosylated haemoglobin and lipid profile in T2DM patients. Further research is needed to identify the mechanism of ZJF action on glucose and lipid metabolism. Copyright © 2017 John Wiley & Sons, Ltd. 10.1002/ptr.5796
    The effect of dried Ziziphus vulgaris on glycemic control, lipid profile, Apo-proteins and hs-CRP in patients with type 2 diabetes mellitus: A randomized controlled clinical trial. Irannejad Niri Zahra,Shidfar Farzad,Jabbari Masoumeh,Zarrati Mitra,Hosseini AghaFateme,Malek Mojtaba,Dehnad Afsaneh Journal of food biochemistry We aimed to evaluate the effect of dried Ziziphus vulgaris [Z. vulgaris] consumption on liver enzymes, blood pressure, inflammatory status, glycemic control, and lipid concentrations in type 2 diabetes patients. Seventy-six diabetic participants (aged 20-65 years) randomly assigned to intervention (n = 38) and placebo (n = 38) groups. The intervention group received 30 g/day dried Z. vulgaris for 12 weeks. At the end of the study, there was a significant reduction in the percentage change of weight, body mass index [BMI], insulin, homeostasis model assessment-insulin resistance [HOMA-IR], Apoprotein B100 [ApoB100], and high-sensitive c-reactive protein [hs-CRP] in the intervention group compared to the controls. Also, increased values of quantitative insulin check index [QUICKI] and Apoprotein A-I [ApoA-I] in Z. vulgaris group compared to the controls were observed. In conclusion, consumption of dried Z. vulgaris fruit could have beneficial effects on improving the glycemic control and reducing the cardiovascular risk factors in the diabetic patients. PRACTICAL APPLICATIONS: In the present study we found that consumption of 30 g/day dried Z. vulgaris fruit in patients with type 2 diabetes for 12 weeks has beneficial anti-inflammatory, anti-hyperglycemic, and anti-hyperlipidemic effects on type 2 diabetes mellitus [T2DM] patients compared to the control group. Thus, it seems reasonable to design a large-scale clinical trial to determine the potential adverse effects of higher doses of this fruit and identify the therapeutic doses for the complementary treatment in T2DM medication. The medication with this popular fruit as an ingredient could be easily accepted by diabetic patients and may reduce the dependency and dosage of some of the routine diabetes medications which often have some adverse side effects. 10.1111/jfbc.13193
    The protective effects of polyphenols from jujube peel (Ziziphus Jujube Mill) on isoproterenol-induced myocardial ischemia and aluminum-induced oxidative damage in rats. Cheng Dai,Zhu Chunqiu,Cao Jiankang,Jiang Weibo Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association This study was aimed to evaluate the preventive effect of the polyphenols from Chinese jujube peel (Ziziphus jujube Mill. cv. Dongzao) against myocardial injury (MI) induced by isoproterenol (ISO) and biotoxicity of aluminum in rats. The free phenols from jujube peel (JPFP) and the bond phenols from jujube peel (JPBP) were administered to rats by gastric gavage. The results showed that prior administration of JPFP or JPBP remarkably inhibited increases in levels of malondialdehyde (MDA) and activities of Ca(2+)-ATPase and Mg(2+)-ATPase, reductions in activities of superoxide dismutase (SOD), glutathione peroxidase, creatine kinase, lactate dehydrogenase and Na(+)/K(+)-ATPase in the rats induced by ISO. The abnormal changes in morphology of heart muscle and in electrocardiograph induced by ISO treatment were also significantly prevented by the JPFP or JPBP. Treatment with aluminum chloride could cause a significant oxidative damage, including a significant increase in MDA level and decreases in glutathione-S- transferase and SOD activities in brain of the rats, the study showed that gavage with JPFP or JPBP could remarkably alleviate the toxic responses of the rats to aluminum chloride. In summary, our study showed that jujube phenolics can prevent ISO-induced myocardial injury and reduce aluminum toxicity in rats. 10.1016/j.fct.2012.01.026