The effects of jujube (Ziziphus jujube) on metabolic and mental health outcomes in patients with metabolic syndrome: A randomized controlled trial.

OBJECTIVES: The effects of jujube (Ziziphus jujube) consumption on metabolic and mental health outcomes in subjects diagnosed with metabolic syndrome (MetS) is unknown and remains to be examined. Hence, we carried out a parallel-group, randomized controlled trial to investigate this issue. METHODS: Eligible participants were randomly assigned to the intervention (n = 30) or the control (n = 30) groups to receive either jujube or a placebo for eight weeks. Subjects were provided with 30 g dried jujube powder or placebo and were asked to consume half of the powder at 10 a.m. and the rest at 4 p.m. Lipid profile, fasting blood glucose (FBG), waist circumference (WC), and blood pressure were evaluated as primary outcomes. Secondary outcomes collected were mental health measures (e.g., depression, anxiety, and stress). RESULTS: Jujube consumption failed to decrease FBG, total cholesterol, low-density lipoprotein cholesterol, and blood pressure, as well as depression and anxiety scores (P > 0.05). However, the between-group comparison revealed a significant improvement in WC (- 3.98 vs. - 0.51, P = 0.01), triglyceride (TG) (- 24.96 vs. - 0.73, P = 0.03), and high-density lipoprotein cholesterol (HDL-C) (2.83 vs. 0.40, P = 0.01) in the jujube group compared to the placebo. In addition, compared to the control group, jujube consumption led to a significant improvement in the score of stress (- 5.80 vs. - 2.86, P = 0.01). CONCLUSION: Jujube consumption only had beneficial effects on WC, TG, and HDL-C in subjects with MetS. However, the current study has methodological weaknesses in blinding and herb purity/potency testing, which should be addressed in future studies.

Validating Interactions of Pathogenic Proteins of Staphylococcus aureus and E. coli with Phytochemicals of Ziziphus jujube and Acacia nilotica.

This study focused on the assessment of the antimicrobial resistance of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) isolated from bovine mastitis milk samples and the revealing anti-mastitis potential of phytocompounds of Ziziphus jujube and Acacia nilotica through molecular docking analysis. The mastitis milk samples were collected from various dairy farms for the isolation of the bacteria (S. aureus and E. coli) and their response to antibiotics. Ethanolic extracts of both plants were prepared. Their antibacterial activity was evaluated, and they were processed for phytochemical analysis after which, molecular docking analysis with pathogenic proteins of the bacteria was carried out. Parametric and non-parametric statistical analyses were performed to reach the conclusions of this study. The findings of the study revealed a higher drug resistance (≥40%) of E. coli against ampicillin, amikacin, and vancomycin, while S. aureus exhibited the highest resistance to ampicillin, erythromycin, and ciprofloxacin. The ethanolic extracts of the Ziziphus jujube and Acacia nilotica plants produced a ZOI between 18 and 23 mm against multidrug-resistant S. aureus and E. coli. Gas chromatography-mass spectrophotometry (GC-MS) was used to explore 15 phytocompounds from Ziziphus jujube and 18 phytocompounds from Acacia nilotica. The molecular docking analysis of 2cyclopenten-1-one,3,4,4 trimethyl and Bis (2ethylhexyl) phthalate of Ziziphus jujube showed a binding affinity of -4.8 kcal/mol and -5.3 kcal/mol and -5.9 kcal/mol and -7.1 kcal/mol against the DNA Gyrase and toxic shock syndrome toxin-1 proteins of S. aureus and E. coli, respectively. The suberic acid monomethyl ester of Acacia nilotica showed a binding affinity of -5.9 kcal/mol and -5 kcal/mol against the outer membrane protein A and Topoisomerase IV protein of E. coli and -5.1 kcal/mol and -5.8 kcal/mol against the toxic shock syndrome toxin-1 and Enterotoxin B proteins of S. aureus. Similarly, 2,2,4-trimethyl-1,3-pentanediol di-iso-butyrate showed a binding affinity of -6.5 kcal/mol and -5.3 kcal/mol against the outer membrane protein A and Topoisomerase IV of E. coli and -5.2 kcal/mol and -5.9 kcal/mol against the toxic shock syndrome toxin-1 and Enterotoxin B proteins of S. aureus, respectively. The study concluded that there was an increasing trend for the antimicrobial resistance of S. aureus and E. coli, while the Ziziphus jujube and Acacia nilotica plant extracts expressed significant affinity to tackle this resistance; hence, this calls for the development of novel evidence-based therapeutics.

Effects of Ziziphus Jujuba Extract Alone and Combined with Boswellia Serrata Extract on Monosodium Iodoacetate Model of Osteoarthritis in Mice.

Background: As a chronic joint condition, osteoarthritis (OA) is a common problem among older people. Pain, aching, stiffness, swelling, decreased flexibility, reduced function, and disability are the symptoms of arthritis. Objectives: In this study, we tested the extracts of Ziziphus jujuba (ZJE) and Boswellia serrata (BSE) to reduce OA symptoms as an alternative treatment. Methods: NMRI mice were administered an intra-articular injection of monosodium iodoacetate (MIA; 1 mg/10 mL) in the left knee joint cavity for the induction of OA. Hydroalcoholic extracts of ZJE (250 and 500 mg/kg), BSE (100 and 200 mg/kg), and combined ZJE and BSE were orally administered daily for 21 days. Following behavioral tests, plasma samples were collected to detect inflammatory factors. To screen for general toxicity, acute oral toxicity was evaluated. Results: Oral administration of all the hydroalcoholic extracts significantly increased the locomotor activity, pixel values of the foot-print area, paw withdrawal threshold, the latency of the withdrawal response to heat stimulation, and decreased the difference between pixel values of hind limbs compared to the vehicle group. Also, the elevated levels of IL-1ß, IL-6, and TNF-α were reduced. As tested in this study, ZJE and BSE were practically nontoxic and had a high degree of safety. Conclusions: This study demonstrated that the oral administration of ZJE and BSE slows the progression of OA through anti-nociceptive and anti-inflammatory properties. Oral co-administration of ZJE and BSE extracts can be used as herbal medicine to inhibit OA progression.

Characterization of the antioxidative polysaccharides from Ziziphus jujube cv. Goutouzao and its tumor-inhibitory effects on human colorectal carcinoma LoVo cells via immunocyte activation.

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.

Zao Ren An Shen for insomnia: a systematic review with meta-analysis.

OBJECTIVE: To assess the effectiveness and safety of Zao Ren An Shen (ZRAS), a Chinese herbal medicine formula, for the treatment of insomnia. METHODS: Seven databases (ie, EMBASE, PubMed, the Cochrane library, and PsycINFO, Chinese National Knowledge Infrastructure, Wanfang and Chongqing VIP) were searched from their inception to 6 November 2018. Controlled trials comparing the effectiveness or safety of ZRAS to conventional treatments, a placebo or no-treatment in an insomnia population were selected. Primary outcomes were: sleep quality (assessed with the Pittsburgh Sleep Quality Index, PSQI), and the number of adverse events at post-treatment. The risk of bias was assessed with the Cochrane Collaboration's tool and meta-analyses were performed using RevMan 5.3. RESULTS: A total of 19 studies (1780 participants) were included. The effect of ZRAS on sleep quality (mean difference) was found to be superior compared to placebo in the sole placebo-controlled study located [-0.90 (-1.56, -0.24; 95% CI), p = 0.007] and similar to Benzodiazepine Receptor Agonists (BzRAs) [0.17 (-0.29, 0.64); 95% CI, p = 0.46]. The number of adverse events (relative risk) was lower for ZRAS than BzRAs [0.16 (0.12, 0.23; 95% CI), p < 0.001]. An overall high risk of bias was found in the selected studies. CONCLUSIONS: The results favor ZRAS against BzRAs and placebo for the treatment of insomnia. However, the poor methodology of the studies prevents strong recommendations for ZRAS. Clinical trials with higher quality designs are required.

Survey of cytotoxic and UV protection effects of biosynthesized cerium oxide nanoparticles.

Cerium oxide nanoparticles (CeO2 NPs) are among the important nanoparticles that are extensively utilized in cosmetics, automotive industries, ultraviolet (UV) filtration, gas sensors, and pharmaceutical products. In this study, CeO2 NPs were synthesized using an aqueous extract of Ziziphus jujube fruit. The synthesized nanoparticles were characterized using UV-visible spectroscopy, powder X-ray diffraction, Fourier transform infrared spectroscopy, energy-dispersive spectroscopy, field energy scanning electron microscopy, and Raman methods. The results indicated that the size of synthesized nanoparticles is between 18 and 25 nm, and they have a spherical shape. UV absorbance of the synthesized nanoparticles was measured through spectrophotometric method in the range of 290 to 320 nm. The cytotoxic activity of synthesized CeO2 NPs against colon (HT-29) cancer cell line was surveyed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The results showed that synthesized nanoparticles are nontoxic on HT-29 cells under 400 µg/mL concentrations after 24 hours of treatment time periods. The increase in treatment time cases increases cytotoxic activity of synthesized nanoparticles. Sun protection factor of CeO2 NPs, as a criterion for amount of sunlight radiation protection, was determined by applying Mansur equation. The results demonstrated that synthesized CeO2 NPs have excellent UV protection and sunscreen physical absorption properties.

Can dietary jujube (Ziziphus jujuba Mill.) fruit extract alter cutaneous mucosal immunity, immune related genes expression in skin and growth performance of common carp (Cyprinus carpio)?

The present study investigates the effect of dietary Ziziphus jujube fruit extract [ZJFE] on skin mucus non-specific immune parameters as well as mRNA levels of immune related gene in the skin of common carp fingerlings. An eight-week feeding trial was performed using different levels of dietary ZJFE (0, 0.25, 0.5 and 1%). At the end of the trial skin mucus immune parameters (total Ig, lysozyme and protease activity), cytokines genes (il1b, il8, il10 and tnf-alpha) expression in skin and growth performance were studied. The result showed highest and lowest skin mucus total Ig were observed in fish fed diet containing 0.5% ZJFE and control group, respectively (P < 0.05). There were no significant difference among treatments regarding skin mucus lysozyme activity (P >0.05). It should be noted that, feeding on 0.5 and 1% ZJFE significantly increased skin mucus protease activity (P <0.05). Likewise, gene expression studies in skin showed significant increase of il1b expression in fish fed 0.5% ZJFE compared other treatments (P <0.05). Also, il8 gene was noticeably up-regulated in 0.5 and 1% treatments compared to the control group (P <0.05). While there were no significant difference between 0.25% JFE treatment and control in case of relative il10 gene expression (P >0.05), feeding on diets containing 0.5% or 1% ZJFE significantly down-regulated il10 gene (P <0.05). Our study indicated that relative expression of tnf-alpha gene significantly increased in treated groups (P <0.05). Also, feeding on ZJFE supplemented diet improved growth performance parameters. Overall, this experiment demonstrated the potentially useful effects of ZJFE on skin mucosal immunity and performance of common carp fingerlings.

Identification of Constituents Affecting the Secretion of Pro-Inflammatory Cytokines in LPS-Induced U937 Cells by UHPLC-HRMS-Based Metabolic Profiling of the Traditional Chinese Medicine Formulation Huangqi Jianzhong Tang.

Within non-communicable diseases, chronic inflammatory conditions represent one of the biggest challenges for modern medicine. Traditional Chinese Medicine (TCM) has been practiced over centuries and has accumulated tremendous empirical knowledge on the treatment of such diseases. Huangqi Jianzhong Tang (HQJZT) is a famous TCM herbal formula composed of Radix Astragali, Ramulus Cinnamomi, Radix et Rhizoma Glycyrrhizae Praeparata cum Melle, Radix Paeoniae Alba, Rhizoma Zingiberis Recens, Fructus Jujubae and Saccharum Granorum (maltose), which has been used for the treatment of various chronic inflammatory gastrointestinal diseases. However, there is insufficient knowledge about its active constituents and the mechanisms responsible for its effects. The present study aimed at identifying constituents contributing to the bioactivity of HQJZT by combining in vitro cytokine production assays and LC-MS metabolomics techniques. From the HQJZT decoction as well as from its single herbal components, extracts of different polarities were prepared. Phytochemical composition of the extracts was analyzed by means of UPLC-QTOF-MS/MS. The inhibitory effects of the extracts on TNF-α, IL-1ß and IFN-γ production were studied in U937 cells. Phytochemical and pharmacological bioactivity data were correlated by orthogonal projection to latent structures discriminant analysis (OPLS-DA) in order to identify those HQJZT constituents which may be relevant for the observed pharmacological activities. The investigations resulted in the identification of 16 HQJZT constituents, which are likely to contribute to the activities observed in U937 cells. Seven of them, namely calycosin, formononetin, astragaloside I, liquiritigenin, 18ß-glycyrrhetinic acid, paeoniflorin and albiflorin were unambiguously identified. The predicted results were verified by testing these compounds in the same pharmacological assays as for the extracts. In conclusion, the anti-inflammatory activity of HQJZT could be substantiated by in vitro pharmacological screening, and the predicted activities of the OPLS-DA hits could be partially verified. Moreover, the benefits and limitations of MVDA for prediction pharmacologically active compounds contributing to the activity of a TCM mixture could be detected.

Ziziphus Jujube: a review study of its anticancer effects in various tumor models invitro and invivo.

The growing rate of cancer incidences and inefficiency of current therapies have made scientists to find novel agents such as medicinal plants. Ziziphus jujube is one of these plants whose pharmaceutical effects have been studied for a long time. Recent investigations have proved that bioactive compounds of Ziziphus jujube including triterpenic acids, flavonoids, cerebrosides, phenolic acids, α tocopherol, ß carotene, and polysaccharides have anti-proliferative effects on several cancerous cell lines and animals. The present study aimed to cover all previous invitro and invivo findings and some of molecular mechanisms of its anticancer property.

Effect of Ziziphus jujube Fruit Infusion on Lipid Profiles, Glycaemic Index and Antioxidant Status in Type 2 Diabetic Patients: A Randomized Controlled Clinical Trial.

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.

Hypnotic effects of a novel anti-insomnia formula on Drosophila insomnia model.

OBJECTIVE: To assess the biological effects of the six-herb mixture Anti-Insomia Formula (AIF) extract using caffeine-induced insomnia Drosophila model and short-sleep mutants. METHODS: Caffeineinduced insomnia wild-type Drosophila and short-sleep mutant flies minisleep (mns) and Hyperkinetic(Y) (Hk(Y)) were used to assess the hypnotic effects of the AIF in vivo. The night time activity, the amount of night time sleep and the number of sleep bouts were determined using Drosophila activity monitoring system. Sleep was defined as any period of uninterrupted behavioral immobility (0 count per minute) lasting > 5 min. Night time sleep was calculated by summing up the sleep time in the dark period. Number of sleep bouts was calculated by counting the number of sleep episodes in the dark period. RESULTS: AIF at the dosage of 50 mg/mL, effectively attenuated caffeine-induced wakefulness (P<0.01) in wild-type Canton-S flies as indicated by the reduction of the sleep bouts, night time activities and increase of the amount of night time sleep. AIF also significantly reduced sleeping time of short-sleep Hk(Y) mutant flies (P<0.01). However, AIF did not produce similar effect in mns mutants. CONCLUSION: AIF might be able to rescue the abnormal condition caused by mutated modulatory subunit of the tetrameric potassium channel, but not rescuing the abnormal nerve firing caused by Shaker gene mutation. This study provides the scientific evidence to support the use of AIF in Chinese medicine for promoting sleep quality in insomnia.

Immunomodulating and antioxidant effects of polysaccharide conjugates from the fruits of Ziziphus Jujube on Chronic Fatigue Syndrome rats.

To detect the treatment effect of the fruits of Ziziphus Jujube in Chronic Fatigue Syndrome (CFS). Jujube polysaccharide conjugates (JPC) were isolated from the fruits of Z. Jujube. General physicochemical properties of JPC were analyzed. A four-week rats CFS model was established and JPC were orally administrated, the behavior experiments were conducted after CFS. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and the levels of malondialdehyde (MDA) in serum were elevated and T lymphocyte proliferation, CD4(+)/CD8(+) ratio and natural killer (NK) cells activity were analyzed. JPC markedly improved behaviors of CFS rats, also decreased MDA levels in serum, and elevated T lymphocyte proliferation, CD4(+)/CD8(+) ratio and natural killer (NK) cells activities. This suggests that JPC can improve the immune system and antioxidant activity of CFS rats and might be regarded as a biological response modifier.

HPLC fingerprint and quantitative determination of 17 introduced Ziziphus jujube varieties in Tarim Basin / 中草药

Objective: To initially establish HPLC fingerprints for analysis of 17 batches of the introdued jujube (Ziziphus jujuba) varieties in order to lay the foundation for scientific evaluation and production quality control of jujube. Methods: TOSOH TSKgel ODS-100V C18 column (150 mm × 4.6 mm, 3 μm) was used. The mobile phase was as follows: methanol and 0.3% KH2PO4 in gradient elution mode. The detective wavelength was 260 nm, the flow rate was 1.0 mL/min, and the separation was performed at 40 ℃. Similarity Evaluation System for Chromatographic Fingerprint of Chinese Materia Medica 2004A published by the state Pharmacopeia Committee of China was adopted for the fingerprint analysis on the 17 batches of introdued jujube varieties in Germplasm Nursery of Tarim University. Results: The HPLC characteristic fingerprint of jujube has been established. A total of 22 common peaks were characterized, the peaks appeared uniform and were well-separated. The uracil, hypoxanthine, adenine, cytidine, uridine, cAMP, and cGMP were determined by HPLC method. Conclusion: HPLC chromatographic fingerprint analysis technology can be used for the identification of jujube and its quality control.