Yup. (2016). Jujube botanically known as Ziziphus jujube, also known as Chinese red date, Da Zao, and Chinese date is a popular “drupe” fruit of Chinese origin. The hydroalcoholic extract of jujube at 200–400 mg/kg was applied onto acute and chronic rat models of inflammation. doi:10.1038/nm.3587 | PubMed Abstract. Pharm. Besides, the extract of jujube possessed the ability to stimulate the activity of ATPase, i.e., Na+-K+-ATPase, Ca2+-ATPase and Ca2+-Mg2+-ATPase, in erythrocyte, and therefore which was shown to promote bone marrow nuclear proliferation and to inhibit atrophy thymus and spleen in blood deficient animals (Miao et al., 2006; Miao et al., 2010). In Morocco, the honey obtained from jujube extract is believed to be beneficial to sore throats (Lim, 2013). Thus, jujube is considered as a popular nutritious food, worldwide (Li et al., 2007; San and Yildirim, 2010; USDA, 2012; Guo et al., 2013; Reche et al., 2019). In vivo antigenotoxic activity of Diplotaxis tenuifolia against cyclophosphamide-induced DNA damage: relevance of modulation of hepatic ABC efflux transporters. Rev. 115, 49–62. Altern Ther Health Med. Molecules 25, 968. doi:10.3390/molecules25040968 | PubMed Abstract, Feng, C., Wang, B., Zhao, A., Wei, L., Shao, Y., and Wang, Y. (2016) reported that the intake of jujube extract showed an improvement in iron deficiency anemia rats. Role of cyclic nucleotides and their downstream signaling cascades in memory function: being at the right time at the right spot. Thirugnanasampandan R, Ramya G, Bhuvaneswari G, Aravindh S, Vaishnavi S, Gogulramnath M. J Complement Integr Med. Med. (2000). Food Chem. Toxicol. Hydroalcoholic extract of Zizyphus jujuba ameliorates seizures, oxidative stress, and cognitive impairment in experimental models of epilepsy in rats. Mice were primed with BA (2.5, 5.0 and 10 mg/kg body weight) for a period of 6 days. Thus, the blood-nourishing function of jujube is being proposed here. For instance, a cellular model of erythrophagocytosis using artificially-aged RBCs and macrophages may be designed to investigate mRNA and protein expressions of target enzymes relating to iron recycling. Erythropoiesis is considered to play critical roles in hematopoiesis, by which production of red blood cells (RBCs) is occurred. Ziziphus jujuba extract for the treatment of chronic idiopathic constipation: a controlled clinical trial. The jujube is a drupe or stone fruit. 8, 73. doi:10.3389/fimmu.2017.00073 | PubMed Abstract, Kovtunovych, G., Eckhaus, M. A., Ghosh, M. C., Ollivierre-Wilson, H., and Rouault, T. A. Articles, University of Studies G. d'Annunzio Chieti and Pescara, Italy, Zhengzhou University of Light Industry, China. 277, 238–245. Phytother Res. Flavonoids of Zizyphus jujuba L. And Zizyphus spina-christi (L.) willd (Rhamnaceae) fruits. This finding indicates the activation of innate immune system in jujube-treated cells. Although the common names are red date and Korean date, the scientific classification of jujube is Ziziphus jujuba. Am. JC and KT: Concept, design, literature search and manuscript review. The dietary nutrient facts of main ingredients in fresh and dried jujubes are summarized in Supplementary Table S1, which provides an appropriate recommendation for selection of different forms of jujube for certain health benefits. Furthermore, the authors described that jujube at various concentrations (30–200 μg/ml) showed a significant dose-dependent promotion of splenocyte proliferation, with the highest response at ∼100% increase. Food Chem. In folk medicine, three pieces of jujube are recommended to be consumed daily, about 15 g of dried weight in total. Food Chem. In the lipopolysaccharide (LPS)-induced macrophages, the pre-treatment with jujube water extract repressed the expressions of IL-1β and IL-6 (Chen et al., 2014a). Shenzhen Science and Technology Innovation Committee (ZDSYS201707281432317; JCYJ20170413173747440; JCYJ20180306174903174), China Post-doctoral Science Foundation (2019M653087), Zhongshan Municipal Bureau of Science and Technology (ZSST20SC03); Guangzhou Science and Technology Committee Research Grant (GZSTI16SC02; GZSTI17SC02); Hong Kong RGC Theme-based Research Scheme (T13-605/18-W); Hong Kong Innovation Technology Fund (UIM/340, UIM/385, ITS/500/18FP; TCPD/17-9); TUYF19SC02, PD18SC01 and HMRF18SC06 to KT. J. Biol. A Chinese herbal decoction, Danggui Buxue Tang, activates extracellular signal-regulated kinase in cultured T-lymphocytes. In addition, the combination of catalpol and puerarin with doses of 65.4 and 32.7 mg/kg, respectively, enhanced the expressions of EPO and EPO receptor in ischemic/reperfusion rats (Xue et al., 2016). fruits are nutritionally rich and have a broad spectrum of health benefits. Environ. Drug Targets 20, 108–115. Spinosa. 2012;10:37–46. (2010). The animals were injected with MMS (10 mg/kg body weight) 24 h later and sacrificed. (i) DNA damage measured as Tail DNA % in human lymphocytes exposed…, DNA damage measured as Tail DNA % induced by betulinic acid (BA) in…, Biochemical stress markers in liver cells of mice primed with betulinic acid (BA)…, Antioxidant enzymes in liver cells of mice primed with betulinic acid (BA) and…, NLM Am. (2010). doi:10.1016/j.fct.2010.02.036, Yu, L., Jiang, B. P., Luo, D., Shen, X. C., Guo, S., Duan, J. Food Res. Med. Iron deficiency in chronic kidney disease: updates on pathophysiology, diagnosis, and treatment. Yoo et al. Sinha S., Biswas D., Mukherjee A. Antigenotoxic and antioxidant activities of palmarosa and citronella essential oils. 2007;26 Suppl 1:3-106. doi: 10.1080/10915810601163939. doi:10.1016/j.phymed.2011.09.071 | PubMed Abstract, Zhao, Z., Li, J., Wu, X., Dai, H., Gao, X., Liu, M., et al. Similarly, the protein level of HIF-1α was markedly up regulated at the treatment of 10 μM quercetin (Nishimura et al., 2017). doi:10.1271/bbb.67.1284 | PubMed Abstract, Huang, X., Kojima-Yuasa, A., Norikura, T., Kennedy, D. O., Hasuma, T., and Matsui-Yuasa, I. The cells were pre-treated with GZT (31.25–1,000 μg/ml) for 4 h prior to application of LPS for an additional 20 h. The treatment with GZT extract enhanced the expression of HO-1 and significantly inhibited pro-inflammatory cytokines, e.g., TNF-α and IL-6, in LPS-induced macrophages. (2020). According to the aforesaid cellular and animal findings, jujube has a promising potential in developing medicinal food and supplement for prevention against anemia, cancer, inflammation and iron/vitamin deficiency. On the other hand, the pre-treatment with jujube water extract (0–3 mg/ml) for 3 h in cultured macrophages, before the addition of LPS at 1 μg/ml for 24 h, dose-dependently repressed the activation of NF-κB activity. The immune response is impaired in anemia condition. Here, the potential effects of jujube on erythrophagocytosis were summarized (Figure 4). This work is supported by Natural Science Foundation of Guangdong Province (2018A030313305), Natural Science Foundation of China (81804052), Shenzhen Science and Technology Plan Project (JSGG20191129102216637 and ZDSYS201606081515458), Traditional Chinese Medicine Bureau of Guangdong Province (20201320) to JC. doi:10.1002/ptr.5160, Chen, J., Lam, C. T., Kong, A. Y., Zhang, W. L., Zhan, J. Y. X., Bi, C. W. C., et al. 30, 267–271. Food Chem. Chin. Nat. In line to this notion, pharmacological studies have reported that jujube has potential hematopoietic functions both in vivo and in vitro (Xu et al., 2004; Chen et al., 2014b). Mitsuhashi, Y., Furusawa, Y., Aradate, T., Zhao, Q. L., Moniruzzaman, R., and Kanamori, M. (2017). Iran J. Pediatr. (2016) reported that application of GZT extract in cultured RAW264.7 macrophages showed anti-inflammatory activity, which involved in blocking ERK and NF-κB signaling pathways. Mice of blood deficiency model were induced by releasing blood and injection of cyclophosphamide. Moreover, jujube extracts at different concentrations of 0–3 mg/ml were applied onto cultured RAW 264.7 cells for 24 h. The extract dose-dependently stimulated the expressions of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, and the highest effect was induced at ∼7-fold, ∼9-fold, and 4-fold, respectively (Chen et al., 2014a). Indeed, kaempferol and quercetin derivatives, including kaempferol 3-O-rutinoside, quercetin, quercetin 3-O-rutinoside, quercetin 3-O-galactoside and quercetin 3-O-β-D-glucoside (Figures 3A), were identified in jujube (Gao et al., 2012; Chen et al., 2013). Ethyl acetate and aqueous fractions of Ziziphus jujuba prevent acute hypertension induced by angiotensin II in rats. 13, 376–387. In this process, EPO, a RBC-specific hormone, is able to regulate erythropoiesis in bone marrow (Ascensao et al., 1991). Biobehav. Besides, jujube cAMP has been found to possess anti-melancholic effect in animal model of depression (Chi and Zhang, 2009). Another animal study showed that jujube essential oil could inhibit the inflammatory responses of skin (Al-Reza et al., 2010). Erythrophagocytosis is a process, where the senescent RBCs are phagocytosed by macrophage (Klei et al., 2017). (2019). (2014c). Please enable it to take advantage of the complete set of features! In Lebanon and Persia, jujube is used as digestive aid being consumed with the desserts. Impact Factor 4.225 | CiteScore 5.0More on impact ›, Food/Diet Supplements from Natural Sources: Current Status and Future Challenges from a Pharmacological Perspective (2016). The extract of Ziziphus jujuba fruit (jujube) induces expression of erythropoietin via hypoxia-inducible factor-1alpha in cultured Hep3B cells. (2019) demonstrated a new goat dairy product adding of jujube pulp as ingredients with satisfactory nutritional quality and sensory property, which provided alternative approach in developing a unique goat dairy product with high nutritional properties. Int. Sci. Edible medicinal and non-medicinal plants. Possible attenuation of nitric oxide expression in anti-inflammatory effect of Ziziphus jujuba in rat. Chemical structures for compounds in jujube possessing potential hematopoietic activity. The polysaccharides extracted from jujube usually consist of five monosaccharides, i.e., galactose, arabinose, rhamnose, glucose and xylose (Zhao et al., 2008) (Figures 3B). Jujube extract stimulated the expression of HIF-1α mRNA, and the induced expression was demonstrated to be in a dose-dependent manner, having the highest effect by ∼80% of increase. Betulinic acid, found in Zizyphi Spinosi Semen and jujube, possessed combined properties of inducing endothelial nitric oxide synthase and decreasing nicotinamide adenine dinucleotide phosphate oxidase. (i) DNA damage measured as Tail DNA % in human lymphocytes exposed to H, DNA damage measured as Tail DNA % induced by betulinic acid (BA), Biochemical stress markers in liver cells of mice primed with betulinic acid (BA) and treated with MMS: MDA (A) BA, (B) BA followed by MMS treatment; H. Antioxidant enzymes in liver cells of mice primed with betulinic acid (BA) and treated with MMS: Catalase activity – (A) BA, (B) BA followed by MMS treatment; Guaiacol peroxidase activity – (C) BA, (D) BA followed by MMS treatment; Total glutathione content – (C) BA, (D) BA followed by MMS treatment. and anticomplementary activity of its sulfated derivatives. (2009). Plant extracts rich in aforesaid flavonoids are considered, therefore, potentially useful as therapeutic agents for anemia. 63, 739–744. (2005). Comparison of antioxidant capacities of extracts from five cultivars of Chinese jujube. Fractions named as ZSP1, ZSP2, ZSP3 and ZSP4 with weight ratio of 29.3:17.6:37.2:15.9 have been purified from jujube (Li et al., 2011). FEBS Lett. 2013 Apr 10;61(14):3351-63. doi: 10.1021/jf4007032. doi:10.1021/jf200371r, Du, C. Y., Choi, R. C., Zheng, K. Y., Dong, T. T., Lau, D. T., and Tsim, K. W. K. (2013). Characterization of water soluble polysaccharides from organs of Chinese jujube (Ziziphus jujuba Mill. Alternat. B Analyt. Physiologically aged red blood cells undergo erythrophagocytosis in vivo but not in vitro. Food Chem. Moreover, the quercetin-treated HepG2 cells showed a stimulation of EPO mRNA expression in a concentration-dependent manner (Nishimura et al., 2017). In southern part of India, jujube is mixed with tamarind, jaggery, salt and chilies, and then pounded into cakes. Effect of Fructus Jujubae polysaccharide on the hematopoietic function in mice model of both qi and blood deficiencies. Actually jujube … Application of Ju-B-2 at 10–100 μg/ml onto cultured spleen cells for 3 days induced cell proliferation. FIGURE 1. Miao, M., Miao, Y., and Sun, Y. 40, 3607–3613. Neurosci. A., et al. Pharmacol. Ziziphus spina-christi fruit extract suppresses oxidative stress and p38 MAPK expression in ulcerative colitis in rats via induction of Nrf2 and HO-1 expression. 2007;103:454–460. J. Biol. In Huangdi Neijing (475–221 BC), a classic medical text from ancient China, jujube was recorded as one of extremely valuable fruits. doi:10.3892/etm.2013.1063 | PubMed Abstract, Li, J., Ding, S., and Ding, X. A., Legua, P., and Amorós, A. Lyophilized powder of catalpol and puerarin protects neurovascular unit from stroke. An acetate switch regulates stress erythropoiesis. Ziziphus Jujuba (Chinese/Korean Date, Jujube) is a plant which bears fruits and seeds that are used for medicinal purposes in Traditional Chinese Medicine. doi:10.1016/j.foodchem.2008.06.053 | PubMed Abstract, Periasamy, S., Wu, W. H., Chien, S. P., Liu, C. T., and Liu, M. Y. In consistent with this, Chen et al. Phenolic, alpha-tocopherol, beta-carotene and fatty acid composition of four promising jujube (Ziziphus jujuba Miller) selections. Keywords: doi:10.1016/j.foodres.2006.05.006, Zhao, Z., Liu, M., and Tu, P. (2008). In particular, the application of jujube polysaccharide at various concentrations (10–100 μg/ml) onto cultured lymphocytes for 3 days demonstrated an enlarging cell volume and an increasing cell number (Zhao et al., 2008). Dietary Ziziphus jujuba fruit attenuates colitis-associated tumorigenesis: a pivotal role of the NF-kappaB/IL-6/JAK1/STAT3 pathway. doi:10.1021/jf305497r, Guo, S., Duan, J. (common jujube). Jujube has a promising source of flavonoids, polysaccharides, terpenoids, saponins, nucleotides and others (Figure 2). doi:10.1016/j.molmed.2004.09.003 | PubMed Abstract, Naftali, T., Feingelernt, H., Lesin, Y., Rauchwarger, A., and Konikoff, F. M. (2008). Immunol. Blood 73, 13–16. Antimelancholic medicine prepared from jujube cAMP materials. In line with this notion, Mohebbati et al. Ziziphus jujuba Mill. Compared with model group, the pre-treatment with jujube extract at different doses (100, 200, and 400 mg/kg/day) in colon of rats for 5 days by oral gavage significantly induced mRNA expressions of Nrf2 and HO-1, giving the highest response by seven and two folds, respectively (Almeer et al., 2018). Flavonoids from jujube have been found to stimulate the expression of erythropoietin (EPO), a hormone stimulating blood production (Zheng et al., 2011), and therefore we speculated that jujube flavonoid might be one of the active compounds that possessed the ability to induce the expression of EPO. J. Agric. RBC, red blood cell; EPO, erythropoietin; HIF, hypoxia inducible factor; HRE, hypoxia response element; PKA, protein kinase A; CREB, cAMP response element-binding protein; FPN, ferroportin; BVR, biliverdin reductase; HO-1, heme oxygenase-1. Thus, it is supposed that the cAMP in the jujube may account for its role on HIF (hypoxia inducible factor)-dependent EPO induction. The photo of dried jujubes collected from Xinjiang province, one of major production regions of jujubes in China. The excessive induction of pro-inflammatory cytokines, i.e., IL-1β and IL-6, also contributes to chronic inflammation. doi:10.1159/000419514 | PubMed Abstract, Gottlieb, Y., Topaz, O., Cohen, L. A., Yakov, L. D., Haber, T., and Morgenstern, A. Exp. Hematopoietic properties of jujube. 73, 2503–2513. To account for the possible mechanism of HIF signaling in jujube-induced HRE activation, the expression of HIF-1α was determined. 8, 5050–5051. doi:10.1080/01635581.2019.1615515 | PubMed Abstract, Post, D. E., and Van Meir, E. G. (2001). - possible role in the treatment of asthma. 2016 Jun;22 Suppl 2:24-31. No use, distribution or reproduction is permitted which does not comply with these terms. Macromol. In addition, jujube was reported to contain numerous minerals, e.g., iron and vitamin. Clinically, several controlled trials have revealed that jujube is a safe and effective herb for human consumption (Naftali et al., 2008; Ebrahimimd et al., 2011; Sabzghabaee et al., 2013); however, there is currently no human study on the blood deficiency effects. doi:10.1016/j.abb.2017.10.013 | PubMed Abstract, Pahuja, M., Mehla, J., Reeta, K. H., Joshi, S., and Gupta, Y. K. (2011). The results showed that dietary jujube intake could attenuate inflammation in model mice. 28, 1527–1532. 48, 639–643. cv. It may possess anxiety -reducing and sedative properties. According to the theory of TCM, blood deficiency shows similarity to anemia of individual in western medicine (Shi et al., 2019). Int. Contrib. Biol. Cytoprotective effects of the aqueous extract of the Ziziphus jujuba fruit on TBHP-induced damage on human fibroblast cells. J. Ethnopharmacol. doi:10.1016/j.jep.2019.01.027 | PubMed Abstract, Steinkamp-Fenske, K., Bollinger, L., Xu, H., Yao, Y., Horke, S., and Förstermann, U. On the other hand, the intake of Jian-Pi-Yi-Shen, a Chinese herbal decoction comprising of Astragali Radix, Atractylodis Macrocephalae Rhizoma, Dioscoreae Rhizoma, Cistanches Herba, and other four herbs, was able to improve renal function and kidney injury in anemia rats suffering from chronic kidney disease (Chen et al., 2019). EPO gene expression regulates primarily at the level of transcription, and which is further controlled by a number of transcriptional and post-transcriptional factors (Schuster et al., 1989; Goldberg et al., 1991). Yazdanpanah, Z., Ghadiri-Anari, A., Mehrjardi, A. V., Dehghani, A., Zardini, H. Z., and Nadjarzadeh, A. Erythropoietin: structure, control of production, and function. About 0.48 mg iron and 69 mg vitamin C per 100 g of fresh fruit were reported (Li et al., 2007; USDA, 2012). da Silva B.V., Barreira J.C.M., Oliveira M.B.P.P. Jian-Pi-Yi-Shen decoction relieves renal anemia in 5/6 nephrectomized rats: production of erythropoietin via hypoxia inducible factor signaling. 23, 102–109. In another investigation, the activities of dietary jujube on the levels of RBC, hemoglobin and hematocrit were analyzed in colitis-associated colon cancer mice. In this work we hypothesized that this natural product rich in polyphenols might protect humans against DNA damage and its consequences. Additional in vivo experiments were carried since BA is an important phytochemical detected in ample amounts in the fruit extract. Flavonoids are common chemical presented in a wide range of plants. The reduction at 60% was observed under the pre-treatment of extract at 3 mg/ml (Chen et al., 2014a). (2014) reported that CREB-binding protein was required for HIF-α acetylation and efficient HIF-mediated EPO production during hypoxic stress. Here, we are focusing on a discussion of jujube associating with hematopoietic functions, i.e., erythropoiesis, erythrophagocytosis and immune functions (Table 2). B., Kozukue, N., Levin, C. E., and Friedman, M. (2011). (2020). (2016) investigated the inductive roles of GZT on EPO expression in cultures. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Our evidence-based analysis on ziziphus jujuba features 56 … that belongs to Rhamnaceae family. Health beneficial properties of jujube. Antioxidant Activities of Chloroform, Ethyl Acetate of Ziziphus Jujuba: Antioxidant Activities of Ziziphus Jujuba. Natural phytochemicals and probiotics as bioactive ingredients for functional foods: extraction, biochemistry and protected-delivery technologies. (2016). The rats were treated with hydroalcoholic extracts of jujube at various concentrations (from 100 to 400 mg/kg) for four weeks, and then L-NAME (10 mg/kg) was injected intravenously into rats to induce hypertension. Stimulation of erythropoietin gene transcription during hypoxia and cobalt exposure. Besides, GZT extract prevented ERK phosphorylation and NF-κB translocation in LPS-treated macrophages (Yoo et al., 2016). doi:10.1002/ptr.5796, Yoo, S. R., Kim, Y., Lee, M. Y., Kim, O. S., Seo, C. S., Shin, H.-K., et al. Jujube is usually called red date or Chinese date, which is the fruit of Ziziphus jujuba Mill. Phytother Res. Failure to up regulate the circulating EPO under hypoxia thereafter leads to anemia (Jelkmann, 1992). Hair growth promoting effect of Zizyphus jujuba essential oil. In addition, GZT stimulated the transcriptional activity of HRE in a dose-dependent manner (Lam et al., 2016). Phytomedicine 19, 239–244. doi:10.2174/1871529X19666191119141400 | PubMed Abstract, Klei, T. R., Meinderts, S. M., van den Berg, T. K., and van Bruggen, R. (2017). Effect of quercetin on cell protection via erythropoietin and cell injury of HepG2 cells. Die Chinesische Jujube (Ziziphus jujuba Mill. von Adeela Amjad, Qasim Raza, et al. The occurrence of renal interstitial fibrosis is accompanied by decrease of fibroblasts, which impairs the production of EPO. Seo, E. J., Lee, S. Y., Kang, S. S., and Jung, Y. S. (2013). (2018) revealed the effects of jujube extract on gene expressions of Nrf2 and HO-1 in colitis rats, as induced by treating intrarectally with acetic acid.

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