Research advances in bioactive components and health benefits of jujube (Ziziphus jujuba Mill.) fruit

Research advances in bioactive components and health benefits of jujube ( Ziziphus jujuba Mill.) fruit 红枣生物活性成分及其保健作用的研究进展 1 first-author 1 2 2 1 3 corresp Wei CHEN, zjuchenwei@zju.edu.cn Wei CHEN, zjuchenwei@zju.edu.cn zjuchenwei@zju.edu.cn https://orcid.org/0000-0002-2373-2437 Department of Food Science and Nutrition, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang University, Hangzhou310058, China Department of Food Science and Nutrition, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang University, Hangzhou310058, China Department of Traditional Chinese Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou310016, China Department of Traditional Chinese Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou310016, China Ningbo Research Institute, Zhejiang University, Ningbo315100, China Ningbo Research Institute, Zhejiang University, Ningbo315100, China Jujube ( Ziziphus jujuba 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. 红枣作为一种膳食补充剂，是公认的健康食品。它含有多种生物活性物质，如多糖、多酚、氨基酸、核苷酸、脂肪酸和维生素等。这些活性物质具有抗癌、抗氧化、抗炎、降血脂、降血糖、免疫调节、神经保护、镇静和抗病毒等生理功能。除此之外，本文还归纳了红枣果实中的生物碱和膳食纤维及其生理功能。同时，对影响枣树果实资源开发利用的相关问题进行了探讨，并提出了未来红枣营养功能的研究方向。本文将为红枣产品的开发及红枣营养成分在功能性食品中的应用提供一定的参考依据。 Jujube Bioactive components Biological activity Functional foods Health benefits 红枣 功能成分 生物活性 功能食品 保健作用 1 Introduction 1 In recent decades, the demand for healthier and safer food products, from cereals to vegetables, has been booming ( Das et al., 2012 Das et al., 2012 ; Ashaolu and Ashaolu, 2020 Ashaolu and Ashaolu, 2020 ; Ashaolu and Reale, 2020 Ashaolu and Reale, 2020 ). Many health factors in foods can improve people's quality of life by preventing diseases ( Chen et al., 2016 Chen et al., 2016 ; Xu et al., 2018 Xu et al., 2018 ; Gowd et al., 2019 Gowd et al., 2019 ). A large proportion of these functional foods are fruits with a variety of nutrients and biological activity ( Cai, 2019 Cai, 2019 ). Ziziphus jujuba Mill., also known as Chinese jujube or red date, belongs to the Rhamnaceae family. As a highly nutritious and functional fruit, jujube is distributed mainly in Europe and most of Asia ( Gao et al., 2013 Gao et al., 2013 ). China is not only the center of origin, but also the main production region of jujube, where annual production accounts for more than 90% of the world's total production. Nearly 700 cultivars of jujube are widely cultivated in the areas of the Yellow River and the northwest region, including the Shandong, Hebei, Shanxi, Shannxi, and Henan provinces, and the Xinjiang Uygur Autonomous Region ( Yuan et al., 2002 Yuan et al., 2002 ; Li et al., 2007 Li et al., 2007 ; Ministry of Agriculture and Rural Affairs of the People's Republic of China, 2020 Ministry of Agriculture and Rural Affairs of the People's Republic of China, 2020 ; Wang BN et al., 2020 Wang BN et al., 2020 ). Jujube fruit have been used in folk medicine for 4000 thousand years. According to Huangdi Neijing , an early classical book of ancient Chinese medicine, the jujube was regarded as one of the five most nutritious and healthy fruits. Furthermore, the jujube fruit was recorded as an excellent herbal medicine in Shennong Bencao Jing , serving to improve the quality of sleep, eliminate toxins, and beautify skin ( Chen et al., 2014 Chen et al., 2014 , 2017 2017 ; Ji et al., 2017 Ji et al., 2017 ). Nowadays, with the evolution of scientific and technological methods, the nutritional components of jujube have been extensively studied and applied in the fields of functional foods and bio-medicine ( Gao et al., 2013 Gao et al., 2013 ; Rodríguez Villanueva and Rodríguez Villanueva, 2017 Rodríguez Villanueva and Rodríguez Villanueva, 2017 ). Most recently, phytochemistry research has indicated that jujube fruit are rich in polysaccharides, polyphenols, amino acids, triterpenic acids, fatty acids, nucleosides, and nucleobases ( Gao et al., 2013 Gao et al., 2013 ; Kou et al., 2015 Kou et al., 2015 ; Hernández et al., 2016 Hernández et al., 2016 ; Rashwan et al., 2020 Rashwan et al., 2020 ). Based on the literature, bioactive compounds extracted from jujube have various bioactivity, including antioxidant ( Zhang et al., 2010 Zhang et al., 2010 ; Zhao HX et al., 2014 Zhao HX et al., 2014 ), anti-inflammatory ( Yu et al., 2012 Yu et al., 2012 ), anticancer ( Choi et al., 2012 Choi et al., 2012 ; Plastina et al., 2012 Plastina et al., 2012 ), anti-hyperglycemic ( Kawabata et al., 2017 Kawabata et al., 2017 ), anti-hyperlipidemic ( Jeong and Kim, 2019 Jeong and Kim, 2019 ), immunomodulatory ( Dash et al., 2015 Dash et al., 2015 ), and other activity. In addition, other biologically active components obtained from jujube, especially alkaloids and saponin, have been explored for their antiviral, sedative, and neuroprotective effects ( Pandey et al., 2008 Pandey et al., 2008 ; Shad et al., 2014 Shad et al., 2014 ; Abdoul-Azize, 2016 Abdoul-Azize, 2016 ; Ninave and Patil, 2019 Ninave and Patil, 2019 ; He SR et al., 2020 He SR et al., 2020 ). As a classic prescription in traditional Chinese medicine (TCM), jujube is often used in combination with other herbs to treat a variety of diseases. Qi Fu Yin, a Ming Dynasty prescription containing seven traditional Chinese herbs, has the effect of promoting blood circulation and calming the spirit. In addition, Suanzaoren decoction ( Ziziphus spinose ) is the most frequently used formula for the treatment of insomnia ( Singh and Zhao, 2017 Singh and Zhao, 2017 ; Ong et al., 2018 Ong et al., 2018 ). At present, with the increasing modernization of TCM, research on the material basis and mechanisms of the jujube prescription has attracted much attention. Many new lines of research on jujube fruit have been explored or established and much knowledge gained. Hence, the aim of this review was to summarize the latest findings on the chemical constituents and biological functional activity of jujube fruit. Also, the potential problems associated with the development and utilization of jujube, and the new research directions are critically discussed and evaluated. 2 Major elements and nutrients in jujube fruit 1 Jujube fruit is well-known as a favored and healthy food, rich in nutritional ingredients such as carbohydrates, proteins, dietary fiber (DF), unsaturated fatty acids, vitamins, and minerals ( Gao et al., 2013 Gao et al., 2013 ). The major nutrient elements contained in jujube fruit are discussed below. 2.1 Carbohydrates and proteins 2 Carbohydrate and protein can provide energy for organs and muscles to keep the body functioning properly ( Jéquier, 1994 Jéquier, 1994 ; Wu, 2016 Wu, 2016 ). Jujube fruit has been identified as an excellent source of carbohydrate and protein. Li et al. (2007) Li et al. (2007) studied the contents of carbohydrate and protein (percentage of dry weight (DW)) in five cultivars of Chinese jujube. They found that the carbohydrate contents among these jujube fruits were similar, ranging from 80.86% (cv. Yazao) to 85.63% (cv. Sanbianhong). In addition, the protein contents of the cultivars ranged from 4.75% (cv. Jianzao) to 6.86% (cv. Yazao). Rahman et al. (2018) Rahman et al. (2018) compared and evaluated the nutrient contents of four cultivars of jujube, namely "Hupingzao," "Huizao," "Xiaozao," and "Junzao," grown in Northwest China. The results showed that the carbohydrate contents of these fruits ranged from (82.35±4.50) to (89.73±5.43) g/100 g DW. The protein contents ranged from (4.43±0.66) to (6.01±0.58) g/100 g DW. 2.2 Dietary fiber 2 DF refers to the polysaccharides, namely lignin, cellulose, and hemicellulose, which cannot be digested by the human body. It is generally classified into two categories: the water-insoluble fibers of cellulose, hemicellulose, and lignin, and the water-soluble fibers of pectin, gums, and mucilages ( Cai, 2019 Cai, 2019 ). DF can selectively promote metabolism and the proliferation of beneficial bacteria to produce energy and nutrients for the body ( Williams et al., 2017 Williams et al., 2017 ). At present, methods for extraction of DF include mainly crude separation, chemical methods, membrane separation, enzymatic methods, enzymatic chemical combination methods, and fermentation methods ( Yan et al., 2019 Yan et al., 2019 ; He YY et al., 2020 He YY et al., 2020 ; Karra et al., 2020 Karra et al., 2020 ). Miklavčič Višnjevec et al. (2019) Miklavčič Višnjevec et al. (2019) performed a modified enzymatic-gravimetric method to determine the total, soluble, and insoluble fiber contents of jujube sample Zj2. Chemical analysis indicated that the content of insoluble fiber ((6.0±0.2) g/100 g) was higher than that of soluble fiber ((3.8±0.4) g/100 g). The results of this study with regards to insoluble DF content were similar to those from the study of Li et al. (2007) Li et al. (2007) , but the mass fraction of soluble fiber in Zj2 was higher. Hernández et al. (2016) Hernández et al. (2016) analyzed the chemical properties of four jujube cultivars ("GAL," "MSI," "PSI," and "DAT") from a commercial farm located in San Isidro, Spain. Their results showed that the crude fiber content ranged from 0.7 to 1.1 g/100 g DW and "GAL" had the lowest crude fiber content. Studies on the optimization of methods for extracting DF from jujube fruit have also been reported in recent years. Liu and Deng (2016) Liu and Deng (2016) optimized the conditions for the extraction of DF from Jinsixiaozao by an acid-based treatment. An orthogonal test showed that the yield of DF could reach 5.1% when 5 g jujube fruit was hydrolyzed in 150 mL sulfuric acid (1.5%) solution for 40 min, and 100 mL potassium hydroxide (1.75%) solution for 30 min. Guo et al. (2014) Guo et al. (2014) also reported optimum conditions for the preparation of soluble DF from jujube by a cellulose enzymatic method, which yielded up to 6.20%. 2.3 Vitamins and minerals 2 Jujube fruits contain plenty of minerals and vitamins (especially vitamin C). Mineral analysis showed that jujube fruits contain 17 minerals including 6 macro-elements (K, Ca, Mg, Na, S, and P) and 11 trace elements (Fe, Zn, Cu, Mn, Ni, Se, Pb, Br, Rb, Sr, and Mo) ( Li et al., 2007 Li et al., 2007 ; Gao et al., 2013 Gao et al., 2013 ; Hernández et al., 2016 Hernández et al., 2016 ; Miklavčič Višnjevec et al., 2019 Miklavčič Višnjevec et al., 2019 ). Studies have shown that K is the most abundant element in jujube fruit, ranging from 12.4 to 17.3 g/kg DW. Differences in K content may be due to the cultivars or growing conditions ( Li et al., 2007 Li et al., 2007 ; Hernández et al., 2016 Hernández et al., 2016 ). The major vitamins detected in jujube fruits are vitamin A, vitamin B complex, carotene, thiamine, riboflavin, and ascorbic acid ( Wojdyło et al., 2016 Wojdyło et al., 2016 ). Ascorbic acid, also known as vitamin C, is a powerful reducing and chelating agent, with numerous biological functions in cells and tissues ( Paciolla et al., 2019 Paciolla et al., 2019 ). Studies have shown that jujube fruits qualify as a good source of vitamin C. A wide range in the concentration of vitamin C was detected among the 15 jujube cultivars analyzed, from 1.671 (cv. Dalongzao) to 4.247 (cv. Guanyangduanzao) mg/g fresh weight (FW) ( Kou et al., 2015 Kou et al., 2015 ). 2.4 Fatty acids 2 Fatty acids are essential nutrients, some of which must be ingested through food to maintain health. The variety and content of fatty acids in jujube fruit could satisfy people's need for nourishment ( Guil-Guerrero et al., 2004 Guil-Guerrero et al., 2004 ). Reche et al. (2019) Reche et al. (2019) reported that a total of 11 fatty acid compounds, including myristic acid, myristoleic acid, palmitic acid, trans -palmitoleic acid, cis -palmitoleic acid, stearic acid, oleic acid, 11-octadecenoic acid, elaidic acid, linoleic acid, and linolenic acid, were available in four jujube cultivars. Song et al. (2019) Song et al. (2019) detected capric acid (C10:0), lauric acid (C12:‍0), myristoleic acid (C14:‍1n5), palmitic acid (C16:‍0), palmitic acid (C16:‍1n7), oleic acid (C18:‍1n9c), and linoleic acid (C18:‍2n6c) from four ripening stages of jujube fruit. Palmitic acid (C16:‍0), palmitic acid (C16:‍1n7), oleic acid (C18:‍1n9c), and linoleic acid (C18:‍2n6c) were the predominant fatty acid components. Another study found a total of 16 different fatty acids in jujube fruit samples (Zj2–Zj6) ( Miklavčič Višnjevec et al., 2019 Miklavčič Višnjevec et al., 2019 ). The predominant fatty acids were linoleic acid (C18:‍2) and oleic acid (C18:1). 3 Bioactive compounds in jujube fruit 1 A variable number of bioactive substances are available in jujube fruit beside the carbohydrates, fatty acids, proteins, and other general nutrients ( Choi et al., 2011 Choi et al., 2011 ). Jujube fruits have rich nutritional and medicinal values. In recent years, increasing attention has been paid to their polysaccharides, polyphenols, saponins, amino acids, triterpenes, alkaloids, and other bioactive compounds ( Plastina et al., 2012 Plastina et al., 2012 ; Tahergorabi et al., 2015 Tahergorabi et al., 2015 ). 3.1 Polysaccharides 2 Jujube fruit polysaccharides are very important water-soluble polysaccharides, most of which are neutral or acid polysaccharides. The extraction, separation, and purification of polysaccharides from jujube fruit are the first step in the study of biological functions. Currently, the mature extraction approaches to improve the yield and quality of plant polysaccharides are hot-water extraction ( Li et al., 2008 Li et al., 2008 ), alkali purification ( Ding et al., 2012 Ding et al., 2012 ), enzymatic hydrolytic methods ( Wu et al., 2014 Wu et al., 2014 ), and ultrasonic and microwave-assisted extraction ( Sun et al., 2019 Sun et al., 2019 ). Generally, the identification and evaluation of jujube polysaccharides are based mainly on their content, composition, and structure. Analysis of the chemical structure of polysaccharides includes a variety of techniques ( Ji et al., 2017 Ji et al., 2017 ), such as gas chromatography (GC) for determining the polysaccharide composition and high-performance liquid chromatography (HPLC) for determining the molecular weight. Infrared (IR) spectroscopy, nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), acid hydrolysis, and methylation analysis are also used to analyze and identify complex polysaccharide structures. In the past five years, numerous studies have discussed the chemical structure of jujube polysaccharides including their monosaccharide composition, monosaccharide sequence, molecular weight, type of glycosyl bonds, and biological activity ( Table 1 Table 1 ). Five polysaccharide fragments (PZMP1, ZMP, SAZMP3, PZMP2-2, and PZMP3-2) were successively isolated with different chemical structures and biological functions from jujube fruit using water extraction, ultrasound-assisted, alkali extraction, and other purification conditions (Ji et al., 2018a (Ji et al., 2018a , 2018b 2018b , Ji et al., 2019a Ji et al., 2019a , 2020b 2020b ; Lin et al., 2019 Lin et al., 2019 ). In addition, Cai et al. (2018) Cai et al. (2018) extracted JCS-1 and JCS-2 from cv. Jinchangzao using a hot-water extraction method. HPLC analysis indicated that JCS-1 and JCS-2 were composed mainly of galacturonic acid (GalA) ( Table 1 Table 1 ). A recent study found that SAZMP4 (a novel antioxidant pectin isolated from jujube) was composed mainly of rhamnose, arabinose, xylose, mannose, and GalA through 1,4-linked GalA (93.48%) ( Lin et al., 2020 Lin et al., 2020 ). No. Z. jujuba cultivar Name of component Molecular weight (kDa) Monosaccharide composition Structure Bioactivity Reference 1 Muzao PZMP1 16.97 Arabinose, galactose, glucose, mannose, and xylose in a molar ratio of 17.36:3.29:2.68:1.05:1.00 Backbone is composed of 1,3,5-linked Ara f , 1,3-linked Ara f , 1,5-linked Ara f , 1,4-linked Glc p , 1-linked Ara f , and 1-linked Glc p ; the repeating unit of PZMP1 is a linear backbone with branches at positions O -3 and O -5 Hypolipidemic Ji et al., 2018b Ji et al., 2018b 2 Jinchangzao JCS-1 71.75 Galacturonic acid (GalA), galactose, and arabinose in a molar ratio of 39.04:1.26:1.39 Had α-configurations; typical resonances of C-6 of the carboxyl groups of GalA were observed at 174.92 and 175.05 ppm (part per million); anomeric region signals were showed in the 96‒107 ppm region Immunomodulatory Cai et al., 2018 Cai et al., 2018 3 Jinchangzao JCS-2 357.39 GalA, mannose, rhamnose, arabinose, and galactose in a molar ratio of 19.87:2.07:1.77:1.65:1.16 Had α-configurations; typical resonances of C-6 of the carboxyl groups of GalA were observed at 175.05 ppm; anomeric region signals showed in the 96‒107 ppm region Immunomodulatory Cai et al., 2018 Cai et al., 2018 4 Muzao ZMP 89.90 Rhamnose, arabinose, xylose, mannose, glucose, galactose, and GalA in a molar ratio of 1.46:2.47:2.27:1.12:1.00:1.57:5.40 Stretching vibration C-CO-C stretching vibration may exist in Z. jujuba cv. Muzao polysaccharides Antioxidant and anti-inflammatory Ji et al., 2018a Ji et al., 2018a 5 Muzao SAZMP3 9.37 Rhamnose, arabinose, xylose, mannose, glucose, galactose, and GalA in a molar ratio of 10.51:6.70:0.50:0.26:0.50:6.75:74.69 Backbone is composed of 1,4-α-D-GalA p with side chains of 1,3-β-D-Gal p , 1,3,5-linked Ara f , 1,2,4-α-L-Rha p , and terminals of 1-linked Ara f , 1-linked Rha p , and 1-linked Gal p Antioxidant Lin et al., 2019 Lin et al., 2019 6 Muzao PZMP2-2 62.73 Rhamnose, arabinose, xylose, galactose, and GalA in a molar ratio of 1.18:5.23:0.22:2.68:2.20 Backbone is composed of 1-linked Gal p , 1,3-linked Ara f , 1,2,4-linked Rha p , 1,3-linked Gal p , 1,4-linked GalpA, and 1,3,5-linked Araf; a linear backbone of (1→4)-linked Glc p A and (1→2,4)-linked Rha p residues, with branches at the O -4 position, consisting of Ara f and Gal p residues Ji et al., 2019a Ji et al., 2019a 7 Muzao PZMP3-2 58.21 Rhamnose, arabinose, galactose, and GalA in a molar ratio of 1.74:2.00:341.00:18.69 A→4]-GalpA-[1→backbone, with few branches at the O -2 position of some Ara f and Rha p residues Ji et al., 2020b Ji et al., 2020b 8 Muzao SAZMP4 28.94 Rhamnos, arabinos, xylose, mannose, and GalA in a molar ratio of 1.00:0.90:0.05:0.07:28.90 A pectic polysaccharide mainly containing 1,4-linked GalA (93.48%) with side chains of 1,2,4-linked Rha and 1,3,5-linked Ara and terminals of 1-linked Rha and 1-linked Ara Antioxidant Lin et al., 2020 Lin et al., 2020 3.2 Polyphenols 2 Polyphenols such as phenolic acids, tannins, flavonoids, stilbenes, and lignans are secondary metabolites of plants ( Al-Dujaili, 2015 Al-Dujaili, 2015 ; Li et al., 2016 Li et al., 2016 ). In the past decade, many studies have focused on the role of jujube polyphenols in treating human diseases. The main aspects of current research on polyphenols from jujube fruit are extraction and purification, identification of polyphenols, and the determination of total and specific contents. The methods available for the extraction of jujube polyphenols are organic solvent extraction ( Lai et al., 2011 Lai et al., 2011 ), ultrasonic-assisted extraction ( Ran et al., 2013 Ran et al., 2013 ), and enzymatic hydrolysis ( Kammerer et al., 2005 Kammerer et al., 2005 ), while the total polyphenol content is measured by the Folin-Ciocalteu colorimetric method. Kou et al. (2015) Kou et al. (2015) analyzed the bioactive compounds of 15 jujube cultivars from the Loess Plateau of Shanxi, China. The study indicated that the total phenolic content (bound+free polyphenols) of jujube fruit ranged from (0.558±0.043) mg gallic acid equivalent (GAE)/g FW (cv. Zanhuangzao) to (2.520±0.032) mg GAE/g FW (cv. Tengzhouchanghongzao), while the content of free polyphenols was much higher than that of bound polyphenols. These 15 jujube cultivars are also rich in flavonoids, with total contents ranging from (0.47±0.06) mg rutin equivalent (RE)/g FW (cv. Hupingzao) to (2.00±0.08) mg RE/g FW (cv. Nanjingyazao). Wojdyło et al. (2016) Wojdyło et al. (2016) applied liquid chromatography (LC)-MS-quadrupole time-of-flight (QTOF), and ultra-performance liquid chromatography-photodiode array-fluorescence detector (UPLC-PDA-FL) methods for the determination of 25 phenolic compounds in Spanish jujube. Their analysis revealed that the jujube contained flavan-3-ols (one of the main phenolic acid components) comprising 89% to 94% of the total polyphenol content, which ranged from 1442 to 3432 mg/100 g dry matter (DM). Recently, another group evaluated the total phenol and flavonoid contents of 16 jujube cultivars from China ( Wang BN et al., 2020 Wang BN et al., 2020 ). They found that the content of polyphenols ranged from 2.534 to 4.949 mg GAE/g, and flavonoids from 1.253 to 4.254 mg rutin/g. Subsequently, a total of ten phenolic acids and two flavonoids were determined in jujube, among which p -hydroxybenzoic acid, protocatechuic acid, chlorogenic acid, and rutin were the main components. However, studies also reported that the phenolic acid composition and content levels of jujube fruits depend mainly on the cultivar and the stage of fruit development ( Gao et al., 2012 Gao et al., 2012 ; Pu et al., 2018 Pu et al., 2018 ; Shi et al., 2018 Shi et al., 2018 ). To facilitate the comprehensive discussion of this review, we have summarized the advanced research on individual phenolic compounds and the range of polyphenols of jujube fruits in Table 2 Table 2 . * Content in mg/100 g fresh weight (FW). # Content in mg/100 g dry weight (DW). Phenolic compound Content Reference Phenolic acid  Gallic acid 0.103‒15.700 * Gao et al., 2012 Gao et al., 2012 ; Shi et al., 2018 Shi et al., 2018  Chlorogenic acid 0.016‒9.480 * Gao et al., 2012 Gao et al., 2012 ; Pu et al., 2018 Pu et al., 2018 ; Shi et al., 2018 Shi et al., 2018  Caffeic acid 0.004‒2.270 * Gao et al., 2012 Gao et al., 2012 ; Pu et al., 2018 Pu et al., 2018 ; Shi et al., 2018 Shi et al., 2018  Ferulic acid 0.002‒5.000 * Gao et al., 2012 Gao et al., 2012 ; Pu et al., 2018 Pu et al., 2018 ; Shi et al., 2018 Shi et al., 2018  Cinnamic acid 0.008‒4.460 * Gao et al., 2012 Gao et al., 2012 ; Pu et al., 2018 Pu et al., 2018 ; Shi et al., 2018 Shi et al., 2018  Protocatechuic acid 0.778‒0.880 * Gao et al., 2012 Gao et al., 2012 ; Pu et al., 2018 Pu et al., 2018   p -Cumaric acid 0.18‒0.66 * Pu et al., 2018 Pu et al., 2018   p -Hydroxybenzoic acid 7.01‒12.53 * Pu et al., 2018 Pu et al., 2018  Ellagic acid 0.0156‒1.5800 * Gao et al., 2012 Gao et al., 2012 ; Pu et al., 2018 Pu et al., 2018 Flavan-3-ol  (+)-Catechin 1.30‒16.82 * Gao et al., 2012 Gao et al., 2012 ; Pu et al., 2018 Pu et al., 2018 ; Shi et al., 2018 Shi et al., 2018  (-)-Epicatechin 0.12‒30.41 * Gao et al., 2012 Gao et al., 2012 ; Pu et al., 2018 Pu et al., 2018 ; Shi et al., 2018 Shi et al., 2018  Polymeric proanthocyanidin 939‒2548 # Wojdyło et al., 2016 Wojdyło et al., 2016  Degree of polymerization (DP) 2.02‒2.34 Wojdyło et al., 2016 Wojdyło et al., 2016  Procyanidin B1 3.119‒29.030 * Shi et al., 2018 Shi et al., 2018  Procyanidin B2 239‒389 # Wojdyło et al., 2016 Wojdyło et al., 2016  Procyanidin B3 3.89‒49.10 * Shi et al., 2018 Shi et al., 2018 Flavanol  Quercetin 0.022‒4.280 * Gao et al., 2012 Gao et al., 2012 ; Pu et al., 2018 Pu et al., 2018 ; Shi et al., 2018 Shi et al., 2018  Rutin 0.52‒7.33 * Gao et al., 2012 Gao et al., 2012 ; Pu et al., 2018 Pu et al., 2018  Quercetin-3-rhamnoside 0.8‒1.9 # Wojdyło et al., 2016 Wojdyło et al., 2016  Quercetin-3-galactoside 0.2‒0.5 # Wojdyło et al., 2016 Wojdyło et al., 2016  Quercetin-3- O -robinobioside 0.3‒1.1 # Wojdyło et al., 2016 Wojdyło et al., 2016  Quercetin-3- O -rutinoside 41.7‒157.0 # Wojdyło et al., 2016 Wojdyło et al., 2016  Quercetin-3- O -robinobioside 0.0‒2.2 # Wojdyło et al., 2016 Wojdyło et al., 2016  Quercetin-3- O -arabino-rhamnoside 21.1‒70.4 # Wojdyło et al., 2016 Wojdyło et al., 2016  Quercetin-3- O -xyloso-rhamnoside 0‒13 # Wojdyło et al., 2016 Wojdyło et al., 2016  Quercetin-3- O -rutinoside-7- O -hexoside 0.6‒3.2 # Wojdyło et al., 2016 Wojdyło et al., 2016  Quercetin-3- O -rutinoside-7- O -pentoside 0.7‒2.9 # Wojdyło et al., 2016 Wojdyło et al., 2016  Kaempferol-3- O -rutinoside 0.6‒1.9 # Wojdyło et al., 2016 Wojdyło et al., 2016  Kaempferol-3- O -robinobioside 7.2‒12.2 # Wojdyło et al., 2016 Wojdyło et al., 2016  Kaempferol-3- O -hexose- O -deoxy-hexose- O -pentoside 7.8‒48.6 # Wojdyło et al., 2016 Wojdyło et al., 2016 Flavanone  Eriodictyol derivative 1.2‒4.5 # Wojdyło et al., 2016 Wojdyło et al., 2016 Dihydrochalcone  Phloretin-3',5'-di-glucoside 1.2‒2.0 # Wojdyło et al., 2016 Wojdyło et al., 2016 3.3 Amino acids 2 Amino acids are essential nutrients for human health ( Hou et al., 2019 Hou et al., 2019 ). The content and composition of amino acids in jujube fruit affect its flavor and biological activity ( Pu et al., 2018 Pu et al., 2018 ). Studies found that jujube fruit contain at least a dozen major amino acids, which vary depending on the cultivar, maturity stage, and processing method ( Rahman et al., 2018 Rahman et al., 2018 ; Song et al., 2019 Song et al., 2019 ; Bao et al., 2021 Bao et al., 2021 ). A study detected a total of 18 amino acids in four jujube cultivars ("Hupingzao," "Huizao," "Xiaozao," and "Junzao") grown in northwest China. Proline (Pro), aspartic acid (Asp), and glutamic acid (Glu) accounted for 64.5%–70.0% of the total amino acids ( Kaeidi et al., 2015 Kaeidi et al., 2015 ). These amino acids have about 76.5%–80.8% of the antioxidant and anti-inflammatory properties of the total amino acids. Essential amino acids (EAAs), such as lysine (Lys), threonine (Thr), tryptophan (Trp), valine (Val), leucine (Leu), isoleucine (Ile), histidine (His), phenylalanine (Phe)‍+tyrosine (Tyr), and methionine (Met)+cysteine (Cys), were also analyzed in the four jujube cultivars. According to the results, cv. Junzao had the highest EAA reference score among these cultivars ( Rahman et al., 2018 Rahman et al., 2018 ). Song et al. (2019) Song et al. (2019) compared the composition and content of amino acids in jujube fruit at four stages of ripening: green maturity (GM), yellow maturity (YM), half-red maturity (HRM), and red maturity (RM). A total of 26 free amino acids were detected, and their total contents gradually decreased with the maturity of the fruit ( Song et al., 2019 Song et al., 2019 ). Pu et al. (2018) found that high temperature accelerates the loss of free amino acids in cv. Junzao fruit during the long-term storage. In contrast, the proline (Pro) content of the fruit increased, which may be related to the environmental and temperature stress response of the fruit under poor storage conditions. 3.4 Nucleosides and nucleobases 2 Nucleosides and nucleobases are often selected as quality control markers for functional foods and are involved in the regulation of a variety of biological processes, such as gene expression, cell proliferation, antioxidant, anti-inflammatory, cardioprotective and anticancer activities ( Yamamoto et al., 1997 Yamamoto et al., 1997 ; Yuan et al., 2008 Yuan et al., 2008 ; Phan et al., 2018 Phan et al., 2018 ). Therefore, it is always important to evaluate and analyze the content of nucleosides/nucleobases to understand the effects of different jujube cultivars or processing methods. Guo et al. (2015b) Guo et al. (2015b) analyzed the content and composition of nucleosides and nucleobases in jujube (cv. Lingwuchangzao) fruits treated by different processing methods. The results of HPLC-diode array detection (DAD) and LC-MS analyses showed that nine nucleosides and nucleobases, including uracil, hypoxanthine, guanine, cytidine, uridine, adenine, cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), and guanosine, were found in jujube. The study also found that the total content of nucleosides and nucleobases in jujube fruit increased with the extension of drying time. However, cAMP and cGMP in the jujube fruit were not stable during the steaming process. The cyclic nucleotides (mainly cAMP and cGMP) in jujube fruit act as secondary messengers, and are involved in the regulation of a variety of physiological and biochemical processes in the body ( Nair et al., 2019 Nair et al., 2019 ). Kou et al. (2015) Kou et al. (2015) revealed that the cAMP content of 15 jujube species ranged from 17.38 to 193.93 μg/g FW. The Z. jujuba cv. Hupingzao showed promising prospects for the extraction and utilization of cAMP. The effects of different drying methods on the contents of cAMP and cGMP in fruit of Z. jujuba cv. Jinsixiaozao were described by Wang et al. (2016) Wang et al. (2016) . The study suggested that the content of cyclic nucleotides in jujube was reduced by air drying (AD), sun drying (SD), or microwave drying (MD). After process optimization, the authors indicated that AD at 50 ℃ was a better choice to obtain product with high levels of cAMP and cGMP from cv. Jinsixiaozao. 3.5 Triterpenic acids 2 Triterpenoids are one of the major functional constituents of Z. jujuba . Similar to most other nutrients of jujube, the content of triterpenoids is affected by the cultivar and processing methods ( Guo et al., 2015a Guo et al., 2015a , 2015b 2015b ; Song et al., 2020 Song et al., 2020 ). The total triterpene contents of 15 types of jujube fruit were analyzed by Kou et al. (2015) Kou et al. (2015) . Values ranged from (7.52±0.18) to (16.57±0.11) mg ursolic acid equivalent (UAE)/g FW. The highest amount of total triterpenes was found in cv. Shenglizao (ShLZ), and the lowest in cv. Xiangfenyuanzao (XFYZ). A recent study showed that the total triterpenoid acid contents of 99 jujube samples ranged from 1.08 to 7.92 μg/g DW, with an average value of 3.73 μg/g DW. Moreover, a total of 16 triterpenoid acid peaks were detected by UPLC, among which betulinic acid, alphitolic acid, maslinic acid, oleanolic acid, and ursolic acid were the major triterpenoid acids ( Song et al., 2020 Song et al., 2020 ). Phytochemical studies have shown that most triterpenoids derived from cereals and vegetables have a variety of functions, such as antioxidant, anti-inflammatory, hepatoprotective, and anti-tumor properties ( Xu et al., 2018 Xu et al., 2018 ; Yang et al., 2018 Yang et al., 2018 ; Ghante and Jamkhande, 2019 Ghante and Jamkhande, 2019 ). Ursonic acid, a pentacyclic triterpenoid extracted from Z. jujuba , may alleviate the deterioration caused by tumors or skin aging by inhibiting the expression of matrix metalloproteinase (MMP) genes ( Son and Lee, 2020 Son and Lee, 2020 ). A research group from Japan uncovered the anti-hyperglycemia effect of the triterpenoids of jujube fruit ( Kawabata et al., 2017 Kawabata et al., 2017 ). They found that betulonic acid, betulinic acid, oleanonic acid, and ursonic acid could promote glucose uptake in rat L6 myotubes in a glucose transporter-4-dependent manner. Li et al. (2018) Li et al. (2018) established a highly efficient, sensitive, and accurate UPLC-MS/MS method to detect the pharmacokinetic characteristics of seven triterpenoids in normal and immunosuppressed rats after oral administration of jujube fruit. They found that the pharmacokinetic parameters of triterpenoids were significantly different between normal and immunosuppressed rats. Thus, these kinetic characteristics may provide a reference value for the clinical application of triterpenic acids from jujube fruit ( Li et al., 2018 Li et al., 2018 ). 3.6 Alkaloids 2 Alkaloids are basic nitrogen-containing organic compounds, most of which have a complex nitrogen-containing heterocyclic ring. They are known to have significant physiological effects ( Cushnie et al., 2014 Cushnie et al., 2014 ; Senchina et al., 2014 Senchina et al., 2014 ). As characteristic components of jujube plants, alkaloids are found mostly in the roots, stems, leaves, and seed ( Yoon et al., 2009 Yoon et al., 2009 ; Kang et al., 2015 Kang et al., 2015 ; Sakna et al., 2019 Sakna et al., 2019 ). Although there are many kinds of alkaloids in jujube fruit, the contents are generally low and they are difficult to separate and extract. As a result, related research has rarely been reported. Zhang et al. (2019) Zhang et al. (2019) reported that the optimal method for the extraction of alkaloids from "Goutou" jujube fruit was as follows: solid-liquid mass ratio 1:‍12, ethanol concentration 70%, and extraction time 2.5 h. They also found that the alkaloids of "Goutou" jujube could effectively scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals, which confirmed their antioxidant activity. 4 Research advances on jujube fruit health functions 1 Jujube fruit is delicious and nutritious, and has always been regarded as a healthy supplement. For more than a thousand years, in China the jujube has also been a traditional herbal medicine to calm the mind and soothe the nerves ( Chen et al., 2017 Chen et al., 2017 ). Now, modern scientific research has revealed that the biologically active substances in jujube have cancer prevention, antioxidant, anti-inflammatory, hepatoprotective, neuroprotective, and antiviral properties, and other healthcare effects including improving immune function ( Table 3 Table 3 ; Fig. 1 Fig. 1 ) ( Gao et al., 2013 Gao et al., 2013 ; Abedini et al., 2016 Abedini et al., 2016 ; Ji et al., 2017 Ji et al., 2017 ). AOM: azoxymethane; DSS: dextran sodium sulphate; NF-κB: nuclear factor-κB; IL: interleukin; JAK1: Janus kinase 1; STAT3: signal transducer and activator of transcription 3; ERK: extracellular signal-regulated kinase; CREB: cyclic adenosine monophosphate (cAMP) response element-binding protein; MMP: matrix metalloproteinase; DPPH: 2,2-diphenyl-1-picrylhydrazyl; ROS: reactive oxygen species; ABTS: 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate); FRAP: ferric-reducing antioxidant power; SOD: superoxide dismutase; GSH: glutathione; TNF-α: tumor necrosis factor-α; IFN-γ: interferon-γ; HFFD: high-fat-fructose diet; BW: body weight; HDL-C: high-density lipoprotein-cholesterol; HOMA-IR: homeostasis model assessment-insulin resistance; APAP: acetaminophen; ALT: alanine aminotransferase. To be continued To be continued Biological function Jujube sample used Experimental model Findings Reference Anticancer activity Jujube fruit was supplemented in feed at 5% and 10% (mass fraction) Colitis-associated colon carcinogenesis in AOM/DSS-treated mice Jujube fruit attenuated aberrant crypt foci and decreased the progression of hyperplasia to dysplasia. In addition, it reduced circulating white blood cells, lymphocytes, neutrophils, monocytes, eosinophils, basophils, and platelets compared to colon cancer mice. Periasamy et al., 2015 Periasamy et al., 2015 Jujube fruit diet for 70 d (5% or 10%, mass fraction) Colitis-associated colon carcinogenesis in AOM/DSS-treated mice Dietary jujube increased colon length and suppressed the activation of NF-κB/IL-6/JAK1/STAT3 signaling pathway. Periasamy et al., 2020 Periasamy et al., 2020 Jujube extract (ursonic acid) A549, H1299, and HaCaT cells Ursonic acid inhibited ERK and CREB signaling pathways and reduced the transcriptional expression levels of gelatinase (MMP-2 and MMP-9) in non-small cell lung cancer cells， thereby exerting remarkable anticancer capabilities. Son and Lee, 2020 Son and Lee, 2020 Jujube fruit aqueous extract Cervical cancer cell line (OV2008), breast cancer cell line (MCF-7), and normal cell line (MCF-10A) Jujube fruit aqueous extract inhibited the proliferation of OV2008 and MCF-7 cancer cells. The potential mechanism is through increasing the expression of Bax gene and reducing the expression of Bcl2 gene. Abedini et al., 2016 Abedini et al., 2016 Jujube polysaccharides AOM/DSS-induced colitis cancer in C57BL/6 mice Jujube polysaccharides could significantly decrease Firmicutes/Bacteroidetes and ward off colon cancer by ameliorating colitis cancer-induced gut dysbiosis. Ji et al., 2020a Ji et al., 2020a Z. jujuba cv. Muzao polysaccharides (ZMP) AOM/DSS-induced colitis cancer in C57BL/6 mice ZMP increased the enrichment of Bifidobacterium , Bacteroides , and Lactobacillus , reduced the expression of proinflammatory factors, increased the concentrations of short-chain fatty acids, and prevented further progression of colon cancer. Ji et al., 2019b Ji et al., 2019b Jujube powder Mouse MC38 colon tumor model Jujube powder increased the species richness of Lachnospiraceae , decreased the abundance of Prevotellaceae , and improved both the response rate and therapeutic efficiency of anti-PD-L1. Wang LYet al., 2020 Wang LYet al., 2020 Antioxidant activity Two active polysaccharides (LZJP3 and LZJP4) extracted from jujube DPPH, hydroxyl radical, superoxide anion, and hydrogen peroxide scavenging activity LZJP3 and LZJP4 extracted from Z. jujuba cv. Linzexiaozao have strong antioxidant effects on DPPH, hydroxyl radicals, hydrogen peroxide, and superoxide radicals. Wang et al., 2018 Wang et al., 2018 Jujube fruit residues polysaccharide extract (SAZMP3) Hydroxyl free radical and DPPH free radical scavenging ability SAZMP3 could scavenge hydroxyl radicals and DPPH radicals in a concentration-dependent manner in vitro. Lin et al.,2019 Lin et al.,2019 Jujube fruit powder supplementation (30 and 150 mg/mL) Fruit flies Jujube fruit powder supplementation increased flies’ ability to resist starvation stress and ROS stress. Ghimire and Kim, 2017 Ghimire and Kim, 2017 Flavonoid extracted from Z. jujuba cv. Jinsixiaozao (ZJF) In vitro (DPPH, ABTS, FRAP); in vivo (male BALB/c mice) ZJF could increase the activity of SOD and GSH in the mouse liver. Huang et al., 2017 Huang et al., 2017 Anti-inflammatory activity Alcohol extract from jujube fruit (EEZJ) 800, 1200, and1600 mg/kg Carrageenan-induced paw oedema in female Wistar rats EEZJ eliminated the carrageenan-induced paw oedema in female Wistar rats by inhibiting inflammation. Mesaik et al., 2018 Mesaik et al., 2018 ZJF Male BALB/c mice ZJF decreased APAP-induced inflammatory mediator production (NO, TNF-α, IL-6, and IL-1β) and inhibited NF-κB signaling pathway to protect the mouse liver. Huang et al., 2017 Huang et al., 2017 Jujube fruit diet for 70 d (5% or 10%, mass fraction) AOM/DSS-treated mice Jujube fruit suppressed intestinal inflammation by blocking pathway of NF-κB/IL-6/JAK1/STAT3. Periasamy et al., 2020 Periasamy et al., 2020 Hydroalcoholic extract of Z. jujuba fruits Rat with induced ulcerative colitis Jujube extract could decrease the myeloperoxidase activity and stimulate SOD and GSH peroxidase activity. Tanideh et al., 2016 Tanideh et al., 2016 Polysaccharides from Z. jujuba cv. Pozao Cyclophosphamide-induced ICR mice for 28 d Polysaccharides from Z. jujuba cv. Pozao could increase the levels of IL-2, IL-4, IL-10, and IFN-γ in the spleens of immunosuppressed mice. Han et al., 2020 Han et al., 2020 Anti-hyperglycemic activity Dried jujube fruit and chokeberry dietary Mice fed 60% high-fat and 10% fructose diet Dried jujube and chokeberry reduced the HFFD mice body weight, attenuated blood glucose and triglyceride concentrations. Jeong and Kim, 2019 Jeong and Kim, 2019 Jujube fruit active substances (betulinic acid, oleanolic acid, and ursonic acid) Rat L6 myotube These polycyclic triterpenoids induced glucose uptake in a glucose transporter-4-dependent manner, and finally promoted glucose uptake in rat L6 myotubes. Kawabata et al., 2017 Kawabata et al., 2017 Jujube(cv. Shaanbeitanzao) polysaccharide (ZSP) 0, 200, and 400 mg/kg BW for four weeks Mice fed high-fructose ZSP significantly improved the HDL-C and HOMA-IR levels, reduced insulin resistance, and balanced blood lipid homeostasis in high-fructose diet mice. Zhao Yet al., 2014 Zhao Yet al., 2014 Jujube water extract from Z. jujuba cv. Muzao (PZMP1) The normal human liver cell line L02 PZMP1 reduced the activity of ALT and inhibited the oleic acid-induced triglyceride and lipid accumulation in a concentration-dependent manner in L02 cells. Ji et al., 2018b Ji et al., 2018b Immunoregulatory activity Z. jujube cv. Jinchangzao ethanol extract (JJC1 and JJC2) Kunming male mice JJC1 and JJC2 stimulated the NO production and phagocytic activity of RAW264.7 cells and promoted the proliferation of spleen lymphocytes. Cai et al., 2017 Cai et al., 2017 Z. jujuba cv. Jinchangzao polysaccharides (JCS-1 and JCS-2) RAW264.7 cells There was a positive dose-dependent relationship between JCS-1, JCS-2 and phagocytic indices. JCS-1 and JCS-2 showed immunological activity in a dose-dependent manner. Sulfated derivatives exhibited stronger immunological activity than native polysaccharides. Cai et al., 2018 Cai et al., 2018 Z. jujuba cv. Huizao polysaccharides (HP1 and HP2) Kunming male mice HP1 and HP2 improved the functions of spleen and thymus, promoted the formation of serum hemolysin, increased the phagocytosis of macrophages, and alleviated the edema of foot pads of mice. Zou et al., 2018 Zou et al., 2018 Neuroprotective activity Jujube aqueous extracts PC12 cells Aqueous extracts promoted the expression of neuronal cell-specific cytoskeleton proteins in PC12 cells. Chen et al., 2015 Chen et al., 2015 Jujube fruit in traditional Chinese medicine prescriptions PC12 cells Jujube-containing herbal decoctions stimulated the growth of neurite and protein expression of neurofilaments afterco-incubation with PC12 cells. Lam et al., 2016 Lam et al., 2016 Antiviral activity Jujube active substance (betulinic acid) Influenza A/PR/8 virus infected A549 cell and mice Betulinic acid (50 μmol/L) showed satisfactory antiviral activity without significant cytotoxicity to influenza A/PR/8 virus-infected cell line A549. In vivo experiments have shown that betulinic acid can relieve the symptoms of lung necrosis and edema caused by influenza A/PR/8 virus in mice. Hong et al., 2015 Hong et al., 2015 Jujube flavonoids (compound 1 and compound 2) Anti-tobacco mosaic virus (TMV) activity was tested using the half-leaf method These two new compounds possessed significant activity against tobacco mosaic virus replication, with inhibition rates of 92.8% and 88.6%, respectively. Li et al., 2013 Li et al., 2013 Jujube fruit in Yakammaoto (a prescription of traditional Chinese medicine) HEp-2, A549, and HK-2 cell lines Inhibited coxsackievirus B4 (CVB4)-induced cellular damage by preventing viral attachment, internalization, and replication. Yen et al., 2014 Yen et al., 2014 4.1 Anticancer activity 2 Many experimental studies have shown that jujube fruit bioactive substances can slow down the occurrence and development of certain cancers by inducing cellular apoptosis, inhibiting the related signaling pathways, and regulating gut microbes. Researchers found that consumption of jujube fruit by dextran sodium sulphate (DSS)/azoxymethane (AOM)-induced colorectal cancer model mice for 62 consecutive days could decrease colon aberrant crypt foci and delay the process of colon carcinogenesis ( Periasamy et al., 2015 Periasamy et al., 2015 ). A recent study found that jujube fruit ultimately reduced the number of colon tumors in DSS/AOM-induced mice by inhibiting the nuclear factor-κB (NF-κB)/interleukin-6 (IL-6)/Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3) signaling pathway ( Periasamy et al., 2020 Periasamy et al., 2020 ). Likewise, Son and Lee (2020) Son and Lee (2020) found that ursonic acid (a pentacyclic triterpenoid compound extracted from jujube fruit) exhibited anticancer activity by inhibiting the extracellular signal-regulated kinase (ERK) and cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) signaling pathways and reducing the transcriptional expression levels of gelatinase (MMP-2 and MMP-9) in non-small cell lung cancer cells. Pro-apoptosis is a classical anticancer mechanism. Jujube aqueous extract from semi-dried fruits was reported to inhibit the proliferation of OV2008 and MCF-7 cancer cells by increasing the expression of B-cell lymphoma 2 (Bcl2)-assosiated X ( Bax ) gene and reducing the expression of the Bcl2 gene ( Abedini et al., 2016 Abedini et al., 2016 ). In recent years, inhibition of tumor development by regulating intestinal microorganisms using jujube extract has attracted much attention. Ji et al. (2020a) Ji et al. (2020a) found that an active polysaccharide purified from jujube fruit significantly reduced the abundance of Firmicutes/Bacteroidetes, and was effective in preventing and treating DSS/AOM-induced colitis cancer in a mouse model by reshaping the intestinal flora. Subsequently, the team also reported that cv. Muzao polysaccharides could significantly increase the Bifidobacterium , Bacteroides , and Lactobacillus in the intestinal tract of mice, reduce the expression of proinflammatory parameters, increase the concentration of short-chain fatty acids, and prevent further progression of colon cancer ( Ji et al., 2019b Ji et al., 2019b ). Moreover, Wang LY et al. (2020) Wang LY et al. (2020) found that jujube fruit powder could increase the species abundance of Lachnospiraceae and decrease the abundance of Prevotellaceae , improving both the response rate and treatment effect of anti-PD-L1 in an MC38 colon tumor model mouse. 4.2 Antioxidant activity 2 Increasing evidence shows that many diseases are closely related to the accumulation of harmful free oxygen radicals ( Halliwell, 2012 Halliwell, 2012 ; Poprac et al., 2017 Poprac et al., 2017 ). Reactive oxygen species (ROS), a general term for oxygen ions, free radicals, and peroxides of both inorganic and organic componds, are involved in various biological pathways such as cell proliferation, apoptosis, and cell signal transduction ( Brieger et al., 2012 Brieger et al., 2012 ; Diebold and Chandel, 2016 Diebold and Chandel, 2016 ; Forrester et al., 2018 Forrester et al., 2018 ). Jujube fruit, as a Chinese herb, has a long history of antioxidant applications. In recent years, studies have found that the two homologous active polysaccharides (LZJP3 and LZJP4) extracted from Z. jujuba cv. Linzexiaozao have strong antioxidant effects, as evaluated by DPPH radicals, hydroxyl radicals, hydrogen peroxide, and superoxide radicals ( Wang et al., 2018 Wang et al., 2018 ). Lin et al. (2019) Lin et al. (2019) reported that an acidic polysaccharide (SAZMP3) from Z. jujuba cv. Muzao fruit could scavenge hydroxyl and DPPH radicals in a concentration-dependent manner in vitro. They also indicated that SAZMP3 showed a strong ferric ion-reducing capacity. In in vivo antioxidant studies, it was reported that fruit flies fed with 150 mg/mL jujube fruit supplement could effectively reduce ROS stress and increase their average survival time ( Ghimire and Kim, 2017 Ghimire and Kim, 2017 ). Huang et al. (2017) Huang et al. (2017) pointed out that flavonoid extracted from Z. jujuba cv. Jinsixiaozao (ZJF) is a natural antioxidant that can increase the activity of superoxide dismutase (SOD) and glutathione (GSH) in the mouse liver. 4.3 Anti-inflammatory activity 2 In general, inflammation is the body's automatic defense response to pathogens and tissue injury ( Kuprash and Nedospasov, 2016 Kuprash and Nedospasov, 2016 ). Chronic inflammation may result in diabetes, stroke, cardiovascular disease, and even cancer ( Mantovani et al., 2008 Mantovani et al., 2008 ; Medzhitov, 2008 Medzhitov, 2008 , 2010 2010 ). Therefore, anti-inflammatory therapeutics are necessary for healthy living. Ulcerative colitis (UC) is one kind of inflammatory bowel diseases (IBDs), which affects the normal functions of the descending colon and rectum. Tanideh et al. (2016) Tanideh et al. (2016) indicated that a hydroalcoholic extract of Z. jujube fruit has a healing effect in damaged colonic tissue and reduces GSH peroxidase and IL-1 levels in 3% acetic acid-induced UC rats. Mesaik et al. (2018) Mesaik et al. (2018) reported that an alcohol extract from jujube fruit (EEZJ) eliminated carrageenan-induced paw oedema in female Wistar rats by inhibiting inflammation. Huang et al. (2017) Huang et al. (2017) studied the anti-inflammatory properties ZJF and found that ZJF decreased acetaminophen (APAP)-induced inflammatory mediator production (NO, tumor necrosis factor-‍α (TNF-‍α), IL‍-‍6, and IL-1β) and inhibited the NF-‍κB signaling pathway to protect the mouse liver. Periasamy et al. (2020) Periasamy et al. (2020) demonstrated that Z. jujuba fruit suppressed intestinal inflammation by blocking the NF-‍κB/IL-6/JAK1/STAT3 pathway in AOM/DSS-induced colorectal mice. Han et al. (2020) Han et al. (2020) found that a dietary supplement of polysaccharides from Z. jujuba cv. Pozao could increase the levels of IL-2, IL-4, IL-10, and interferon-‍γ (IFN-‍γ) in the spleen of immunosuppressed mice, which effectively improved the inflammatory response to cyclophosphamide-induced hypoimmunity. 4.4 Anti-hyperglycemic and anti-hyperlipidemic properties 2 The incidence of diabetes is linked to abnormal glucose metabolism and dyslipidemia ( Matschinsky, 2005 Matschinsky, 2005 ; Wu and Parhofer, 2014 Wu and Parhofer, 2014 ). In many in vivo experiments, the effect of jujube fruit on the regulation of glucose and lipids has been proved. Jeong and Kim (2019) Jeong and Kim (2019) reported the effects of dried jujube fruit and chokeberry dietary intervention in high-fat-fructose diet (HFFD) mice for 11 weeks. The results showed that the diet significantly reduced the mouse body weight, and attenuated blood glucose and triglyceride concentrations. The consumption of chokeberry and dried jujube activated the insulin receptor substrate-1 (IRS-1)/phosphatidylinositol-3-OH kinase (PI3K)/protein kinase B (Akt) signaling pathway and increased insulin sensitivity in the HFFD-induced obese mice. Kawabata et al. (2017) Kawabata et al. (2017) found that jujube fruit contains polycyclic triterpenoids (betulinic acid, oleanolic acid, betulinic acid, and ursonic acid). These compounds induced glucose uptake in a glucose transporter-4-dependent manner, and promoted glucose uptake in rat L6 myotubes. Zhao Y et al. (2014) Zhao Y et al. (2014) fed mice with 20% high-fructose water and jujube (cv. Shaanbeitanzao) polysaccharide (ZSP) for four weeks. The results showed that the serum glucose and insulin concentrations of the mice were lowered by 6.5% and 12.5%, respectively, in the HF+LZSP (20% high-fructose water+200 mg/kg body weight (BW) ZSP) group, and by 10.0% and 38.4%, respectively, in the HF+HZSP (20% high-fructose water+400 mg/kg BW ZSP) group, compared to the HF group. The homeostasis model assessment-insulin resistance (HOMA-IR) score of the mice in the HF+LZSP and HF+HZSP groups showed a decrease of about 25.0% and 31.3%, respectively, compared to the HF group. In addition, in vitro studies showed that PZMP1 (a kind of neutral polysaccharide isolated from Z. jujuba cv. Muzao) reduced the activity of alanine aminotransferase (ALT) and inhibited oleic acid-induced triglyceride and lipid accumulation in a concentration-dependent manner in L02 cells ( Ji et al., 2018b Ji et al., 2018b ). 4.5 Immunoregulatory activity 2 In general, functional foods can regulate the immune system by enhancing or suppressing the immune response, providing host defenses against infection, and suppressing allergies and inflammation ( Ashaolu, 2020 Ashaolu, 2020 ). Cai et al. (2017) Cai et al. (2017) studied the immunological activity of two biological water-soluble lignins (JJC1 and JJC2) from Z. jujuba cv. Jinchangzao. They showed that both JJC1 and JJC2 could stimulate NO production and phagocytic activity of RAW264.7 cells, and promote the proliferation of spleen lymphocytes. Moreover, they found that JCS-1 and JCS-2, two active polysaccharides isolated from cv. Jinchangzao, had the ability to regulate the immune function. The immunomodulatory activity of polysaccharides was further enhanced after sulfated modification ( Cai et al., 2018 Cai et al., 2018 ). Zou et al. (2018) Zou et al. (2018) recently demonstrated that two acidic polysaccharides (HP1 and HP2) purified from Z. jujuba cv. Huizao could significantly improve the function of the spleen and thymus, promote the formation of serum hemolysin, increase the phagocytosis of macrophages, and alleviate edema of the foot pads of mice. Furthermore, polysaccharide component HP2 had a more significant and stable effect on immune regulation than HP1. 4.6 Neuroprotection 2 Chen et al. (2015) Chen et al. (2015) compared the neuroprotective effects of ripe and unripe jujube fruit cultivated in Cangzhou, Hebei Province, China. They revealed that aqueous extracts from the two developmental stages of jujube fruit promoted the expression of the neuronal cell-specific cytoskeleton protein, neurofilament 68, in PC12 cells. The neuroprotective effect of the mature jujube fruit extract was the most significant. ( Chen et al., 2015 Chen et al., 2015 ). Guizhi Tang (GZT), Neibu Dangguijianzhong Tang (NDT), and Zao Tang (ZOT) are three TCM prescriptions containing jujube fruit which have been found to stimulate the growth of neurite and the expression of neurofilament proteins after co-incubation with PC12 cells. Most importantly, jujube as a synergistic agent of these three kinds of decoctions, can significantly increase neuroprotective activity and reduce drug toxicity ( Lam et al., 2016 Lam et al., 2016 ). 4.7 Antiviral activity 2 Effectively dealing with the damage caused by infectious viruses to animals and plants is a major challenge for the world's public health systems. In developing research work, the effective antiviral effects and active ingredients of jujube have attracted great attention in the field of medicine. Betulinic acid, a pentacyclic triterpenoid, was first extracted from jujube fruit. Hong et al. (2015) Hong et al. (2015) found that betulinic acid had a special inhibitory activity against influenza A/PR/8 virus. The study indicated that 50 μmol/L of betulinic acid showed satisfactory antiviral activity without significant cytotoxicity to influenza A/PR/8 virus-infected cell line A549. In vivo experiments showed that betulinic acid can relieve the symptoms of lung necrosis and edema caused by influenza A/PR/8 virus in mice. Jujube is a traditional herbal medicine and is frequently used in many traditional Chinese antiviral formulas. For example, Yakammaoto is a prescription of TCM containing nine components, including jujube fruit. In cellular experiments, Yakammaoto was proven to inhibit coxsackievirus B4 (CVB4)‍-‍induced cellular damage by preventing viral attachment, internalization, and replication ( Yen et al., 2014 Yen et al., 2014 ). Furthermore, Kang et al. (2015) Kang et al. (2015) extracted eight cyclopeptide alkaloids (1‍–‍8) from dried roots of Z. jujuba using an acid-base method. Their data suggested that compounds 2 (jubanines-G), 3 (jubanines-H), and 6 (nummularine-B) had potential inhibitory effects on porcine epidemic diarrhea virus (PEDV). It was also the first report of antiviral activity from plant-derived cyclopeptide alkaloids, especially in Z. jujube . Li et al. (2013) Li et al. (2013) also reported two new flavonoids, 8-formyl-3',4'-dihydroxy-6,7-dimethoxyflavone (compound 1) and 8-formyl-4'-hydroxy-3',6,7-trimethoxyflavone (compound 2), isolated from the fruits of jujube. Their results suggested that these two new compounds had significant activity against tobacco mosaic virus replication, with inhibition rates of 92.8% and 88.6%, respectively. 5 Future perspectives and conclusions 1 As a dietary supplement, jujube fruit is now considered to be a cheap, readily applicable, acceptable, and available product for the prevention and treatment of a variety of diseases ( Rodríguez Villanueva and Rodríguez Villanueva, 2017 Rodríguez Villanueva and Rodríguez Villanueva, 2017 ). When nutrients and non-nutritive phytochemicals in jujube fruit, such as polysaccharides, polyphenols, amino acids, nucleotides, fatty acids, DF, and other key components, are absorbed by human body, they coordinate and interact with each other to fulfil physiological functions such as anti-oxidative, anti-inflammatory, liver protective, antiviral, anticancer, neuroprotective, and sedative functions. However, caution is essential when attempting to extrapolate relationships between nutrients and health functions in jujube. This is because the cultivar, stage of maturation, and storage and processing conditions of the fruit can affect its nutritional value and eventually lead to an increase or loss of some active functions ( Ding et al., 2017 Ding et al., 2017 ; Pu et al., 2018 Pu et al., 2018 ; Shi et al., 2018 Shi et al., 2018 ). Overall, jujube fruit contains a large number of functional substances with a variety of physiological effects. Apart from providing nutrition for the body, there have been few clinical studies on the significant effects of jujube, which limits the application of its active components in clinical medicine. In many experiments, the biological effects of jujube nutritional components in cell models are achievable only at supraphysiological intracellular concentrations, which are usually higher than those available in the human body. Moreover, the bioavailability of most nutrients could be reduced after being digested and absorbed by the human intestinal tract. Therefore, in-depth analysis of the metabolic pathways and pharmacokinetics of the active components of jujube is crucial for future clinical applications. Currently, although many TCM prescriptions containing jujube have been used in the prevention and treatment of diseases, more studies are needed to clarify the correspondence between the content of active components and biological functions of jujube and the molecular mechanisms. These studies also will provide a more safe, scientific, and rigorous theoretical basis for applying the jujube as a functional food. References Abdoul-Azize S , 2016 . Potential benefits of jujube ( Zizyphus lotus L.) bioactive compounds for nutrition and health . J Nutr Metab , 2016 : 2867470 . https://doi.org/10.1155/2016/2867470 https://doi.org/10.1155/2016/2867470 Potential benefits of jujube ( Zizyphus lotus L.) bioactive compounds for nutrition and health Abedini MR , Erfanian N , Nazem H , et al. , 2016 . Anti-proliferative and apoptotic effects of Ziziphus jujube on cervical and breast cancer cells . Avicenna J Phytomed , 6 ( 2 ): 142 - 148 . Anti-proliferative and apoptotic effects of Ziziphus jujube on cervical and breast cancer cells Al-Dujaili EA , 2015 . Natural polyphenols: potential for disease prevention . EC Nutr , 2 ( 2 ): 337 - 345 . Natural polyphenols: potential for disease prevention Ashaolu TJ , 2020 . Immune boosting functional foods and their mechanisms: a critical evaluation of probiotics and prebiotics . Biomed Pharmacother , 130 : 110625 . https://doi.org/10.1016/j.biopha.2020.110625 https://doi.org/10.1016/j.biopha.2020.110625 Immune boosting functional foods and their mechanisms: a critical evaluation of probiotics and prebiotics Ashaolu TJ , Ashaolu JO , 2020 . Perspectives on the trends, challenges and benefits of green, smart and organic (GSO) foods . Int J Gastron Food Sci , 22 : 100273 . https://doi.org/10.1016/j.ijgfs.2020.100273 https://doi.org/10.1016/j.ijgfs.2020.100273 Perspectives on the trends, challenges and benefits of green, smart and organic (GSO) foods Ashaolu TJ , Reale A , 2020 . A holistic review on Euro-Asian lactic acid bacteria fermented cereals and vegetables . Microorganisms , 8 ( 8 ): 1176 . https://doi.org/10.3390/microorganisms8081176 https://doi.org/10.3390/microorganisms8081176 A holistic review on Euro-Asian lactic acid bacteria fermented cereals and vegetables Bao T , Hao X , Shishir MRI , et al. , 2021 . Cold plasma: an emerging pretreatment technology for the drying of jujube slices . Food Chem , 337 : 127783 . https://doi.org/10.1016/j.foodchem.2020.127783 https://doi.org/10.1016/j.foodchem.2020.127783 Cold plasma: an emerging pretreatment technology for the drying of jujube slices Brieger K , Schiavone S , Miller FJ , et al. , 2012 . Reactive oxygen species: from health to disease . Swiss Med Wkly , 142 : w13659 . https://doi.org/10.4414/smw.2012.13659 https://doi.org/10.4414/smw.2012.13659 Reactive oxygen species: from health to disease Cai M , 2019 . Fruit-based functional food . In: Galanakis CM (Ed.), The Role of Alternative and Innovative Food Ingredients and Products in Consumer Wellness . Academic Press , New York , p. 35 - 72 . https://doi.org/10.1016/B978-0-12-816453-2.00002-4 https://doi.org/10.1016/B978-0-12-816453-2.00002-4 Fruit-based functional food Cai YQ , Zhou XP , Han AZ , et al. , 2017 . In vitro immunological and anti-complementary activities of two water-soluble lignins from Zizyphus jujube cv . Jinchangzao . Int J Biol Macromol , 105 ( Pt 1 ): 204 - 212 . https://doi.org/10.1016/j.ijbiomac.2017.07.026 https://doi.org/10.1016/j.ijbiomac.2017.07.026 In vitro immunological and anti-complementary activities of two water-soluble lignins from Zizyphus jujube cv. Jinchangzao Cai YQ , Chen P , Wu CY , et al. , 2018 . Sulfated modification and biological activities of polysaccharides derived from Zizyphus jujuba cv. Jinchangzao . Int J Biol Macromol , 120 ( Pt A ): 1149 - 1155 . https://doi.org/10.1016/j.ijbiomac.2018.08.141 https://doi.org/10.1016/j.ijbiomac.2018.08.141 Sulfated modification and biological activities of polysaccharides derived from Zizyphus jujuba cv. Jinchangzao Chen JP , Maiwulanjiang M , Lam KYC , et al. , 2014 . A standardized extract of the fruit of Ziziphus jujuba (jujube) induces neuronal differentiation of cultured PC12 cells: a signaling mediated by protein kinase A . J Agric Food Chem , 62 ( 8 ): 1890 - 1897 . https://doi.org/10.1021/jf405093f https://doi.org/10.1021/jf405093f 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 JP , Chan PH , Lam CTW , et al. , 2015 . Fruit of Ziziphus jujuba (jujube) at two stages of maturity: distinction by metabolic profiling and biological assessment . J Agric Food Chem , 63 ( 2 ): 739 - 744 . https://doi.org/10.1021/jf5041564 https://doi.org/10.1021/jf5041564 Fruit of Ziziphus jujuba (jujube) at two stages of maturity: distinction by metabolic profiling and biological assessment Chen JP , Liu XY , Li ZG , et al. , 2017 . A review of dietary Ziziphus jujuba fruit (jujube): developing health food supplements for brain protection . Evid Based Complement Alternat Med , 2017 : 3019568 . https://doi.org/10.1155/2017/3019568 https://doi.org/10.1155/2017/3019568 A review of dietary Ziziphus jujuba fruit (jujube): developing health food supplements for brain protection Chen W , Xu Y , Zhang LX , et al. , 2016 . Blackberry subjected to in vitro gastrointestinal digestion affords protection against Ethyl Carbamate-induced cytotoxicity . Food Chem , 212 : 620 - 627 . https://doi.org/10.1016/j.foodchem.2016.06.031 https://doi.org/10.1016/j.foodchem.2016.06.031 Blackberry subjected to in vitro gastrointestinal digestion affords protection against Ethyl Carbamate-induced cytotoxicity Choi SH , Ahn JB , Kozukue N , et al. , 2011 . Distribution of free amino acids, flavonoids, total phenolics, and antioxidative activities of jujube ( Ziziphus jujuba ) fruits and seeds harvested from plants grown in Korea . J Agric Food Chem , 59 ( 12 ): 6594 - 6604 . https://doi.org/10.1021/jf200371r https://doi.org/10.1021/jf200371r Distribution of free amino acids, flavonoids, total phenolics, and antioxidative activities of jujube (Ziziphus jujuba) fruits and seeds harvested from plants grown in Korea Choi SH , Ahn JB , Kim HJ , et al. , 2012 . Changes in free amino acid, protein, and flavonoid content in jujube ( Ziziphus jujube ) fruit during eight stages of growth and antioxidative and cancer cell inhibitory effects by extracts . J Agric Food Chem , 60 ( 41 ): 10245 - 10255 . https://doi.org/10.1021/jf302848u https://doi.org/10.1021/jf302848u Changes in free amino acid, protein, and flavonoid content in jujube (Ziziphus jujube) fruit during eight stages of growth and antioxidative and cancer cell inhibitory effects by extracts Cushnie TPT , Cushnie B , Lamb AJ , 2014 . Alkaloids: an overview of their antibacterial, antibiotic-enhancing and antivirulence activities . Int J Antimicrob Agents , 44 ( 5 ): 377 - 386 . https://doi.org/10.1016/j.ijantimicag.2014.06.001 https://doi.org/10.1016/j.ijantimicag.2014.06.001 Alkaloids: an overview of their antibacterial, antibiotic-enhancing and antivirulence activities Das A , Raychaudhuri U , Chakraborty R , 2012 . Cereal based functional food of Indian subcontinent: a review . J Food Sci Technol , 49 ( 6 ): 665 - 672 . https://doi.org/10.1007/s13197-011-0474-1 https://doi.org/10.1007/s13197-011-0474-1 Cereal based functional food of Indian subcontinent: a review Dash SK , Chattopadhyay S , Tripathy S , et al. , 2015 . Self-assembled betulinic acid augments immunomodulatory activity associates with IgG response . Biomed Pharmacother , 75 : 205 - 217 . https://doi.org/10.1016/j.biopha.2015.07.033 https://doi.org/10.1016/j.biopha.2015.07.033 Self-assembled betulinic acid augments immunomodulatory activity associates with IgG response Diebold L , Chandel NS , 2016 . Mitochondrial ROS regulation of proliferating cells . Free Radic Biol Med , 100 : 86 - 93 . https://doi.org/10.1016/j.freeradbiomed.2016.04.198 https://doi.org/10.1016/j.freeradbiomed.2016.04.198 Mitochondrial ROS regulation of proliferating cells Ding SH , Wang RR , Shan Y , et al. , 2017 . Changes in pectin characteristics during the ripening of jujube fruit . J Sci Food Agric , 97 ( 12 ): 4151 - 4159 . https://doi.org/10.1002/jsfa.8285 https://doi.org/10.1002/jsfa.8285 Changes in pectin characteristics during the ripening of jujube fruit Ding X , Zhu FS , Gao SG , 2012 . Purification, antitumour and immunomodulatory activity of water-extractable and alkali-extractable polysaccharides from Solanum nigrum L . Food Chem , 131 ( 2 ): 677 - 684 . https://doi.org/10.1016/j.foodchem.2011.09.060 https://doi.org/10.1016/j.foodchem.2011.09.060 Purification, antitumour and immunomodulatory activity of water-extractable and alkali-extractable polysaccharides from Solanum nigrum L Forrester SJ , Kikuchi DS , Hernandes MS , et al. , 2018 . Reactive oxygen species in metabolic and inflammatory signaling . Circ Res , 122 ( 6 ): 877 - 902 . https://doi.org/10.1161/CIRCRESAHA.117.311401 https://doi.org/10.1161/CIRCRESAHA.117.311401 Reactive oxygen species in metabolic and inflammatory signaling Gao QH , Wu CS , Yu JG , et al. , 2012 . Textural characteristic, antioxidant activity, sugar, organic acid, and phenolic profiles of 10 promising jujube ( Ziziphus jujuba Mill.) selections . J Food Sci , 77 ( 11 ): C1218 - 1225 . https://doi.org/10.1111/j.1750-3841.2012.02946.x https://doi.org/10.1111/j.1750-3841.2012.02946.x Textural characteristic, antioxidant activity, sugar, organic acid, and phenolic profiles of 10 promising jujube (Ziziphus jujuba Mill.) selections Gao QH , Wu CS , Wang M , 2013 . The jujube ( Ziziphus jujuba Mill.) fruit: a review of current knowledge of fruit composition and health benefits . J Agric Food Chem , 61 ( 14 ): 3351 - 3363 . https://doi.org/10.1021/jf4007032 https://doi.org/10.1021/jf4007032 The jujube (Ziziphus jujuba Mill.) fruit: a review of current knowledge of fruit composition and health benefits Ghante MH , Jamkhande PG , 2019 . Role of pentacyclic triterpenoids in chemoprevention and anticancer treatment: an overview on targets and underling mechanisms . J Pharmacopuncture , 22 ( 2 ): 55 - 67 . https://doi.org/10.3831/KPI.201.22.007 https://doi.org/10.3831/KPI.201.22.007 Role of pentacyclic triterpenoids in chemoprevention and anticancer treatment: an overview on targets and underling mechanisms Ghimire S , Kim MS , 2017 . Jujube ( Ziziphus Jujuba Mill.) fruit feeding extends lifespan and increases tolerance to environmental stresses by regulating aging-associated gene expression in Drosophila . Biogerontology , 18 ( 2 ): 263 - 273 . https://doi.org/10.1007/s10522-017-9686-8 https://doi.org/10.1007/s10522-017-9686-8 Jujube (Ziziphus Jujuba Mill.) fruit feeding extends lifespan and increases tolerance to environmental stresses by regulating aging-associated gene expression in Drosophila Gowd V , Bao T , Chen W , 2019 . Antioxidant potential and phenolic profile of blackberry anthocyanin extract followed by human gut microbiota fermentation . Food Res Int , 120 : 523 - 533 . https://doi.org/doi.org/10.1016/j.foodres.2018.11.001 https://doi.org/doi.org/10.1016/j.foodres.2018.11.001 Antioxidant potential and phenolic profile of blackberry anthocyanin extract followed by human gut microbiota fermentation Guil-Guerrero JL , Díaz Delgado A , Matallana González MC , et al. , 2004 . Fatty acids and carotenes in some ber ( Ziziphus jujuba Mill) varieties . Plant Foods Hum Nutr , 59 ( 1 ): 23 - 27 . https://doi.org/10.1007/s11130-004-0017-2 https://doi.org/10.1007/s11130-004-0017-2 Fatty acids and carotenes in some ber (Ziziphus jujuba Mill) varieties Guo S , Duan JA , Qian DW , et al. , 2015a . Content variations of triterpenic acid, nucleoside, nucleobase, and sugar in jujube ( Ziziphus jujuba ) fruit during ripening . Food Chem , 167 : 468 - 474 . https://doi.org/10.1016/j.foodchem.2014.07.013 https://doi.org/10.1016/j.foodchem.2014.07.013 Content variations of triterpenic acid, nucleoside, nucleobase, and sugar in jujube (Ziziphus jujuba) fruit during ripening Guo S , Duan JA , Zhang Y , et al. , 2015b . Contents changes of triterpenic acids, nucleosides, nucleobases, and saccharides in jujube ( Ziziphus jujuba ) fruit during the drying and steaming process . Molecules , 20 ( 12 ): 22329 - 22340 . https://doi.org/10.3390/molecules201219852 https://doi.org/10.3390/molecules201219852 Contents changes of triterpenic acids, nucleosides, nucleobases, and saccharides in jujube (Ziziphus jujuba) fruit during the drying and steaming process Guo XX , Mu JL , Wang J , et al. , 2014 . Preparation of soluble dietary fiber of jujube fruit residues with cellulase . J Agric Sci Technol , 16 ( 5 ): 154 - 159 (in Chinese) . https://doi.org/10.13304/j.nykjdb.2014.211 https://doi.org/10.13304/j.nykjdb.2014.211 Preparation of soluble dietary fiber of jujube fruit residues with cellulase Halliwell B , 2012 . Free radicals and antioxidants: updating a personal view . Nutr Rev , 70 ( 5 ): 257 - 265 . https://doi.org/10.1111/j.1753-4887.2012.00476.x https://doi.org/10.1111/j.1753-4887.2012.00476.x Free radicals and antioxidants: updating a personal view Han X , Bai BY , Zhou Q , et al. , 2020 . 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 . Food Funct , 11 ( 7 ): 5992 - 6006 . https://doi.org/10.1039/D0FO00008F https://doi.org/10.1039/D0FO00008F 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 He SR , Zhao CB , Zhang JX , et al. , 2020 . Botanical and traditional uses and phytochemical, pharmacological, pharmacokinetic, and toxicological characteristics of Ziziphi Spinosae Semen : a review . Evid Based Complement Alternat Med , 2020 : 5861821 . https://doi.org/10.1155/2020/5861821 https://doi.org/10.1155/2020/5861821 Botanical and traditional uses and phytochemical, pharmacological, pharmacokinetic, and toxicological characteristics of Ziziphi Spinosae Semen: a review He YY , Li W , Zhang XY , et al. , 2020 . Physicochemical, functional, and microstructural properties of modified insoluble dietary fiber extracted from rose pomace . J Food Sci Technol , 57 ( 4 ): 1421 - 1429 . https://doi.org/10.1007/s13197-019-04177-8 https://doi.org/10.1007/s13197-019-04177-8 Physicochemical, functional, and microstructural properties of modified insoluble dietary fiber extracted from rose pomace Hernández F , Noguera-Artiaga L , Burló F , et al. , 2016 . Physico-chemical, nutritional, and volatile composition and sensory profile of Spanish jujube ( Ziziphus jujuba Mill.) fruits . J Sci Food Agric , 96 ( 8 ): 2682 - 2691 . https://doi.org/10.1002/jsfa.7386 https://doi.org/10.1002/jsfa.7386 Physico-chemical, nutritional, and volatile composition and sensory profile of Spanish jujube (Ziziphus jujuba Mill.) fruits Hong EH , Song JH , Kang KB , et al. , 2015 . Anti-influenza activity of betulinic acid from Zizyphus jujuba on influenza A/PR/8 virus . Biomol Ther (Seoul) , 23 ( 4 ): 345 - 349 . https://doi.org/10.4062/biomolther.2015.019 https://doi.org/10.4062/biomolther.2015.019 Anti-influenza activity of betulinic acid from Zizyphus jujuba on influenza A/PR/8 virus Hou YQ , He WL , Hu SD , et al. , 2019 . Composition of polyamines and amino acids in plant-source foods for human consumption . Amino Acids , 51 ( 8 ): 1153 - 1165 . https://doi.org/10.1007/s00726-019-02751-0 https://doi.org/10.1007/s00726-019-02751-0 Composition of polyamines and amino acids in plant-source foods for human consumption Huang WZ , Wang YJ , Jiang XY , et al. , 2017 . Protective effect of flavonoids from Ziziphus jujuba cv . Jinsixiaozao against acetaminophen-induced liver injury by inhibiting oxidative stress and inflammation in mice . Molecules , 22 ( 10 ): 1781 . https://doi.org/10.3390/molecules22101781 https://doi.org/10.3390/molecules22101781 Protective effect of flavonoids from Ziziphus jujuba cv. Jinsixiaozao against acetaminophen-induced liver injury by inhibiting oxidative stress and inflammation in mice Jeong O , Kim HS , 2019 . Dietary chokeberry and dried jujube fruit attenuates high-fat and high-fructose diet-induced dyslipidemia and insulin resistance via activation of the IRS-1/PI3K/Akt pathway in C57BL/6 J mice . Nutr Metab , 16 : 38 . https://doi.org/10.1186/s12986-019-0364-5 https://doi.org/10.1186/s12986-019-0364-5 Dietary chokeberry and dried jujube fruit attenuates high-fat and high-fructose diet-induced dyslipidemia and insulin resistance via activation of the IRS-1/PI3K/Akt pathway in C57BL/6 J mice Jéquier E , 1994 . Carbohydrates as a source of energy . Am J Clin Nutr , 59 ( 3 ): 682S - 685S . https://doi.org/10.1093/ajcn/59.3.682S https://doi.org/10.1093/ajcn/59.3.682S Carbohydrates as a source of energy Ji XL , Peng Q , Yuan YP , et al. , 2017 . Isolation, structures and bioactivities of the polysaccharides from jujube fruit ( Ziziphus jujuba Mill.): a review . Food Chem , 227 : 349 - 357 . https://doi.org/10.1016/j.foodchem.2017.01.074 https://doi.org/10.1016/j.foodchem.2017.01.074 Isolation, structures and bioactivities of the polysaccharides from jujube fruit (Ziziphus jujuba Mill.): a review Ji XL , Peng Q , Yuan YP , et al. , 2018a . Extraction and physicochemical properties of polysaccharides from Ziziphus Jujuba cv . Muzao by ultrasound-assisted aqueous two-phase extraction. Int J Biol Macromol , 108 : 541 - 549 . https://doi.org/10.1016/j.ijbiomac.2017.12.042 https://doi.org/10.1016/j.ijbiomac.2017.12.042 Extraction and physicochemical properties of polysaccharides from Ziziphus Jujuba cv Ji XL , Liu F , Peng Q , et al. , 2018b . Purification, structural characterization, and hypolipidemic effects of a neutral polysaccharide from Ziziphus Jujuba cv . Muzao. Food Chem , 245 : 1124 - 1130 . https://doi.org/10.1016/j.foodchem.2017.11.058 https://doi.org/10.1016/j.foodchem.2017.11.058 Purification, structural characterization, and hypolipidemic effects of a neutral polysaccharide from Ziziphus Jujuba cv Ji XL , Zhang F , Zhang R , et al. , 2019a . An acidic polysaccharide from Ziziphus Jujuba cv . Muzao: purification and structural characterization . Food Chem , 274 : 494 - 499 . https://doi.org/10.1016/j.foodchem.2018.09.037 https://doi.org/10.1016/j.foodchem.2018.09.037 An acidic polysaccharide from Ziziphus Jujuba cv. Muzao: purification and structural characterization Ji XL , Hou CY , Zhang XL , et al. , 2019b . Microbiome-metabolomic analysis of the impact of Zizyphus jujuba cv . Muzao polysaccharides consumption on colorectal cancer mice fecal microbiota and metabolites . Int J Biol Macromol , 131 : 1067 - 1076 . https://doi.org/10.1016/j.ijbiomac.2019.03.175 https://doi.org/10.1016/j.ijbiomac.2019.03.175 Microbiome-metabolomic analysis of the impact of Zizyphus jujuba cv. Muzao polysaccharides consumption on colorectal cancer mice fecal microbiota and metabolites Ji XL , Hou CY , Gao YG , et al. , 2020a . Metagenomic analysis of gut microbiota modulatory effects of jujube ( Ziziphus jujuba Mill.) polysaccharides in a colorectal cancer mouse model . Food Funct , 11 ( 1 ): 163 - 173 . https://doi.org/10.1039/C9FO02171J https://doi.org/10.1039/C9FO02171J Metagenomic analysis of gut microbiota modulatory effects of jujube (Ziziphus jujuba Mill.) polysaccharides in a colorectal cancer mouse model Ji XL , Yan YZ , Hou CY , et al. , 2020b . Structural characterization of a galacturonic acid-rich polysaccharide from Ziziphus Jujuba cv . Muzao . Int J Biol Macromol , 147 : 844 - 852 . https://doi.org/10.1016/j.ijbiomac.2019.09.244 https://doi.org/10.1016/j.ijbiomac.2019.09.244 Structural characterization of a galacturonic acid-rich polysaccharide from Ziziphus Jujuba cv. Muzao Kaeidi A , Taati M , Hajializadeh Z , et al. , 2015 . Aqueous extract of Zizyphus jujuba fruit attenuates glucose induced neurotoxicity in an in vitro model of diabetic neuropathy . Iran J Basic Med Sci , 18 ( 3 ): 301 - 306 . Aqueous extract of Zizyphus jujuba fruit attenuates glucose induced neurotoxicity in an in vitro model of diabetic neuropathy Kammerer D , Claus A , Schieber A , et al. , 2005 . A novel process for the recovery of polyphenols from grape ( Vitis vinifera L.) pomace . J Food Sci , 70 ( 2 ): C157 - C163 . https://doi.org/10.1111/j.1365-2621.2005.tb07077.x https://doi.org/10.1111/j.1365-2621.2005.tb07077.x A novel process for the recovery of polyphenols from grape (Vitis vinifera L.) pomace Kang KB , Ming G , Kim GJ , et al. , 2015 . Jubanines F‒J, cyclopeptide alkaloids from the roots of Ziziphus jujuba . Phytochemistry , 119 : 90 - 95 . https://doi.org/10.1016/j.phytochem.2015.09.001 https://doi.org/10.1016/j.phytochem.2015.09.001 Jubanines F‒J, cyclopeptide alkaloids from the roots of Ziziphus jujuba Karra S , Sebii H , Yaich H , et al. , 2020 . Effect of extraction methods on the physicochemical, structural, functional, and antioxidant properties of the dietary fiber concentrates from male date palm flowers . J Food Biochem , 44 ( 6 ): e13202 . https://doi.org/10.1111/jfbc.13202 https://doi.org/10.1111/jfbc.13202 Effect of extraction methods on the physicochemical, structural, functional, and antioxidant properties of the dietary fiber concentrates from male date palm flowers Kawabata K , Kitamura K , Irie K , et al. , 2017 . Triterpenoids isolated from Ziziphus jujuba enhance glucose uptake activity in skeletal muscle cells . J Nutr Sci Vitaminol , 63 ( 3 ): 193 - 199 . https://doi.org/10.3177/jnsv.63.193 https://doi.org/10.3177/jnsv.63.193 Triterpenoids isolated from Ziziphus jujuba enhance glucose uptake activity in skeletal muscle cells Kou XH , Chen Q , Li XH , et al. , 2015 . Quantitative assessment of bioactive compounds and the antioxidant activity of 15 jujube cultivars . Food Chem , 173 : 1037 - 1044 . https://doi.org/10.1016/j.foodchem.2014.10.110 https://doi.org/10.1016/j.foodchem.2014.10.110 Quantitative assessment of bioactive compounds and the antioxidant activity of 15 jujube cultivars Kuprash DV , Nedospasov SA , 2016 . Molecular and cellular mechanisms of inflammation . Biochemistry (Moscow) , 81 ( 11 ): 1237 - 1239 . https://doi.org/10.1134/S0006297916110018 https://doi.org/10.1134/S0006297916110018 Molecular and cellular mechanisms of inflammation Lai RH , Lai XF , Zhao WX , et al. , 2011 . Influence of different extraction methods of tea polyphenols on proportions of catechins . Adv Mater Res , 311 - 313 : 2114 - 2120 . https://doi.org/10.4028/www.scientific.net/AMR.311-313.2114 https://doi.org/10.4028/www.scientific.net/AMR.311-313.2114 Influence of different extraction methods of tea polyphenols on proportions of catechins Lam CTW , Gong AGW , Lam KYC , et al. , 2016 . Jujube-containing herbal decoctions induce neuronal differentiation and the expression of anti-oxidant enzymes in cultured PC12 cells . J Ethnopharmacol , 188 : 275 - 283 . https://doi.org/10.1016/j.jep.2016.05.015 https://doi.org/10.1016/j.jep.2016.05.015 Jujube-containing herbal decoctions induce neuronal differentiation and the expression of anti-oxidant enzymes in cultured PC12 cells Li GP , Wu LF , Wei J , et al. , 2013 . Two new flavonoids from the fruits of Ziziphus jujuba . Chem Nat Comp , 49 ( 4 ): 617 - 620 . https://doi.org/10.1007/s10600-013-0692-z https://doi.org/10.1007/s10600-013-0692-z Two new flavonoids from the fruits of Ziziphus jujuba Li JW , Fan LP , Ding SD , et al. , 2007 . Nutritional composition of five cultivars of Chinese jujube . Food Chem , 103 ( 2 ): 454 - 460 . https://doi.org/10.1016/j.foodchem.2006.08.016 https://doi.org/10.1016/j.foodchem.2006.08.016 Nutritional composition of five cultivars of Chinese jujube Li SG , Wang DG , Tian W , et al. , 2008 . Characterization and anti-tumor activity of a polysaccharide from Hedysarum polybotrys Hand. -Mazz . Carbohydr Polym , 73 ( 2 ): 344 - 350 . https://doi.org/10.1016/j.carbpol.2007.12.001 https://doi.org/10.1016/j.carbpol.2007.12.001 Characterization and anti-tumor activity of a polysaccharide from Hedysarum polybotrys Hand. -Mazz Li WJ , Guo Y , Zhang CY , et al. , 2016 . Dietary phytochemicals and cancer chemoprevention: a perspective on oxidative stress, inflammation, and epigenetics . Chem Res Toxicol , 29 ( 12 ): 2071 - 2095 . https://doi.org/10.1021/acs.chemrestox.6b00413 https://doi.org/10.1021/acs.chemrestox.6b00413 Dietary phytochemicals and cancer chemoprevention: a perspective on oxidative stress, inflammation, and epigenetics Li Y , Guo S , Hua TT , et al. , 2018 . Comparative pharmacokinetics of triterpenic acids in normal and immunosuppressed rats after oral administration of Jujubae Fructus extract by UPLC-MS/MS . J Chromatogr B , 1077 - 1078 : 13 - 21 . https://doi.org/10.1016/j.jchromb.2018.01.026 https://doi.org/10.1016/j.jchromb.2018.01.026 Comparative pharmacokinetics of triterpenic acids in normal and immunosuppressed rats after oral administration of Jujubae Fructus extract by UPLC-MS/MS Lin XM , Ji XL , Wang M , et al. , 2019 . An alkali-extracted polysaccharide from Zizyphus jujuba cv . Muzao: structural characterizations and antioxidant activities . Int J Biol Macromol , 136 : 607 - 615 . https://doi.org/10.1016/j.ijbiomac.2019.06.117 https://doi.org/10.1016/j.ijbiomac.2019.06.117 An alkali-extracted polysaccharide from Zizyphus jujuba cv. Muzao: structural characterizations and antioxidant activities Lin XM , Liu KS , Yin S , et al. , 2020 . A novel pectic polysaccharide of jujube pomace: structural analysis and intracellular antioxidant activities . Antioxidants , 9 ( 2 ): 127 . https://doi.org/10.3390/antiox9020127 https://doi.org/10.3390/antiox9020127 A novel pectic polysaccharide of jujube pomace: structural analysis and intracellular antioxidant activities Liu AH , Deng P , 2016 . Optimization of extraction condition of dietary fiber from red dates . Food Ferment Sci Technol , 52 ( 4 ): 58 - 61 (in Chinese) . https://doi.org/10.3969/j.issn.1674-506X.2016.04-013 https://doi.org/10.3969/j.issn.1674-506X.2016.04-013 Optimization of extraction condition of dietary fiber from red dates Mantovani A , Allavena P , Sica A , et al. , 2008 . Cancer-related inflammation . Nature , 454 ( 7203 ): 436 - 444 . https://doi.org/10.1038/nature07205 https://doi.org/10.1038/nature07205 Cancer-related inflammation Matschinsky FM , 2005 . Glucokinase, glucose homeostasis, and diabetes mellitus . Curr Diab Rep , 5 ( 3 ): 171 - 176 . https://doi.org/10.1007/s11892-005-0005-4 https://doi.org/10.1007/s11892-005-0005-4 Glucokinase, glucose homeostasis, and diabetes mellitus Medzhitov R , 2008 . Origin and physiological roles of inflammation . Nature , 454 ( 7203 ): 428 - 435 . https://doi.org/10.1038/nature07201 https://doi.org/10.1038/nature07201 Origin and physiological roles of inflammation Medzhitov R , 2010 . Inflammation 2010: new adventures of an old flame . Cell , 140 ( 6 ): 771 - 776 . https://doi.org/10.1016/j.cell.2010.03.006 https://doi.org/10.1016/j.cell.2010.03.006 Inflammation 2010: new adventures of an old flame Mesaik AM , Poh HW , Bin OY , et al. , 2018 . In vivo anti-inflammatory, anti-bacterial and anti-diarrhoeal activity of Ziziphus jujuba fruit extract . Open Access Maced J Med Sci , 6 ( 5 ): 757 - 766 . https://doi.org/10.3889/oamjms.2018.168 https://doi.org/10.3889/oamjms.2018.168 In vivo anti-inflammatory, anti-bacterial and anti-diarrhoeal activity of Ziziphus jujuba fruit extract Miklavčič Višnjevec A , Baruca Arbeiter A , Hladnik M , et al. , 2019 . An integrated characterization of jujube ( Ziziphus jujuba Mill.) grown in the north Adriatic region . Food Technol Biotechnol , 57 ( 1 ): 17 - 28 . https://doi.org/10.17113/ftb.57.01.19.5910 https://doi.org/10.17113/ftb.57.01.19.5910 An integrated characterization of jujube (Ziziphus jujuba Mill.) grown in the north Adriatic region Ministry of Agriculture and Rural Affairs of the People’s Republic of China , 2020 . Data and Statistics . http://zdscxx.moa.gov.cn:8080/nyb/pc/index.jsp http://zdscxx.moa.gov.cn:8080/nyb/pc/index.jsp (in Chinese) . Data and Statistics Nair A , Chauhan P , Saha B , et al. , 2019 . Conceptual evolution of cell signaling . Int J Mol Sci , 20 ( 13 ): 3292 . https://doi.org/10.3390/ijms20133292 https://doi.org/10.3390/ijms20133292 Conceptual evolution of cell signaling Ninave PB , Patil SD , 2019 . Antiasthmatic potential of Zizyphus jujuba Mill and Jujuboside B. —possible role in the treatment of asthma . Respir Physiol Neurobiol , 260 : 28 - 36 . https://doi.org/10.1016/j.resp.2018.12.001 https://doi.org/10.1016/j.resp.2018.12.001 Antiasthmatic potential of Zizyphus jujuba Mill and Jujuboside B. —possible role in the treatment of asthma Ong WY , Wu YJ , Farooqui T , et al. , 2018 . Qi Fu Yin—a Ming dynasty prescription for the treatment of dementia . Mol Neurobiol , 55 ( 9 ): 7389 - 7400 . https://doi.org/10.1007/s12035-018-0908-0 https://doi.org/10.1007/s12035-018-0908-0 Qi Fu Yin—a Ming dynasty prescription for the treatment of dementia Paciolla C , Fortunato S , Dipierro N , et al. , 2019 . Vitamin C in plants: from functions to biofortification . Antioxidants , 8 ( 11 ): 519 . https://doi.org/10.3390/antiox8110519 https://doi.org/10.3390/antiox8110519 Vitamin C in plants: from functions to biofortification Pandey MB , Singh AK , Singh JP , et al. , 2008 . Three new cyclopeptide alkaloids from Zizyphus species . J Asian Nat Prod Res , 10 ( 8 ): 709 - 713 . https://doi.org/10.1080/10286020802016024 https://doi.org/10.1080/10286020802016024 Three new cyclopeptide alkaloids from Zizyphus species Periasamy S , Liu CT , Wu WH , et al. , 2015 . Dietary Ziziphus jujuba fruit influence on aberrant crypt formation and blood cells in colitis-associated colorectal cancer mice . Asian Pac J Cancer Prev , 16 ( 17 ): 7561 - 7566 . https://doi.org/10.7314/APJCP.2015.16.17.7561 https://doi.org/10.7314/APJCP.2015.16.17.7561 Dietary Ziziphus jujuba fruit influence on aberrant crypt formation and blood cells in colitis-associated colorectal cancer mice Periasamy S , Wu WH , Chien SP , et al. , 2020 . Dietary Ziziphus jujuba fruit attenuates colitis-associated tumorigenesis: a pivotal role of the NF-‍κB/IL-6/JAK1/STAT3 pathway . Nutr Cancer , 72 ( 1 ): 120 - 132 . https://doi.org/10.1080/01635581.2019.1615515 https://doi.org/10.1080/01635581.2019.1615515 Dietary Ziziphus jujuba fruit attenuates colitis-associated tumorigenesis: a pivotal role of the NF-‍κB/IL-6/JAK1/STAT3 pathway Phan CW , Wang JK , Cheah SC , et al. , 2018 . A review on the nucleic acid constituents in mushrooms: nucleobases, nucleosides and nucleotides . Crit Rev Biotechnol , 38 ( 5 ): 762 - 777 . https://doi.org/10.1080/07388551.2017.1399102 https://doi.org/10.1080/07388551.2017.1399102 A review on the nucleic acid constituents in mushrooms: nucleobases, nucleosides and nucleotides Plastina P , Bonofiglio D , Vizza D , et al. , 2012 . Identification of bioactive constituents of Ziziphus jujube fruit extracts exerting antiproliferative and apoptotic effects in human breast cancer cells . J Ethnopharmacol , 140 ( 2 ): 325 - 332 . https://doi.org/10.1016/j.jep.2012.01.022 https://doi.org/10.1016/j.jep.2012.01.022 Identification of bioactive constituents of Ziziphus jujube fruit extracts exerting antiproliferative and apoptotic effects in human breast cancer cells Poprac P , Jomova K , Simunkova M , et al. , 2017 . Targeting free radicals in oxidative stress-related human diseases . Trends Pharmacol Sci , 38 ( 7 ): 592 - 607 . https://doi.org/10.1016/j.tips.2017.04.005 https://doi.org/10.1016/j.tips.2017.04.005 Targeting free radicals in oxidative stress-related human diseases Pu YF , Ding T , Wang WJ , et al. , 2018 . Effect of harvest, drying and storage on the bitterness, moisture, sugars, free amino acids and phenolic compounds of jujube fruit (Zizyphus jujuba cv. Junzao) . J Sci Food Agric , 98 ( 2 ): 628 - 634 . https://doi.org/10.1002/jsfa.8507 https://doi.org/10.1002/jsfa.8507 Effect of harvest, drying and storage on the bitterness, moisture, sugars, free amino acids and phenolic compounds of jujube fruit (Zizyphus jujuba cv. Junzao) Rahman E , Momin A , Zhao L , et al. , 2018 . Bioactive, nutritional composition, heavy metal and pesticide residue of four Chinese jujube cultivars . Food Sci Biotechnol , 27 ( 2 ): 323 - 331 . https://doi.org/10.1007/s10068-017-0256-2 https://doi.org/10.1007/s10068-017-0256-2 Bioactive, nutritional composition, heavy metal and pesticide residue of four Chinese jujube cultivars Ran JJ , Fan MT , Li YH , et al. , 2013 . Optimisation of ultrasonic-assisted extraction of polyphenols from apple peel employing cellulase enzymolysis . Int J Food Sci Technol , 48 ( 5 ): 910 - 917 . https://doi.org/10.1111/ijfs.12041 https://doi.org/10.1111/ijfs.12041 Optimisation of ultrasonic-assisted extraction of polyphenols from apple peel employing cellulase enzymolysis Rashwan AK , Karim N , Shishir MRI , et al. , 2020 . Jujube fruit: a potential nutritious fruit for the development of functional food products . J Funct Foods , 75 : 104205 . https://doi.org/10.1016/j.jff.2020.104205 https://doi.org/10.1016/j.jff.2020.104205 Jujube fruit: a potential nutritious fruit for the development of functional food products Reche J , Almansa MS , Hernández F , et al. , 2019 . Fatty acid profile of peel and pulp of Spanish jujube ( Ziziphus jujuba Mill.) fruit . Food Chem , 295 : 247 - 253 . https://doi.org/10.1016/j.foodchem.2019.05.147 https://doi.org/10.1016/j.foodchem.2019.05.147 Fatty acid profile of peel and pulp of Spanish jujube (Ziziphus jujuba Mill.) fruit Rodríguez Villanueva J , Rodríguez Villanueva L , 2017 . Experimental and clinical pharmacology of Ziziphus jujuba Mills . Phytother Res , 31 ( 3 ): 347 - 365 . https://doi.org/10.1002/ptr.5759 https://doi.org/10.1002/ptr.5759 Experimental and clinical pharmacology of Ziziphus jujuba Mills Sakna ST , Mocan A , Sultani HN , et al. , 2019 . Metabolites profiling of Ziziphus leaf taxa via UHPLC/PDA/ESI-MS in relation to their biological activities . Food Chem , 293 : 233 - 246 . https://doi.org/10.1016/j.foodchem.2019.04.097 https://doi.org/10.1016/j.foodchem.2019.04.097 Metabolites profiling of Ziziphus leaf taxa via UHPLC/PDA/ESI-MS in relation to their biological activities Senchina DS , Hallam JE , Kohut ML , et al. , 2014 . Alkaloids and athlete immune function: caffeine, theophylline, gingerol, ephedrine, and their congeners . Exerc Immunol Rev , 20 : 68 - 93 . Alkaloids and athlete immune function: caffeine, theophylline, gingerol, ephedrine, and their congeners Shad AA , Ahmad S , Ullah R , et al. , 2014 . Phytochemical and biological activities of four wild medicinal plants . Sci World J , 2014 : 857363 . https://doi.org/10.1155/2014/857363 https://doi.org/10.1155/2014/857363 Phytochemical and biological activities of four wild medicinal plants Shi QQ , Zhang Z , Su JJ , et al. , 2018 . Comparative analysis of pigments, phenolics, and antioxidant activity of Chinese jujube ( Ziziphus jujuba Mill.) during fruit development . Molecules , 23 ( 8 ): 1917 . https://doi.org/10.3390/molecules23081917 https://doi.org/10.3390/molecules23081917 Comparative analysis of pigments, phenolics, and antioxidant activity of Chinese jujube (Ziziphus jujuba Mill.) during fruit development Singh A , Zhao KC , 2017 . Treatment of insomnia with traditional Chinese herbal medicine . Int Rev Neurobiol , 135 : 97 - 115 . https://doi.org/10.1016/bs.irn.2017.02.006 https://doi.org/10.1016/bs.irn.2017.02.006 Treatment of insomnia with traditional Chinese herbal medicine Son J , Lee SY , 2020 . Ursonic acid exerts inhibitory effects on matrix metalloproteinases via ERK signaling pathway . Chem Biol Interact , 315 : 108910 . https://doi.org/10.1016/j.cbi.2019.108910 https://doi.org/10.1016/j.cbi.2019.108910 Ursonic acid exerts inhibitory effects on matrix metalloproteinases via ERK signaling pathway Song JX , Bi JF , Chen QQ , et al. , 2019 . Assessment of sugar content, fatty acids, free amino acids, and volatile profiles in jujube fruits at different ripening stages . Food Chem , 270 : 344 - 352 . https://doi.org/10.1016/j.foodchem.2018.07.102 https://doi.org/10.1016/j.foodchem.2018.07.102 Assessment of sugar content, fatty acids, free amino acids, and volatile profiles in jujube fruits at different ripening stages Song LJ , Zhang L , Xu L , et al. , 2020 . Optimized extraction of total triterpenoids from jujube ( Ziziphus jujuba Mill.) and comprehensive analysis of triterpenic acids in different cultivars . Plants , 9 ( 4 ): 412 . https://doi.org/10.3390/plants9040412 https://doi.org/10.3390/plants9040412 Optimized extraction of total triterpenoids from jujube (Ziziphus jujuba Mill.) and comprehensive analysis of triterpenic acids in different cultivars Sun HY , Li CY , Ni YJ , et al. , 2019 . Ultrasonic/microwave-assisted extraction of polysaccharides from Camptotheca acuminata fruits and its antitumor activity . Carbohydr Polym , 206 : 557 - 564 . https://doi.org/10.1016/j.carbpol.2018.11.010 https://doi.org/10.1016/j.carbpol.2018.11.010 Ultrasonic/microwave-assisted extraction of polysaccharides from Camptotheca acuminata fruits and its antitumor activity Tahergorabi Z , Abedini MR , Mitra M , et al. , 2015 . “ Ziziphus jujube ”: a red fruit with promising anticancer activities . Pharmacogn Rev , 9 ( 18 ): 99 - 106 . https://doi.org/10.4103/0973-7847.162108 https://doi.org/10.4103/0973-7847.162108 “Ziziphus jujube”: a red fruit with promising anticancer activities Tanideh N , Jamshidzadeh A , Ghanbari Saghesloo A , et al. , 2016 . Effects of hydroalcoholic extract of Ziziphus jujuba on acetic acid induced ulcerative colitis in male rat ( Rattus norvegicus ) . J Coloproctol , 36 ( 4 ): 189 - 195 . https://doi.org/10.1016/j.jcol.2016.04.007 https://doi.org/10.1016/j.jcol.2016.04.007 Effects of hydroalcoholic extract of Ziziphusjujuba on acetic acid induced ulcerative colitis in male rat (Rattus norvegicus) Wang BN , Liu LG , Huang QY , et al. , 2020 . Quantitative assessment of phenolic acids, flavonoids and antioxidant activities of sixteen jujube cultivars from China . Plant Foods Hum Nutr , 75 ( 2 ): 154 - 160 . https://doi.org/10.1007/s11130-020-00796-1 https://doi.org/10.1007/s11130-020-00796-1 Quantitative assessment of phenolic acids, flavonoids and antioxidant activities of sixteen jujube cultivars from China Wang LY , Jing N , Liu XR , et al. , 2020 . Nurturing and modulating gut microbiota with jujube powder to enhance anti-PD-L1 efficiency against murine colon cancer . J Funct Foods , 64 : 103647 . https://doi.org/10.1016/j.jff.2019.103647 https://doi.org/10.1016/j.jff.2019.103647 Nurturing and modulating gut microbiota with jujube powder to enhance anti-PD-L1 efficiency against murine colon cancer Wang RR , Ding SH , Zhao DD , et al. , 2016 . Effect of dehydration methods on antioxidant activities, phenolic contents, cyclic nucleotides, and volatiles of jujube fruits . Food Sci Biotechnol , 25 ( 1 ): 137 - 143 . https://doi.org/10.1007/s10068-016-0021-y https://doi.org/10.1007/s10068-016-0021-y Effect of dehydration methods on antioxidant activities, phenolic contents, cyclic nucleotides, and volatiles of jujube fruits Wang YG , Xu Y , Ma XQ , et al. , 2018 . Extraction, purification, characterization and antioxidant activities of polysaccharides from Zizyphus jujuba cv . Linzexiaozao . Int J Biol Macromol , 118 : 2138 - 2148 . https://doi.org/10.1016/j.ijbiomac.2018.07.059 https://doi.org/10.1016/j.ijbiomac.2018.07.059 Extraction, purification, characterization and antioxidant activities of polysaccharides from Zizyphus jujuba cv. Linzexiaozao Williams BA , Grant LJ , Gidley MJ , et al. , 2017 . Gut fermentation of dietary fibres: physico-chemistry of plant cell walls and implications for health . Int J Mol Sci , 18 ( 10 ): 2203 . https://doi.org/10.3390/ijms18102203 https://doi.org/10.3390/ijms18102203 Gut fermentation of dietary fibres: physico-chemistry of plant cell walls and implications for health Wojdyło A , Carbonell-Barrachina ÁA , Legua P , et al. , 2016 . Phenolic composition, ascorbic acid content, and antioxidant capacity of Spanish jujube ( Ziziphus jujube Mill.) fruits . Food Chem , 201 : 307 - 314 . https://doi.org/10.1016/j.foodchem.2016.01.090 https://doi.org/10.1016/j.foodchem.2016.01.090 Phenolic composition, ascorbic acid content, and antioxidant capacity of Spanish jujube (Ziziphus jujube Mill.) fruits Wu GY , 2016 . Dietary protein intake and human health . Food Funct , 7 ( 3 ): 1251 - 1265 . https://doi.org/10.1039/C5FO01530H https://doi.org/10.1039/C5FO01530H Dietary protein intake and human health Wu H , Zhu JX , Diao WC , et al. , 2014 . Ultrasound-assisted enzymatic extraction and antioxidant activity of polysaccharides from pumpkin ( Cucurbita moschata ) . Carbohydr Polym , 113 : 314 - 324 . https://doi.org/10.1016/j.carbpol.2014.07.025 https://doi.org/10.1016/j.carbpol.2014.07.025 Ultrasound-assisted enzymatic extraction and antioxidant activity of polysaccharides from pumpkin (Cucurbita moschata) Wu LY , Parhofer KG , 2014 . Diabetic dyslipidemia . Metabolism , 63 ( 12 ): 1469 - 1479 . https://doi.org/10.1016/j.metabol.2014.08.010 https://doi.org/10.1016/j.metabol.2014.08.010 Diabetic dyslipidemia Xu H , Yuan ZZ , Ma X , et al. , 2018 . Triterpenoids with antioxidant activities from Myricaria squamosa . J Asian Nat Prod Res , 20 ( 3 ): 292 - 298 . https://doi.org/10.1080/10286020.2017.1321636 https://doi.org/10.1080/10286020.2017.1321636 Triterpenoids with antioxidant activities from Myricaria squamosa Xu Y , Xie LH , Xie JH , et al. , 2019 . Pelargonidin-3- O -rutinoside as a novel α‍-glucosidase inhibitor for improving postprandial hyperglycemia . Chem Commun , 55 ( 1 ): 39 - 42 . https://doi.org/10.1039/C8CC07985D https://doi.org/10.1039/C8CC07985D Pelargonidin-3-O-rutinoside as a novel α‍-glucosidase inhibitor for improving postprandial hyperglycemia Yamamoto S , Wang MF , Adjei AA , et al. , 1997 . Role of nucleosides and nucleotides in the immune system, gut reparation after injury, and brain function . Nutrition , 13 ( 4 ): 372 - 374 . https://doi.org/10.1016/S0899-9007(96)00376-0 https://doi.org/10.1016/S0899-9007(96)00376-0 Role of nucleosides and nucleotides in the immune system, gut reparation after injury, and brain function Yan JK , Wu LX , Cai WD , et al. , 2019 . Subcritical water extraction-based methods affect the physicochemical and functional properties of soluble dietary fibers from wheat bran . Food Chem , 298 : 124987 . https://doi.org/10.1016/j.foodchem.2019.124987 https://doi.org/10.1016/j.foodchem.2019.124987 Subcritical water extraction-based methods affect the physicochemical and functional properties of soluble dietary fibers from wheat bran Yang HM , Yin ZQ , Zhao MG , et al. , 2018 . Pentacyclic triterpenoids from Cyclocarya paliurus and their antioxidant activities in FFA-induced HepG2 steatosis cells . Phytochemistry , 151 : 119 - 127 . https://doi.org/10.1016/j.phytochem.2018.03.010 https://doi.org/10.1016/j.phytochem.2018.03.010 Pentacyclic triterpenoids from Cyclocarya paliurus and their antioxidant activities in FFA-induced HepG2 steatosis cells Yen MH , Lee JJ , Yeh CF , et al. , 2014 . Yakammaoto inhibited human coxsackievirus B4 (CVB4)-induced airway and renal tubular injuries by preventing viral attachment, internalization, and replication . J Ethnopharmacol , 151 ( 3 ): 1056 - 1063 . https://doi.org/10.1016/j.jep.2013.11.049 https://doi.org/10.1016/j.jep.2013.11.049 Yakammaoto inhibited human coxsackievirus B4 (CVB4)-induced airway and renal tubular injuries by preventing viral attachment, internalization, and replication Yoon SR , Jo YJ , Yang SL , et al. , 2009 . Sanjoinine A isolated from Semen Zizyphi Spinosi protects against kainic acid-induced convulsions . Arch Pharm Res , 32 ( 11 ): 1515 - 1523 . https://doi.org/10.1007/s12272-009-2103-3 https://doi.org/10.1007/s12272-009-2103-3 Sanjoinine A isolated from Semen Zizyphi Spinosi protects against kainic acid-induced convulsions Yu L , Jiang BP , Luo D , et al. , 2012 . Bioactive components in the fruits of Ziziphus jujuba Mill. against the inflammatory irritant action of Euphorbia plants . Phytomedicine , 19 ( 3-4 ): 239 - 244 . https://doi.org/10.1016/j.phymed.2011.09.071 https://doi.org/10.1016/j.phymed.2011.09.071 Bioactive components in the fruits of Ziziphus jujuba Mill. against the inflammatory irritant action of Euphorbia plants Yuan JP , Zhao SY , Wang JH , et al. , 2008 . Distribution of nucleosides and nucleobases in edible fungi . J Agric Food Chem , 56 ( 3 ): 809 - 815 . https://doi.org/10.1021/jf0719205 https://doi.org/10.1021/jf0719205 Distribution of nucleosides and nucleobases in edible fungi Yuan YH , Gao ZP , Shi YG , 2002 . Industrialization of Chinese jujube . J Northwest Sci-Tech Univ Agric For (Nat Sci Ed) , 30 ( S1 ): 95 - 98 (in Chinese) . https://doi.org/10.3321/j.issn:1671-9387.2002.z1.023 https://doi.org/10.3321/j.issn:1671-9387.2002.z1.023 Industrialization of Chinese jujube Zhang H , Jiang L , Ye S , et al. , 2010 . Systematic evaluation of antioxidant capacities of the ethanolic extract of different tissues of jujube ( Ziziphus jujuba Mill.) from China . Food Chem Toxicol , 48 ( 6 ): 1461 - 1465 . https://doi.org/10.1016/j.fct.2010.03.011 https://doi.org/10.1016/j.fct.2010.03.011 Systematic evaluation of antioxidant capacities of the ethanolic extract of different tissues of jujube (Ziziphus jujuba Mill.) from China Zhang XQ , Qu XY , Liu C , et al. , 2019 . Optimization of extraction technology and oxidation resistance analysis of alkaloids in jujube . Mol Plant Breed , 17 ( 3 ): 972 - 977 (in Chinese) . https://doi.org/10.13271/j.mpb.017.000972 https://doi.org/10.13271/j.mpb.017.000972 Optimization of extraction technology and oxidation resistance analysis of alkaloids in jujube Zhao HX , Zhang HS , Yang SF , 2014 . Phenolic compounds and its antioxidant activities in ethanolic extracts from seven cultivars of Chinese jujube . Food Sci Hum Well , 3 ( 3-4 ): 183 - 190 . https://doi.org/10.1016/j.fshw.2014.12.005 https://doi.org/10.1016/j.fshw.2014.12.005 Phenolic compounds and its antioxidant activities in ethanolic extracts from seven cultivars of Chinese jujube Zhao Y , Yang XB , Ren DY , et al. , 2014 . Preventive effects of jujube polysaccharides on fructose-induced insulin resistance and dyslipidemia in mice . Food Funct , 5 ( 8 ): 1771 - 1778 . https://doi.org/10.1039/C3FO60707K https://doi.org/10.1039/C3FO60707K Preventive effects of jujube polysaccharides on fructose-induced insulin resistance and dyslipidemia in mice Zou M , Chen YL , Sun-Waterhouse D , et al. , 2018 . Immunomodulatory acidic polysaccharides from Zizyphus jujuba cv. Huizao: insights into their chemical characteristics and modes of action . Food Chem , 258 : 35 - 42 . https://doi.org/10.1016/j.foodchem.2018.03.052 https://doi.org/10.1016/j.foodchem.2018.03.052 Immunomodulatory acidic polysaccharides from Zizyphus jujuba cv. Huizao: insights into their chemical characteristics and modes of action Yang LU and Wei CHEN conducted this review. Yang LU, Wei CHEN, and Tao BAO wrote and edited the manuscript. Yang LU, Jianling MO, and Jingdan NI participated in creating and editing the tables. All authors have read and approved the final manuscript and, therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data. This work was supported by the National Natural Science Foundation of China (No. U1703105) and the Zhejiang Provincial Key R&D Program of China (No. 2019C02074). 10.1631/jzus.B2000594 1673-1581（2021）06-0431-19 2020-09-27 2021-01-04 2021-06-15 2022-05-09 2021-04-23 © Zhejiang University Press 2021 Yang LU, Tao BAO, Jianling MO, Jingdan NI, and Wei CHEN declare that they have no conflict of interest. This article does not contain any studies with human or animal subjects performed by any of the authors. Compliance with ethics guidelines 浙江大学学报（英文版）（B辑：生物医学和生物技术） 6 22