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Ziziphus jujuba Mill., a plant used as medicinal food: a review of its phytochemistry, pharmacology, quality control and future research

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Abstract

Jujubae Fructus (ZJF) [called Dazao (大枣) in Chinese], the fruit of Ziziphus jujuba Mill. (ZJ), is utilized as a food and traditional medicine in China. In TCM use, ZJF is traditionally used to treat and nourish the stomach, tonify the spleen, and nourish the blood, as well as for overall nourishing and strength. According to the available literature from 1974 to March 2019, more than 278 compounds have been isolated and identified from ZJ. Local books, papers and dissertations were also searched. The aim of this review was to examine this plant’s traditional uses, botany, phytochemistry, pharmacological effects, toxicity, pharmacokinetics, quality control and economically important uses. In vivo and in vitro scientific investigations have initially confirmed its pharmacological potential by showing anti-inflammatory, antioxidant, antimicrobial, gastrointestinal protective, cardiovascular, neuroprotective, anticancer, anti-HIV, sedative-hypnotic and anxiolytic effects. Bioactive metabolites belonging to different classes are responsible for these activities, including triterpenoid acids, saponins, cyclopeptide alkaloids, flavonoids and neo-lignans, which are considered the characteristic and active components of ZJ. The TCM use of ZJF, including tonifying and replenishing the middle Qi and nourishing the blood to tranquilize, is based on its gastrointestinal protective, cardiovascular, neuroprotective, sedative-hypnotic and anxiolytic properties. Its detoxification effects are attributed to its anti-inflammatory, antiviral, anticancer and antibacterial activities. Moreover, the TCM characteristics of ZJF (sweet flavour; warm nature; and spleen, stomach, and heart meridian effects) support its traditional uses and pharmacological effects. We encourage more studies to further clarify the relationship between modern applications and traditional uses in the future. Furthermore, no one has studied ZJ blossoms, and researchers should allocate more time to the study of ZJ blossoms. Additionally, unsolved problems include the scientific principle of the Chinese material medica processing [CMMP (中药炮制) in Chinese] of ZJF, the molecular mechanisms of the biological activity of ZJ and its other medicinal parts, the overall pharmacokinetics rather than single molecule pharmacokinetics, the efficacy and the toxicology. All of the unsolved problems noted above require further study.

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Abbreviations

ABTS:

2,2′-azino-bis-3-ethylbenzo-thiazoline-6-sulfonic acid

AD:

Alzheimer’s disease

AMPK:

AMP-activated protein kinase

BAL:

Bronchoalveolar lavage

BHA:

Butylated hydroxyl anisole

BHT:

Butylated hydroxyl toluene

CAIA:

Collagen antibody-induced arthritis

CHCl3-F:

Chloroform fraction

CI:

Confidence interval

CMMP:

Chinese material medica processing

CSIETP:

College Students’ Innovative Entrepreneurial Training Programme

DPPH:

2,2-diphenyl-1-picrylhydrazyl

DW:

Dry weight

FRAP:

Ferric-reducing antioxidant power

FW:

Fresh weight

GAE:

Gallic acid equivalents

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

HFWD:

High-fat Western-style diet

IL:

Interleukin

ISO:

Isoproterenol

JPBP :

The bond phenols from jujube peel

JPFP :

The free phenols from jujube peel

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinase

MIC:

Minimum inhibitory concentration

NAFLD:

Non-alcoholic fatty liver disease

NF:

Neurofilament

NF-κB:

Nuclear factor-kappa B

NFs:

Neurofilaments

NGF:

Nerve growth factor

NNSFC:

National Natural Science Foundation of China

PEDV:

Porcine epidemic diarrhoea virus

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

SRB:

Sulforhodamine B

TCM:

Traditional Chinese medicine

TH2:

T-helper type 2

TI:

Therapeutic index

TNF:

Tumour necrosis factor

ZJ :

Ziziphus jujuba Mill.

ZJB :

Ziziphus jujuba bark

ZJC :

Ziziphus jujuba core

ZJF :

Ziziphus jujuba Fructus (Jujubae Fructus)

ZJJ :

Ziziphus jujuba cv. Jinsixiaozao

ZJL :

Ziziphus jujuba leaves

ZJR :

Ziziphus jujuba roots

ZJS :

Ziziphus jujuba seeds

ZJRB :

Ziziphus jujuba root bark

ZJSB :

Ziziphus jujuba stem bark

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Acknowledgements

This work was supported by the NNSFC [81803744 and 81773919]; Shaanxi Project [15JF001, 2015KTCL03-14, 2018TD-005, and 2018SF-285]; SEF [(2013)171]; Key Disciplines of the Pharmaceutical Engineering of TCM by the Shaanxi Administration of TCM (2017), and CSIETP [201805099, 201710716010, and 201610716009]. In addition, the authors would like to thank the authors of two recently published review papers on Ziziphus jujuba (Ding et al. 2016, Rodríguez Villanueva and Rodríguez Villanueva 2017).

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  1. Shaanxi University of Chinese Medicine/Shaanxi Collaborative Innovation Center of Chinese Medicinal Resource Industrialization, Wei Yang Middle Road, Xianyang, 712083, People’s Republic of China

    Shi-Jun Liu, Yan-Ping Lv, Zhi-Shu Tang, Yu Zhang, Hong-Bo Xu, Dong-Bo Zhang, Chun-Li Cui, Hong-Bo Liu, Huan-Huan Sun, Zhong-Xing Song & Si-Min Wei

  2. Shaanxi Province Key Laboratory of New Drugs and Chinese Medicine Foundation Research, Xianyang, 712083, People’s Republic of China

    Shi-Jun Liu, Yan-Ping Lv, Zhi-Shu Tang, Yu Zhang, Hong-Bo Xu, Dong-Bo Zhang, Chun-Li Cui, Hong-Bo Liu, Huan-Huan Sun, Zhong-Xing Song & Si-Min Wei

  3. Shaanxi Rheumatism and Tumor Center of TCM Engineering Technology Research, Xianyang, 712083, People’s Republic of China

    Shi-Jun Liu, Yan-Ping Lv, Zhi-Shu Tang, Yu Zhang, Hong-Bo Xu, Dong-Bo Zhang, Chun-Li Cui, Hong-Bo Liu, Huan-Huan Sun, Zhong-Xing Song & Si-Min Wei

  4. State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources (Cultivation), Xianyang, 712083, People’s Republic of China

    Shi-Jun Liu, Yan-Ping Lv, Zhi-Shu Tang, Yu Zhang, Hong-Bo Xu, Dong-Bo Zhang, Chun-Li Cui, Hong-Bo Liu, Huan-Huan Sun, Zhong-Xing Song & Si-Min Wei

  5. Shaanxi Innovative Drug Research Center, Xianyang, 712083, People’s Republic of China

    Shi-Jun Liu, Yan-Ping Lv, Zhi-Shu Tang, Yu Zhang, Hong-Bo Xu, Dong-Bo Zhang, Chun-Li Cui, Hong-Bo Liu, Huan-Huan Sun, Zhong-Xing Song & Si-Min Wei

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Contributions

S-JL and Z-ST conceived and designed the review. S-JL, C-LC, H-BL, YZ, H-BX, D-BZ, Y-PL, H-HS, Z-XS, and S-MW were responsible for collecting the documents. S-JL, Z-ST and Y-PL analysed the data. S-JL and Z-ST wrote the paper.

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Correspondence to Shi-Jun Liu or Zhi-Shu Tang.

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Qi: In terms of acupuncture, “Qi” is the “life force”. It provides the circulation of nourishment in the bloodstream and maintains body temperature (Wang et al. 2018c). Chinese heat-clearing herbs are considered to be antipyretic in TCM. They are mostly cold in nature and can clear away heat and toxic materials (Liu et al. 2018c).

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Liu, SJ., Lv, YP., Tang, ZS. et al. Ziziphus jujuba Mill., a plant used as medicinal food: a review of its phytochemistry, pharmacology, quality control and future research. Phytochem Rev 20, 507–541 (2021). https://doi.org/10.1007/s11101-020-09709-1

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