The fruit of Ziziphus jujuba Mill., known as jujube or Chinese date, is commonly consumed as health supplement worldwide. Traditionally, the main functions of jujube were considered to benefit our brain, nourish “Blood” and raise the “Qi”, as such which prolonged one’s life-span. However, the action mechanisms of jujube have not been done. Here, we aimed to reveal the biological effects of jujube in neuron protection and blood stimulation in different cell models.

Chemical and biological properties of 24 common jujube cultivars were revealed. 11 nucleotides and their derivatives (uracil, cytidine, uridine, cGMP, xanthine, hypoxanthine, guanine, guanosine, cAMP, adenosine and adenine), 7 flavonoids [(-)-catechin, procyanidin B2, (-)-epicatechin, quercetin 3-O-galactoside, quercetin 3-O-...[ Read more ]

The fruit of Ziziphus jujuba Mill., known as jujube or Chinese date, is commonly consumed as health supplement worldwide. Traditionally, the main functions of jujube were considered to benefit our brain, nourish “Blood” and raise the “Qi”, as such which prolonged one’s life-span. However, the action mechanisms of jujube have not been done. Here, we aimed to reveal the biological effects of jujube in neuron protection and blood stimulation in different cell models.

Chemical and biological properties of 24 common jujube cultivars were revealed. 11 nucleotides and their derivatives (uracil, cytidine, uridine, cGMP, xanthine, hypoxanthine, guanine, guanosine, cAMP, adenosine and adenine), 7 flavonoids [(-)-catechin, procyanidin B2, (-)-epicatechin, quercetin 3-O-galactoside, quercetin 3-O-rutinoside, quercetin 3-O-β-D-glucoside and kaempferol 3-O-rutinoside], and polysaccharides in jujube were determined. Different sources of jujubes showed similar chemical profiles; however, the amounts of identified chemicals showed a great variation. The amount of nucleotides, flavonoids and polysaccharides in jujubes could be affected by its maturity and drying process. Here, we proposed several chemical parameters for the standardization of a well-prepared jujube water extract: (i) jujube water extract provided 7 characteristic peaks in their chromatographic fingerprints; (ii) the amounts of nucleotides and flavonoids in the extract were no less than 330 μg/g and 35 μg/g of dried extract powder.

The application of standardized jujube water extract induced neurite outgrowth of PC12 cells; this effect was similar to that of nerve growth factor (NGF). In parallel, the expressions of neurofilaments (NFs) in jujube-treated cultures showed a dose-dependent increase, with the highest induction by ~150% for NF68, 150% for NF160 and 100% for NF200. The application of H89, a protein kinase A (PKA) inhibitor, attenuated jujube-induced neurite outgrowth and neurofilament expression of the cultures. In addition, the induction of cAMP responsive element binding protein (CREB) phosphorylation was observed after the treatment with jujube water extract for 5 min on PC12 cells, and the effect of which was fully blocked by H89. Moreover, the neurotrophic factor expression was also investigated in cultured astrocytes. The treatment with jujube water extract stimulated the expressions of neurotrophic factors in a dose-dependent manner, with the highest induction of ~100% for NGF, 100% for brain-derived neurotrophic factor (BDNF), 100% for glial cell line-derived neurotrophic factor (GDNF) and 50% for neurotrophin 3 (NT3). These results supported the neurotrophic role of jujube on the brain.

In hematopoietic function, application of jujube water extract dose-dependently induced the expression of erythropoietin (EPO) on cultured Hep3B liver cells, with the highest induction by ~100% of increase. On the other hand, jujube water extract stimulated the expression of heme oxygenase 1 (HO-1) on cultured RAW 264.7 macrophages, having the highest induction at ~100%. In addition, the application of jujube water extract stimulated the transcriptional expressions of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in cultured RAW 264.7 macrophages, with the highest induction of 7-fold, 9-fold and 4-fold. In contrast, the pre-treatment with jujube water extract robustly suppressed the expression of IL-1β and IL-6, but not that of TNF-α, in lipopolysaccharide (LPS)-stimulated macrophages. The current results revealed the role of jujube in enhancing the erythropoietic functions, and verified the bi-directional immune-modulatory roles of jujube.

The results provided by this thesis have achieved three different aspects of jujube: (i) chemical standardization; (ii) brain protection; and (iii) blood stimulation. Overall, the proposed chemical standardization parameters could be applied for the quality control of jujube; and this standardized jujube water extract might be served as health food supplement for the prevention and/or treatment of neurological and blood deficiency diseases.