Jujuboside A

Evid Based Complement Alternat Med. 2016;2016:9593716.

Jujuboside A Protects H9C2 Cells from Isoproterenol-Induced Injury via Activating PI3K/Akt/mTOR Signaling Pathway.[Pubmed: 27293469 ]

Jujuboside A is a kind of the saponins isolated from the seeds of Ziziphus jujuba, which possesses multiple biological effects, such as antianxiety, antioxidant, and anti-inflammatory effects; however, its mediatory effect on isoproterenol-stimulated cardiomyocytes has not been investigated yet. In this study, we tried to detect the protective effect and potential mechanism of JUA on ISO-induced cardiomyocytes injury.
METHODS AND RESULTS:
H9C2 cells were treated with ISO to induce cell damage. Cells were pretreated with JUA to investigate the effects on the cell viability, morphological changes, light chain 3 conversion, and the activation of PI3K/Akt/mTOR signaling pathway. Results showed that ISO significantly inhibited the cell viability in a time- and dose-dependent manner. JUA pretreatment could reverse the reduction of cell viability and better the injury of H9C2 cells induced by ISO. Western blot analysis showed that JUA could accelerate the phosphorylation of PI3K, Akt, and mTOR. Results also indicated that JUA could significantly decrease the ratio of microtubule-associated protein LC3-II/I in H9C2 cells.
CONCLUSIONS:
Taken together, our research showed that JUA could notably reduce the damage cause by ISO via promoting the phosphorylation of PI3K, Akt, and mTOR and inhibiting LC3 conversion, which may be a potential choice for the treatment of heart diseases.

Northwest Pharmaceutical Journal, 2013, 28(3):281-4.

Inhibitory effect of jujuboside A on proliferation of human normal liver cells,hepatic stellate cells and human hepatoma cells by MTT assay[Reference: WebLink]

To observe the effect of different mass concentration of Jujuboside A(JuA)on proliferation of human normal liver cells LO2,rat hepatic stellate cells and human hepatoma cells SMMC-7721,respectively.
METHODS AND RESULTS:
The three cells were respectively divided into control group and six experimental groups which had different mass concentration of JuA.MTT assay was used to detect the activeness of cells.Effective mass concentration range and optimal dosing time were obtained by inhibition ratio.Results There was no difference in inhibitory effect of JuA on proliferation of human normal liver cells LO2and rat hepatic stellate cells(P0.05).But for human hepatoma cells SMMC-7721,there was a significant difference in inhibitory effect of JuA on proliferation(P0.05).The effective mass concentration was ranged from 5to 80μg.mL-1,the optimal dosing time was 48hand the IC50was 1.996μg.mL-1.
CONCLUSIONS:
JuA has a potential anti-hepatoma activity but has no toxicity to human normal liver cells LO2and rat hepatic stellate cells.

Eur J Pharmacol. 2014 Sep 5;738:206-13.

Jujuboside A, a neuroprotective agent from semen Ziziphi Spinosae ameliorates behavioral disorders of the dementia mouse model induced by Aβ 1-42.[Pubmed: 24886882]

Semen Ziziphi Spinosae (SZS) has been used as a hypnotic-sedative medicine for thousands of years. Recently, SZS has also shown notable neuroprotective activities via anti-oxidative and anti-inflammatory effects in dementia animals. Jujuboside A (JuA), isolated from SZS, has been proved to be a major hypnotic-sedative component of SZS.
METHODS AND RESULTS:
In the present study, we firstly evaluated the effects of intracerebroventricular (ICV) injection of JuA (0.02 and 0.2mg/kg) for five consecutive days on cognitive impairment induced by ICV injection of Aβ 1-42. The results showed that ICV treatment with JuA significantly mitigated learning and memory impairment in mice induced by Aβ 1-42 as measured by the Y-maze, active avoidance and Morris water maze. Furthermore, ICV treatment with JuA reduced the level of Aβ 1-42 in hippocampus, significantly inhibited the activities of acetylcholinesterase (AChE) and NO, and decreased the amount of the increased malondialdehyde (MDA) in the hippocampus and cerebral cortex of mice treated with ICV injection of Aβ 1-42. Shrinkage of nuclei, swollen and eccentrically dispersed neuronal bodies were observed in hippocampus of AD mice induced by Aβ 1-42, however, JuA noticeably improved the histopathological damage.
CONCLUSIONS:
Cumulatively, the present study indicates that JuA may serve as a potential therapeutic agent for the treatment of Alzheimer' disease.

Planta Med. 2003 Aug;69(8):692-5.

Inhibitory effect of jujuboside A on glutamate-mediated excitatory signal pathway in hippocampus.[Pubmed: 14531016]

Jujuboside A (JuA) is a main component of jujubogenin extracted from the seed of Ziziphus jujuba Mill var spinosa (Bunge) Hu ex H F Chou (Ziziphus), which is widely used in Chinese traditional medicine for the treatment of insomnia and anxiety. Previously, we reported the inhibitory effects of JuA on hippocampal formation in vivo and in vitro, the present study was carried out to examine the effects of JuA on glutamate (Glu)-mediated excitatory signal pathway in hippocampus.
METHODS AND RESULTS:
Microdialysis coupled with high-performance liquid chromatography (HPLC) was used to monitor the changes of Glu levels in the hippocampus induced by penicillin sodium, or a mixture of penicillin sodium and JuA. The results showed that penicillin increased the hippocampal Glu concentration (p < 0.01) and a high dose of JuA (0.1 g/L) significantly blocked penicillin-induced Glu release (p < 0.05). Moreover, the effect of JuA on intracellular Ca2+ changes after the stimulation by Glu was studied in cultured hippocampal neurons with confocal laser scanning microscope (CLSM). It was found that Glu (0.5 mM) induced an intracellular [Ca2+]i increase (p < 0.01), and JuA significantly inhibited the Glu-induced Ca2+ increase. The calmodulin (CaM) antagonist trifluoperazine (TFP) showed a similar inhibitory effect as JuA.
CONCLUSIONS:
These observations suggested that JuA has inhibitory effects on Glu-mediated excitatory signal pathway in hippocampus and probably acts through its anti-calmodulin action.

J Ethnopharmacol. 2010 Mar 24;128(2):419-23.

Effects on the expression of GABAA receptor subunits by jujuboside A treatment in rat hippocampal neurons.[Pubmed: 20083184]

To determine the effect of Jujuboside A (JuA) in modulating the gamma-aminobutyric acid (GABA(A)) receptor subunits gene expression of hippocampal neurons at different terms in vitro.
METHODS AND RESULTS:
Hippocampal neurons of rat were cultured in vitro, treated with JuA or diazepam (DZP). Then GABA(A) receptor mRNAs were evaluated by semi-quantitative RT-PCR. JuA at the low dose of 41 microM (about 0.05 g/l) induced significant increase of GABA(A) receptor alpha1, alpha5, beta2 subunit mRNAs in both 24 and 72h treatments. JuA at the high dose of 82 microM (about 0.1g/l) significantly increased GABA(A) receptor alpha1, alpha5 subunit mRNA levels and decreased beta2 subunit mRNA level at 24h treatment, and decreased GABA(A) receptor subunit alpha1, beta2 mRNAs expression at 72h treatment. DZP of 10 microM significantly increased expression of GABA(A) receptor subunit alpha1, alpha5 and decreased expression of beta2 at 24h treatment, and decreased alpha1, alpha5, beta2 subunits gene expression at 72h treatment.
CONCLUSIONS:
Differences in alterations in GABA(A) receptor subunit mRNAs expression following JuA and DZP treatments could help to explain the differences in the pharmacological action of the two drugs..

Acta Pharmacol Sin. 2001 Nov;22(11):986-90.

Inhibitory effect of jujuboside A on penicillin sodium induced hyperactivity in rat hippocampal CA1 area in vitro.[Pubmed: 11749788]

To study the effect of Jujuboside A (JuA), one constituent of Chinese herbal medicine Ziziphus jujuba Mill Var spinosa (Bunge) Hu,on the penicillin sodium induced hyperactivity in rat CA1 neurons in vitro.
METHODS AND RESULTS:
Hippocampal slices were obtained from the Sprague-Dawley rat brain and populational signals were measured from CA1 neurons of hippocampal slices using the extracellular recording technique. Penicillin sodium of 500, 1000, and 2000 kU/L were found to excite hippocampal CA1 neurons in a concentration-dependent manner in vitro. This excitatory effect of penicillin sodium could be inhibited by phenobarbital sodium of 0.02 - 0.05 g/L and JuA of 0.05 - 0.10 g/L.
CONCLUSIONS:
A high dose of JuA can inhibit the hyperactivity of hippocampal CA1 area induced by penicillin sodium. The inhibition of the amplitude of the first population spike (PS) and the latency of PS are more pronounced than the slope of the field excitatory post-synaptic potential.

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2002 Apr;31(2):103-106.

Sedative and anticonvulsant effect of jujuboside A.[Pubmed: 12539270]

To study the sedative effects of Jujuboside A (JuA) on the Central Nervous System of mice.
METHODS AND RESULTS:
Using a novel jiggle-cage test, we compared the sedative effect of JuA with that of Diazepam (DZP) both with a single and cumulative dose of JuA. We also assessed the anticonvulsant effect of JuA on pentylenetetrazol (PTZ)-induced seizures in mice. JuA significantly decreased total activity intensity and increased the quiet state time of mice. The sedative effects of JuA were more stable and more lasting than that of DZP. However, JuA failed to resist and delay the induced seizure activity in mice.
CONCLUSIONS:
Though JuA has sedative effects on mice CNS, it has no anticonvulsant effect on PTZ-induced seizures.